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Y Berger

Publications and source records attributed to Y Berger.

At least 19 recordsLinked to original sources
PubMed1992

Delta 2-valproate biotransformation using human liver microsomal fractions.

The metabolism of 2-n-propyl-2-pentenoate (delta 2-VPA) was evaluated in human hepatic microsomal fractions. Two biotransformation pathways have been particularly investigated. In the presence of the cytochrome P-450 co-factor, NADPH, the main metabolites recovered were delta 3-VPA, delta 2,4-VPA and VPA. The glucuronidation of delta 2-VPA was also studied on various hepatic microsomal fractions using Brij 35 as activator and UDP-glucuronic acid as co-factor. A large interindividual variability occurred in this metabolic pathway. Km and Vmax were 0.85 mmol/l and 1.75 nmol.min-1.mg-1, respectively, for delta 2-VPA and 1.11 mmol/l and 5.71 nmol.min-1.mg-1 for VPA, respectively. The good correlation (r = 0.82; p less than 0.001) observed between the glucuronidation of VPA and delta 2-VPA as well as the mutual inhibition of each other's glucuronidation strongly suggests that (a) common single UDP-glucuronosyltransferase isoenzyme(s) was (were) involved in this glucuronidation step. The glucuronidation of specific substrates for various UDP-glucuronosyltransferase isoenzymes showed a good relationship between the glucuronidations of delta 2-VPA and morphine, a substrate for UDP-glucuronosyltransferase-2B. Moreover, morphine competitively inhibits delta 2-VPA glucuronidation. It seems the same isoenzyme or, at least, (a) very closely related isoenzyme(s) belonging to UDP-glucuronosyltransferase-2 isoenzyme, is involved in delta 2-VPA glucuronidation.

Anticonvulsants↗
PubMed1992

Urodynamics in the early stages of spinal cord compression from prostate adenocarcinoma.

Acute urinary retention developed in 2 patients with a history of prostate cancer. Urodynamic evaluation revealed autonomic dysfunction, which contrasted with a prior urodynamic study, indicating a possible spinal lesion. Radiographic evaluation led to early diagnosis and treatment of spinal cord compression from metastatic prostate adenocarcinoma. We discuss the diagnostic role of urodynamics in such cases.

Adenocarcinoma↗
PubMed1992

Bladder involvement in metastatic breast carcinoma.

The literature concerning the uncommon findings of bladder involvement of breast carcinoma is suggestive of a recent increase in reported cases. We report on 3 additional women with vesical deposits of metastatic breast carcinoma. The clinical presentation and dire significance of such cases, and their relationship to progesterone and estrogen receptor expression are discussed. We also postulate on the possible increase in the numbers of reported cases.

Aged↗
PubMed1992

Disposition of minaprine in animals and in human extensive and limited debrisoquine hydroxylators.

1. The disposition of 14C-minaprine was studied after oral administration of 5 and 20 mg/kg to rats, dogs and macaques, and of 200 mg to human volunteers with a genetic status of either limited or extensive hydroxylation of debrisoquine. 2. The drug was readily absorbed and a large proportion of the administered radioactivity was excreted within 48 h. The total excretion over 5 days ranged from 83% in monkeys to almost 100% in human with a status of extensive hydroxylators. 3. In the two limited hydroxylators Cmax values of total radioactivity in plasma were 4.6 and 3.7 mg equiv/l respectively. Those in the two extensive hydroxylators were 1.9 and 1.6 respectively. The highest value in the animal species was 8.1 in rats at a dose of 20 mg/kg. Plasma Cmax values of minaprine were 4.0 and 1.4 mg/l in limited hydroxylators and 0.35 and 0.23 mg/l in extensive ones. The highest value in the animal species was 2.7 mg/l in dogs treated with 20 mg/kg. 4. In rats and dogs, the ratios of the plasma AUC values for 20 mg/5 mg doses were close to those of the ratios of the doses administered, whereas in the macaque a slower clearance of radioactivity occurred with the higher dose (t 1/2 beta 5.5 h at 5 mg/kg dose versus 25.7 h at 20 mg/kg dose). 5. Marked species differences were observed in the metabolic pathways. The dog and limited hydroxylators showed higher levels of minaprine and its N-oxide (M4) whereas p-hydroxy-minaprine (M3) prevailed in monkey, rat and extensive hydroxylators. 6. In dogs only, seizures appeared within 10-15 min after dosage with minaprine at 20 mg/kg, when the concentrations of minaprine in erythrocytes (6.9 mg/l) and of M4 in plasma (0.40 mg/l) and erythrocytes (0.25 mg/l), were high. 7. The measurements and clinical observations indicate that onset of an adverse behavioural response in humans is unlikely at the dose of 200 mg.

Adult↗
PubMed1992

Regulation of cytochrome P450IA1 gene expression in a human intestinal cell line, Caco-2.

The expression and inducibility of cytochrome P450IA1 isozyme was investigated in the human carcinoma cell line Caco-2 cultured between days 7 and 35 in the absence or the presence of various enzyme inducers such as 3-methylcholanthrene, beta-naphthoflavone (beta NF), dioxin, isosafrole, rifampycin, dexamethasone or phenobarbital. 7-Ethoxyresorufin O-deethylase activity (EROD) was maximal at day 25 when the differentiation of Caco-2 cells, characterized by the level of the brush border associated enzymes such as sucrase isomaltase and alkaline phosphatase, was higher. The inducibility of this enzyme activity was found to be maximal when cells were treated between days 7 and 10. After a 3-day treatment of Caco-2 cells with 50 microM beta NF, EROD achieved 36.6 +/- 14.6 pmol/min/mg compared to 2.5 +/- 1.1 pmol/min/mg in untreated cells. This enzyme activity appeared to be supported only by P450IA1 isozyme because: 1) EROD was quantitatively inhibited by alpha-naphthoflavone, a P450IA1-specific inhibitor; otherwise, phenacetin O-deethylation was completely abolished in the presence of alpha-naphthoflavone and not by furafylline, a P450IA2-specific inhibitor; 2) EROD was induced after treatment with 3-methylcholanthrene, beta NF and dioxin, which are P450IA1 inducers, but not by isosafrole, a P450IA2-specific inducer; 3) cytochrome P450IA1 apoprotein could be immunodetected by antibodies directed against rabbit cytochrome P450-LM6, orthologous to P450IA1, in polycyclic hydrocarbon-treated cells; 4) under the latter conditions, P450IA1 mRNA accumulation was specifically detected, but not P450IA2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoflavones↗
PubMed1991

Quantitative high-performance liquid chromatographic, gas chromatographic, and gas chromatographic-mass spectrometric analysis of ticlopidine in baboon plasma after solid-phase extraction.

High-performance liquid chromatography with UV detection (HPLC-UV) and gas chromatography with either nitrogen phosphorus (GC-NPD) or mass spectrometry (GC-MS) detection were used for the determination of ticlopidine in plasma. Solid-phase extraction of ticlopidine from plasma was performed using Extrelut columns without pH adjustment, and using hexane as the solvent of elution. With HPLC, a mobile phase of 0.01 M pH 7.8 phosphate buffer:acetonitrile (70:30) was passed through a mu Bondapack C-18 column at a rate of 1.3 mL/min. Ultraviolet detection at 235 nm was sensitive to plasma ticlopidine concentrations of 0.05 micrograms/mL. The GC-NPD and GC-MS were performed on a DB-17 fused-silica column using on-column injection. For GC-NPD and GC-MS, limits of quantification were found to be 0.020 and 0.005 micrograms/mL, respectively. Compared with HPLC-UV, the GC methods were found to be more reproducible, sensitive, and specific and therefore more suitable for pharmacokinetic applications.

Animals↗
PubMed1990

Urinary dysfunction in transverse myelitis.

Six men and 2 women with a history of transverse myelitis and persistent lower urinary tract symptoms underwent neurourological evaluation. Of the patients, 4 were neurologically intact, while the remainder had residual neurological deficits. Urodynamic studies revealed detrusor-external sphincter dyssynergia in 6 patients. Two patients had detrusor hyperreflexia, of whom 1 also had an incompetent sphincter. Erectile or ejaculatory dysfunction was reported by 3 men. We conclude that prolonged bladder and sexual dysfunction, caused by spinal cord inflammatory insult, may persist despite a systemic neurological recovery. Therefore, bladder management guided by initial and followup urodynamics is recommended.

Adult↗
PubMed1990

Routine and quantitative EEG analysis in Gilles de la Tourette's syndrome.

Gilles de la Tourette's syndrome (GdlT) is a neurobehavioral disorder, with a reportedly high frequency of EEG abnormalities. We performed EEGs on 48 consecutive patients with GdlT, and frequency analysis in 26 patients (17 males), and compared the results with those from age- and sex-matched normal controls. Routine 18-channel EEG revealed minimal diffuse nonspecific slowing in only 3 of 48 patients (6%) and in 2 of 26 controls (7.7%). The frequency analysis of the EEG of the 26 GdlT patients and their normal controls showed similar brain activity. We conclude that no significant differences exist between the EEG activity in GdlT patients as compared with that in sex- and age-matched controls in routine as well as in quantitative EEG.

Adult↗
PubMed1990

Pharmacokinetic profile and bioavailability of a new galenic formulation of ticlopidine.

The bioavailability of a new film-coated tablet of ticlopidine hydrochloride was compared in 12 healthy male subjects to that of the older sugar-coated tablet. Plasma levels of ticlopidine were measured by gas-liquid chromatography up to 120 h after a single 500 mg dose of each preparation. Drug intake was separated by a four-week interval. No statistically significant differences could be found between the pharmacokinetic parameters for these two preparations. Bioequivalence was confirmed when applying the test of Westlake to the area under the curves (calculated difference: 8.3%; upper limit: 20%). No unwanted effect was reported during the study.

Adult↗
PubMed1989

Effect of renal failure on the pharmacokinetics of ethyl loflazepate (Victan) in man.

The kinetics of ethyl loflazepate were studied in patients with various degrees of renal failure. A strong correlation was noted between urinary excretion of metabolite loflazepate and creatinine clearance. In contrast, elimination half-life and total plasma clearance of the sum of loflazepate + descarboxyloflazepate seemed to be independent of the degree of renal impairment. These results indicate the absence of a risk of accumulation of the 2 main and active metabolites of ethyl loflazepate in patients with renal failure.

Administration, Oral↗
PubMed1988

Determination of (4-chlorophenyl)thiomethylene bisphosphonic acid, a new bisphosphonate, in biological fluids by high-performance liquid chromatography.

A rapid and sensitive high-performance liquid chromatographic method for the assay of the bisphosphonate (4-chlorophenyl)thiomethylene bisphosphonic acid in plasma and urine is described. It requires selective precipitations and dissolutions of calcium salts prior to reversed-phase chromatography with UV detection. This method used semi-micro scale material and 200-microliters biological aliquots. The limit for accurate quantification is 50 ng/ml. Data on reliability criteria and application to a pharmacokinetic study are presented.

Chromatography, High Pressure Liquid↗
PubMed1988

New approach in bioavailability study of two formulations of ethyl loflazepate.

The disposition of ethyl loflazepate (Victan) was studied on 12 healthy male volunteers after administration of the two oral formulations of the drug: one 4-mg tablet and two 2-mg tablets according to an open crossover single dose comparison. A model-independent analysis and a model-dependent approach were used to treat experimental data. Appropriate statistical tests (ANOVA, Wilcoxon test, Westlake test for model-independent parameters; principal components analysis, Hotelling T2 test for model-dependent parameters) demonstrated the bioequivalence of the two formulations.

Administration, Oral↗
PubMed1987

Urodynamic findings in Parkinson's disease.

Neurological evaluation was performed in 24 men and 5 women with Parkinson's disease who had persistent bladder symptoms. Detrusor hyperreflexia was found in 26 (90 per cent) of the patients. Sporadic involuntary electromyography activity of the external sphincter during involuntary detrusor contractions was encountered in 61 per cent but in none did this cause obstruction. Coordinated striated sphincter relaxation during voluntary detrusor contraction was found in 13 patients (45 per cent). Among 22 men who were in the prostatic disease age group only 4 (18 per cent) had definite prostatic obstruction. Moreover, none of 8 men with persistent symptoms after prostatectomy had evidence of bladder outlet obstruction.

Abdomen↗
PubMed1987

Plasma levels and pharmacokinetics of single and multiple dose of tetrazepam in healthy volunteers.

The pharmacokinetics of tetrazepam (Myolastan, Musaril), were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg and repeated administration for 5 consecutive days of 50 mg at 12-h intervals, in tablet form. Tetrazepam was measured in plasma using a selective and sensitive GLC method. Tetrazepam is rapidly absorbed after oral administration with a peak plasma level of 0.49 +/- 0.10 mg/l at 0.94 +/- 0.47 h. The drug is widely distributed in the organism with an apparent volume of distribution of 6.7 +/- 2.1 l/kg. Tetrazepam is eliminated with a half-life of 22 +/- 4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed. No differences were observed between the pharmacokinetic values after a single dose or after repeated administration.

Administration, Oral↗
PubMed1986

Amiodarone and N-desethylamiodarone concentrations in plasma, red blood cells, and myocardium after a single oral dose: relation to hemodynamic effects in surgical patients.

In an attempt to assess their respective values for purposes of drug monitoring, plasma, red blood cell, atrial, and ventricular concentrations of amiodarone and N-desethylamiodarone (NDA) were measured, in 50 surgical patients, after a single oral dose (30 mg/kg); hemodynamic changes were assessed also. Amiodarone concentration was lower in red blood cells than in plasma and in myocardium. A relationship was found between the red blood cell concentration and plasma or myocardial concentrations of amiodarone (r = 0.79 and r = 0.68, p less than 0.00001). Hemodynamic studies were available in 17 treated patients and 13 control subjects before and at the time of surgery. In control subjects, hemodynamics did not change with time and general anesthesia. Oral amiodarone decreased the cardiac index (p less than 0.05) and heart rate (p less than 0.001) without significant changes in arterial pressure, systemic vascular resistance, or stroke volume index. The increase in capillary wedge pressure was related to amiodarone or NDA plasma, myocardial, and red blood cell concentrations (for amiodarone: r = 0.61, p = 0.006; r = 0.69, p less than 0.001; and r = 0.53, p = 0.02, respectively). We concluded that oral amiodarone impairs hemodynamics and that measurement of the amiodarone plasma concentration rather than the red blood cell concentration is the easiest method of monitoring the drug. However, establishment of the clinical utility of drug monitoring during chronic administration of amiodarone needs further investigation.

Administration, Oral↗
PubMed1986

Urological evaluation in the Shy Drager syndrome.

Nine patients with the Shy-Drager syndrome underwent complete urological and neurological investigation of bladder symptoms. Urodynamic studies revealed detrusor areflexia in 6 patients (67 per cent), detrusor hyperreflexia in 3 (33 per cent), a lower motor neuron lesion involving the periurethral striated muscle in 9 (100 per cent) and an open vesical neck at rest in all 5 patients in whom cystography was performed. These findings support the current view that parasympathetic, pudendal and sympathetic involvement is part of the pathophysiology of the Shy-Drager syndrome.

Aged↗