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  • 2000-2004  (103)
  • 1995-1999  (1.214)
  • 1985-1989  (1.583)
  • 1980-1984  (1.330)
  • Life Sciences  (1.607)
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Journal of comparative physiology 186 (2000), S. 347-357 
    ISSN: 1432-1351
    Schlagwort(e): Key words Crustacean ; Sensorimotor ; Ultrastructure ; Multilamellar sheath ; Myelinated axons
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1437-773X
    Schlagwort(e): Key words Mitogen-activated protein kinase (MAPK) ; Ischemia reperfusion injury ; Heart ; Ultrastructure ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The mitogen-activated protein kinase (MAPK) family is considered to be activated by stress, but the role of the MAPK family is still unknown in cardiac pathology. In the present study, not only the localization of MAPKs such as the extracellular responsive kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK (p38), but also ultrastructural changes were investigated in the ischemia-reperfusion model of Wistar rats. At 5, 10, 30, 60, and 180 min reperfusion after 30 min ischemia by occluding the coronary artery, the expression of these MAPKs was increased in blood vessels and cardiomyocytes by Western blotting and immunohistochemical methods. In addition, after ischemia reperfusion, various ultrastructural changes such as decreased glycogen granules, mitochondrial swelling, and myolysis were observed in the blood vessels and cardiomyocytes. These results suggest that protein kinases may regulate numerous biological processes, including the regulation of contraction and ion transport.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1437-773X
    Schlagwort(e): Key words Gonadotroph adenoma ; FSH ; Childhood ; Ultrastructure ; Immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Female gonadotroph adenomas with endocrinological symptoms are uncommon. Six cases of such adenomas have been reported in the literature: two were girls who presented with precocious puberty and four were premenopausal women with accompanying multiple ovarian cysts. We describe here a 10-year-old Japanese girl with a gonadotroph macroadenoma and present detailed morphological findings of the tumor. The patient's chief complaints were nausea, abdominal distention, and abdominal pain. Abdominopelvic ultrasonography and magnetic resonance imaging (MRI) revealed bilateral multiple ovarian cysts. Endocrinological assays showed elevated serum follicle-stimulating hormone (FSH) (33.7 mIU/ml) and estradiol (3840 pg/ml). MRI of the head showed a large pituitary tumor. Two transsphenoidal operations and subsequent radiation therapy were performed. Immunohistochemically, more than half the tumor cells were positive for anti-FSH-β monoclonal antibody. Ultrastructurally, the tumor cells exhibited a fairly uniform picture of rounded cells. Their nuclei were slightly irregular and contained heterochromatin, and their cytoplasm contained many round, dense core granules, measuring 140–260 nm in diameter, together with well-developed organelles. An in vitro study showed that the tumor cells in primary culture produced FSH (1089.0 mIU/ml). To our knowledge, this is the first immunohistochemical and ultrastructural study of an FSH-secreting gonadotroph adenoma occurring in childhood.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1437-773X
    Schlagwort(e): Key words Apoptosis ; Helicobacter pylori ; Fibroblasts ; Smooth muscle cells ; Ultrastructure ; Gastroduodenal ulcer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract It has been considered that Helicobacter pylori (H. pylori) infection is a major cause of human gastritis and gastroduodenal ulcers (G-DU). Many investigations of the relationship between H. pylori and apoptosis have been reported recently. However, these studies focused mostly on epithelium, using the TUNEL method. In the present study, we evaluated by electron microscopy the occurrence of apoptosis in the mesenchymal cells of lamina propria mucosae infected with H. pylori. Gastric biopsy specimens from 37 H. pylori-infected G-DU patients and 8 noninfected volunteers were examined with both light and electron microscopy and analyzed by the TUNEL method. The TUNEL method showed no significant difference between H. pylori-infected and noninfected cases. In contrast, electron microscopy revealed significant numbers of apototic fibroblasts and smooth muscle cells in H. pylori-infected lamina propria mucosae, with a diminished number of collagen fibers in surrounding areas. These areas showed edematous changes histopathologically. These results indicated that H. pylori infection induces apoptosis of fibroblasts and smooth muscle cells in lamina propria, with decrease in the numbers of collagen fibers, suggesting that these alterations may be affected by exaggerate acid secretion, decrease mucus protecting factors, and result in ulcer formation.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Medical electron microscopy 33 (2000), S. 109-114 
    ISSN: 1437-773X
    Schlagwort(e): Key words Ciliogenesis ; Ciliated cell ; Abnormal cilia ; Basal body ; Ultrastructure ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cilia are motile processes extending from the basal bodies, playing important roles in the mucociliary clearance in the respiratory tract and the transport of the ovum from the ovary to the uterus in mammals. Ciliogenesis is divided into four stages: (1) duplication of centrioles; (2) migration of centrioles to the apical cell surface to become basal bodies; (3) elongation of cilia containing the axoneme; and (4) formation of accessory structures of basal bodies. The orderly course of ciliogenesis appears to be disturbed by various internal and external factors and, as a result, various unusual forms of the ciliary apparatus develop in the cell. Inhibition of basal body migration results in development of intracytoplasmic axonemes, cilia within periciliary sheaths, and intracellular ciliated cysts. Swollen cilia and the bulging type of compound cilia are formed during ciliary budding and elongation. This review also discusses the origin, composition, and function of the centriolar precursor structures.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Medical electron microscopy 33 (2000), S. 135-142 
    ISSN: 1437-773X
    Schlagwort(e): Key words Elastic system fiber ; Ultrastructure ; Fibrotic human liver ; Oxytalan fiber ; Elaunin fiber
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The network of elastic system fibers in human fibrotic liver was investigated by histological methods, immunohistochemical staining, and electron microscopy. Type III collagen was seen not only in regions of portal fibrosis but also in the sinusoidal wall. However, elastic system fibers were not found in the Disse space of the sinusoidal wall. Elastic system fibers including oxytalan, elaunin, and elastic fibers were found successively in the course of elastogenesis. A few normal oxytalan fibers and abnormal oxytalan fibers were observed in the periportal tracts. Few normal elaunin and abnormal elaunin fibers were observed in regions of portal fibrosis but not in the surrounding margin. Elastic fibers, only in scarce amounts, were observed around the portal veins in the case of chronic active hepatitis but not in acute hepatitis. Abnormal oxytalan fibers were seen as a bundle of wavelike microfibrils and had an irregular arrangement. Abnormal elaunin fibers were not associated with bundles of microfibrils. Abnormal elaunin fibers in large amounts were found interspersed with spiraled collagen, which most likely indicates that the oxytalan fibers degenerated in the course of elastogenesis. Thus, in a fibrotic liver it is possible that synthesis of normal elaunin and elastic fibers does not occur or that the quantity of such fibers synthesized may be small because of the effect of the degenerated oxytalan fibers. As a characteristic of liver fibrosis, the composition of abnormal elastic system fibers and spiraled collagen differs from that in other fibrotic organs.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1437-773X
    Schlagwort(e): Key words Adenoid basal carcinoma ; Uterine cervix ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Adenoid basal carcinoma of the uterine cervix is a rare tumor with a favorable prognosis. A case of adenoid basal carcinoma (ABC) of the uterine cervix was studied using light and electron microscopy. The patient was a 74-year-old Japanese woman who had undergone hysterectomy due to cervical intraepithelial neoplasia 3. Incidentally, ABC was found in the resected uterus. The tumor cells made small nests and infiltrated the cervical portion of the uterus. In the nests, glands, cribriform patterns with glandlike structures, and squamous differentiation were seen. Immunohistochemically, the glandlike structures were positive for laminin and type IV collagen. Ultrastructurally, the tumor cells had irregular nuclei, scanty cytoplasm, and cribriform patterns in which glandlike structures were covered with basal lamina. No myoepithelial differentiation of the tumor cells was seen. These findings suggest a similarity between adenoid basal carcinomas and adenoid cystic carcinomas. Furthermore, both tumors are considered to originate in the reserve cells of the uterine cervix. Because their outcomes are different, they should be distinguished from each other.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-2161
    Schlagwort(e): Key words Giant rice body ; Ultrastructure ; Immunohistochemistry ; Histogenesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Objective: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. Design and patients: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. Results: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. Conclusion: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-2307
    Schlagwort(e): Key words Arteriogenesis ; Collateral vessels ; Ultrastructure ; Cell adhesion molecules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Previous studies in the canine heart had shown that the growth of collateral arteries occurs via proliferative enlargement of pre-existing arteriolar connections (arteriogenesis). In the present study, we investigated the ultrastructure and molecular histology of growing and remodeling collateral arteries that develop after femoral artery occlusion in rabbits as a function of time from 2 h to 240 days after occlusion. Pre-existent arteriolar collaterals had a diameter of about 50 µm. They consisted of one to two layers of smooth muscle cells (SMCs) and were morphologically indistinguishable from normal arterioles. The stages of arteriogenesis consisted of arteriolar thinning, followed by transformation of SMCs from the contractile- into the proliferative- and synthetic phenotype. Endothelial cells (ECs) and SMCs proliferated, and SMCs migrated and formed a neo-intima. Intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) showed early upregulation in ECs, which was accompanied by accumulation of blood-derived macrophages. Mitosis of ECs and SMCs started about 24 h after occlusion, whereas adhesion molecule expression and monocyte adhesion occurred as early as 12 h after occlusion, suggesting a role of monocytes in vascular cell proliferation. Treatment of rabbits with the pro-inflammatory cytokine MCP-1 increased monocyte adhesion and accelerated vascular remodeling. In vitro shear-stress experiments in cultured ECs revealed an increased phosphorylation of the focal contacts after 30 min and induction of ICAM-1 and VCAM-1 expression between 2 h and 6 h after shear onset, suggesting that shear stress may be the initiating event. We conclude that the process of arteriogenesis, which leads to the positive remodeling of an arteriole into an artery up to 12 times its original size, can be modified by modulators of inflammation.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 99 (2000), S. 310-316 
    ISSN: 1432-0533
    Schlagwort(e): Key words Ganglioglioma ; Ependymoma (tanycytic variant) ; Neurofibrillary tangle ; Immunohistochemistry ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We studied a cystic ganglioglioma (GG) located in the right frontal lobe of the brain. Interestingly, the fibrillary spindle glial cells were often arranged in a fascicular pattern, and the generally uniform, round-to-oval delicate nuclei appeared to resemble those of ependymoma; and the neoplastic neurons often contained neurofibrillary tangles (NFTs). The glial component was positive for glial fibrillary acidic protein and occasionally contained granular or microvesicular structures positive for epithelial membrane antigen. Ultrastructural investigation revealed that the glial cells were ependymal in nature; intracytoplasmic lumina and intercellular microrosettes lined with cilia and microvilli, as well as long zonulae adherentes, were evident. In addition, chromogranin A-positive granular staining, neurosecretory-granule-like structures, and parallel arrays of microtubules were sometimes associated with the blood vessels. We considered the present case to be an unusual example of GG with an ependymoma, more precisely a tanycytic ependymoma, as the glial component; to our knowledge, the existence of ependymoma as the main glial component of this particular tumor has not been described before. The occurrence of NFTs, which has been reported in several cases of GG, was an additional, unusual feature.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Acta neuropathologica 99 (2000), S. 214-218 
    ISSN: 1432-0533
    Schlagwort(e): Key words Eosinophilic inclusion body ; Inclusion ¶body ; Ependymoma ; Microlumina ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A study was undertaken to determine the pathological significance of previously unrecognized intracytoplasmic eosinophilic inclusions (IEIs) in ependymoma. The study group consisted of 58 ependymomas, all of which were pathologically characterized and graded according to the 1993 WHO classification. Electron microscopic studies were performed in 16 cases. The study showed that 33 (57%) ependymomas had IEIs and that in 8 cases these were abundant. Round and eosinophilic, their sizes varied from 10 μm to a tiny dot. Similar eosinophilic bodies were also observed between tumor cells. The inclusions were weakly PAS positive. On immunostains, IEIs were frequently positive for glial fibrillary acidic protein, less often for S-100 protein, and for epithelial membrane protein and CAM 5.2. They were negative for AE1/AE3, carcinoembryonic antigen and Ber-EP4. Ultrastructurally, IEIs represented intracytoplasmic lumens containing microvilli and cilia. These microlumina also frequently contained granulo-tubular materials. With reference to tumor subtypes, IEIs occurred most frequently in ordinary and clear cell ependymomas. IEIs were also present in 4 of 6 anaplastic ependymomas studied. In conclusion, IEIs represent microlumina and occur in more than a half of ependymomas including malignant examples. Their finding is a helpful diagnostic feature of ependymoma.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Anatomy and embryology 201 (2000), S. 51-61 
    ISSN: 1432-0568
    Schlagwort(e): Key words Female prostate (Skene gland) ; Ultrastructure ; Secretory (luminal) cells ; Basal (reserve) cells ; Intermediary cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The predominant cells of female prostatic glands lining their lumen were found to be tall cylindrical secretory cells with short stubby microvilli, protuberances of the apical cytoplasm, and with bleb formation. Abundant secretory vacuoles and granules, rough endoplasmic reticulum, developed Golgi complexes and numerous mitochondria are characteristic of their active secretory configuration with apocrine (apical blebs) and merocrine (secretory vacuoles and granules) type of secretion. Basal (reserve) cells were seen to be located between the secretory (luminal) cells and the basement membrane. Their ground cytoplasm is dense with rough endoplasmic reticulum and mitochondria. Their nuclei, unlike those of secretory cells, possess more peripheral condensed chromatin, denser dispersed chromatin and sporadic nucleoli. Besides the two basic types of mature prostatic cells intermediary cells were also seen, located between the basal and secretory cells or in their close vicinity. Their cytoplasm exhibits numerous profiles of rough endoplasmic reticulum and free ribosomes. Secretory vacuoles and granules were mostly practically absent (type 1 intermediary cells) so that they resembled basal (reserve) cells. In some of them, however, as in secretory cells, such secretory elements do gradually appear (type 2 intermediary cells). The finding of intermediary cells in the lining of prostatic glands supports the role of basal (reserve) cells in the renewal of cells in glands of the female prostate. The first ultrastructural analysis of the normal female prostate performed by transmission electron microscopy showed that, as in the postpubertal male, the prostatic glands in the adult female display mature secretory and basal cells. The results of the presented study further corroborate the contemporary concept of the female prostate as a functional genitourinary organ.
    Materialart: Digitale Medien
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  • 13
    ISSN: 1432-0533
    Schlagwort(e): Key words Alzheimer disease ; Fibrillar amyloid-β ; Astrocytes ; Microglial cell ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ultrastructural three-dimensional reconstruction of human classical plaques in different stages of development shows that microglial cells are the major factor driving plaque formation by fibrillar amyloid-β (Aβ) deposition. The amount of fibrillar Aβ released by microglial cells and the area of direct contact between amyloid and neuron determine the extent of dystrophic changes in neuronal processes and synapses. The volume of hypertrophic astrocytic processes separating fibrillar amyloid from neuron is a measure of the protective activation of astrocytes. On the bases of the volume of amyloid star, microglial cells, dystrophic neurites, and hypertrophic astrocytic processes, and spatial relationships between plaque components, three stages in classical plaque development have been distinguished: early, mature, and late. In early plaque, the leading pathology is fibrillar Aβ deposition by microglial cells with amyloid star formation. The mature plaque is characterized by a balance between amyloid production, neuronal dystrophy, and astrocyte hypertrophy. In late classical plaque, microglial cells retract and expose neuropil on direct contact with amyloid star, enhancing both dystrophic changes in neurons and hypertrophic changes in astrocytes. In late plaques, activation of astrocytes predominates. They degrade amyloid star and peripheral amyloid wisps. The effect of these changes is classical plaque degradation to fibrillar primitive and finally to nonfibrillar, diffuse-like plaques.
    Materialart: Digitale Medien
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  • 14
    ISSN: 1432-0533
    Schlagwort(e): Key words GM1-gangliosidosis ; Ultrastructure ; Electrospray ionisation tandem mass spectrometry ; Diagnosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels of GM1-ganglioside within the tissue using the novel technique of electrospray ionisation tandem mass spectrometry. Electron microscopic examination of ultrathin sections of resin-embedded tissue revealed cytoplasmic inclusions (membranous cytoplasmic and zebra bodies) in brain stem and cerebellar neurons that were characteristic of a gangliosidosis. Glycolipids were extracted from the fixed tissue and analysed by tandem mass spectrometry. Two major ions were detected, which corresponded to GM1 (d18:1–C18:0) and GM1 (d20:1–C18:0). Their identity was confirmed by comparison of their fragmentation patterns with those of authentic standards. The concentration of GM1 was approximately sixfold higher on a wet weight basis than in the brain of a normal control dog, confirming the diagnosis of GM1-gangliosidosis.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Virchows Archiv 436 (2000), S. 249-256 
    ISSN: 1432-2307
    Schlagwort(e): Key words Endothelial cells ; Cell culture ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The aim of the present work was to examine and compare the ultrastructure of bovine retinal endothelial cells (BRECs) in vitro during several passages in a medium selective for endothelial cells. The identity of the endothelial cells was confirmed immunohistochemically, up to the tenth passage. Changes in their ultrastructure in comparison to endothelial cells in vivo occurred at the onset of culturing and not progressively with repeated passages. The cultured BRECs show high metabolic activity in all passages. While retaining their identity as endothelial cells, they modify their lipid metabolism, so that lipids are stored. This change in lipid metabolism was induced by the medium.
    Materialart: Digitale Medien
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  • 16
    ISSN: 1432-2013
    Schlagwort(e): Key words Pineal organ ; Photoreceptor cells ; Ultrastructure ; Proteus anguinus ; Regressive evolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We studied ultrastructure of the photoreceptor cells in the pineal organ of blind, depigmented, neotenic cave salamander, Proteus anguinus. Unlike in epigean vertebrates the outer segments of most photoreceptor cells consists of concentrically arranged lamellae, however; in few cells, the outer segments contain 7-9 plasma membrane disks. In both types of photoreceptor cells the outer segments enclose lumps of vesicles of different sizes. The photoreceptor cells of Proteus anguinus are similar to those in other cavernicolous fish species.
    Materialart: Digitale Medien
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  • 17
    ISSN: 1569-8041
    Schlagwort(e): cisplatin ; pharmacokinetics ; phase I ; oral topotecan
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 18
    ISSN: 1569-8041
    Schlagwort(e): dosing ; inhibitor ; matrix metalloproteinase ; pharmacokinetics ; solid tumours ; toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background:This phase I study was performed to evaluatethe safety, tolerability, and efficacy of the oral matrixmetalloproteinase inhibitor BAY 12-9566 in patients with advanced solidtumours, and to identify the maximum tolerated dose and dose for use insubsequent studies. Patients and methods:BAY 12-9566 was administered to 29 patientsat doses ranging from 100 mg o.d. to 1600 mg (given either 400 mg q.i.d. or800 mg b.i.d.). Blood samples for pharmacokinetic analyses were drawn on days1–5, day 15 and days 29 and 30. Patients were continued on daily oraltreatment of BAY 12-9566 until a dose limiting toxicity or tumour progressionoccurred. Results:A maximum tolerated dose was not defined because plasmalevels of BAY 12-9566 could not be sufficiently increased, even withescalating doses of drug. Pharmacokinetic analysis suggested that absorptionwas saturable at higher doses. The predominant toxicities related to drug wereasymptomatic reversible effects on platelets and transaminases and mildanemia. There were no significant musculoskeletal toxicities. No objectiveresponses were seen at the doses tested, but stable disease was observed insome patients based on tumour measurements. Conclusions:The recommended dose of BAY 12-9566 for furtherstudies is 800 mg b.i.d. as this dose provides maximal plasma levels that canbe achieved with a convenient dosing schedule for a chronically administeredoral agent
    Materialart: Digitale Medien
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  • 19
    ISSN: 1569-8041
    Schlagwort(e): 776C85 ; bioequivalence ; dihydropyrimidine dehydrogenase inhibitor ; eniluracil ; 5-fluorouracil ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background:This study was performed to evaluate thepharmacokinetics, bioequivalence, and feasibility of a combined oralformulation of 5-flurouracil (5-FU) and eniluracil (Glaxo Wellcome Inc.,Research Triangle Park, North Carolina), an inactivator of dihydropyrimidinedehydrogenase (DPD). The rationale for developing a combined eniluracil/5-FUformulation oral dosing form is to simplify treatment with these agents, whichhas been performed using separate dosing forms, and decrease the probabilityof severe toxicity and/or suboptimal therapeutic results caused byinadvertently high or conversely insufficient 5-FU dosing. Patients and methods:The trial was a randomized, three-waycrossover bioequivalence study of three oral dosing forms of eniluracil/5-FUtablets in adults with solid malignancies. Each period consisted of two daysof treatment and a five- to seven-day washout phase. Eniluracil at a dose of20 mg, which results in maximal DPD inactivation, was administered twice dailyon the first day and in the evening on the second day of each of the threetreatments. On the morning of the second day, all patients received a totaleniluracil dose of 20 mg orally and a total 5-FU dose of 2 mg orally as eitherseparate tablets (treatment A) or combined eniluracil/5-FU tablets in twodifferent strengths (2 tablets of eniluracil/5-FU at a strength (mg/mg) of10/1 (treatment B) or 8 tablets at a strength of 2.5/0.25 (treatment C)). Thepharmacokinetics of plasma 5-FU, eniluracil, and uracil, and the urinaryexcretion of eniluracil, 5-FU, uracil, and α-fluoro-β-alanine (FBAL),were studied. To determine the bioequivalence of the combined eniluracil/5-FUdosing forms compared to the separate tablets, an analysis of variance onpharmacokinetic parameters reflecting eniluracil and 5-FU exposure wasperformed. Results:Thirty-nine patients with advanced solid malignancies hadcomplete pharmacokinetic studies performed during treatments A, B, and C. Thepharmacokinetics of eniluracil and 5-FU were similar among the three types oftreatment. Both strengths of the combined eniluracil/5-FU dosing form and theseparate dosing forms were bioequivalent. Mean values for terminal half-life,systemic clearance, and apparent volume of distribution for oral 5-FU duringtreatments A/B/C were 5.5/5.6/5.6 hours, 6.6/6.6/6.5 liters/hour, and50.7/51.5/50.0 liters, respectively. The intersubject coefficient of variationfor pharmacokinetic variables reflecting 5-FU exposure and clearance intreatments ranged from 23% to 33%. The urinary excretion ofunchanged 5-FU over 24 hours following treatments A, B, and C averaged52.2%, 56.1%, and 50.8% of the administered dose of 5-FU,respectively. Parameters reflecting DPD inhibition, including plasma uraciland urinary FBAL excretion following treatments A, B, and C were similar.Toxicity was generally mild and similar following all three types oftreatments. Conclusions:The pharmacokinetics of 5-FU and eniluracil weresimilar and met bioequivalence criteria following treatment with the separateoral formulations of 5-FU and eniluracil and two strengths of the combinedformulation. The availability of a combined eniluracil/5-FU oral dosing formwill likely simplify dosing and decrease the probability of severe toxicityor suboptimal therapeutic results caused by an inadvertent 5-FU overdose orinsufficient 5-FU dosing in the case of separate oral formulations, therebyenhancing the overall feasibility and therapeutic index of oral 5-FU therapy.
    Materialart: Digitale Medien
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  • 20
    ISSN: 1569-8041
    Schlagwort(e): BBR3464 ; phase I ; platinum analog ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objectives:To define the maximum tolerated dose (MTD), thetoxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. Patients and methods:Fourteen patients with advanced solid tumorsnot responsive to previous antitumor treatments received BBR 3464 on a daily× 5 schedule every twenty-eighth day. The drug was given as a one-hourinfusion with pre-and post-treatment hydration (500 ml in one hour) and noantiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. Amodified accelerated titration escalation design was used. Total and freeplatinum (Pt) concentrations in plasma and urine were assessed by ICP-MS ondays 1 and 5 of the first cycle. Results:Dose was escalated four times up to 0.17mg/m2/day. Short-lasting neutropenia and diarrhea of late onsetwere dose-limiting and defined the MTD at 0.12 mg/m2. Nausea andvomiting were rare, neither neuro- nor renal toxic effects were observed.BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-lifeof several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 werehigher than on day 1, indicating drug accumulation. Approximately 10%of the equivalent dose of BBR3464 (2.2%–13.4%) wasrecovered in a 24-hour urine collection. Conclusions:The higher than expected incidence of neutropenia andGI toxicity might be related to the prolonged half-life and accumulation oftotal and free Pt after daily administrations. Lack of nephrotoxicity and thelow urinary excretion support the use of the drug without hydration. Thesingle intermittent schedule has been selected for clinical development.
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  • 21
    ISSN: 1569-8041
    Schlagwort(e): interferon-α ; pharmacokinetics ; renal carcinoma ; retinoids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Although advanced renal-cell carcinoma (RCC) responds poorly to standardtherapies, phase I–II trials have shown activity for combinations ofinterferon-α2b (IFN) with a retinoid. Alitretinoin (9-cis RA) isan endogenous retinoid with high binding affinity for both RAR and RXRreceptor families. This phase I–II study enrolled 38 patients with RCCin a dose-escalation study of tolerability, pharmacokinetics (PK), andefficacy of twice daily oral 9-cis RA with subcutaneous IFN. Incontrast to studies with similar doses of daily 9-cis RA, PK studiesfound a consistent reduction in 9-cis RA concentrations of about50% after multiple b.i.d. doses of 30 or 50 mg/m2,independent of cotreatment with IFN. In the phase I portion, toxicitiesincluded systemic symptoms typical of IFN and biochemical abnormalitiespreviously associated with retinoids. Two patients experienced dose-limitingtoxicity at 50 mg/m2 b.i.d. of 9-cis RA, thus therecommended phase II dose was 30 mg/m2 b.i.d. One of twenty-sixevaluable patients achieved a durable objective partial remission, andrepeated dosing with this regimen was poorly tolerated. This combination ofretinoid and interferon is not recommended for further study in RCC.
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  • 22
    ISSN: 1569-8041
    Schlagwort(e): chemotherapy ; doxorubicin ; hepatocellular carcinoma ; liposome ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background:There is lack of effective and safe chemotherapy foradvanced hepatocellular carcinoma. Polyethylene glycol-coated (pegylated)liposomal doxorubicin (PLD) has long circulation time and enhanced drugaccumulation in the tumor tissues. It has significant activity in Kaposi'ssarcoma, breast and ovarian cancers and the acute adverse effects of free drugare reduced. Patients and methods:A patient with advanced hepatocellularcarcinoma was treated with PLD and a pharmacokinetic study was performed.Initial serum total and direct bilirubin were 3.6 and 6.8 folds of uppernormal, respectively, and an indocyanine green clearance test at 15 minuteswas 26.3% (normal 〈 15%). Results:Compared to cases with normal liver function, increasedvolume of distribution of doxorubicin correlated with a large amount ofascites (P〈 0.05). The clearance of drug was unexpectedly higherthan in cases with normal liver function (P〈 0.05). According tothe pharmacokinetic studies, the disposition of PLD in this case has not beenretarded even in the presence of severe liver dysfunction. Only minimaltoxicities including grade 2 stomatitis and moderate leukopenia were observed.The tumor had a partial remission and the patient survived nine months afterPLD treatment. Conclusion:PLD could serve as a safe and effective treatment forhepatocellular carcinoma even in the presence of impaired liver function. Itsrole in treating advanced hepatocellular carcinoma is worthy of further study.
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  • 23
    ISSN: 1439-7609
    Schlagwort(e): Key words Septic arthritis ; Surface antigens ; Ultrastructure ; Burkholderia pseudomallei ; IEM
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Burkholderia pseudomallei is the causative agent of melioidosis, a disease that frequently runs a protracted course and is very difficult to eradicate. The mechanisms that this organism uses to escape from host defense mechanisms and antibiotics are not well understood. The aim of the study was to compare the morphological characteristics and surface antigen expression of B. pseudomallei in naturally infected human synovial tissues with the characteristics of bacteria grown in culture media. Immunoelectron microscopic study was performed in four synovial biopsies taken from four B. pseudomallei septic arthritis patients. Colonies of pathogenic B. pseudomallei collected from culture media were used as positive controls. Polyclonal antibody to whole cell B. pseudomallei was used as a primary antibody. Complete bacteria-like particles were demonstrated both extracellularly and intracellularly in all four synovial specimens. The intracytoplasmic location of B. pseudomallei and mononuclear phagosome containing microcolony-like structures were demonstrated. B. pseudomallei found in the synovial membrane samples were mostly atypical, with fewer cytoplasmic electron lucent granules. Immunogold staining of bacterial surface antigens was weaker than staining of positive controls. We demonstrated atypical forms of B. pseudomallei and evidence for suppression of its surface antigens in naturally infected human synovial tissues. This adaptation may help bacteria to survive despite host immune surveillance and treatment with antibiotics.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Mycorrhiza 10 (2000), S. 15-21 
    ISSN: 1432-1890
    Schlagwort(e): Anthoceros punctatus ; Arbuscular mycorrhiza ; Bryophytes ; Glomus ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Glomus claroideum (Schenck & Smith emend. Walker & Vestberg) were investigated for ability to form arbuscular mycorrhiza-like symbioses with the hornwort Anthoceros punctatus (L.). Spores were transferred to a cellulose acetate filter on water agar and a small portion of an Anthoceros thallus was placed directly upon the spores. Light-microscope observations 20 days after inoculation revealed branched hyphae growing within the thallus. After 45 days, arbuscules and vesicles were studied by light- and electron-microscopy. After 60 days in water agar culture, the colonised Anthoceros thalli were transferred to a low-nutrient medium agar. Hyphae spread in the agar and newly formed spores were observed 5 weeks after the transfer. After 4 months, about 1000 spores were formed in each Petri dish. This is the first report of an experimentally established arbuscular mycorrhiza-like symbiosis between an identified fungus belonging to the Glomales and a bryophyte.
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  • 25
    ISSN: 1432-5233
    Schlagwort(e): Key words Streptozotocin ; Diabetes ; Ventricular myocyte ; Cardiac muscle ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Contractile dysfunctions have been demonstrated in different experimental models of diabetes which have similar characteristics to many of the abnormalities found in the clinical setting. Administration of streptozotocin (STZ) to young adult rats induces β-cell necrosis of the pancreas which gives rise to hypoinsulinaemia and hyperglycaemia, features which are also seen in untreated type 1 clinical diabetes. We have investigated the chronic effects of STZ-induced diabetes on contraction in rat ventricular myocytes and ultrastructure of cardiac muscle. Diabetes was induced in male Wistar rats (230–270 g) with a single injection of STZ (60 mg kg−1). At 2 and 10 months after STZ treatment, the amplitude of contraction was larger in diabetic compared to control myocytes. Time to peak contraction was significantly longer at 2 months but appeared to normalise at 10 months after STZ treatment. In contrast, time to half relaxation of contraction was not significantly different after 2 months but was significantly reduced at 10 months after STZ treatment compared to control. Transmission electron microscope examination of cardiac muscle showed that the ultrastructure of cardiac muscle, especially structures associated with contraction, were not greatly altered after STZ treatment. Sarcomere lengths were not significantly different in papillary or ventricular muscle at 4 or 8 months after STZ treatment compared to control. Our data provide evidence that morphological defects in contractile myofilaments and associated structures cannot explain contractile dysfunctions seen in ventricular myocytes from STZ-treated animals.
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  • 26
    ISSN: 1615-6102
    Schlagwort(e): Arabidopsis thaliana ; Cryopreservation ; Dehydration ; Thermal analysis ; Sucrose ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Arabidopsis thaliana suspension cells were preserved in liquid nitrogen for over three years, using embedding of cells in calcium-alginate prior to subculture in sucrose-enriched medium, air-drying, and direct quenching in liquid nitrogen. Survival of cells reached 34%, yielding regrowth at the surface of all cryopreserved beads in less than 7 days. Following pretreatment and dehydration, the water content dropped from 2300% to 34% with respect to dry weight. Differential scanning calorimetry showed that glass transition occurred on cooling, followed by a slight crystallization event on rewarming. The survival of cells was independent of the cooling rate. The tolerance of the acute dehydration step increased progressively with sucrose pretreatment duration, indicating the requirement for adaptative cellular alterations. Ultrastructural studies revealed several changes in cells after sucrose pretreatment prolonged from 1 to 7 days: reversal of the initially plasmolyzed state, microvacuolation, numerous autophagic structures, scarcity of ribosomes, increase in number and size of starch grains. No cell division seemed to occur during this period. After air-drying and after a freeze-thaw cycle, followed by 24 h rehydration, regenerating cells had recovered a high level of ultrastructural organization and contained numerous polysomes suggesting an intense metabolic activity. Trehalose, a cryoprotective disaccharide not considered to be a metabolic substrate, yielded only 70% regrowth after freezing. Biochemical analysis showed that soluble sugars accumulated during the pretreatment, essentially sucrose or trehalose; the monosaccharide content also increased. In the light of these results, the action of sucrose in inducing freezing tolerance is discussed.
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  • 27
    ISSN: 1615-6102
    Schlagwort(e): Beta vulgaris ; Cyst nematodes ; Histology ; Resistance mechanism ; Syncytium ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Using susceptible and resistant sugar beet lines, comparative analyses of root histology and ultrastructure were made during invasion by nematodes and the induction and formation of specific feeding structures (syncytia).The resistant line carried the resistance geneHs1pro−1.Nematodes were able to invade and induce functional syncytia in roots of resistant and susceptible lines. However, syncytia in resistant roots were smaller and less hypertrophied. The vacuolar system of syncytia in susceptible plants contained many small vacuoles. In resistant plants vacuoles were larger but less numerous. Smooth endoplasmic reticulum prevailed in syncytial protoplasts of susceptible plants, whereas almost only rough endoplasmic reticulum occurred in syncytia in resistant plants. The most conspicuous and hitherto undescribed trait of syncytia in resistant roots was the initial appearance of loose, and later compact, aggregations of the endomembrane system which composed most of the endoplasmicreticulum system of syncytia at later stages. Syncytia in resistant plants usually degraded before the nematodes reached their adult stage. The appearance of membrane aggregations and the other resistance-specific features are discussed in relation to their possible effects on syncytium function and role in nematode resistance.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    Protoplasma 211 (2000), S. 94-102 
    ISSN: 1615-6102
    Schlagwort(e): Androgenesis ; Embryogenesis ; Microspore culture ; Pollen ; Ultrastructure ; Wheat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary We have made a detailed cytological examination of the development of wheat embryoids, monitoring their initial divisions from two to ten cells by both light and electron microscopy. According to our observations the first embryogenic division is symmetrical. After the androgenesis induction treatment, there is a decrease in ribosome population with cells that have inactive nucleoli made up almost exclusively of a dense fibrillar component. This population is restored after initial embryogenic divisions. During the initial divisions the embryogenic pollen grains do not appear to change in size and the pollen wall remains intact. The exine undergoes no modification but the intine thickens, and we have observed that the thickness of the intine can be used as a cytological marker of androgenesis. The walls separating the cells obtained after embryogenic division contained numerous plasmodesmata. The beginnings of embryo polarization and cell differentiation could be made out in the very early pollen embryoids.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Investigational new drugs 18 (2000), S. 373-381 
    ISSN: 1573-0646
    Schlagwort(e): clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Veterinary research communications 24 (2000), S. 189-196 
    ISSN: 1573-7446
    Schlagwort(e): cattle ; dosage ; fluoroquinolone ; pefloxacin ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The disposition kinetics and urinary excretion of pefloxacin after a single intravenous administration of 5 mg/kg were investigated in crossbred calves and an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of pefloxacin in the plasma was 18.95±0.892 μg/ml, which declined to 0.13±0.02 μg/ml at 10 h. The pefloxacin was rapidly distributed from the blood to the tissue compartment as shown by the high values for the initial distribution coefficient, α (12.1±1.21 h–1) and the constant for the rate of transfer of drug from the central to the peripheral compartment, K 12 (8.49±0.99 h–1). The elimination half-life and volume of distribution were 2.21±0.111 h and 1.44±0.084 L/kg, respectively. The total body clearance (ClB) and the ratio of the drug present in the peripheral to that in the central compartment (P/C ratio) were 0.454±0.026 L/kg h) and 5.52±0.519, respectively. On the basis of the pharmacokinetic parameters obtained in the present study, an appropriate intravenous dosage regimen for pefloxacin in cattle for most of the bacteria sensitive to it would be 6.4 mg/kg repeated at 12 h intervals.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    Veterinary research communications 24 (2000), S. 245-260 
    ISSN: 1573-7446
    Schlagwort(e): anthelmintic ; antibiotic ; camel ; chemotherapy ; enzymes ; pharmacokinetics ; xenobiotic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recent publications dealing mainly with the kinetics of antiparasitic and antibacterial agents, NSAIDs, and other drugs in camels are briefly reviewed. The kinetic data for most of these drugs indicated that they have longer absorption and elimination half-lives and slower systemic clearance in the camel compared to other animals. This corroborates earlier reports that suggested that the activities of drug-metabolizing enzymes and the capacity to biotransform and eliminate xenobiotics is lower in camels than in other ruminants. There is a clear need to establish basic kinetic data for the camel in order to avoid extrapolation of drug dosage regimens and withdrawal times from data for other animals, as this may result in irrational use of drugs in camels.
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    Veterinary research communications 24 (2000), S. 339-348 
    ISSN: 1573-7446
    Schlagwort(e): anthelmintic ; benzimidazole ; chromatography ; enantiomer ; metabolism ; pharmacokinetics ; sex ; sheep
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Benzimidazole anthelmintic drugs are widely used in veterinary practice. Albendazole sulphoxide (ABZSO) is a benzimidazole drug with two enantiomers, as a consequence of a chiral centre in the sulphoxide group. The kinetics of these enantiomers were studied in male and female sheep. Plasma samples were obtained from the animals between 0.5 and 72 h after oral administration of 7.5 mg/kg of a racemic formulation of ABZSO (total-ABZSO). After a liquid–liquid extraction, the samples were analysed by HPLC to determine the concentrations of total-ABZSO and of the sulphone metabolite (ABZSO2). During the chromatographic analysis, the ABZSO peak was collected and reanalysed by an HPLC technique using a Chiral AGP column to quantify the enantiomeric proportion therein. After kinetic analysis, the AUCs obtained for the (+)-ABZSO were 5.8 and 4.0 times higher than those for the (–)-ABZSO in male and female animals, respectively. The mean residence times were 23.4 and 16.1 h for (+)-ABZSO and 22.2 and 17.4 h for (–)-ABZSO for male and female animals, respectively. The only significant difference between the sexes (p〈0.05) was in the T max of the (–)-ABZSO. Comparing both enantiomers within each sex, significant differences were found in all the kinetic parameters. Finally, no kinetic differences were found between sex for total-ABZSO or ABZSO2.
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  • 33
    ISSN: 1573-904X
    Schlagwort(e): allometric scaling ; interspecies scaling ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
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  • 34
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
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  • 35
    ISSN: 1573-904X
    Schlagwort(e): (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 17 (2000), S. 782-787 
    ISSN: 1573-904X
    Schlagwort(e): stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
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  • 37
    ISSN: 1573-904X
    Schlagwort(e): morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
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  • 38
    ISSN: 1573-904X
    Schlagwort(e): bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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  • 39
    ISSN: 1573-904X
    Schlagwort(e): SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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  • 40
    ISSN: 1573-904X
    Schlagwort(e): glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
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  • 41
    ISSN: 1573-904X
    Schlagwort(e): luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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  • 42
    ISSN: 1573-904X
    Schlagwort(e): methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 43
    ISSN: 1573-904X
    Schlagwort(e): 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 17 (2000), S. 903-905 
    ISSN: 1573-904X
    Schlagwort(e): P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    ISSN: 1573-904X
    Schlagwort(e): in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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  • 46
    ISSN: 1573-904X
    Schlagwort(e): α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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  • 47
    ISSN: 1573-904X
    Schlagwort(e): IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
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  • 48
    ISSN: 1615-6102
    Schlagwort(e): Glutathione ; Root ; Chromosomal aberration ; Ultrastructure ; Picea abies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Young spruce seedlings (Picea abies [L.] Karst.) grown in hydroponic culture were exposed to three different concentrations (50,100, and 500 μM) of reduced glutathione for 24 h. These physiologically relevant concentrations of glutathione had a multiple effect on the investigated tissue. Feeding of glutathione to roots increased the concentrations of thiols (glutathione, cysteine, and γ-glutamyl-cysteine) in roots, decreased the rate of cell divisions, induced mitotic abnormalities, and affected the cell ultrastructure. Electron micrographs showed effects such as advanced vacuolation, dilated rough-endoplasmic-reticulum cisternae, and separations of the plasma membrane from the cell wall.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Fish physiology and biochemistry 23 (2000), S. 225-232 
    ISSN: 1573-5168
    Schlagwort(e): methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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  • 50
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; 5-fluorouracil ; methotrexate ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A novel approach is described to simulate effect site pharmacodynamics of anticancer drugs. This approach is based on (i) the in vivo measurement of unbound, interstitial drug pharmacokinetics (PK) in solid tumor lesions in patients and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. For this purpose, breast cancer cells (MCF-7) were exposed in vitro to the time versus interstitial tumor concentration profiles of 5-fluorouracil (5-FU) and methotrexate (MTX) from primary breast cancer lesions in patients. This led to a maximal reduction in the viable cell count of 69 on day 4, and of 71 on day 7 for 5-FU and MTX, respectively. This effect was dependent on the initial cell count and was characterized by a high interindividual variability. For 5-FU there was a significant correlation between the maximum antitumor effect and the intratumoral AUC (r = 0.82, p = 0.0005), whereas no correlation could be shown for MTX (r = 0.05, p = 0.88). We conclude, that the in-vivo-PK / in-vitro-PD model presented in this study may provide a rational approach for describing and predicting pharmacodynamics of cytotoxic drugs at the target site. Data derived from this approach support the concept that tumor penetration of 5-FU may be a response-limiting event, while the response to MTX may be determined by events beyond interstitial fluid kinetics.
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  • 51
    ISSN: 1573-7241
    Schlagwort(e): colesevelam hydrochloride ; bile acid sequestrant ; drug interactions ; pharmacokinetics ; digoxin ; warfarin ; quinidine ; verapamil ; metoprolol ; valproic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Colesevelam hydrochloride (colesevelam) is a novel, potent, bile acid–binding agent that has been shown to lower LDL cholesterol a mean of 19% at a dose of 3.8 g/d. We studied the pharmacokinetics of colesevelam coadministered with six drugs: digoxin and warfarin, agents with narrow therapeutic indices; sustained-release verapamil and metoprolol; quinidine, an antiarrhythmic with a narrow therapeutic index; and valproic acid, an antiseizure medication. Six individual studies were single-dose, crossover, with or without a 4.5-g dose of colesevelam. Plasma levels were determined using validated analytical methods. Values for the ratio of ln[AUC(0-t)] with and without colesevelam were 107% for quinidine, 102% for valproic acid, 89% for digoxin, 102% for warfarin, 82% for verapamil, and 112% for metoprolol. Values for the ratio of ln[Cmax] with and without colesevelam were 107% for quinidine, 92% for valproic acid, 96% for digoxin, 99% for warfarin, 69% for verapamil, and 112% for metoprolol. The 90% confidence intervals for these ratios and for values of ln[AUC(0-inf)] that could be determined were within the 80–125% range, with the exception of verapamil. In this study, verapamil had great interindividual variability, with a 28-fold range in Cmax and an 11-fold range in AUC(0-t). In summary, pharmacokinetic studies with colesevelam did not show clinically significant effects on absorption of six other coadministered drugs.
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  • 52
    ISSN: 1573-2568
    Schlagwort(e): azathioprine ; 6-mercaptopurine ; gastrointestinal ; pharmacokinetics ; bioavailability ; inflammatory bowel disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 ± 30.1 ng×hr/ml) was higher compared to the stomach (39.9 ± 38.1 ng/hr/ml) and cecum (29.2 ± 10.9 ng×hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 ± 7.4, 52.3 ± 67.2, and 132 ± 151 ng×hr/ml, respectively, and the AUCs of 6-MP were 22.2 ± 14.9, 63.4 ± 50.6, and 104 ± 115 ng×hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    Neurological sciences 21 (2000), S. S27 
    ISSN: 1590-3478
    Schlagwort(e): Key words Neuronal ceroid lipofuscinoses ; Lipopigments ; Ultrastructure ; Classification ; Genes ; Neuronal loss
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphological aspects of the neuronal ceroid lipofuscinoses (NCL) encompass two main features: loss of nerve cells and accumulation of autofluorescent lipopigments within cellular compartments. The former requires histology and morphometry for assessment, while the latter necessitates fluorescence microscopy, electron microscopy, and immunohistochemistry. Accumulation of lipopigments is widespread throughout the central nervous system and extracerebrally. The latter feature enables diagnosis of NCL and its clinical subtype. Loss of neurons is most pronounced in cerebral and cerebellar cortices, in early childhood forms. In subcortical grey matter and in later-onset forms, juvenile and adult NCL, reduction in neurons and possible preceding dendritic pathology may only correctly be ascertained by age-matched, controlled morphometric investigations which, to date, have not yet completely assessed subcortical neuronal damage. Presently, clinical and morphological evaluations are mandatory for genetic analysis, genetic counselling, and prenatal diagnosis, the latter often being based on combined genetic and morphological studies.
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 17 (2000), S. 1426-1431 
    ISSN: 1573-904X
    Schlagwort(e): eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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  • 55
    ISSN: 1573-904X
    Schlagwort(e): amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 17 (2000), S. 1236-1242 
    ISSN: 1573-904X
    Schlagwort(e): aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
    Materialart: Digitale Medien
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  • 57
    ISSN: 1573-904X
    Schlagwort(e): oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
    Materialart: Digitale Medien
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  • 58
    ISSN: 1573-904X
    Schlagwort(e): benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
    Materialart: Digitale Medien
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  • 59
    ISSN: 1573-8221
    Schlagwort(e): acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.
    Materialart: Digitale Medien
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Brain tumor pathology 17 (2000), S. 15-19 
    ISSN: 1861-387X
    Schlagwort(e): Hemangioblastoma ; Supratentorial tumor ; Immunohistochemistry ; Ultrastructure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Supratentorial hemangioblastomas are rarely seen, especially in children and adolescents. We report the case of a 17-year-old male with supratentorial hemangioblastoma. Neuroimaging demonstrated a cystic lesion within the right parietal lobe. Systemic examination revealed no abnormality. The lesion was not attached to the dura and was not associated with von Hippel-Lindau disease. It was very difficult to confirm the final diagnosis of this case, in spite of extensive examination by light microscopy, immunohistochemical studies, and electron microscopy.
    Materialart: Digitale Medien
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  • 61
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 119-128 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The increasing requirements in wastewater treatment have led to the development of new wastewater treatment processes based on the know-how and experience in reaction and process engineering of the chemical industry. Due to their compactness, closed operation and high flexibility, these new processes show a large potential for process integration and significant cost reduction in particular for highly polluted industrial wastewaters.This paper discusses the HCR (high-performance compact reactor) - process, developed at the Mass Transfer Laboratory of the Technical University of Clausthal within the last decade. This process has been realized in more than 30 technical applications with a volume loading of up to 70 kg COD/m3 d and an energy consumption of about 0.4 kWh per kg CODelim.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
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  • 62
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 63
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 64
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 169-174 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Nitrogen fixing Anabaena azollae strains isolated from four different Azolla cultures were characterized based on their total protein profile and RAPD profile to study the existing variation among them. As expected, the isolates showed almost similar protein banding patterns, but exhibited differences in 40-70 KDa protein subunits. Polymerase chain reaction of the DNA of the isolates, using four different primers, amplified specific sequences of DNA and showed clear polymorphism among the isolates. The RAPD profile generated the fingerprinting pattern characteristic of each strain based on the sequence of the primers used. Common band sharing observed between the strains A. azollae-RS-KK-SK-AM and A. azollae-RS-KK-SK-RP probably represents maternal inheritance of DNA to the progeny. The polymorphic bands were generated specifically for the isolates A. azollae-RS-KK-SK-RP and A. azollae-RS-KK-SK-AM with primers numbered 2 and 4, respectively, which could be developed as possible markers for these isolates.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
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  • 65
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 175-183 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Mature seed-derived callus from an elite Chinese japonica rice cv. Eyl 105 was transformed with a plasmid containing the selectable marker hygromycin phosphotransferase (hpt) and the reporter β-glucuronidase (gusA) genes via particle bombardment. After two rounds of selection on hygromycin (30 mg/l)-containing medium, resistant callus was transferred to hygromycin (30 mg/l)-containing regeneration medium for plant regeneration. Twenty-three independent transgenic rice plants were regenerated from 127 bombarded callus with a transformation frequency of 18.1%. All the transgenic plants contained both gusA and hpt genes, revealed by PCR/Southern blot analysis. GUS assay revealed 18 out of 23 plants (78.3%) proliferated on hygromycin-containing medium had GUS expression at various levels. Genetic analysis confirmed Mendelian segregation of transgenes in progeny. From R2 generations with their R1 parent plants showing 3:1 Mendelian segregation, we identified three independent homozygous transgenic rice lines. The homozygous lines were phenotypically normal and fertile compared to the control plants. We demonstrate that homozygous transgenic rice lines can be obtained via particle bombardment-mediated transformation and through genetic analysis-based selection.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 202-202 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 67
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 219-233 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The GRAM-positive bacterium Rhodococcus erythropolis K2-3 and the GRAM-negative Ochrobactrum anthropi K2-14 are capable of synergistically degrading 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB). The two strais execute this task in a symbiotic manner, but the nature of the interaction involved in the degradation is only partially understood as yet. An essential first step in elucidating the interaction is to be able to monitor the two strans separately, at the cellular level, within mixed populations. Therefore a method exploiting fluorescently labelled lectin probes was developed. Since Concanavalin A (Con A) binds specifically to R. erythropolis K2-3, it was selected and linked to the fluoresent dye Bodipy 630/650, which has an excitation maximum in the red part of the visible light spectrum. Forward light scatter (FSC) and DNA fluorescence from both strains were also measured to obtain simultaneous information about their physiological states. The three parameters were conveniently monitored by dual and triple excitation flow cytometry in conjunction with double fluorescent staining techniques. In addition, the strains were identified using an epifluorescence microscope. These techniques were found powerful tools for the population analysis of this mixed bacterial system.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
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  • 68
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 235-274 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: A quite unconventional, innovative scientific methodology called “macroscopic pattern analysis” is presented in this paper. This approach is more adequate in the case of complex systems than the well-known microscopic, mechanistic approach. Complex systems are not only attracting more engineering interest, but their scientific treatment is increasingly wanted by society due to the manifold problems in Earth's ecosphere. The macroscopic pattern approach will be explained in depth and illustrated in some case studies from the ecosphere (sustainability, hurricanes and avalanches), where nature serves as a teacher for the solution of the sustainability problem. Then, a series of case studies on macropatterns are described showing the problem-solving capacity for anthropo- and technosphere: sustainability in society with an index of sustainability, the eco-social market economy with eco-tech as an instrument, biokinetics, bioreactor mixing and integrated bioprocessing with models, design of cars and houses and even quality of life as an attempt to quantify macropatterns.The innovations are briefly compared in their problem-solving capacity with known approaches such as the microscopic method in science, technology and society (free market economy), including the evaluation of other indices and cleaner production, industrial ecology and zero emission initiative. Finally, a deeper integration of sciences, ethics, arts and nature will be introduced based on the vision with macroscopic pattern analysis, where the different domains of human life are integratable to effect a reconciliation.
    Zusätzliches Material: 22 Ill.
    Materialart: Digitale Medien
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  • 69
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 70
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 17-29 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The dynamic behaviour of biofilters intended to remove toluene and xylene from air was studied during transient states. Laboratory scale biofilters were filled with a mixture of peat, bark and wood and inoculated with a mixed microbial population. Toluene and xylene were applied both as single pollutants and as mixtures. Attention was focused on the evaluation of the following transients: the response of biofilters to step changes and peaks in pollutant concentrations, the effect of changes between single and multiple pollutant loadings and the response to shutdown periods.The biofilters demonstrated a good dynamic stability during transient states induced by change in inlet pollutant concentrations. Their time periods did not exceed three hours. No interaction between xylene and toluene degradation was observed during changes in loading with single pollutants or their mixture. The performance interruptions lasting less than 24 hours were found to have no significant influence on the removal efficiency of biofilters. When the biofilters were reacclimated after longer starvation periods, a short temporary decrease in efficiency whose minimum and duration were proportional to the length of a preceding shutdown period was observed. The longest starvation period (7 days) resulted in a reacclimation lasting 7 hours only. Adaptations of a microbial population to new operating conditions as well as sorption/desorption processes were suggested as the main factors influencing the dynamic reponse characteristics.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
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  • 71
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 31-38 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: In this paper, the in vivo decolourization of the polymeric dye Poly R-478 by semi-solid-state cultures of Phanerochaete chrysosporium BKM-F-1767 (ATCC 24725) was investigated, employing corncob as a support. In order to stimulate the ligninolytic system of the fungus, the cultures were supplemented with veratryl alcohol (2 mM) or manganese (IV) oxide (1 g/l).Maximum manganese-dependent peroxidase (MnP) and lignin peroxidase (LiP) activities of around 2,000 U/l and 400 U/l were attained by the former, whereas the activities reached by the latter were of about 1,500 U/l and 200 U/l, respectively. Furthermore, laccase activity (around 150 U/l) was only detected in manganese (IV) oxide supplemented cultures.The polymeric dye Poly R-478 (0.02 w/v) was added to three-day-old cultures. A percentage of biological decolourization of about 85% was achieved using cultures supplemented with veratryl alcohol, whereas MnO2 cultures showed a rather lower percentage of around 58% after nine days of dye incubation. Moreover, a correlation between MnP activity and Poly R-478 decolourization could be observed, indicating that this enzyme is mainly responsible for dye degradation.In the present work, the in vivo decolourizing capability of the ligninolytic complex secreted by P. chrysosporium was investigated under the above-mentioned cultivation conditions, employing a model compound, such as the polymeric dye Poly R-478.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 187-187 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 73
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 189-201 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Desulfovibrio vulgaris strain PY1 was isolated from a 3-chlorobenzoic acid (3CBA) degrading anaerobic enrichment culture, using anaerobic Percoll density centrifugation. When grown on pyruvate (20 mM), in the absence of sulphate and under strict anaerobic conditions, this organism converted not only the co-substrates benzoate (BA), 3-amino-BA and 3CBA to the corresponding alcohols but also ten other different halogenated benzoic acids, viz., 4-Cl-, 3-Br-, 4-Br-, 3-I-, 3-F-, 4-F-, 2,4-di-Cl-, 2,5-di-Cl-, 3,4-di-Cl- and 3,5-di-Cl-BA. This was verfied with HPLC and GC/MS spectrometric analyses. The yields of the co-substrate converted after 30 days of growth were between 20% and 88%, depending on the compounds which had been added at initial concentrations of 500 μM. Sulphate, sulphite, thiosulphate and disulphite inhibited the formation of 3-Cl-benzyl alcohol (3CBOH), i.e. a 97 to 99% inhibition, and nitrate and sulphur had no effect (a 7-10% inhibition). In cell-free extracts, the reduction of 3CBA to 3CBOH required strict anaerobic conditions, pyruvate or H2 as electron donors and the addition of methylviologen (MV), FAD, FMN or ferredoxin as electron carriers. The specific activity of the reduction of 3CBA to 3CBOH in crude extract was 5.3 nmol/(mg protein min). The reaction was not inhibited by additions of sulphate or sulphite (5 mM), but was completely inhibited at concentrations of 10 mM 3CBA or 50 mM BA. A carboxylic acid reductase (aldehyde dehydrogenase), which acted on non-activated 3CBA and was responsible for the reduction of 3CBA to 3-Cl-benzaldehyde, was found in the solube fraction (94% of the total activity). These results demonstrate that strain PY1 was able to effectively reduce a wide range of halogenated benzoic acids to the corresponding alcohols.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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  • 74
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 203-218 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The recent upsurge in information technology has provided the international community with an easy access to professional journals (e.g. Electronic Journal of Biotechnology at http://www.ejb.org; etc.), discussion groups (e.g. bioenergy@cret.org; digestion@crest.org; etc.) and recently to electronic international conferences (e.g. ICIBS; http://www.cid.harvard.edu/cidbiotech, etc.) as well as a series of biotechnological information material (e.g. http://www.psrast.org, etc.) to stay in contact and receive up-to-date information in biotechnology. There is no doubt that this new technology will be more cost effective in future and reach more people in communities around the globe.This review reports on one such an electronic conference aiming at bridging the communication gap between developed and developing countries. This conference dealt with integrated biosystems and has provided an excellent forum for more than 100 active participants from all regions of the world. As has been demonstrated in this review, the conference was able to show the very different approaches towards the use of biotechnology in developed and developing countries, cold and tropical climate regions owing to their different ecological, economical and societal problems. It also demonstrated very clearly that the field of molecular genetics and/or genetic engineering is not a priority issue in developing countries, but rather the need for clean technologies, multiproduct formation through socio-economic integrated biosystems, e.g. incorporating microbial waste management into agro-industries, in human activities and their roles in creating better health conditions, a better environment and sustain development.It is hoped that this review will lead to a greater use of the electronic facilities available to inform and educate both the northern and the southern communities more readily of their needs and requirements to improve understanding and efforts for a sustainable future.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 75
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 275-288 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The purpose and scope of this article is to introduce capable zeolites into downstream processing of natural compounds, especially flavour compounds like 2,5-dimethyl-4-hydroxy-3(2H)-furan-3-one (Furaneol®Furaeol is a registered trademark of FIRMENICH, Ch). The synthesis and the recovery of Furaneol from L-rhamnose are presented. Therefore adsorption isotherms of the zeolites ZSM5 and DAY with varying modules have been determined and adsorption experiments using model and reaction mixtures of Furaneol synthesis were performed and will be discussed.
    Zusätzliches Material: 11 Ill.
    Materialart: Digitale Medien
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  • 76
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: A fermentation process for manufacturing 1,4-piperazinium-(L,L)-dilactate from renewable raw materials and a method for processing this product into L,L-dilactide are described. Lactic acid fermentation with Lactobacillus paracasei was modified in such a way that pH control occurred by using an aqueous solution of piperazine as a correcting agent instead of sodium hydroxide solution. The production of a stoichiometrically composed piperazinium lactate was possible when the pH was 5.0. From 5.0 kg of glucose and 2.15 kg of piperazine, 6.65 kg of 1,4-piperazinium-(L,L)-dilactate were formed in the fermentation process. Separation from fermentation broth, purification and concentration of the product in aqueous solutions were carried out by means of ultrafiltration, nanofiltration and electrodialysis. Total product retention by the membranes used was about 33%. The crystalline salt was obtained by vacuum evaporation. Processing of the 1,4-piperazinium-(L,L)-dilactate into L,L-dilactide was performed in a special glass reactor. A product yield of 70% was achieved. The purified product was characterized by elementary analysis, as well as solubility behaviour, polarity and spectroscopic data. An overall process consisting of the stages fermentation, purification and concentration of piperazinium dilactate as well as cyclization of the latter to dilactide is described.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
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  • 77
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 161-168 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Five different chemical reagents and γ-rays were tested for the sanitization of immobilized biocatalysts with high penicillin G acylase (PGA) activity. The most effective chemical reagents were N-cetyl-N,N,N-trimethylammonium bromide (CTAB) and 2-isopropyl-5-methylphenol (thymol). The optimum concentration of CTAB for the treatment of the immobilized enzyme was 0.25% [w/v] and 1 h, for immobilized cells 0. [w/v] and 3 h. The optimum concentration of thymol for the immobilized enzyme was found to be 0.1% [w/v] and 1 h, for immobilized cells 0.27% [w/v] and 2 h. The optimum dose of γ-rays for the sanitization of the immobilized enzyme was established as 3.2 kGy, for immobilized cells as 4.5 kGy.
    Zusätzliches Material: 5 Tab.
    Materialart: Digitale Medien
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  • 78
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 79
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 53-64 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: An advanced primary treatment process for a municipal waste water was systematically studied, using a bio-flocculation-adsorption, sedimentation and stabilzation process (BSS). It was shown that the organic removal efficiency was higher than that of the traditional primary treatment processes but lower than that of the traditional secondary treatment processes. Both adsorption and bio-flocculation played an important role in the removal of pollutants. The activated sludge within the bio-flocculation-adsorption tank could be considered a bio-flocculent which improved the quality of the effluent from the primary treatment process. As the effluent of the BSS process did not meet the requirements for a typical secondary effluent, the process may be regarded as an advanced (or enhanced) primary treatment process, suitable for waste water containing a high concentration of suspended solids and colloidal particles.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 67-73 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The concentration of airborne fungal spores and bacteria as related to room temperature, humidity and occupancy levels within a library building in Singapore was determined. Measurement of indoor air quality with respect to microorganisms is of particular importance in tropical environments due to the extensive use of air-conditioning systems and the potential implications for human health. This study has revealed a number of interesting relationships between the concentrations of fungal spores and bacteria in relation to both environmental and human factors. The levels of fungal spores measured in the indoor environment were approximately fifty times lower than those measured outside, probably because of the lowered humidity caused by air-conditioning in the indoor environment. The variation in fungal spore concentration in the outdoor environment is likely to be due to the diurnal periodicity of spore release and the response to environmental factors such as light temperature and humidity. The indoor concentration of fungal spores in air was not clearly correlated to concentrations measured in air outside of the library building and remained relatively constant, unaffected by the difference in the numbers of occupants in the library. In contrast, the indoor concentrations of bacteria in air were approximately ten times higher than those measured outdoors, indicating a signficant internal source of bacteria. The elevated levels of indoor bacteria were primarily attributed to the number of library occupants. Increased human shedding of skin cells, ejection of microorganisms and particulates from the respiratory tract, and the transport of bacteria on suspended dust particles from floor surfaces probably accounts for the strong positive correlation between occupancy levels and the concentration of bacteria in internal air.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 81
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000) 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 82
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 96-96 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 83
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 87-96 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Preliminary results on the novel use of the bacterium Thiobacillus ferrooxidans (ATCCJ 3598 and ATCC33020) for the micro-machining (or biomachinig) of metals are reported. Biomachning is a controlled microbiological process to selectively form microstrucutures on a metal work-piece by metal removal (or dissolution) using microorganisms. Applying copper and mild steel as work-pieces, it was shown that the mass removed increased proportionately with machining time. In another experiment, the work-pieces were coated with organic photo-resistive materials to mask (i.e. protect) certain regions of the metlas, thereby defining the microstructure to be formed. The unmasked regions were successfully biomachined; the final machined profile was shown to be similar to the coating image on the original metal. Although biomachining proceeded at a slower rate than chemical machining, the undesired leaching of the metal in the region under the masked area (termed undercutting) was not as severely encountered when compared with the latter. This work demonstrates the potential use of microorganisms for the biomachining of metals. As a “green process”, the innovative use of T. ferrooxidans for the micro-machining of metals opens up the possibility of biomachining as an alternative to conventional metal processing.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 84
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: During the microbial treatment of a sandy model soil artificially contaminated with polycyclic aromatic hydrocarbons (PAHs), a large residual pollution was found. The remainig PAHs were sorbed into the micropores of the soil and were therefore not bioavailable. Using a lab-scale precolator, the microbially pretreated soil was subjected to aftertreatment with surfactants with the aim of further degradation of its pollution. Two commercial nonionic surfatants of the polyethoxylate type, Präwozell F1214/5 N and Sapogenat T-300, were used. The surfactants differ both in their physicochemical properties (CMC value, PAH solubilization capacity, adsorption onto soil) and in their microbial degradability. During aftertreatment under permanently aerobic conditions, only a weak PAH accumulation in the liquid phase was observed, which was due to a low solubilization rate as well as to simultaneous microbial degradation of the dissolved PAHs. Temporary anaerobiosis successfully suppressed the microbial degradation of both the surfactant and the solubilized PAHs, resulting in a more intensive PAH accumulation. But the PAH content of the soil - the essential criterion for evaluating the efficiency of surfactant application - was not decreased to a larger extent with surfactants than without them. To find out why the surfactants failed to act, the surfactant and hydrocarbon distribution among the liquid and solid phases was studied in mixtures of phenantherne-spiked solis and Präwozell-containig liquids; at heavy phenanthrene loading, the aqueous phase was saturated with PAH; at weak loading, it was unsaturated. Model-aided data analysis showed that the soil may contain PAH in two fractions: strongly sorbed into soil pores and, in the case of heavy loading, also weakly attached to the soil surface. The latter is easily extractable, resulting in a PAH-saturated liquid, while strongly adsorbed PAH is only partially dissolved due to competition between the micelles and the soil pores for the PAH. The microbially pretreated soil contains only strongly bound PAHs, which are as difficult to extract by surfactants as they are poorly accessible for microbes.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 85
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Autochthonous bacteriocenoses in semiarid soils in Patagonia were found to be capable of rapidly adapting to high contamination with crude oil. This adaptation at community level is due to the selective enrichment of hydrocarbon-utilizing bacteria always present in these soils. Immediately after a heavy contamination with crude oil, the authochthonous bacteriocenosis contained about 28% hydrocarbon-utilizing bacteria which could be classified into eight ecotypes with characteristic metabolic profiles. Mainly n-alkanes were used as growth substrates of representative strains. After seven months' exposure to crude oil, the bacteriocenosis consisted almost entirely of hydrocarbon-utilizing bacteria. At least fourteen ecotypes were distinguishable, and the majority of representative strains were able to metabolize a broad spectrum of aliphatic and aromatic hydrocarbons. Corresponding to the significant alteration of the physiological diversity, drastic changes to the taxonomic diversity were also found. Whereas at the beginning of the study the autochthonous bacteriocenoses were dominated by GRAM-positive genera of the Actinomycetales (Dietzia, Gordona, Nocardia, Rhodococcus, Streptomyces) with high ecological potency, after just two months' exposure to crude oil, GRAM- negative bacteria (especially Pseudomonas stutzeri) became predominant within the hydrocarbon-utilizing bacteriocenoses accompanied by some GRAM-positive genera of the Actinomycetales with a significantly lower abundance. These findings underline the importance of Pseudomonas and some genera of Actinomycetales for processes of natural attenuation and the technically supported in situ bioremediation of soil polluted by crude oil in Patagonia.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 86
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 149-159 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Some parameters of the production of an alkaline protease by Rhizopus oryzae in the solid state fermentation of wheat bran were optimized. Using the optimum parameters of an inoculum age of 7 days, an incubation time of 9 days, an amount of CZAPEK-DOX (liquid medium) of 6 ml/g bran and an incubation temperature of 33°C, an activity of 50 U/g bran was achieved. The initial pH of the CZAPEK-DOX medium had little effect. Re-incubation of mouldy bran with only fresh CZAPEK-DOX yielded 3 times total activity compared to single-cycle fermentation. As for the effect of the amount CZAPEK-DOX medium, the water constituent contributed more to activity increase than did the salt component. The ARRHENIUS activation energies were 23 and 7.9 kcal/mole below and above the optimum of 33°C, respectively. In all the studies, along with protease production, variation of protein content and specific activity were also observed. Attempts were made to explain the effects and also gauge their implications for large-scale production.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 87
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 184-184 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 88
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000) 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 89
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 305-312 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Because of the growing utilization of renewable raw materials, the technical use of lignocellulosic fibres from wood and other annual plant materials is becoming increasingly important. The conventional production process of fibreboards is characterized by high-energy consumption and use of ecologically insecure synthetic lesins. Approximately 40 to 45% of the total energy expenditure are used for the thermo-mechanical pulping. Because of high plastication temperatures, an inactive lignin crust on the fibre surface is formed. For that reason, for glueing of the fibres, urea formaldehyde and melamin resins are usually used. The costs for the resin amount to approximately 50% of the entire material costs. In addition, environmental problems are caused. The aim of our investigation is the reduction of energy and resin consumption by enzymatic modification of wood chips and the enzymatic activation of the inherent bonding strength of the material. The first industrial use of fungi for the modification of wood was in the production of “Myco wood”. Pleurothus ostreatus and Trametes versicolor were applied for nonsterile delignification of beech wood. The present investigation of the authors deals with the mycological pre-treatment of wood chips in order to reduce the energy consumption during wood pulping. The screening results favour the brown rotter Gleophyllum trabeum for pinewood (Pinus silvestris) and the white rotter Trametes hirsuta for beech (Fagus silvatica). Both species show resistance against mould fungi. The use of submerged inoculum of these fungi has the advantage over wheat inoculum that the lag phase is less than 12 hours and that the addition of nutrients or fungicides is not necessary. Short-time wood chip incubation results in a 40% decrease of energy consumption during thermo-mechanical pulping and in improved fibreboard properties. Lignin reduction could not be determined by gravimetrical and x-ray microanalysis.Comparative investigations of fibre incubation using laccase, a submerged culture of Trametes versicolor and rape straw fibres show a high increase in bending and tensile strength and an improvement in the hygroscopic properties of glue-free fibre boards for the last two incubation kinds. Similar effects have been obtained incubating pine wood fibres for the production of fibre sheets with enzyme medium of Trichoderma reseei.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 90
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 335-350 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: During the 20th century, important relationships developed between the oil industry and both microbiological and biotechnological research. Basic microbiological research has played an important role in both the exploration and production sectors of the oil industry, but as the maturity of the industry has progressed, such contributions have been relegated with respect to their importance. With respect to refining and petrochemicals manufacture, process routes have been extensively researched, but only rarely have the biotechnological solutions developed satisfied the economic criteria that resulted in major investment. In fact, situations exist where investment has occurred, but project life was unrealistically short, suggesting a need for extreme caution when evaluating biotechnological processes for the oil industry. However, as far as engineered processes for both biotreatment and bioremediation are concerned, the fundamental research that has underpinned other areas of hydrocarbon microbiology will finally prove to be of both technical and economic value, in ensuring that the essential needs of treatment, rather than disposal, and restoration, rather than environmental destruction, can be satisfied by the oil and other industries involved in both geochemical manipulation and natural resource exploitation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 91
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 369-372 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The influence of different growth-limiting factors - namely the sources of carbon, nitrogen and phosphorus and the dilution (growth) rate - on the ice-nucleation activity of Pseudomonas syringe CCM 4073 was studied. A higher ice-nucleation activity was observed at a lower dilution (growth) rate (D = 0.1 h-1) than at a higher dilution (growth) rate (D = 0.3 h-1). Remarkable differences in ice-nucleation activity were found in its dependence on the growth-limiting factor. The highest ice-nucleation activity was observed under carbon limitation (T90 = -2.7°C), a medium activity under nitrogen limitation (T90 = -5°C) and lowest activity under phosphorus limitation (T90 = -12.3°C). After the addition of excess nitrogen or phosphorus to steady-state cultures, the ice-nucleation activity was restored.
    Zusätzliches Material: 1 Tab.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 92
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 93
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 65-65 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 94
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 41-52 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Studies were carried out to evaluate the feasibility of using coffee industry residues, viz. coffee husk, coffee leaves and spent coffee ground as substrates in solid state fermentation (SSF) to cultivate edible mushrooms Pleurotus. Eight strains of Pleurotus ostreatus and two strains of Pleurotus sajor-caju were screened on a medium prepared from aqueous extract of coffee husk and agar. Based on best mycelial growth (9.68 mm/day) and biomass production (43.4 mg/plate in 9 days at 24°C), the strain P. ostreatus LPB 09 was selected for detailed studies. SSF was carried out using these substrates under different moisture conditions (45-75%) and spawn rates (2.5-25%). In general, although a 25% spawn rate appeared superior, the 10% spawn rate was recommended for all the three substrates in view of the process economics, as there was not any significant difference in the increase with 10 to 15%. The ideal moisture content for mycelial growth was 60-65% for coffee husk and spent coffee ground, and 60-70% for coffee leaves. The biological efficiency (BE), which is defined as the ratio of the weight of fresh fruiting bodies to the weight of dry substrate, multiplied by 100, and which indicates the fructification ability of the fungus for utilizing the substrate, was best with coffee husk. With coffee husk as the substrate, the first fructification occurred after 20 days of inoculation, and the biological efficiency reached about 97% after 60 days. When coffee leaves were used as the substrate, no fructification was observed even upon prolonged cultivation. With spent ground as the substrate, the first fructification occurred 23 days after inoculation and the biological efficiency reached about 90% in 50 days. There was a significant decrease in the caffeine and tannin contents (61 and 79%, respectively) of coffee husk after 60 days. It was remarkable to observe that caffeine was adsorbed onto the fruiting body (0.157%), indicating that it was not completely degraded by the fungal culture. However, no tannins were found in the fruiting body, indicating that the fungal strain was capable of degrading them. The results showed the feasibility of using coffee husk and spent coffee ground as substrates without any pre-treatment for the cultivation of edible fungi in SSF, and provided one of the first steps towards an economical utilization of these otherwise unutilized or poorly utilized residues.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 96
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 75-81 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Serratia marcescens biovar A2/A6 is able to produce a red pigment as a secondary metabolite which has antimicrobial activity. This paper describes its growth and biopigment formation in batch cultures, in media containing different concentrations of lactic acid and beef extract as carbon and nitrogen sources, respectively. An unstructured model has also been developed to describe its growth, lactic acid uptake and biopigment formation. The comparison of simulated and experimental data shows that the proposed model predicts reasonably well the system behaviour over a range of conditions.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 97-98 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 98
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000) 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 334-334 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 100
    Digitale Medien
    Digitale Medien
    Berlin : Wiley-Blackwell
    Acta Biotechnologica 20 (2000), S. 313-333 
    ISSN: 0138-4988
    Schlagwort(e): Life Sciences ; Life Sciences (general)
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: The impact of hydrocarbon remediation on several enzyme activities (catalase, dehydrogenase, lipase, protease, urease, alkaline phosphomonoesterase, fluorescein diacetate hydrolysis) and microbial properties (biomass-C, respiration, N-mineralization, qCO2, microbial counts) was evaluated in a laboratory study over a period of 10 weeks. A pristine soil was contaminated with diesel oil (10 mg/g soil) or with a mixture of phenanthrene and naphthalene (total amount 1 mg/g soil) and supplemented with inorganic nutrients to give a C:N ratio of 20:1. The corresponding controls consisted of uncontaminated nutrient-supplemented soil. Oil contamination caused a significant initial increase of all biological parameters measured. In the presence of PAHs, biomass-C, respiration, protease activity and heterotrophic counts were significantly enhanced, while urease activity was depressed. N-mineralization was initially, however, reversibly inhibited in the presence of oil and PAHs.The measured parameters behaved differently over time: Biomass-C, respiration and alkaline phosphomonoesterase activity reached a maximum activity after about 2-5 weeks, corresponding to the period during which the majority of hydrocarbons disappeared, and declined thereafter to the background level. Activities of catalase and dehydrogenase also followed this pattern, however, were characterized by fluctuations. Activities of lipase, protease, urease and fluorescein diacetate hydrolysis increased and remained almost constant throughout the incubation period.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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