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  • 1985-1989  (3,801)
  • 1970-1974  (3,840)
  • 1920-1924  (1,159)
  • Organic Chemistry  (8,066)
  • Electron microscopy  (734)
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  • 1
    ISSN: 1432-2307
    Keywords: Clear cell sarcoma ; Melanosomes ; Cytochemistry ; Electron microscopy ; Nude mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the histogenesis of clear cell sarcoma of tendons and aponeuroses (CCS), two cases of human and one nude mouse-transplanted CCS line were studied using an ultrastructural and enzyme cytochemical approach. Most of the tumour cells obtained from the primary and transplanted CCS demonstrated melanosomes in various stages of development within the cytoplasm, whereas no melanosomes could be identified in the metastatic CCS. However, cholinesterase and tyrosinase activities could be demonstrated not only in the melanotic primary and transplanted CCS but also in the amelanotic metastatic CCS. The results therefore support the hypothesis that CCS is a soft tissue tumour derived from the neural crest.
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  • 2
    ISSN: 1432-2307
    Keywords: Human heart ; Papillary muscle ; Hypertrophy ; Mitochondria ; Specific staining ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biopsy material of the hypertrophied human papillary muscle has been processed according to various electron microscopical techniques in order to study the mitochondrial ultrastructure and the association between mitochondria and sarcoplasmic reticulum (SR).En bloc staining with a Cu-Pb citrate solution resulted in specifically contrasted mitochondrial and sarcotubular membranes, characterized by numerous, discrete, electron-dense particles. The differences in staining patterns between the perinuclear mitochondria and their subsarcolemmal and interfibrillar counterparts suggest differences in chemical properties and/or metabolic activities. The selectively contrasted mitochondrial particles may represent a conglomorate of extrinisic and intrinisic respiratory enzymes and other membrane-associated proteins, while the majority of the electron-dense particles of the sarcotubular membrane may represent positively stained Ca2+-pumps. Ultrastructural findings in the present study strongly indicate that the slender mitochondrial projections represent an initial stage in a process leading to the formation of large and pleomorphic mitochondria. Intimate contact between adjacent mitochondria as well as between mitochondria and SR are documented. In the contact regions some of the specifically contrasted particles of the adjacent membranes had fused with each other. It is suggested that these particles represent membrane-bound transport proteins providing a system for interorganelle exchanges of metabolites and/or ions.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 91-95 
    ISSN: 1432-2307
    Keywords: Carcinosarcoma ; Urinary bladder ; Immunohistochemistry ; Electron microscopy ; Rhabdomyoblast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of urinary bladder carcinosarcoma (UBCS) is reported with light, immunohistochemical and electron microscopical findings. The tumour consisted of a squamous cell carcinoma, variable spindle cell stromal elements compatible with fibrosarcoma, and rhabdomyoblasts. Intermediate filament co-expression of cytokeratin and vimentin was shown by immunohistochemistry. Electron microscopy (EM) confirmed the nature of the three components, and indicated some similarities between the three cell-types present. Comparisons with the previous UBCS in the literature are made.
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  • 4
    ISSN: 1432-2307
    Keywords: Human acute pancreatitis ; Zymogen granules ; Acinar cells ; Electron microscopy ; Immunocytochemistry ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study fine structural changes of acinar zymogen granules were investigated in human acute pancreatitis. Pancreatic tissue was obtained at surgery from 6 patients, prepared for ultrastructural analysis, and stained immunocytochemically for trypsinogen. Stereological parameters of zymogen granules were evaluated. The density of the immunocytochemical labelling for trypsinogen was estimated over zymogen granules, the rough endoplasmic reticulum, Golgi apparatus and the acinar lumina. In acute pancreatitis the number of zymogen granules was diminished and their size reduced. The density of the labelling for trypsinogen was unchanged over zymogen granules but showed a significant reduction over the rough endoplasmic reticulum, Golgi apparatus, and the acinar lumina. In general the integrity of zymogen granules was well preserved. Focally degenerative changes of zymogen granules and large autophagosomes were observed. From the immunogold labelling a disturbance of enzyme synthesis and secretion was suggested. Evidence is given that a disruption of the zymogen granule membranes and a fusion with lysosomal bodies might contribute to the pathogenesis of human acute pancreatitis.
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  • 5
    ISSN: 1432-2307
    Keywords: Hyperoxia ; Lung broncho-vascular reaction ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the early phenomena involved in the lung reaction to hyperoxia, twenty adult male rats were exposed to 100% oxygen at 1 ATA. Morphological pulmonary lesions were detectable after only 24 h hyperoxia, and included vasoconstriction and perivascular oedema, bronchiolar constriction, and pericyte reaction. The lesions were irregularly scattered within the lung parenchyma and occurred preferentially in areas centred on bronchiolo-vascular stems. Even at the latest stages, pulmonary heterogeneity was obvious, from the coexistence of areas damaged at different times. Neuro-epithelial-bodies were found under the bronchiolar epithelium; the morphological aspect of the neuro-endocrine cells observed was consistent with hyperoxia-induced modulation of their secretory activity. Taken together, our findings show the speed of development of hyperoxia-induced pulmonary changes and raise some pathogenic considerations.
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  • 6
    ISSN: 1432-2307
    Keywords: Thyroid neoplasms ; Electron microscopy ; Immunohistochemistry ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural study, both morphological and immunohistochemical, has been carried out on eight thyroglobulin-positive and nine thyroglobulin-negative medullary carcinomas of the thyroid. The morphometric analysis of granule size showed that all tumours contained cells with small granules and cells with medium size granules, whereas eight tumours had additional cells with large granules. The small granules had an electron dense core, while the medium and large sized granules were both pale-cored and dense-cored. The cells with small, medium or large secretory granules were all immunoreactive for calcitonin and CGRP. No ultrastructural differences were observed between thyroglobulin-positive and thyroglobulin-negative cases of medullary carcinoma of the thyroid.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 1-6 
    ISSN: 1432-2307
    Keywords: Visceral leishmaniasis ; L. donovani ; Parasitism ; Liver pathology ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Liver parenchymal cell parasitism with the amastigotes form ofL. donovani was detected by electron microscopy in human visceral leishmaniasis. Endocytosis was considered to be the mechanism by which the leishmania entered the cell. Evidence of well preserved parasites within hepatocytes suggest this parasitism as a possible reservoir for recrudescence.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 297-300 
    ISSN: 1432-2307
    Keywords: Non-Hodgkin's lymphoma ; Electron microscopy ; Immunohistochemistry ; Intercellular junction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A rare example of pleomorphic B cell non-Hodgkin's lymphoma is described in which tumour cells possessed simple intercellular junctions.
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  • 9
    ISSN: 1432-2307
    Keywords: Collagen secretion granule ; Myofibroblast ; Spindle cell tumour ; Electron microscopy ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Collagen secretion granules, representing stages in the intracellular packaging, transport and secretion of collagen-fibril precursor, have been studied by transmission electron microscopy in non-neoplastic human myofibroblasts and in neoplastic cells from a preliminary study of tumours exclusively or partly of spindle cell type. Vesicles, newly separated from Golgi saccules and containing finely fibrillar material, were identified as early presecretory granules, the most immature type of granule. Later stages exhibited longitudinally arranged, densely fibrillar bundles. Subsequently, secretory granules developed more homogeneously dense content. Fibril-containing cisternae near the plasma membrane were interpreted as either endocytotic or lysosomal structures, or as participants in the final stages of secretion. The features by which collagen secretion granules can be distinguished from other Golgi products, in particular melanosomes, Weibel-Palade bodies and lysosomes, are pointed out. The significance of these organelles for cell identification and tumour diagnosis is discussed.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2307
    Keywords: Salivary gland ; Myoepithelioma ; Neoplasm ; Electron microscopy ; Immunohistochemistry ; Cytoplasmic filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was wide-spread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonalshaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.
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  • 11
    ISSN: 1432-198X
    Keywords: IgA nephropathy ; Electron microscopy ; Glomerular basement membrane lesions ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventy-three patients with IgA nephropathy (IgAGN), under the age of 15 years at the time of the discovery of the disease, were investigated with respect to glomerular basement membrane (GBM) lesions. Irregular attenuation or widening of GBM, especially on the epithelial side, was observed in 28 cases (38%). These two changes are referred to aslysis of GBM and were considered to be the primary and specific changes among the GBM lesions in IgAGN. GBM thickening with layering of lamina densa was found in 37 of 73 cases (51%), but this change has been observed in other types of glomerular diseases. GBM lesions similar to those seen in IgAGN were also observed in Henoch-Schönlein purpura nephritis (HSPN) and poststreptococcal acute glomerulonephritis (PSAGN). Lysis of GBM was observed only in IgAGN, HSPN and PSAGN. Subepithelial and intramembranous deposits appeared to have an important role in the development of these GBM lesions. The presence of GBM lesions was correlated with a high incidence of cellular crescents but not with other clinical or light microscopic findings. The presence of these GBM lesions in IgAGN does not have a significant effect on the prognosis, at least in childhood. The affected GBM seemed to recover without leaving any significant residual damage in most cases. In the long-term prognosis of the disease non-immunological factors, such as ageing or hypertension, seem to be important.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 180 (1989), S. 237-242 
    ISSN: 1432-0568
    Keywords: Perineurium ; Lanthanum ; Diffusion barriers ; In vivo ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary While the perineurium as a diffusion barrier has been extensively investigated by light and electron microscopy, copy, such studies have been largely restricted to the use of protein tracers. In the present study the permeability of the perineurium to a physiologically more relevant ionic tracer has been assessed. In vivo the rat sural or tibial nerve was either microinjected with lanthanum nitrate solution for endoneurial application or bathed in the lanthanum solution for epineurial application. The findings generally demonstrated an effective barrier to the tracer which failed to penetrate the inner layers of the perineurium. Only at the highest lanthanum concentration and longest time intervals employed did trace quantities occasionally penetrate the barrier and then only in the presence of some cytopathological changes to the outermost perineurial cells. The usefulness of the microinjection method was limited by the slight but unavoidable trauma to the perineurium. The findings are related to those of other studies which have used electron dense tracers, also to studies using physiological including electrophysiological techniques and morphological including freeze-fracture methods.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 281 (1989), S. 165-172 
    ISSN: 1432-069X
    Keywords: Netherton's syndrome ; Retinoid therapy ; Etretin ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A young female patient, expressing the symptom triad of Netherton's syndrome, i.e., ichthyosis linearis circumflexa Comèl, trichorrhexis invaginata and other hair shaft defects, and atopic diathesis, has been treated successfully with the new retinoid preparation Etretin. Our electron microscopical study especially focused on the ultrastructural effect on the characteristic, active part of the skin lesions, which is only found within a narrow borderline just preceding the lesion's margin. In untreated skin, this part is characterized by dermal inflammation, immigrating inflammatory cells, and specific keratinization disturbances: synthesis of keratinization proteins is suppressed, serum exudates invade the epidermis, either filling the intercellular spaces of the upper spinous and the granular layer as finely granular, amorphous material, or they are partly phagocytosed and lie within intracellular, round-oval inclusions. The portions of the lesions lying towards the center are unspecific and represent recovery stages, ultrastructurally resembling stages of normal wound repair. Oral therapy with Etretin did not heal the basic defect, but drastically reduced exoserosis and the deposition of intra- and extracellular material. Keratinization seemed to normalize. The condition of the hair was also improved.
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  • 14
    ISSN: 1432-0533
    Keywords: Senile plaque-like structure ; Periodicacid methenamine silver (PAM) method ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Numerous diffuse senile plaque-like structures (SPLSs) were found in the cerebral cortex from cases with dementia of the Alzheimer type by means of the methenamine-Bodian method. SPLSs varied in shape and size. They were never recognized in the original Bodian, PAS and Congo red preparations, but were positive with anti-β-protein immunostaining and periodic-acid methenamine silver (PAM) methods, which are thought to specifically stain amyloid substance. With PAM electron microscopy, we found sparse aggregations of amorphous, often ramified, structures with fine granular silver deposits in SPLS. Routine electron microscopic examination on the same portion where SPLS were confirmed by PAM electron microscopy revealed amorphous, partially fibrous structures. These structures might be amyloid or amyloid-precursor substance. In SPLSs only a few degenerated neurites and astrocytic processes with glycogen granules were seen. We consider SPLSs to be a kind of senile plaque.
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  • 15
    ISSN: 1432-0533
    Keywords: Schwann cell ; Oligodendrocyte ; Electron microscopy ; Myelin ; Optic nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neonatal rats were exposed to Tellurium (Te), via the mother's milk, from the day of birth until sacrifice at 7, 14, 21, and 28 days of age. Light and electron microscopy revealed Schwann cell and myelin degeneration in the sciatic nerves at each age studied. These changes were similar to those described in weanling rats as a result of Te intoxication. In the CNS, hypomyelination of the optic nerves was convincingly demonstrated at 14, 21, and 28 days of age, accompanied by some evidence of myelin degeneration. These changes were also seen in the ventral columns of the cervical spinal cords, although less markedly, and were confirmed by quantitative methods. There was little evidence of oligodendrocyte pathology in the CNS, and it appears that degeneration of these cells is not the primary cause of the CNS hypomyelination, in contrast to the PNS where Schwann cell degeneration has been shown to precede the myelin pathology.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 472-483 
    ISSN: 1432-0533
    Keywords: Astroblastoma ; Electron microscopy ; Immunohistochemistry ; Organ culture ; Tanycytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two examples of cerebral astroblastoma have been studied by electron microscopy and immunohistochemistry, one of them having been maintained in vitro in an organ-culture matrix system for 8 months and the explants studied by light and electron microscopy at different time intervals. The fine structural characteristics were those of a glial cell type with features intermediary between those of astrocytes and ependymocytes. They recapitulated the structure of the tanycyte, a glial precursor cell which is normally found scattered along the ependymal lining of the embryonal and neonatal mammalian brain, but is distinct from epithelial ependymocytes. The possible origin of some astroblastomas from such a cell would account for a number of characteristics in this enigmatic type of glioma.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 180 (1989), S. 273-280 
    ISSN: 1432-0568
    Keywords: Wallerian degeneration ; Myelin breakdown ; Light microscopy ; Electron microscopy ; Marchi staining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphological aspects of myelin breakdown in the posterior funiculus during Wallerian degeneration were studied in kittens subjected to lumbosacral dorsal rhizotomies 6–8 days after birth. The first sign of myelin breakdown was characterized by swollen or shrunken nerve fibers. Shortly thereafter there was an increased occurrence of collapsed myelin sheaths and later of rounded myelin bodies. Myelin was clearly seen in microglial cells. Correlative observations on Marchi-stained material indicated the simultaneous and frequent appearance of Marchi-positive bodies (MPB:s) and myelin bodies. Due to the rapidity of the degeneration process in the kitten, the increase in the occurrence of Marchi-positive granules (MPG:s) seemed to start concomitantly with increased occurrence of MPB:s. However, the frequent occurrence of MPG:s outlasted that for MPB:s. The findings indicate that the MPB:s may be the counterpart to myelin bodies and the MPG:s to lipid droplets. Microglial cells may be responsible for the primary uptake of degenerating myelin and the subsequent transformation of myelin bodies to lipid droplets. The much faster breakdown of myelin and elimination of lipid material in the degenerating posteror funiculus of the kitten, as compared to the adult, seemed to be due not only to the lower myelin content in the kitten, but also to a higher density of microglia and a greater efficiency in the myelin breakdown process in the degenerating posterior funiculus of the kitten.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1989), S. 10-17 
    ISSN: 1432-0533
    Keywords: Locus ceruleus ; Pick bodies ; Lewy bodies ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In classical Pick's disease with typical Pick bodies, inclusions resembling those present in the cerebral cortex are frequently found in the locus ceruleus. In three such cases Pick bodies were studied by light and electron microscopy and compared with Lewy bodies, inclusions more commonly found in this location. In contrast to the situation in the cerebral cortex, nerve cells with multiple Pick bodies were often found in the locus ceruleus, but in other respects definite light and electron microscopic differences between Pick bodies and Lewy bodies were present. Pick bodies were slightly basophilic and never had a central core or a peripheral halo. They were intensely argyrophilic. Differences in immunocytochemical reactions were especially marked with antibodies to tau and to paired helical filaments. Pick bodies displayed an intense reaction with these two antibodies, contrasting with that of Lewy bodies, which either lacked reactivity or reacted in a peripheral band. By electron microscopy the Pick bodies were composed of random filaments with smooth contour, whereas typical Lewy bodies had fuzzy deposits on filaments that radiated from a central core. Pick bodies in the locus ceruleus therefore maintained their immunocytochemical and electron microscopic characteristics and did not take on the character of Lewy bodies. Such differences point to a different pathogenesis and perhaps etiology of these two types of inclusions and attest to the marked difference clinically and pathologically between Pick's and Parkinson's diseases.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 77 (1989), S. 664-666 
    ISSN: 1432-0533
    Keywords: Hemimegalencephaly ; Golgi study ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pathological findings in a case of hemimegalencephaly are presented. Hemispherectomy, performed because of intractable seizures, allowed an electron microscopic and Golgi study. Glial abnormalities consisted of hyperplasia of glia cells with giant astrocytes often containing several nuclei and proliferation of numerous Rosenthal fibers. Golgi stain showed many giant neurons with a perikaryon covered by perisomatic processes, and a complex dendritic tree. Glial abnormalities could be correlated with the firmness of the hemisphere and intense hypersignal on magnetic resonance imaging. Giant neurons were associated with an increase in size of the perikaryon and dendritic tree; this pattern suggests a polyploidy.
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  • 20
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Ischemic neuronal injury ; Long-term recovery ; Mongolian gerbil ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unilateral transient cerebral ischemia was produced in Mongolian gerbils by clipping the left common carotid artery for 1h. About 60% of the gerbils with neurological symptoms had post-ischemic seizures. The majority of those that had seizures died within a few days, and sections of their cerebral cortices contained many dark and shrunken neurons. However, the gerbils that did not have seizures survived without any severe complications. In the cerebral cortex of the latter, the neurons with diffuse or peripheral pallor of the perikarya were seen along with a small number of dark and shrunken neurons. Diffuse pallor occurred within a few hours following ischemia in layers III, V and VI, and disappeared 1 or 2 days after recirculation. Electron microscopically, these neurons showed dispersion of ribosomes, simple and elongated profiles of rough endoplasmic reticulum (r-ER), clustered vacuoles, and mild to moderate mitochondrial swelling. Occasional net-like tubulomembranous structures, probably derived from r-ER, were observed. On the other hand, peripheral pallor became apparent after 5 days following ischemia, usually involving layer II first and gradually extending to the deeper layers. Concomitantly, the amount of neuropil decreased and the dendrites exhibited tortuosity and irregularity in layer II. Electron microscopically, these neurons showed marked swelling of peripheral perikarya and polyribosomes and organelles were located peripherally to the nuclei. In addition, numerous degenerated axon terminals and distended dendrites were observed around the neurons. These observations indicate that diffuse pallor represents damage directly induced by ischemia and subsequent recirculation, while peripheral pallor is the delayed and remote effect of ischemia, probably due to degeneration of neuronal processes.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 555-560 
    ISSN: 1432-0533
    Keywords: Sporadic motor neuron disease ; Lewy body-like hyaline inclusions ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lewy body-like hyaline inclusions were immunocytochemically and electron microscopically investigated in a patient with sporadic motor neuron disease. The hyaline inclusions were chiefly observed within the perikarya of both normal-looking and chromatolytic anterior horn cells in the lumbar spinal cord, but some were detected in the axons and dendrites. Usually, a single inclusion was found in the perikaryon, but in rare cases two or more were observed. Immunocytochemically, these inclusions were intensely immunostained with anti-ubiquitin anti-body. Ultrastructurally, the hyaline inclusions were chiefly composed of randomly arranged linear structures associated with ribosome-like granules, varying from compactly arranged linear densities to more loosely packed ones. They contained scattered vesicles of various sizes and occasionally a focal accumulation of randomly arranged 10-nm neurofilaments or 13–25-nm filamentous structures.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 594-604 
    ISSN: 1432-0533
    Keywords: Neurocysticercosis ; Pathogenesis ; Histochemistry ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was based on two cases of disseminated human neurocysticercosis from India. The material availabel was examined grossly, and by light microscopy, histochemistry, immunomorphology and electron microscopy. The results showed that the parasites commonly embolized to the anatomically discernable gray-white matter junction of the brain and were located in cavities, the walls of which were dilated vascular channels. The parasite-nutrition process was through endocytosis and microtrichal activity. To camouflage themselves from the host-defense mechanisms, the parasites apparently covered themselves with host-tissue-like material. Host reactivity to the parasite was heralded morphologically by the physical anchoring of the parasite by activated endothelial cells, loss of the host-tissue-like cover and an acute polymorphonuclear leucocytic response.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1989), S. 340-346 
    ISSN: 1432-0533
    Keywords: Paraganglioma ; Melanin ; Orbit ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A paraganglioma of the orbit in a 21-year-old woman is presented, containing oculo-cutaneous melanin in many tumor cells, occasionally adjacent to neurosecretory granules, and in macrophages. This tumor expands the list of neuroectodermal tumors with potential melaninization.
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  • 24
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 180 (1989), S. 243-257 
    ISSN: 1432-0568
    Keywords: Dorsal lateral geniculate nucleus ; Synapse formation ; Synaptic glomerulus ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synapse formation and maturation were examined in the rat dorsal lateral geniculate nucleus (dLGN) from birth to adulthood. Examination of animals, whose ages were closely spaced in time, showed that the maturation of the synaptic organization of the nucleus takes place chiefly during the first 3 weeks of postnatal life. This period of maturation may be divided into 3 broad stages. During the first stage, which spans the first 4 days of life, there are only a few immature synapses scattered throughout the nucleus; occasionally aggregates of 3 or 4 synapses are encountered. Dendrodendritic synapses first appear at the end of this stage. The second stage, which lasts from the end of the first stage through day 8, is characterized by intensive synaptogenesis as well as extensive growth and degeneration. For the first time, large boutons resembling retinal terminals form multiple synaptic contacts with dendrites and dendritic protrusions; these synaptic arrangements are partially covered by glial processes. A feature characteristic of the developing dLGN during the first 2 postnatal weeks, and particularly during the second stage, is the presence of membrane specializations that resemble vacant postsynaptic densities. These specializations, which may be unapposed or opposite another neuronal process, decrease in frequency as the number of synapses increases. It is not known whether these densities are converted to synapses or whether they result from loss of presynaptic elements. The third stage in the process of synaptogenesis, which spans a period between days 10 and 20, is characterized by myelination and by the diminution of growth cones, degenerating profiles and vacant postsynaptic densities. There is also a very significant increase in the number and maturation of synapses including synaptic glomeruli. However, it is not until the end of this stage that synapses appear qualitatively indistinguishable from synaptic arrangements identified in adult animals.
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  • 25
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 281 (1989), S. 254-259 
    ISSN: 1432-069X
    Keywords: Innermost cell layer ; Tonofilaments ; Huxley's cells ; Henle's cells ; Anagen hair follicles ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To elucidate the biologic roles and further cytologic characteristics of the innermost cell (IMC) layer of the outer root sheath (ORS), human anagen hair follicles were ultrastructurally examined. In the lower follicle, the transeversely running tonofilaments in the inner side of the cytoplasm of the IMCs showed a massive accumulation, facing the keratinized part of a Huxley's cell protruding through a Henle's pore. In a rare instance, a spindle-shaped cell was seen between the IMC layer and the keratinized Henle's layer. At the lower isthmus portion, some of the IMCs containing a large number of tonofilaments showed a partial degeneration of the inner side of the cytoplasm. More distally, intercellular spaces between the keratinized IMCs and keratinized Henle's cells were partly dilated and contained amorphous substances. It is suggested that the IMCs in the lower follicle may play a role to support and cover the inner hair structures, tightly as hoops of a barrel. In the isthmus portion, the IMCs may loosely support and guide the keratinized Henle's cells undergoing degeneration.
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  • 26
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    Experimental brain research 75 (1989), S. 563-568 
    ISSN: 1432-1106
    Keywords: Retina ; Diencephalon ; Co-culture ; Synapses ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Explants of chick embryo diencephalon co-cultured with explants of retina display areas of complex neuropil containing large retinal-like endings which establish synaptic contact with conventional and presynaptic dendrites. Transection of fibre bundles linking retinal to diencephalic explants results in the degeneration of endings of this type, suggesting that axons of extrinsic (retinal) origin innervate the diencephalic explants in an in-vivo-like manner.
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  • 27
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    Experimental brain research 78 (1989), S. 425-434 
    ISSN: 1432-1106
    Keywords: Avian forebrain ; Synapses ; Stereology ; Disector ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The lobus parolfactorius (LPO) of the chick has been shown to undergo an increase in the mean synaptic numerical density (Nv syn) in response to one-trial passive avoidance learning (Stewart et al. 1987). The present study was undertaken in order to describe the pattern of normal development of synapses in the LPO, to further investigate the significance of this plastic response. The LPO's from each hemisphere of pre-hatch (16 days), and post-hatch (1 day, 9 day and 22 day old) chicks were processed for electron microscopy. Synapses were classified into asymmetric spine, asymmetric shaft, symmetric spine, and symmetric shaft synapses, on the basis of the density of the post-synaptic thickening and the nature of the post-synaptic target. A 3-dimensional stereological probe was used (the ‘disector’) to calculate Nv syp, and mean projected height (H syp) of the post-synaptic density (PSD). Mean values for each age and hemisphere were compared with a 2-way analysis of variance test using paired samples. A six-fold increase in Nv syp was seen between 16 days in ovo, and 9 days post-hatch. There was a hemispheric asymmetry at 9 days post-hatch, with the left hemisphere LPO containing 1.6 times as many synapses per μm-3. There was a subsequent period of reduction in synaptic density in the left hemisphere LPO between 9 and 22 days post-hatch. The Nv of all classes of synapse increased with age, but the proportions of the symmetrical synapses with respect to the total number of synapses, decreased with age. This decrease was of a similar magnitude for each hemisphere. A hemispheric difference was seen in post-hatch asymmetric synapses, with a greater proportion of asymmetric spine synapses in the left hemisphere. The magnitude of the hemispheric asymmetry was constant throughout the 3 week period of post-hatch development, but was not present in pre-hatch chicks. The PSD increased in length in each hemisphere by approximately 40% between post-hatch day 1 and post-hatch day 9. These data show that the LPO contains a synaptic population which undergoes substantial modification during the first week post-hatch. An asymmetry exists at post-hatch day 9 which is not present at the earlier ages investigated, nor indeed after 22 days post-hatch. This may have significance with regard to studies of passive avoidance learning in the one-day old chick, where an increase in both the size and number of synapses in the LPO has been demonstrated (Stewart et al. 1987). It is possible that ‘training’, in this situation, may simply enhance the timing of synaptic events that result as a consequence of normal development.
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  • 28
    ISSN: 1432-1106
    Keywords: Nerve growth factor ; C6 glioma cells ; Chromaffin cells histofluorescence ; Electron microscopy ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to maintain a chronic supply of growth factor for medulla cells in vitro, chromaffin cells from rat, African green monkeys and man were co-cultured with C6 glioma cells, which secrete growth factors that sustain sympathetic neurons in vitro. The response of chromaffin cells to coculture was compared to treatment of medullary cells with nerve growth factor (NGF) alone. Dispersed chromaffin cell preparations were obtained by a trypsin-collagenase procedure, and subjected to differential plating on collagen-coated surfaces. With both human and monkey tissue, non-chromaffin cells did attach to the culture plates and an enriched chromaffin cell population could be replated. Rat adrenal medulla cells survived very poorly in vitro and were not enriched in this procedure. Cultured human and monkey chromaffin cells survived as epithelial cells (50%) and showed neuritic outgrowth on 55 to 66% of the cells after eight days when treated with nerve growth factor (NGF). These cells showed strong catecholamine histofluorescence, tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) immunoreactivity. In contrast, only ten percent of adult rat chromaffin cells survived in culture, although NGF treatment rescued an additional 20% of the cells and induced neuritic outgrowth after one week in vitro. C6 glioma cells were treated with mitomycin C bromodeoxyuridine to inhibit mitosis and were plated with the various medulla cells in a one to one ratio. Both human and monkey chromaffin cells expressed extensive and enhanced neuritic arborization within eight days of co-culture, (64–82% respectively) and exhibited intimate contact with the glioma cells as seen at the ultrastructural level. Importantly, survival of adult rat adrenal medulla cells was enhanced to 50% or more with 40% of the cells extending neurites when co-cultured with glioma cells for seven days. Chromaffin cells from all three species reacted for TH, DBH and PNMT in co-culture and were histofluorescent. The majority of these cells were also immunoreactive for serotonin and enkephalin, while only 37% of chromaffin cells indicated the presence of NPY. These data indicate that adrenal medulla can be maintained in vitro as the neuronal phenotype when co-cultured with growth factor producing cells and that this strategy may be useful for in vivo transplantation studies.
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  • 29
    ISSN: 1432-072X
    Keywords: Aggregation substance ; Enterococcus faecalis ; Electron microscopy ; Field emission scanning electron microscopy ; Immunogold labelling technique ; Sex pheromone system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The distribution of sex pheromone induced aggregation substance was studied on the cell surface of various Enterococcus faecalis strains. In the accompanying paper we have shown that the aggregation substance appears as a layer of hairlike structures. Using direct and indirect immunogold technique, transmission electron microscopy and high resolution scanning electron microscopy we investigated the appearance and distribution of the aggregation substance. The “hairs” increase in number with increasing exposure to sex pheromones (maximum density: 1300/μm2). We show that these structures are unequally distributed over the cell surface, even if the cells were induced by sex pheromones for a long period of time. Statistical analysis of the unequal distribution indicates that aggregation substance is incorporated into pre-existing “old” cell-walls and that this incorporation shows a saturation ca. 40 min after addition of sex pheromones.
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  • 30
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    Archives of gynecology and obstetrics 246 (1989), S. 169-179 
    ISSN: 1432-0711
    Keywords: Human fetal endometrium ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human fetal endometrium was examined by light and electron microscopy. Our study shows the following new morphological aspects: (1) Glands are already present. (2) Endometrium undergoes a maturation process during gestation and at late gestational age resembles late proliferative endometrium. (3) The nuclear bodies are present in cell nuclei throughout gestation. (4) Nucleolar channel systems (NCS) sometimes appear at a late gestational age. (5) Cells with the same morphology as that of endocrine cells are found in the basal layers of endometrium at a late gestational age. The significance of these morphological aspects is discussed.
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  • 31
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    Rheumatology international 9 (1989), S. 49-51 
    ISSN: 1437-160X
    Keywords: Synovium ; Monoclonal antibodies ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cells making up the lining of the synovium have long been known as type A and B synoviocytes, with an intermediate form sometimes also described. Accumulating evidence shows that the type A cells are macrophages and the type B cells are fibroblasts. Recently, a definite orientation of these cells within the synovial lining has been observed. The number of synovial lining cells increases in joint disease, and this now seems more likely to be due to cellular recruitment rather than local proliferation.
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  • 32
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    Journal of neurology 236 (1989), S. 361-363 
    ISSN: 1432-1459
    Keywords: Mitochondrial encephalomyopathy ; MELAS ; Mitochondrial inclusion ; Pilovacuolar inclusion ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The case of a 33-year-old man with clinical features of mitochondrial encephalomyopathy is presented. He suffered from recurrent cerebral infarctions, cerebellar ataxia, deafness, retinopathy, weakness, and cardiac and renal disorders. Biochemical and light microscope investigations of skeletal muscle did not show any mitochondrial abnormality. Electron microscopy revealed the presence of a hitherto unreported peculiar “pilovacuolar” inclusion in numerous mitochondria, composed of an electron dense pile or rod within a vacuole, while globular or crystalline inclusions were absent.
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  • 33
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    European archives of oto-rhino-laryngology and head & neck 246 (1989), S. 428-432 
    ISSN: 1434-4726
    Keywords: Otitis media with effusion ; Mucociliary system ; Eustachian tube ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have examined the function and fine structure of the mucociliary system of the eustachian tube in an experimental study of otitis media with effusion induced by X-ray irradiation. Functional examination demonstrated that the ciliary activity was diminished in such a condition, while morphological observations showed pathological findings including compound cilia, vacuolation of ciliated cells and expansion of intercellular space. These findings show that irradiation-induced otitis media with effusion results in impairment of the mucociliary system. As evidenced by these studies, the mucociliary system in the eustachian tube has an important role in the clearance of fluid produced in the tympanic cavity as well as affording improvement in this disease.
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  • 34
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    Journal of Physical Organic Chemistry 2 (1989), S. 26-34 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A set of 4-monosubstituted cyclopentenes, , were synthesized and their relative rates (kX/kH) for bromination and chlorination were determined in methanol, ethanol and acetic acid at 25 °C by competitive method. log(kX/kH) for most of the substituents can be correlated by means of Taft's equation, log(kX/kH) = ρI σI + C. In methanol ρI, Br2 = -2·91, ρI, Cl2 = -0·49, in ethanol ρI, Br2 = -3·07, ρI, Cl2 = -0·70 and in acetic acid ρI, Br2 = -1·64, ρI, Cl2 = -0·65. The presence of C(〈0) is due to a constant steric effect. The deviation of X = H is ascribed to the absence of the steric effect and that of X = CO2Me and CO2Et is accounted for in terms of anchimeric assistance. For chlorination no anchimeric assistance was observed.
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  • 35
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    Journal of Physical Organic Chemistry 2 (1989), S. 57-88 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The cation radical vinylcyclobutane (VCB) rearrangement is found to be a reaction of substantial scope, synthetic utility, and exceptional kinetic facility. In conjuction with cation radical cyclobutanation, it constitutes an effective method for net (indirect) Diels-Alder addition to electron rich dienophiles. Reactions can be carried out with either aminium salt or photosensitized electron transfer (PET) initiation and are powerfully facilitated by ionizable substituents such as p-anisyl, phenylthio, and phenoxy at the 2-position of the vinylcyclobutane. The intramolecularity of the reaction is clearly established and in four discrete systems preferred sr (suprafacial/retention) stereochemistry is observed. A theoretical basis for sr stereochemistry in the cation radical VCB rearrangement is advanced. The transition state for the reaction is considered to be similar to that for the direct cation radical Diels-Alder cycloaddition, another cation radical pericyclic reaction which converges on the same product. This model of the VCB rearrangement transition state is used to rationalize the strong rate-retarding effect of a Z-methyl substituent attached to the vinyl group and of a methyl substituent at the 4-position of the vinylcyclobutane ring cis to the vinyl substituent.
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  • 36
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    Journal of Physical Organic Chemistry 2 (1989), S. 1-14 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The mechanism of aromatic nucleophilic substitutions by amines in protic solvents is well established; on the contrary the mechanism/s of the reactions in aprotic solvents is/are still subject of controversy. The present paper describes several systems for which fourth-order kinetics (third-order in amine) were observed. A mechanism is proposed to account for this as well as other observation such as: overall negative energies of activation, quadratic dependence of kA with non-nucleophilic tertiary bases, spectacular effects of hydrogen-bond donor (HBD) and hydrogen-bond acceptor (HBA) catalysts, etc. Other alternative mechanisms are also discussed.
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  • 37
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The kinetics and mechanisms of the reactions between 1-phenylethyl benzenesulfonates (1-PEB) with N,N-dimethylanilines are investigated in methanol at 35·0°C. Reactivity and selectivity trends were found to be similar to those for the reactions of 1-PEB with anilines, but the magnitudes of cross interaction constants, ρXZ, between substituents X in the nucleophile and Z in the leaving group were substantially smaller indicating no hydrogen-bond bypass bridge formation in the transition state. However, the magnitude of ρXZ suggested a direct electrostatic interaction between the reaction centers in the nucleophile and leaving group in the frontside nucleophilic attack with a loose transition state structure.
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  • 38
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    Journal of Physical Organic Chemistry 2 (1989), S. 183-186 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The harmonic vibrational frequencies were calculated analytically at the 6-31** level for azetidine using the GAUSSIAN 82 program. The results strongly indicate the presence of several errors in a recent assignment of the fundamentals of azetidine based on a normal coordinate analysis and a revised assignment is suggested. It is concluded that reliable vibrational data for azetidine in the gas phase are needed in order to resolve the remaining ambiguities in the interpretation of the spectra.
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  • 39
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    Journal of Physical Organic Chemistry 2 (1989) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 40
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    Journal of Physical Organic Chemistry 2 (1989), S. 110-116 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The transamination reaction of α-amino acids with glyoxylic acid as catalyzed by copper(II) ions was investigated kinetically in an aqueous medium at pH 5·0 and 30·0°C. L-Phenylalanine transferred its amino group to glyoxylic acid most readily among seven different amino acids used here in the single-walled bilayer vesicle formed with N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-L-histidinamide bromide (N+C5His2C16). Such rate enhancement was found to originate from the cooperative trifunctional catalysis: a coordination effect exercised by copper(II) ions, a general acid-base catalysis by the imidazolyl group of the lipid, and a hydrophobic field effect provided by the bilayer vesicle. Lack of any of the three functions failed to give out significant rate enhancement. As regards correlation between the reactivity and the nature of α-amino acids, the copper(II)-catalyzed transamination was progressively enhanced as hydrophobicity of the α-amino acid was increased in the N+C5His2C16 vesicle.
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  • 41
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    Journal of Physical Organic Chemistry 2 (1989), S. 43-50 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The cyclic vinyl ether dihydro-1,4-dioxin is converted to its cyclic hemiacetal hydration product, 2-hydroxy-1,4-dioxane, in aqueous solution by an acid-catalyzed reaction for which kH+ = 1·80 × 10-5 M-1 S-1 at 25°C. This reactivity and the solvent isotope effect kH+/kD+ = 2·2 show that the reaction occurs by rate-determining proton transfer from catalyst to substrate and not by a pre-equilibrium mechanism as recently proposed.2
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  • 42
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    Journal of Physical Organic Chemistry 2 (1989), S. 161-176 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Cyclobutanediyl (2) has been studied in both its singlet and triplet states by ab initio electronic structure theory. The triplet, which is the ground state of the molecule, exists in both C2h and C2v forms which interconvert via a Cs transition state. For the singlet, only a C2h form is found. It passes, via a Cs transition state, onto the C2v surface on which bicyclobutane (3) is the only minimum. The ring-flipping (inversion) process in 3 includes the singlet biradical as an intermediate, and involves a novel, non-least motion path similar to one previously proposed by Gassman. Semiclassical periodic orbit theory indicates that the various minima on both the singlet and triplet surfaces can interconvert via quantum mechanical tunneling.
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  • 43
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    Journal of Physical Organic Chemistry 2 (1989), S. 89-92 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Spectral characteristics of several simple substituted B,B-bis(mesityl)pyrroloboranes are reported which support a theoretical treatment by Bonacic-Koutecky and Michl (J. Am. Chem. Soc. 107, 1765 (1985)) describing the excited states of simple aminoboranes as an example of twisted internal charge transfer. In the aminoboranes the pyrrolo moiety functions as the electron donor group and the empty p-orbital of the boron atom as the acceptor.
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  • 44
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    Journal of Physical Organic Chemistry 2 (1989), S. 103-109 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A preliminary theoretical study of the mechanisms for the reactions of the perchlorofluoroethanes CF2ClCCl3 (1), CF2ClCCl2F (2) and CF3CCl3 (3), with nucleophiles has been carried out by the MNDO method, following the experimentally suggested process shown in Scheme 1. The unlikely chlorophilic attack in the first step of Scheme 1 has been shown to be feasible for 1, 2 and 3 by analysis of the MO interactions. The second step has been found to be affected by the anionic hyperconjugation which stabilizes the anions CF2ClCCl2- (4), CF2ClCClF- (5) and CF3CCl2- (6) and would make reactions (2) (the second step) unfeasible in gas phase, but in solution reaction (2) may still easily occur for 4 and 5.
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  • 45
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    Journal of Physical Organic Chemistry 2 (1989), S. 146-160 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The alkaline hydrolysis of several alkylphosphonates and alkylphosphonyl chlorides has been investigated by molecular mechanics calculations (MM2, 1985 version). The difference of the steric energies (ΔE) between tetracoordinate substrate and pentacoordinate transition state of phosphorus compounds represents the activation energy (ΔE≠) in hydrolysis. The change of ΔE for various alkyl groups relative to methyl group (ΔΔER) is suggested as a measure of the steric effect of substituents. Thus the correlation analysis involving log k and ΔΔER of the branched alkyl group gives good results and it is reasonable to anticipate that analogous treatment using ΔΔER for the straight chain alkyl group is not satisfactory owing to the minor contribution of steric effect of the latter. However, the multiple regression analysis of log k with ΔΔER and Taft's σ* provides very good results. As shown by us, for the hydrolytic reactions studied, the proposed ΔΔER is much better than Taft's Es and Charton's ν, the commonly used well-known steric parameters in the chemistry of carbon compounds.
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  • 46
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    Journal of Physical Organic Chemistry 2 (1989), S. 205-213 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Mechanism of the Grignard reactions of aromatic ketones in THF was studied by spectroscopic and kinetic methods. The stable radical intermediates generated in the initial electron transfer from Grignard reagent to ketones are in a state of aggregated dimer of corresponding ion-radical pairs; in which two ketone anion radicals are bridged by a dimer di-cation of Grignard reagent. Subsequent alkyl radical transfer from dimeric Grignard reagent cation moiety to ketone anion radical aggregated each other are promoted by a participation of another neutral Grignard reagent. Proposed mechanism by present authors is able to explain well addition products/reduction products ratios in the Grignard reactions.
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  • 47
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    Journal of Physical Organic Chemistry 2 (1989), S. 232-242 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Characteristic vector analysis of a set of six physical and empirical parameters of 103 commonly used organic solvents (bp, ∊r, μ, nD, ETN, and δ) gives four vectors describing 95% of the total data variability. Non-hierarchical cluster analysis, applied to our results, leads to ten separate classes of organic solvents.
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  • 48
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    Journal of Physical Organic Chemistry 2 (1989) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 49
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    Journal of Physical Organic Chemistry 2 (1989), S. 15-25 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Solvolysis of 2-X-2-phenylpropane (1-X) in 25 vol% acetonitrile in water at 25°C produces 2-hydroxy-2-phenylpropane (1-OH) and 2-phenylpropene (3). The carbocationic intermediate discriminates between different nucleophiles; azide anion, acetate anion, and methanol are more efficient nucleophiles than water, kN3/kH2O = 42 kOAc/kH2O = 3, and kMeOH/kH2O = 2·9 (ratio of second-order rate constants). The fraction of the elimination product 3 increases with increasing basicity of the leaving group X as well as by addition of general bases. The Brønsted parameter for this catalysis is small, β = 0·13, with substituted acetate anions. The kinetic deuterium isotope effect for the dehydronation of the intermediate has been measured (assuming the reaction from intermediate to alcohol is insensitive to isotopic substitution) employing the hexadeuterated substrate d6-1-X as k3H/k3d6 = 3·5 ± 0·2 for the chloride 1-Cl with acetate anion, and, without added base, 3·1 ± 0·2 for the acetate 1-OAc, and 3·1 ± 0·2 for the p-nitrobnzoate 1-PNB, respectively, and ∼5 for the protonated methyl ether 1-OMeH+. The variation in isotope effect with change in leaving group is discussed in terms of elimination from contact ion pairs and ‘free’ carbocation. The overall kinetic isotope effect for the solvolysis was found to be kobsH/kobsd6 = 1·31 (1-OMeH+), 1·38 (1-OAc), 1·40 (1-PNB), and 5·7 (1-OH2+). These isotope effects consist of the isotope effect k12H/k12d6 for the formation of the substitution product 1-OH and k13H/k13d6 for production of the olefin 3. It is concluded that the latter isotope effect is enlarged owing to a branched mechanism in which the deprotonation of the carbocationic intermediate competes with formation of the substitution product. As large an isotope effect as k13H/k13d6 ∼6·5 has been measured for 1-OMeH+.
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  • 50
    ISSN: 1432-0878
    Keywords: Anterior pituitary gland ; Electron microscopy ; Growth hormone ; Spontaneous dwarf rats (dr/dr)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The spontaneous dwarf rat is a novel experimental model animal on the study of pituitary dwarfism. The fine structure of the anterior pituitary cells was studied in the immature and mature dwarf rats. Pituitary glands were removed from 5-, 10-, 20-day-old immature dwarfs, adult (45 days-16 weeks) dwarfs and normal 3-month-old rats and processed for electron-microscopic observation. In the control animals, growth hormone cells were readily identified by their ultrastructural characteristics, such as the presence of numerous electron-dense secretory granules, 300–350 nm in diameter, well developed rough endoplasmic reticulum and a prominent Golgi complex. In contrast, growth hormone cells were not found in the anterior pituitary gland of the spontaneous dwarf rat at any age examined. Other pituitary cell types, i.e., luteinizing hormone/ follicle stimulating hormone, thyroid stimulating hormone, adrenocorticotropic hormone and prolactin cells, appeared similar in their fine structure to those found in the control rats. In the pituitary gland of dwarf rats, a number of polygonal cells were observed either with no or relatively few secretory granules. The rough endoplasmic reticulum was arranged in parallel cisternae and the Golgi complex was generally prominent in these cells. In addition, many were found to have abundant lysosomes. A few minute secretory granules were occasionally observed; however, the immunogold technique failed to localize growth hormone or prolactin in the granules. The nature of these cells remained obscure in this study. Since their incidence and fine structural features, other than the secretory granules, were quite similar to those of the growth hormone cells in normal rats, we postulate that these cells are dysfunctional growth hormone cells. These results suggest that the cause of the growth impairment in the spontaneous dwarf rat is due to a defect in the functional growth hormone cells in the pituitary gland, and since other pituitary cell types appeared normal, the disorder seems to be analogous to the isolated growth hormone deficiency in the human.
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  • 51
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    Chirality 1 (1989), S. 99-120 
    ISSN: 0899-0042
    Keywords: asymmetry ; enantiomers ; geometric isomers ; (+)- (-)-isomers ; D- and L-isomers ; R- and S-isomers ; Z- and E-isomers ; drug metabolism ; stereoselectivity and stereospecificity in drug action ; stereoselectivity and stereospecificity in drug metabolism ; psychotropic drugs ; stimulants ; antidepressants ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Many drugs contain a chiral centre, or such a centre is introduced during metabolism of the drug in man and in animals. If a single chiral centre is present, the drug will normally exist as a mixture of two enantiomers, of which one may have quite different pharmacologic and/or toxic effects than the other. Chiral drugs that are used in psychiatry, and some other pharmacologically related drugs are identified, and the implications of the presence of one or two chiral centres in these drugs are discussed. Differences in pharmacologic properties of drug and metabolite enantiomers are identified and discussed. Also reviewed are the properties of some drugs used in psychiatry that both are chiral and display geometric isomerism.
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  • 52
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    Chirality 1 (1989), S. 10-13 
    ISSN: 0899-0042
    Keywords: (S)-, (R,S)-propranolol ; pharmacokinetic ; human study ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The pharmacokinetics of (S)-propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)-propranolol. The results of this study indicate that the bioavailability of (S)-propranolol, as expressed by the mean area uner the concentration-time curve (AUC) and maximum serum concentration, is lower after 40mg of the optically pure drug than after the racemic drug.
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  • 53
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    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 54
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    Chirality 1 (1989), S. 192-196 
    ISSN: 0899-0042
    Keywords: propranolol enantiomers ; enantiomers ; propranolol ; β-receptor-blocking drugs ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Only limited information is available on the stereochemistry of the in vivo distribution of β-receptor-blocking drugs. In this study we determined the levels of the propranolol enantiomers in plasma, cerebrospinal fluid (CSF) and central nervous system (CNS), and peripheral tissues in the dog following an intravenous dose of a deuterium-labeled pseudoracemate. The appearance of the propranolol enantiomers in the CSF was rapid and nonstereoselective, with maximum concentrations reached at 15 min after dosing. The levels of the enantiomers in both CSF and plasma then declined in a parallel biphasic fashion, with a terminal t1/2 of about 125 min. Except for an early high CSF/plasma concentration ratio of 0.35, the CSF propranolol levels corresponded to the unbound concentration in plasma, CSF/plasma 0.20. All areas of the brain showed a similar uptake of propranolol, with a tissue concentration exceeding that in plasma about 10-fold during the terminal phase of elimination. The uptake of propranolol by peripheral tissues varied widely, ranging from a 50-fold accumulation by the lungs compared to plasma to no accumulation by adipose tissue. However, as for the CSF, there was no evidence of stereoselective uptake of propranolol by any CNS or peripheral tissue except for the liver. A significantly higher level of (+)- vs. (-)-propranolol in liver tissue presumably was a reflection of stereoselective hepatic metabolism of (-)-propranolol by this tissue. The slight stereoselectivity in plasma binding of propranolol known to exist in the dog had no significant influence on tissue or CSF distribution.
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  • 55
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    Chirality 1 (1989), S. 209-215 
    ISSN: 0899-0042
    Keywords: enantiomeric separation ; bioanalysis ; α1-acid glycoprotein column ; disposition (R)- and (S)-atenolol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A method for the determination of (R)- and (S)-atenolol in human plasma and urine is described. The enantiomers of atenolol are extracted into dichloromethane containing 3% heptafluorobutanol followed by acetylation with acetic anhydride at 60°C for 2 h. The acetylated enantiomers were separated on a chiral α1-AGP column. Quantitation was performed using fluorescence detection. A phosphate buffer pH 7.1 (0.01 M phosphate) containing 0.25% (v/v) acetonitrile was used as mobile phase. The described procedure allows the detection of less than 6 ng of each enantiomer in 1 ml plasma. The relative standard deviation is 4.4% at 30 ng/ml of each enantiomer in plasma. The plasma concentration of (R)- and (S)- atenolol did not differ significantly in two subjects who received a single tablet of racemic atenolol. The R/S ratio of atenolol in urine was ∼ 1.
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  • 56
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    Chirality 1 (1989), S. 246-248 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 57
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    Chirality 1 (1989), S. 243-245 
    ISSN: 0899-0042
    Keywords: stereochemistry ; enantiomers ; direct separation ; alfuzosin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Described is a direct enantioselective separation of the enantiomers of alfuzosin hydrochloride on the second generation α1-AGP column which offers improved efficiency, shorter analysis, and improved stability with respect to the first generation columns. The method has been applied to the analysis of drug substance in rat plasma. This highly efficient extraction method and the use of fluorimetric detection result in selective and sensitive determination of the enantiomers. The analytical validation parameters demonstrate the applicability of this method to pharmacokinetic and metabolic studies.
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  • 58
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    Chirality 1 (1989), S. 251-264 
    ISSN: 0899-0042
    Keywords: optical activity ; optical rotation ; chiroptical detection ; enantiomeric purity ; chiral separation ; enantioselective reactions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiroptical detection for HPLC is particularly useful as a selective detection method for chiral molecules, and in enantiomeric purity determination with partial chiral separation or without chiral separation. The recent development of laser-based polarimeters with microdegree sensitivity has increased the applicability of optical rotation detection in HPLC. The detection limit of these instruments is submicrogram on-column for many chiral compounds in analytical HPLC. A variety of applications of the selective detection of optically active molecules are reviewed. The use of polarimetric detection with partial chiral separation is considered, both as an aid to method development and for enantiomeric purity determination. Finally applications to enantiomeric purity determination without chiral separation are reviewed, with the dual use of nonchirally selective and chiroptical detectors to determine the total amount and optical purity of the analyte. Determinations of chiral purity for samples of high enantiomeric excess are described, which with laser-based instrumentation may give accuracies of better than ± 1% with sample loadings of 50 μg on an achiral column. Applications to the study of enantioselective reactions are also considered, with determination of enantiomeric excess in near-racemates to better than ± 0.1%.
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  • 59
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    Chirality 1 (1989), S. 271-275 
    ISSN: 0899-0042
    Keywords: HSA-affinity chromatography ; interconverting conformers ; conformational selectivity ; conformational diastereomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2,3-Benzodiazepines containing a centre of asymmetry at C-5 possess both central and helical chiralities, and the solution of their racemates contains four molecular species. The binding of these compounds to human serum albumin (HSA) was studied by affinity chromatography. The binding strength depended both on the steric orientation of the 5-ethyl substituent and on the conformation of the diazepine ring. Conformation P (defined by the positive sign of C-1-N-2-N-3-C-4 torsion angle) is favoured, while the quasiaxial orientation -of the 5-ethyl substituent is not favoured by the albumin molecule.
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  • 60
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    Chirality 1 (1989), S. 293-300 
    ISSN: 0899-0042
    Keywords: optical isomers ; chirality and odour ; chiral flavour compound resolution ; enantiomer separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioseparation of the sherry aroma components 5-oxo-4-hydroxyhexanoic acid γ-lactone (solerone) and 4,5-dihydroxyhexanoic acid γ-lactone (solerole) is achieved, using Chiraspher (Merck) as the chiral HPLC phase and the optical purity ascertained directly by HRGC with heptakis(3-O-acetyl-2,6-di-O-pentyl)-β-cyclodextrin (Lipodex D) as the chiral stationary phase. The absolute configurations of 4,5-dihydroxyhexanoic acid γ-lactones are assigned by 1H-NMR spectral data of diastereomeric α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) esters, according to Mosher's model. Sensory qualities of the isomers are given.
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  • 61
    ISSN: 0899-0042
    Keywords: ifosfamide enantiomers, GC chiral stationary phase, pharmacokinetic studies, clinical validation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An enantioselective gas chromatographic method has been developed and validated for the determination of the plasma concentration of the enantiomers of the anticancer drug ifosfamide (IFF). In this approach, the IFF enantiomers are separated from the plasma matrix by solid phase extraction, chromatographically resolved by gas chromatography on a chiral stationary phase, and detected by mass selective detection using selective ion monitoring. The assay has been validated for routine clinical and pharmacokinetic use and has a limit of detection in plasma of 250 ng/ml of each isomer.
    Additional Material: 3 Ill.
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  • 62
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    Chirality 1 (1989), S. 137-141 
    ISSN: 0899-0042
    Keywords: resolution by crystallization ; racemic mixture ; dansyl-D-leucine ; dansyl-L-leucine ; dansyl-D-norleucine ; dansyl-L-norleucine ; dansyl-D-phenylalanine ; dansyl-L-phenylalanine ; β-cyclodextrin ; γ-cyclodextrin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optical enrichment from racemic dansyl-leucine, dansyl-norleucine, and dansyl-phenylalanine with both β- and γ-cyclodextrins in water is reported. Initial crystallization yielded the dansyl-L-leucine isomer complexed in excess with β-cyclodextrin with an optical purity of 62-78% depending on experimental conditions. The optical purities obtained for L-norleucine and L-phenylalanine were 71 and 64%, respectively. The optical purity can be increased with continued recrystallization. The dansyl-D-leucine isomer was obtained in the mother liquor with an optical purity of 54-93% depending on experimental conditions. The optical purities obtained for D-norleucine and D-phenylalanine were 72 and 58%. The optical purity of the isomer depended on the molar ratio of host:guest and the pH value of the solution. Optimum enrichment of both enantiomers was achieved with host:guest ratios of 2 : 1 and 3 : 1. Although maximum crystalline yield of the dansyl-leucine/CD inclusion complex was obtained at a pH of 3.5, optical purity of both enantiomers was less than that obtained at other pHs. The influence of the molar ratio of host:guest and the pH value of the solution are discussed. This method is suitable for large-scale enantiomeric separations.
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  • 63
    ISSN: 0899-0042
    Keywords: enantiomeric separations ; chiral stationary phase ; Pirkle-type phases ; HPLC ; anthelmintics ; benzimidazole sulfoxides ; albendazole ; fenbendazole ; oxfendazole ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The direct enantiomeric resolution of albendazole sulfoxide (SOABZ), an anthelmintic drug belonging to the benzimidazole class, is reported on a chiral stationary phase (CSP) synthesized by covalent binding of (S)-N-(3,5-dinitrobenzoyl)tyrosine-O-(2-propen-1-yl) methyl ester on a γ-mercaptopropylsilanized silica gel. A comparison with the resolution achieved on commercially available Pirkle-type CSPs obtained from N-(3,5-dinitrobenzoyl) derivatives of (R)-phenyglycine or (S)-phenylalanine is described. Some structurally related chiral sulfoxides including oxfendazole (SOFBZ) are also studied. Optimization of the mobile phase nature and composition is investigated showing that a hexane-dioxane-ethanol ternary mixture affords an almost baseline resolution (Rs = 1.25); however, in this case, albendazole sulfone (SO2ABZ) is eluted between the two sulfoxide enantiomers; accordingly, a hexane-ethanol mobile phase would be preferred for biological samples containing both metabolites. The influence of temperature on the resolution is depicted with a hexane-ethanol mobile phase. Finally, application to the enantiomeric assays of SOABZ in plasmatic extracts of rat, sheep, bovin, and man after oral administration of albendazole (sulfoxidized to SOABZ and SO2ABZ) is reported. Some distortions in the enantiomeric ratios are evidenced depending on the species.
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  • 64
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    Chirality 1 (1989), S. 1-1 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 65
    ISSN: 0899-0042
    Keywords: terutaline ; enantiomers ; determination ; liquid ; chromatography ; coupled columns ; cyclodextrin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The purpose of this work was to develop and validate a method for the separation and determination of the enantiomers of terbutaline in plasma and intestinal juice. Terbutaline was extracted from plasma and intestinal juice by liquid-solid extraction on small C18 cartridges. The extract was then analyzed by coupled column liquid chromatography with amperometric detecton. For ciral separation a β-cyclodextrin phase was used.The within-day variation (Cv) on spiked plasma samples was in the rane 0.8-6.4% at 3.8-33.8 nmol/liter for the (-)-enantiomer, and 2.6-23.0% at 1.3-11.3 nmol/liter for the (+)-enantiomer. The between-day variation on spiked plasma samples was 5.5% at 10.7 nmol/liter and 13.6% at 4.3 nmol/liter for the (-)- and (+)-enantiomers, respectively. The within-day variation for inestinal juice was i the range 0.7-1.5% at 5.6-30.0 μmol/liter for the (+)-enantiomer.
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  • 66
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    Chirality 1 (1989), S. 69-79 
    ISSN: 0899-0042
    Keywords: chiral recognition ; three-point model ; distance matrix ; molecular graph ; molecular complexes ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A general criterion is formulated for molecular recognition. The criterion for recognition is the ineqality of the distance matrices of complexes of different compounds with a resolving agent under ambient experimental conditions. It is shown how this criterion provides for an objective, cell-defined, and simple explanation for recognition of chiral compounds. This approach may be used to explain models (e.g., three-point of attachment1) and relationships for chiral recognition. It is also shown how one-, two-, or three-point mechanisms are equivalent in this formalism and could result in chiral recognition. Examples are used to illustrate how the so called one- or two-point mechanisms may be operative in many experimental findings. Symmetry rreqirements of resolving agents may also be derived from considerations of distance matrices. Finally, the reciprocal relationship of chiral resolving agents is easily derived from the present method of analysis.
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  • 67
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    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 68
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    Chirality 1 (1989), S. 97-97 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 69
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    Chirality 1 (1989), S. 57-62 
    ISSN: 0899-0042
    Keywords: chiral stationary phase ; α-amino phosphonate ; chromatographic separation of enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A chiral statonary phase (CSP) derived from an N-(3,5-dinitrobenzoyl)-α-aminobenzylphosphonate has been prepared and evaluated for its utility in the direct separation of enantiomers. This CSP, 2, is structurally related to earlier N-(3,5-dinitrobenzoyl)-α-acids acid-derived phases (e.g., CSP 1), but the mode of attachment to the support is different. In scope; CSP 2 is qualitaively similar to CSP 1. However, it differs quantitatively from CSP 1, showing either greater or lesser selectivity for different pairs of enantiomers.
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  • 70
    ISSN: 0899-0042
    Keywords: enantiomeric separations ; chiral stationary phases ; tyrosine chiral selector ; γ-mercaptopropyl silica gel ; HPLC ; SubFC ; preparative LC ; chiral recognition mechanisms ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chromatographic applications of three novel chiral stationary phases (CSPs) deriving from (S)-(N)-(3,5-dinitrobenzoyl)tyrosine are reported, under liquid chromatographic (LC) and subscritical fluid chromatographic (SubFC) conditions. Two grafting modes of the chiral moiety have been experimented starting either from γ-mercaptopropyl-silanized (type 1) or γ-aminopropyl-silanized (type 2) silica gels. For type 2 CSPs an evaluation of the stability of the amide linkage was achieved by means of SubFC; the relative contriution of ionic and covalent bindings to the ciral recognitio aility was then outlined. The chromatographic properties of these CSPs were compared with those of the corresponding CSPs deriving from phenylglycine, p-hydroxyphenylglycine, and phenylalanine for the resolution of some tertiary phosphine oxide, naphthoyl amide, and α-methylene γ-lactam enantiomers. Some simple requirements regarding the solute and CSP structures for chiral recognition ability can be inferred from these results. In addition, the resolutio of π-acid α-N-(3,5-dinitrobenzoyl)amino esters was investigated on these π-acid CSPs. An example of preparative scale chromatography is also presented.
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  • 71
    ISSN: 0899-0042
    Keywords: crystal structure ; inclusion ; chiral host ; complexation ; glucopyranose ; cellulose triacetate ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: X-ray analysis of the crystalline product obtained by reaction of 2,3,4,6-Tetra-O-acetyl-D-glycopyranose with phenylethylamine revealed the formation of a real one-to-one inclusion complex. This complexaion is highly stereoselective, because only the (+)-R-enantiomeric form of the amine is included. Analogies to the mode of complexation of cellulose triaceate with chiral molecules in „inclusion chromatography“ are discussed.
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  • 72
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    Chirality 1 (1989), S. 89-91 
    ISSN: 0899-0042
    Keywords: asmmetric induction ; bacterial cell wall ; D-Ala-D-Ala ; dipeptide ; peptidoglycan ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Absolute stereochemical control is employed in the synthesis of isosteres for dipeptide subunits 1; see Fig. (1) in which the amide linkage has been replaced by a trans carbon-caron double bond. The synthesis affords access to the four stereoisomers of 1 in which R and R' = CH3, including the isostere of D-alanine-d-alanine (D-ala-D-Ala), 2.
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  • 73
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    Chirality 1 (1989), S. 92-93 
    ISSN: 0899-0042
    Keywords: ciral resolution ; high-performance liquid chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Epinephrine enantiomers were derived into diastereoisomers with the chiral reagent 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylisothiocyanate. The resolutions was carried out on a C18 column. The RS between (-)-R- and (+)-S-isomers was 2.3. The retention time could be changed by adding a proper amount of acetonirile into the mobile phase. The results showed that (+)-S-isomer in the epinephrine hydrochloride injections increased during the period of storage.
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  • 74
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    Chirality 1 (1989), S. 183-191 
    ISSN: 0899-0042
    Keywords: enantiomorphism ; dissymmetry ; chirality ; enantioselectivity ; diastereoselectivity ; steric complementarity ; asymmetric induction ; three-point contact ; circularly polarized radiation ; circular dichroism ; parity nonconservation ; electroweak interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Pasteur's conjecture (1860) that biomolecular homochirality arose from a chiral natural force as yet inaccessible in the laboratory was supplanted by Fischer's (1894) “key and lock” hypothesis of stereoselection in enantiomer to diastereomer conversions, whether in the laboratory or in living organisms. Elaborations of the “key and lock” hypothesis by Haldane (1930) and Pauling (1948) have been illustrated and supported with modification by X-ray diffraction crystal structures of enzyme-substrate complexes over the past quarter century.Two types of mechanism for the product diastereoselectivity in the reactions of an enantiomer with an achiral reagent, early proposed, have recent support: one proposes a quasidiastereomeric structure for the enantiomer attacked in the ground state, the other for the corresponding transition state of the reaction. Approaches to the differential biological activity of two enantiomers postulate either the complete binding of each isomer to a chiral receptor site, resulting in diastereomeric complexes with inequivalent bioactivities, or the differential binding of the two isomers to a set of three sites, with which only one isomer is sterically congruent.Biochemical homochirality, based on the chiral stereoselectivity of both biosynthetic and metabolic reactions, derives from the evolutionary pressure for a progressive enhancement of the kinetic efficiency and economy of those reactions. Recently Pasteur has been vindicated in part, and the problem of the original prebiotic enantiomeric excess left outstanding by Fischer has been solved. The unification of the electromagnetic with the weak interaction provided a universal chiral natural force, the electroweak interaction, which favours the chiral series selected during the course of biochemical evolution, both the D-sugars and the L-amino acids.
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  • 75
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    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 76
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    Chirality 1 (1989), S. 249-250 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 77
    ISSN: 0899-0042
    Keywords: benzo[a]pyrene diol-epoxides ; benzo[a]pyrene tetrols ; high-performance liquid chromatography ; chiral stationary phase ; optical isomers ; resolution of enantiomers ; absolute configuration ; circular dichroism spectra ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantiomers of diastereomeric benzo[a]pyrene (BP) diol-epoxides, r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydro-BP (BP 7,8-diol-anti-9,10-epoxide), r----7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydro-BP (BP 7,8-diol-syn-9,10-epoxide), r-9,t-10-dihydroxy-t-7,8-epoxy-7,8,9,10-tetrahydro-BP (BP 9,10-diol-antiy7,8-epoxide), and several 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (BP tetrols) were resolved by high-performance liquid chromatography (HPLC) using columns packed with either (R)-N-(3,5-dinitrobenzoyl)phenylglycine[(R)-DNBPG] or (S)-N-(3,5-dinitrobenzoyl)leucine [(S)-DNBL], which is either ionically or covalently bonded to γ-aminopropylsilanized silica. Resolution of enantiomers was confirmed by ultraviolet-visible absorption and circular dichroism spectral analyses. Resolved enantiomers of BP diol-epoxides were each hydrolyzed in acidic solution to a pair of diastereomeric tetrols which were separated by reversed-phase HPLC. Absolute stereochemistries of enantiomeric diol-epoxides were deduced by the absolute configuration of their hydrolysis products.
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  • 78
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    Chirality 1 (1989), S. 284-292 
    ISSN: 0899-0042
    Keywords: absolute configuration ; crystal structure ; resolution ; solid-state circular dichroism ; torsional isomerism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The crystal structure and absolute configuration of the (-)589-dibenzoylmonohydrogentartrate salt of the cation [Co(pyridine)4Cl2]+ have been determined from a three-dimensional X-ray analysis. Single crystals were grown from dimethylsulfoxide: space group P212121, Z = 4, and cell dimensions a = 21.463(4), b = 23.112(3), and c = 7.490(1) Å. Full-matrix least-squares refinement on F converged at R = 0.075, 196 variables and 2029 observations. The cation has pseudotetragonal coordinate geometry, with axial Cl and equatorial N atoms. The dihedral angles between the pyridine ligands and the equatorial plane are 47(1), 39(1), 50(1), and 45(1)° and torsional isomerism is responsible for the solid-state chiroptical properties of the cation. The preferential crystallization of the P atropisomer of the cation is attributed to a general electrostatic attraction between cation and anion.
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  • 79
    ISSN: 0899-0042
    Keywords: enantiomers ; diastereoisomeric ureas ; high-performance liquid chromatography (HPLC) ; fluorophores ; inversion of optical rotation ; antiarrhythmics ; propranolol ; plasma ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis and analytical testing of two new fluorescent chiral derivatizing agents (-)-(S)-flunoxaprofen and (-)-(S)-naproxen isocyanate, is described. In a few simple steps the free carboxylic acids [(S)-flunoxaprofen and (S)-naproxen] are activated with ethyl chloroformate/sodium azide and transformed to the corresponding isocyanates. The crystalline reaction products display high enantiomeric and chemical purity and stability. The direction of the optical rotation of both substances is inverse to that of the corresponding carboxylic acids. At ambient temperature the reagents swiftly react with primary and secondary amines, yielding highly fluorescent ureas. The applicability of the two reagents for the resolution of racemic amines was tested with a number of pharmaceuticals (antiarrhythmics, β-adrenergic antagonists, calcium channel blockers, centrally acting antidepressants). The diastereoisomeric derivatives were efficiently resolved and separated from side-products by means of normal and reversed-phase high-performance liquid chromatography (HPLC). The use and sufficient sensitivity of the two reagents for pharmacokinetic studies were demonstrated with a determination of plasma levels of propranolol enantiomers after oral administration of the racemic drug [80 mg (R,S)-propranolol-HCl] to two volunteers.
    Additional Material: 7 Ill.
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  • 80
    ISSN: 0899-0042
    Keywords: optical resolution ; HPLC ; chromatography ; antiinflammatory drug ; ibuprofen ; ketoprofen ; flurbiprofen ; tiaprofenic acid ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Direct optical resolution of antiinflammatory drugs such as ibuprofen, ketoprofen, flurbiprofen, and tiaprofenic acid were attempted by high-performance liquid chromatography using tris(3,5-dimethylphenylcarbamate)s of cellulose and amylose as chiral stationary phases. Although ibuprofen was not sufficiently resolved, the other three 2-arylpropionic acids were completely resolved by amylose tris(3,5-dimethylphenylcarbamate). Ibuprofen was resolved as anilide derivative.
    Additional Material: 2 Ill.
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  • 81
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereoselectivity of carvedilol, a novel β-adrenoceptor antagonist and vasodilator with one asymmetric carbon atom, was examined at α1- and β1-adrenoceptors in vitro and in vivo. (-)-(S)-Carvedilol is a potent, competitive antagonist of the β1-adrenoceptor-mediated positive chronotropic response to isoproterenol in guinea pig atrium, with a dissociation constant (KB) of 0.4 nM. (+)-(R)-Carvedilol was more than 100-fold less potent than the (-)-S-enantiomer as an antagonist of β;1-andrenoceptors, having a KB of approximately 45 nM. Consistent with these findings (-)-(S)-carvedilol (0.1 mg/kg, i.v.) produced a 25-fold rightward shift in the β1-adrenoceptor-mediated positive chronotropic response to isoproterenol in pithed rats, whereas the (+)-R-enantiomer had no β1-adrenoceptor blocking activity in vivo at this dose. In contrast to the marked degree of stereoselectivity observed at βl1-adrenoceptors, both (-)-(S)- and (+)-(R)-carvedilol produced equal antagonism of the α1----adrenoceptor-mediated vasoconstrictor response to norepinephrine in rabbit aorta, with KB values of 14 and 16 nM, respectively. Furthermore, in the pithed rat, the α1-adrenoceptor-mediated pressor dose-response curve to cirazoline was shifted approximately 6-fold to the right by both the (+)-R- and (-)-S-enantiomers of carvedilol at a dose of 1 mg/kg, i.v. In anesthetized spontaneously hypertensive rats, (-)-(S)-carvedilol was 6-fold more potent as an antihypertensive than (+)-(R)-carvedilol. The vasodilator and acute antihypertensive activity of carvedilol results from α1-andrenoceptor blockade produced by both enantiomers, and the concomitant β1-adrenoceptor blockade produced by the (-)-S-enantiomer, which prevents reflex tachycardia that can offset the antihypertensive response, leading to greater overall antihypertensive potency of (-)-(S)-carvedilol relative to the (+)-R-enantiomer. These data also suggest that distinct regions of the carvedilol molecule are responsible for blocking α1- and β1-adrenoceptors, with β1-adrenoceptor blockade resulting from an area of the molecule containing the asymmetric carbon atom, specifically the carbazolyloxy propanolamine moiety, and α1-adrenoceptor blockade resulting from a part of the molecule that does not contain the asymmetric carbon atom, most likely the phenoxyethylamine moiety.
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  • 82
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    Chirality 1 (1989), S. 309-312 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 83
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    Chirality 1 (1989), S. 7-9 
    ISSN: 0899-0042
    Keywords: substrate enantioselectivity ; product enantioselectivity ; Michaelis-Menten analysis ; intrinsic activity ; potency ; receptor affinity ; efficacy ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 84
    ISSN: 0899-0042
    Keywords: affinity ; efficacy ; dissociation ; constants ; steroselectivity ; entropy ; enthalpy ; receptor ; interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: After alkylation of a fraction of the total α-adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (-)- and (+)-epinephrine in functional studies were 7 × 10-7 M and 2 × 10-5 M, respectively. In the adrenoreceptor-containing tissue fraction, when 3H-labeled WB4101 was used as the interacting ligand, for each enantiomer who affinity sites were found. Only the low-affinity dissociation consant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy. ΔG°, is calculated from the low-affinity binding constants, the values -8.1 and -6.2 kcal/mol for (-)- and (+)-isomer, respectively, are obained. The small difference in the value between isomers forms a hydrogen bond with the receptor. The interaction of epinephrine with this receptor appears to be driven largely by the entropy of the drug-receptor interaction with only a small nonsteroselective contribution from the enthalpy of ineraction.
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  • 85
    ISSN: 0899-0042
    Keywords: column liquid chromatography ; chiral separations ; chymotrypsin on silica ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereochemical separation of free and derivatized amino acids on active α-chymotrypsin bonded to silica is governed by two mechanisms based on the structure of the solutes or on the enzymatic activity of the enzyme. Te deactivation of the hydrolytically active site of the enzyme demonstrated that a significant portion of the retention on this support is due to hydrophobic interactions at other sites. These sites appear to be stereoselective for the ester derivatives of amino acids but not for the other studied solutes.
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  • 86
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    Chirality 1 (1989), S. 63-68 
    ISSN: 0899-0042
    Keywords: optical resolution ; chromatography ; amino acid derivatives ; molecular recognition ; preparative ciral separation ; macroporous polymers ; mass transfer limitaions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A moleclar imprinting technique based on electrostatic and hydrogen bonding interactions was used to prepare polymers of high selectvity for the original print molecule (D or L form of an amino acid derivative). In the chromatographic mode ig enantioselectivity was observed, in particular for amino acid amides and basic amino acid esters. As indicated y he broad peaks obtained, the mass transfer, including the kinetics of the binding and dissociation process, was slow and appeared to be slower in systems where a higher number of interactions between the solute and the stationary phase could be expected. In such systems enhanced selectivity was observed. For polymers prepared at a lower temperature the mass transfer was more rapid and a higher selectivity was observed, wich allowed the separations to be performed at room temperature. A more rapid mass transfer and a higher selectivity could also be achieved by increasing the column temperature. Furthermore the polymers showed a high sample load capacity and a high stability, and the can easily be prepared.
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  • 87
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    Chirality 1 (1989), S. 86-88 
    ISSN: 0899-0042
    Keywords: stereochemistry ; stereoselective snthesis ; (S)-2-hydroxypropanoic acid ; chiral synthon ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The (+)- and (-)-enantiomers of benproperinium dihydrogen phosphate, an antitussive drug, have been assigned the R- and S-configurations, respectively, by syntheses of both enantiomers using (S)-2-hydroxypropanoic acid (L-lactic acid) as chiral synthon. The key intermediate, (S)-2-metyl-2-[-2-(phenylmethyl)phenoxy]ethyl p-toluenesulfonate, was subjected to an SN2-type reaction with piperidine furnishing (+)-(R)-benproperinium dihydrogen phosphate. (-)-(S)-Benproperinium dihydrogen phosphate was obtained by submitting the same tosylate to two consecutive SN2-type reactions with Br- and piperidine, respectively, acting as nucleophiles.
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  • 88
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    Chirality 1 (1989), S. 94-95 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 89
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    Chirality 1 (1989), S. 170-173 
    ISSN: 0899-0042
    Keywords: phenglutarimide enantiomers ; enantioselectivity ; antiparkinsonian drugs ; M1-selective antagonists ; rabbit vas deferens ; pirenzepine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The affinity of the enantiomers of phenglutarimide at three muscarinic receptor subtypes was examined in vitro using field-stimulated rabbit vas deferens (M1 receptors) and guinea pig atria (M2α receptors) and ileum (M2β receptors). Extremely high stereoselectivity was observed and higher affinities (up to 6000-fold) were found for the (+)-S-enantiomer. The stereoselectivity ratios were different at the three subtypes, and the stereochemical demands made by the muscarinic receptors were most stringent at M1 receptors. (+)-(S)-Phenglutarimide was found to be a potent M1-selective antagonist (pA2 at M1 = 8.53). Its receptor selectivity profile is qualitatively similar to that of pirenzepine. (-)-(R)-Phenglutarimide showed no comparable discriminatory properties.
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  • 90
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 91
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    Chirality 1 (1989), S. 2-6 
    ISSN: 0899-0042
    Keywords: optical isomers ; stereochemistry ; enantiomers ; Food and Drug Administration ; drug development ; drug regulation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The current regulatory position of the Food and Drug Administration is discussed with regard to the approval of racemates and pure stereoisomers. Circumstances in which stereochemically sensitive analytical methods are necessay to ensure the safety and efficacy of a drug are described. Regulatory guidelines are interpreted for applications for the approval of a pure enantiomer in which the racemate is marketed, for the approval of eitehr a racemate or a pure enantiomer in which neither is marketed, and for clinical investigations to compare the safety and efficacy of a racemate and its enantiomers. Examples of te basis for such regulation are drawn from historical situations (thalidomide, benoxaprofen) as well as currently marketed drugs (arylproionic acids, disopyramide, indacrinone).
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  • 92
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    Chirality 1 (1989), S. 27-37 
    ISSN: 0899-0042
    Keywords: mutarotation ; sugars ; carbohydrates ; isomeric ; separation ; temperature effects ; selectvity ; optimization ; hemiacetal ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A brief review of sugar stereochemistry is given. The separation of 84 different pairs of anomers was accomplished on both α- and β-cyclodextrin columns. Five different mobile phases were evaluated. The separation of anomers temperature, flow rate, and so on. The separation of anomers that mutarotate is somewhat more difficult than those that do not. Prior knowledge as to the rate of mutaroation is useful so that the chromatographic conditions can be arranged to minimize any deleterious effects on the separation.
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  • 93
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    Chirality 1 (1989), S. 121-126 
    ISSN: 0899-0042
    Keywords: stereoselective metabolism ; sulfate conjugation ; in vitro sulfation ; sympathomimetic amines ; chiral separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Little is known about the stereochemistry of sulfation of chiral phenolic drugs. In this study we examined several in vitro approaches to this question, using (+)-, (-)-, or (±)-terbutaline as the substrate and the rat liver cytosol as the phenolsulfotransferase enzyme source. The cosubstrate PAPS was either generated by the cytosol from inorganic sulfate and ATP or added to the cytosol. The intact sulfate conjugates formed were determined by HPLC. Using the PAPS generating system, which is best suited for the production of relatively large quantities of sulfate conjugates, with the individual enantiomers as substrates, (+)-terbutaline was conjugated to a much greater extent than (-)-terbutaline; the (+)/(-)-enantiomer ratio was 7.3 ± 0.3 (mean ± SE). When (±)-terbutaline was the substrate and chiral derivatization was employed to separate the sulfate enantiomers formed, a similar (+)/(-)-enantiomer ratio of 7.9 ± 0.2 was obtained. With PAP35S added to the cytosol, an approach best suited for kinetic studies, the substrate concentration dependence of sulfation could be determined. The Km app for this reaction was identical for (+)- and (-)-terbutaline. However, the Vmax app was 8.1 ± 0.4 times greater for (+)-terbutaline. This study for the first time shows enantioselectivity in sulfation of a chiral phenolic drug. The experimental approaches used should be valuable for human studies of stereoselectiven sulfation of terbutaline and other chiral drugs.
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  • 94
    ISSN: 0899-0042
    Keywords: chromatography ; chirality ; chiral recognition ; β-aminoalcohols ; stereochemistry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Three chiral stationary phases, obtained by derivatizing γ-mercaptopropylsilanized silica gel with quinine, quinidine, and cinchonidine, have been employed in the resolution of N-acyl derivatives of β-hydroxyphenethylamines. The use of circular dichroism for detection and NMR analysis of analyte-selector mixtures provides an experimental basis for preliminary assignment of a recognition mechanism.
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  • 95
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    Chirality 1 (1989), S. 154-160 
    ISSN: 0899-0042
    Keywords: enantiomers ; chiral discrimination ; drugs ; hydrophobic interaction ; biopolymers ; elution order ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optical resolution on the analytical scale of a number of racemic pharmaceuticals and some other biologically active compounds has been studied using immobilized bovine serum albumin (BSA) as the stationary phase. For some of the compounds the elution order was determined by the use of optically enriched fractions obtained from a preceding passage of a sample through a preparative column containing microcrystalline triacetylcellulose (MCTA). The reversal in the sign of optical rotation shown in the polarimetric elution profile from the latter, combined with the integrated peak area ratio obtained on resolution on the analytical column, gave directly the order of elution. For one of the benzothiadiazines studied (bendroflumethiazide), increasing the pH of the mobile phase produced opposite effects on the retention of the two enantiomers, leading to a large effect on the separation factor. For many of the compounds studied, high separation factors (α 〉 2) could be achieved.
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  • 96
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    Chirality 1 (1989), S. 178-179 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 97
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    Chirality 1 (1989), S. 174-177 
    ISSN: 0899-0042
    Keywords: pharmacokinetics ; terbutaline ; enantiomers ; human ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Terbutaline is a β2-agonist and administered as the racemic mixture. The pharmacokinetics of the separate enantiomers differ with respect to degree of absorption and clearance. In the present study, repeated doses of racemic terbutaline were given to six healthy volunteers. Plasma was analyzed for the concentrations of the two enantiomers. The observed plasma concentrations at steady state differed from those predicted from the values observed after single dose administration of the separate enantiomers. The difference between the observed and predicted values can be tentatively explained by a combined influence of (-)-terbutaline on the absorption of (+)-terbutaline and the influence of (+)-terbutaline on the elimination of (-)-terbutaline. The results have implications for the interpretation of effect/concentration studies with terbutaline, but do not affect the doses used in clinical practice.
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  • 98
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    Chirality 1 (1989), S. 98-98 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 99
    ISSN: 0899-0042
    Keywords: enantioselective epoxidation ; cytochrome P-450-dependent monooxygenases ; species dependence of microsomal epoxidation ; product enantioselectivity ; substrate enantioselectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioselectivity of the in vitro conversion of simple prochiral and chiral aliphatic alkenes into oxiranes by liver microsomes of untreated or induced (phenobarbital) rats, of untreated or induced (phenobarbital, benzo[α] pyrene) mice, and of humans was determined by complexation gas chromatography. The enantiomeric excess (ee) of the epoxides extends from 0 (trimethyloxirane) to 50% (ethyloxirane). The configuration (R or S) of the enantiomers formed in excess is consistent for homologous oxiranes but is species dependent and in some cases influenced by enzyme induction. Enantioselectivity differences of aliphatic alkene epoxidation by human liver microsomes of four individuals are negligible.
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  • 100
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    Chirality 1 (1989), S. 167-169 
    ISSN: 0899-0042
    Keywords: enantioselectivity ; three-point model ; chiral receptors ; chiral separations ; didactic model ; elusion of the three-point model ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hands can be used to demonstrate the three-point model of chiral recognition. The points of attachment are thumb, forefinger, and middle finger. This vivid model has the advantages of simplicity, perspicuity, and availability at any time, although two persons are necessary. It can be shown that two interactions are not sufficient for chiral recognition but that three attractive or two attractive and one repulsive attraction are needed. It can also be used to explain some possibilities of weakening or elusion of the three-point model.
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