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  • 1
    Electronic Resource
    Electronic Resource
    Neutron Reflectivity Studies of End-Grafted Polymers (1995)
    s.l. : American Chemical Society
    Macromolecules 28 (1995), S. 492-499 
    Details
    ISSN: 1520-5835
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ma00106a012
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  • 2
    Electronic Resource
    Electronic Resource
    Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats (1996)
    Springer
    Inflammation research 45 (1996), S. 531-540 
    Details
    ISSN: 1420-908X
    Keywords: Antiinflammatory ; Analgesic ; Antipyretic ; pKa ; Octanol-water partition coefficient ; NSAIDs ; Animal models ; Carrageenin ED50
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective and Design: Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. Material: Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pKa), octanolwater partition coefficient and elimination half-life. Treatment: Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. Methods: The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. Results: Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose is carrageenin 〉yeast induced fever〉pressure induced pain=adjuvant arthritis in rats. The analysis suggested that the pain and adjuvant arthritis models in rats may also involve a prostaglandin independent mechanism. Of the two physicochemical factors tested, pKa contributed best to the carrageenin model towards predicting the clinical potency of NSAIDs. Mathematical relationships between human dose, carrageenin ED50 and pKa were established that may assist in the future clinical development of NSAIDs. Conclusions: Carrageenin-induced paw edema model in rats is the most robust predictor of the clinical potency of NSAIDs. Acid dissociation constant (pKa) appears to be a secondary contributor to the potency of NSAIDs. The relevance of the data analyses for developing cyclooxygenase-2 (COX-2) selective NSAIDs is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02342223
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of inhibitory neurotransmitters on the mudpuppy (Necturus maculatus) locomotor pattern in vitro (1999)
    Springer
    Experimental brain research 129 (1999), S. 172-184 
    Details
    ISSN: 1432-1106
    Keywords: Key words GABA ; Glycine ; Central pattern generator ; Spinal cord ; Locomotion ; In vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Effects of inhibitory neurotransmitters on the locomotor rhythm and pattern generation were investigated using an in vitro preparation isolated from the mudpuppy (Necturus maculatus). The preparation consisted of the first five segments of the spinal cord and the right forelimb attached by the brachial nerves. During N-methyl-d-aspartate (NMDA)-induced locomotion, the rhythmic motor output (EMG) was recorded unilaterally from elbow flexor and extensor muscles. While neither glycine nor γ-aminobutyric acid (GABA)-related substances induced locomotion in the absence of NMDA, they modulated NMDA-induced locomotion. Bath application of glycine and GABA suppressed the rhythmic motor pattern induced by NMDA. Addition of glycine receptor antagonist strychnine or GABAA receptor antagonist bicuculline disrupted the phase relationship between antagonistic motor pools during ongoing locomotion, thereby changing the normal alternating pattern into synchronous EMG bursts. Both the GABAA receptor agonist muscimol and GABAB receptor agonist baclofen mimicked the effects of GABA as they either slowed down or stopped locomotion. Nipecotic acid, a GABA uptake blocker, had a similar effect. This suggested that an endogenous release of GABA modulated the locomotor rhythm. The endogenous release was antagonized by the GABAA and GABAB receptor antagonists bicuculline and CGP-35348, respectively. Immunocytochemistry revealed that glycine and GABA-positive neurons and fibers were present in mudpuppy spinal cord. Although the GABAergic neurons were more numerous than glycinergic neurons, both cell types contributed processes directed towards the white matter and occasionally towards the ependymal lining of the central canal. Our results suggest that inhibitory neurotransmitters exert powerful actions upon the neuronal network governing forelimb locomotion in the mudpuppy. The effects we observed may be mediated by a network of segmentally distributed glycinergic and GABAergic spinal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050887
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  • 4
    Electronic Resource
    Electronic Resource
    Serotonergic modulation of the mudpuppy (Necturus maculatus) locomotor pattern in vitro (1996)
    Springer
    Experimental brain research 111 (1996), S. 57-67 
    Details
    ISSN: 1432-1106
    Keywords: 5-HT ; Locomotion ; Motor control ; Pattern generation ; Spinal cord ; Mudpuppy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aims of the present study were to: (1) study the role of serotonin (5-HT) in modulating the central pattern generator (CPG) underlying locomotion in the mudpuppy (Necturus maculatus); (2) investigate whether there is an intrinsic spinal serotonergic system. These aims were achieved by the use of pharmacological and immunocytochemical methods. To study modulation of the locomotor pattern and rhythm, we applied 5-HT, its uptake blocker zimelidine, and a variety of 5-HT receptor agonists and antagonists to an in vitro brainstemspinal cord preparation isolated from the mudpuppy. The preparation consisted of the first five segments of the spinal cord and the right forelimb attached by the brachial plexus. The spinal CPG for locomotion was activated chemically by adding NMDA to the superfusing solution. During locomotion, bipolar electromyographic (EMG) recordings were made unilaterally from flexor and extensor ulnae muscles. 5-HT on its own did not induce locomotion, but it did have a profound modulatory effect on NMDA-induced locomotion. 5-HT produced a dose-dependent increase in the overall cycle duration and enhanced the EMG burst duration. Use of zimelidine indicated that there is an endogenous release of 5-HT which modulated the locomotor rhythm. The endogenous release was antagonized by 5-HT1/5-HT2 receptor antagonist methiothepin. Immunocytochemical analysis, in which the entire spinal cord of the mudpuppy was used, revealed that there were more than one type of spinal serotonergic neuron. They were differentiated according to the cell diameter, shape, and arborization pattern of their processes. These neurons were located within the central gray matter ventrolateral to the central canal. Our results suggest that 5-HT plays an important role in modulating the locomotor CPG in the mudpuppy, by acting through a well-developed spinal serotonergic system. This is in contrast to what has been reported in higher vertebrates, where serotonergic innervation is derived from supraspinal structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229556
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  • 5
    Electronic Resource
    Electronic Resource
    Social integration, sexual behaviour and fertility in patients with bladder exstrophy —a long-term follow up (1996)
    Springer
    European journal of pediatrics 155 (1996), S. 678-683 
    Details
    ISSN: 1432-1076
    Keywords: Bladder exstrophy ; Interpersonal relations ; Sexual behaviour ; Fertility and education
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After primary bladder closure or urinary diversion, other factors apart from the reconstruction itself gain importance for individuals with the exstrophy-epispadias complex: social integration and, after reaching puberty, sexuality and fertility. Between 1968 and July 1994 115 patients with bladder exstrophy or incontinent epispadias underwent surgery at our institution. A total of 104 patients could be followed, 2 of whom died in the meantime. Of the remaining 102 patients 48 attend school, 4 are in college, 40 have completed or are currently undergoing vocational training, 3 are unemployed, 1 lives in a therapeutic centre and 6 are younger than 6 years of age. A total of 95% of the patients with continent urinary diversion are continent day and night, whereas only three of five patients with a sling plasty (incontinent epispadias) or with primary bladder closure followed by a Young-Dees procedure are continent. None of the patients showed deterioration of renal function. In 25 females the external genitalia were reconstructed. Fixation of the uterus was done in 13 to correct or prevent uterine prolapse. Of the 17 women older than 18 years of age with genital reconstruction, 16 are satisfied with the cosmetic result. All adults engage in sexual intercourse. Five women have delivered seven children by Caesarean section. Of the 35 male adults 32 underwent reconstruction of the external genitalia and 34 males achieve erection. One developed necrosis of the penis early in life following primary bladder closure performed at an outside hospital. Penile deviation was present in 11 of the 32 patients with genital reconstruction, which is distressing in only 2. Thirty patients are satisfied with the cosmetic result. After genital reconstruction 9 males developed epididymitis, necessitating two orchiectomies and three vasectomies. No patient with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas ejaculation was normal in the three men who did not undergo genital reconstruction and in two patients prior to post-pubertal reconstruction. Furthermore, two of these three men have fathered four children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01957152
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  • 6
    Electronic Resource
    Electronic Resource
    Social integration, sexual behaviour and fertility in patients with bladder exstrophy – a long-term follow up (1996)
    Springer
    European journal of pediatrics 155 (1996), S. 678-683 
    Details
    ISSN: 1432-1076
    Keywords: Key words Bladder exstrophy ; Interpersonal relations ; Sexual ; behaviour ; Fertility and education
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After primary bladder closure or urinary diversion, other factors apart from the reconstruction itself gain importance for individuals with the exstrophy-epispadias complex: social integration and, after reaching puberty, sexuality and fertility. Between 1968 and July 1994 115 patients with bladder exstrophy or incontinent epispadias underwent surgery at our institution. A total of 104 patients could be followed, 2 of whom died in the meantime. Of the remaining 102 patients 48 attend school, 4 are in college, 40 have completed or are currently undergoing vocational training, 3 are unemployed, 1 lives in a therapeutic centre and 6 are younger than 6 years of age. A total of 95% of the patients with continent urinary diversion are continent day and night, whereas only three of five patients with a sling plasty (incontinent epispadias) or with primary bladder closure followed by a Young-Dees procedure are continent. None of the patients showed deterioration of renal function. In 25 females the external genitalia were reconstructed. Fixation of the uterus was done in 13 to correct or prevent uterine prolapse. Of the 17 women older than 18 years of age with genital reconstruction, 16 are satisfied with the cosmetic result. All adults engage in sexual intercourse. Five women have delivered seven children by Caesarean section. Of the 35 male adults 32 underwent reconstruction of the external genitalia and 34 males achieve erection. One developed necrosis of the penis early in life following primary bladder closure performed at an outside hospital. Penile deviation was present in 11 of the 32 patients with genital reconstruction, which is distressing in only 2. Thirty patients are satisfied with the cosmetic result. After genital reconstruction 9 males developed epididymitis, necessitating two orchiectomies and three vasectomies. No patient with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas ejaculation was normal in the three men who did not undergo genital reconstruction and in two patients prior to post-pubertal reconstruction. Furthermore, two of these three men have fathered four children. Conclusion Education, occupation and social development of patients with urinary diversion are uneventful. The cosmetic results achieved by genital reconstruction are satisfactory. In female patients, antefixation of the uterus should be performed before or together with an introitusplasty to prevent uterine prolapse. In male patients, however, surgery is performed at the expense of fertility. Detailed discussions with the patients and their parents should include not only the question of primary bladder closure versus urinary diversion, but also the pros and cons of correction of the external and – in females – the internal genitalia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01957152
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  • 7
    Electronic Resource
    Electronic Resource
    A phase II study of ifosfamide and bleomycin in advanced or recurrent cervical carcinoma (1996)
    Suite 500, 5th Floor, 238 Main Street, Cambridge, Massachusetts 02142, USA : Blackwell Science Inc.
    International journal of gynecological cancer 6 (1996), S. 0 
    Details
    ISSN: 1525-1438
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Thirty-seven patients with advanced or recurrent cervical squamous cell carcinoma were treated with ifosfamide 1.5 g m−2 on days 1–5 (with mesna as a uroprotector), and bleomycin 30 mg on day 1, every 3 weeks. A partial response rate of 21% (95%CI: 6–36%) was obtained in patients who had not received prior chemotherapy, with a median duration of response of 5 months. No complete responses were seen. The median survival of all patients was 6 months. Nausea and vomiting, white cell suppression and encephalopathy were the main toxic effects. The results suggest that the addition of bleomycin to ifosfamide is not advantageous and increases toxicity, and that the interaction between these two agents is not contributory to the activity of the bleomycin, ifosfamide and cisplatin combination regimen (BIP). The potentially more severe toxicity of combination regimens must be considered when treating this group of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1525-1438.1996.06040323.x
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  • 8
    Electronic Resource
    Electronic Resource
    Isoquinoline (1999)
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 55 (1999), S. 1565-1567 
    Details
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1107/S0108270199006320
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  • 9
    Electronic Resource
    Electronic Resource
    Long-term metabolic effects in patients with urinary diversion (1998)
    Springer
    World journal of urology 16 (1998), S. 292-297 
    Details
    ISSN: 1433-8726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of intestinal segments in genitourinary reconstruction could influence vitamin metabolism and affect the skeletal bone and its mineral content in the long term. In 137 patients, serum levels of the vitamins A, B1, B2, B6, B12, D, and E and of folic acid, bile acid, and ammonia as well as levels of intracorpuscular vitamin B12 and folic acid were examined and a red blood cell count was performed. The patients were divided into three groups (≤2 years, 〉2 to ≤4 years, and 〉4 years after surgery) as well as into children and adults. In addition, bone mineral density (dual-photon absorptiometry) was measured in 25 patients. Of these, 16 patients were ≈16.8 years s/p rectal reservoir, 6 were ≈20.5 years s/p colonic conduit, two were 6 and 8 years s/p ileocecal pouch, and one adolescent was 5 years s/p ileal bladder augmentation. In all patients the levels of vitamins A, B1, B2, B6, D, and E and of folic acid, bile acid, and ammonia as well as the red blood cell count were within normal ranges. In children (n= 51) there was no significant drop in vitamin B12 levels after the operation. In adults (n= 86), serum vitamin B12 levels dropped significantly from 402 ± 182 ng/l during the first 2 years after the operation to 292 ± 204 ng/l after the 4th year (normal range 240–1,100 ng/l). No significant increase in the intracorpuscular vitamin B12 level was observed during the same period. The bone mineral density was normal in all 25 patients with different types of urinary diversion. In addition to regular examination (sonography, creatinine levels, and base excess), vitamin B12 levels should be determined at 4 years after urinary diversion. It remains unclear whether substitution is necessary. However, substitution is easy to achieve and cheaper than the regular determination of vitamin B12. No decrease in bone mineral content was seen in the long-term follow-up with early correction of the base excess (below −2.5).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003450050069
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  • 10
    Electronic Resource
    Electronic Resource
    The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible implications for Parkinson's Disease (1997)
    Springer
    Apoptosis 2 (1997), S. 149-155 
    Details
    ISSN: 1573-675X
    Keywords: Apoptosis ; bcl-2 ; dopamine ; Parkinson's disease ; PC-12 ; proto-oncogene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It is currently believed that excessive oxidant stress induced by metabolism of dopamine (DA), plays a major role in the pathogenesis of the selective nigrostriatal neuronal loss in Parkinson's disease. We recently showed that the neurotransmitter DA, in physiological concentrations, is capable of initiating apoptosis in cultured, post-mitotic sympathetic neurons. Bcl-2 is a proto-oncogene that blocks apoptosis. We now report that Bcl-2 is a powerful inhibitor of DA toxicity in PC-12 pheochromocytoma cells. We induced stable expression of Bcl-2 in PC-12 cells by transfection with recombinant pCMV5 expression vector, containing mouse bcl-2 (coding-sequence) cDNA. Cells expressing Bcl-2 manifested marked resistance to otherwise lethal (300 uM) in vitroconcentrations of DA. This protective effect was reflected in the trypan-blue test of cell survival, 3 H-thymidine incorporation and inhibition of the characteristic apoptotic morphologic alterations in scanning electron microscopic studies. Bcl-2 and associated control systems of apoptosis may have an important physiological role in restraining the apop-tosis-triggering potential of DA in nigrostriatal neurons. This novel field of research may yield insights into the pathogenesis of Parkinson's disease and lead to development of novel therapeutic approaches.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026408313758
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