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  • 11
    Electronic Resource
    Electronic Resource
    Comparative study of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tritiated thymidine in a chemosensitivity test using collagen gel matrix (1993)
    Springer
    Urological research 21 (1993), S. 83-88 
    Details
    ISSN: 1434-0879
    Keywords: Chemosensitivity test ; Collagen gel matrix ; 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ; Human transitional cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An organ culture system using collagen gel matrix (CGM) was modified and established successfully as a rapid and convenient method for determination of anti-cancer drug sensitivities. The cell viability of a tumor fragment was measured by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to a colored formazan product, which allowed for quantitative and simple analysis. The sensitivities of KK-47 bladder tumor from nude mice to various anti-cancer drugs tested corresponded closely to those determined in the originial CGM assay system using tritiated thymidine, which has a high clinical correlation. Our modified method can be used as a practical and highly reproducible chemosensitivity test in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01788824
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  • 12
    Electronic Resource
    Electronic Resource
    Responses of tumour cell lines implanted onto the chorioallantoic membrane of chick embryo to anticancer agents in combination with hyperthermia (1992)
    Springer
    Urological research 20 (1992), S. 237-239 
    Details
    ISSN: 1434-0879
    Keywords: Chorioallantoic membrane ; Anticancer agents ; Hyperthermia ; thermo-chemotherapy ; Sensitivity test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The chorioallantoic membrane of chick embryos was used to examine the responses of three tumour cell lines to anticancer agents, alone and in combination with hyperthermia. Fifteen minutes of hyperthermia at 42.5°C produced the most favourable anticancer effect in the B 16-F 10 grafts. The use of Adriamycin (ADM) alone and the combined use of hyperthermia and either cisplatin (CDDP), cyclophosphamide (CY) or ADM resulted in a significantly higher rate of tumour regression in the B 16-F 10 grafts from a murine melanoma. In the KK-47 grafts derived from a transitional cell carcinoma of the bladder, the use of CY alone and the combination of CY and hyperthermia produced a significant tumour regression rate. In the T24 grafts neither the use of CY or CDDP alone, nor the combination of these drugs with hyperthermia demonstrated any significant effect. This method of screening anticancer agents was found to be rapid, simple to perform and inexpensive.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00299724
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  • 13
    Electronic Resource
    Electronic Resource
    Purealidin A, a new cytotoxic bromotyrosine-derived alkaloid from the Okinawan marine spongePsammaplysilla purea (1991)
    Springer
    Cellular and molecular life sciences 47 (1991), S. 299-300 
    Details
    ISSN: 1420-9071
    Keywords: Antileukemic activity ; purealidin A ; bromotyrosine-derived alkaloid ; sponge ; Psammaplysilla purea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A new bromotyrosine-derived alkaloid with antileukemic activity, purealidin A (5), has been isolated from the Okinawan marine spongePsammaplysilla purea and its chemical structure elucidated on the basis of the spectroscopic data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01958166
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  • 14
    Electronic Resource
    Electronic Resource
    Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage (1990)
    Springer
    Acta neurochirurgica 107 (1990), S. 11-15 
    Details
    ISSN: 0942-0940
    Keywords: Subarachnoid haemorrhage ; chronic cerebral vasospasm ; calcium antagonist ; AT877 ; HA 1077
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibiton of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120–180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo-controlled double-blind trial (which is currently being carried out).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01402606
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  • 15
    Electronic Resource
    Electronic Resource
    Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma (1993)
    Springer
    Experimental brain research 95 (1993), S. 41-50 
    Details
    ISSN: 1432-1106
    Keywords: Drug uptake ; Brain capillary endothelial cells ; Tumor cell membrane ; 9L glioma ; P-glyco-protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two weeks after the inoculation of 1.5 × 105 9L glioma cells into the rat brain, the uptake of radiolabelled drugs into the brain and the experimental 9L glioma during the first cerebral circulation was measured with a liquid scintillation counter and analyzed by the method of Oldendorf (1970). The expression of P-glycoprotein, which is known to be associated with the efflux of drugs, was also studied, using anti-P-glycoprotein monoclonal antibody, C-219. Furthermore, the ultrastructure of brain capillaries, tumor vessels, and glioma cells was studied by conventional and immunoelectron microscopy. Sucrose (control), the transport of which through the blood-brain barrier is known to be negligible, accumulated to fivefold higher levels in the tumor than in normal brain. Ranimustine (MCNU), 5-fluorouracil (5-FU), and doxorubicin showed little accumulation in the normal brain, whereas nimustine (ACNU) showed an increased accumulation. MCNU and doxorubicin showed negligible accumulation in the glioma cells despite diffusion into the tumor interstitial space. In contrast, ACNU and 5-FU showed an increased accumulation in tumor cells. The accumulation of 5-FU in the cultured 9L glioma cells was decreased by ATP inhibitors or by low temperature. Although both brain capillary endothelial cells and glioma cell membrane were immunohisto-chemically positive for P-glycoprotein, the tumor vasculature showed low expression of P-glycoprotein. The endothelial cells of tumor vessels ultrastructurally showed increased fenestrations, swelling, and disrupted junctions. Accordingly, it is suggested that hydrophobic drugs such as doxorubicin, being pumped out by P-glycoprotein, do not accumulate in 9L glioma cells as do other lipophilic drugs such as ACNU, or drugs such as 5-FU, which accumulate by a carrier-mediated mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229652
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  • 16
    Electronic Resource
    Electronic Resource
    Circulating anti-DNA immune complexes in acitve lupus (1992)
    Springer
    Pediatric nephrology 6 (1992), S. 364-364 
    Details
    ISSN: 1432-198X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00869740
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  • 17
    Electronic Resource
    Electronic Resource
    Nonlinear kinetics of threo-methylphenidate enantiomers in a patient with narcolepsy and in healthy volunteers (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 79-84 
    Details
    ISSN: 1432-1041
    Keywords: Methylphenidate enantiomers ; Narcoleptic patient ; oral administration ; healthy volunteers ; plasma concentration ; nonlinear kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of methylphenidate enantiomers after the oral administration of different doses of racemic methylphenidate to one patient with narcolepsy and to four healthy volunteers. The plasma concentrations of (+)-methylphenidate were much higher than those of (−)-methylphenidate after each dose in all subjects. In the patient the oral clearance (CL/f) of (+)-methylphenidate fell 3-fold and the area under the concentration-time curve (AUC) rose 7-fold when the dose was increased from 20 to 40 mg (from 0.27 to 0.53 mg·kg−1), in spite of the relatively constant terminal half-life of 2.6–2.7 h. Similar dose-dependency was also observed in the healthy volunteers in the dose range of 10–60 mg (0.12–0.77 mg·kg−1). The mean value of CL/f for the 40 mg dose was significantly lower than that for the 20 mg dose. The mean AUC of the (+)-isomer corrected to a dose of 10 mg increased significantly between the 20 mg and 40 mg doses. In the urine (+)- and (−)-ritalinic acid were excreted for 48 h after each dose as 32–37% and 34–40% of the dose respectively. The mean total recoveries (sum of enantiomers of methylphenidate and its metabolite, ritalinic acid) in the urine were relatively constant (63–78% of the doses), suggesting that the changes in AUC with dose may not be due to a change in the intestinal absorption of racemic methylphenidate. We conclude that the nonlinear kinetics of (+)-methylphenidate may be due to saturation of its presystemic elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315285
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  • 18
    Electronic Resource
    Electronic Resource
    Renal effects of manidipine hydrochloride (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 321-325 
    Details
    ISSN: 1432-1041
    Keywords: Manidipine ; Essential hypertension ; renal function ; glomerular hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal effects of manidipine hydrochloride were investigated in ten hospitalised patients with mild-to-moderate essential hypertension. After a one-week placebo period, manidipine was given for 1 week in a dose rising from 5 mg to 10 mg or 20 mg daily to normalise the mean blood pressure measured after 2 h. Blood pressure had decreased from 171/101 to 147/86 mm Hg at the end of manidipine treatment. The pulse rate was unaltered. Renal vascular resistance decreased from 1.90 to 1.33 dyn · s · cm−5/1.48 m2 × 104, and renal blood flow and glomerular filtration rate increased from 522 to 662 ml · min−1 · 1.48 m−2 and from 81 to 93 ml · min−1 · 1.48 m−2, respectively, in spite of a fall in renal perfusion pressure. Manidipine reduced the filtration fraction from 0.260 to 0.243, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium and potassium did not change. Manidipine did not produce any significant alteration in plasma renin activity or in the plasma aldosterone concentration. The results indicate that manidipine has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265948
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  • 19
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 411-414 
    Details
    ISSN: 1432-1041
    Keywords: SUN 1165 ; renal failure ; antiarrhythmic agent ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 1 · kg−1, the absorption rate constant was 2.2 h−1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min−1 · 1.48 m−2). Dosage adjustment of SUN 1165 is necessary in renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265853
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  • 20
    Electronic Resource
    Electronic Resource
    A study of the association between schizophrenia and the dopamine D3 receptor gene (1993)
    Springer
    Human genetics 〈Berlin〉 92 (1993), S. 336-338 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A study of the genetic association between schizophrenia and aBalI polymorphism in exon 1 of the dopamine D3 (DRD3) gene, a candidate gene for schizophrenia, was conducted. The polymorphism was examined in 91 patients whose symptoms satisfied DSM-III-R for schizophrenia and 90 controls. There were no significant differences between the groups in allele frequencies or genotype counts. Contrary to a previous report, the patients were no more likely to be homozygous than controls. Moreover, no association with the presence of illness could be demonstrated when the patients were grouped according to sex, age of onset, history of admission to psychiatric institutions or positive family history.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01247330
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