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S D Weitman

Publications and source records attributed to S D Weitman.

29 records · Page 2Linked to original sources
PubMed1989

Propranolol-induced alterations in rat erythrocyte membrane fluidity and apparent phase-transition temperatures. A depth-dependent process.

Propranolol-induced alterations of membrane structure were studied in rat erythrocytes using electron spin resonance techniques. Propranolol produced a concentration-dependent change in membrane fluidity in hydrophobic membrane regions, while producing virtually no change in hydrophilic membrane regions. The changes were associated with depth-dependent alterations in "apparent" phase-transition profiles and transition temperatures. The effects of propranolol on these membrane characteristics were similar to those produced by cholesterol. Propranolol fluidized erythrocyte membranes in a depth-specific fashion, by virtue of its association with the rigid phospholipid acyl chains and cholesterol sterol rings in the hydrophilic regions of the membrane, which produced distant perturbations within the hydrophilic regions of the membrane.

Animals↗
PubMed1987

Determination of in utero fetal rat heart rate by ultrasound.

A technique for in utero determination of rat fetal heart rat in conscious and anesthetized animals is described. Fetal heart rate was analyzed using echocardiography by recording two-dimensional ultrasound images along with the derived M-mode tracing. This method allows for the simultaneous and sequential analysis of both maternal and fetal heart rate after exposure to therapeutic or environmental agents. When compared to other techniques, this noninvasive approach can clearly yield a more accurate assessment of drug effects on the fetal cardiovascular system. The method eliminates the influence of surgical manipulation on cardiac activity. More importantly, this approach can avoid the use of cardiodepressant anesthetic drugs and their potential interaction with agents under investigation. This method is thereby more sensitive and specific for determining the effects of compounds under study than previously described techniques. To illustrate this system, fetal heart rates are compared after maternal propranolol administration in conscious and anesthetized animals.

Animals↗
PubMed1986

Mechanism of enhanced parathion/paraoxon toxicity during pregnancy in the mouse.

The mechanism of enhanced parathion/paraoxon toxicity during pregnancy was examined. Enhanced toxicity following exposure to paraoxon in the pregnant mouse as determined by cholinesterase suppression was observed at 0.10 and 0.58 mg/kg after ip administration on Day 19 of gestation. However, there were no significant differences in cholinesterase activity between pregnant animals and virgin controls after either po or iv paraoxon. Higher systemic and lower hepatic levels of parathion were demonstrated in pregnant mice following ip administration of parathion (5 mg/kg). Data herein also suggest that during pregnancy, larger quantities of paraoxon bypass initial liver detoxification after ip dosing. The mechanism of increased toxicity of parathion/paraoxon during pregnancy may result from alterations in absorption from the peritoneal cavity.

Animals↗
PubMed1986

Influence of pregnancy on the hepatic metabolism of parathion.

The effect of pregnancy on the hepatic metabolism of parathion was examined. The in vitro rate of hepatic microsomal activation of parathion to paraoxon was significantly reduced in mice at 19 days of gestation when compared to nonpregnant controls. Total hepatic metabolism of parathion was determined during in situ perfusion of livers from pregnant and nonpregnant mice. Levels of parathion, paraoxon, and p-nitro-phenol in the perfusate after 45 min of perfusion did not differ significantly between livers from the pregnant and nonpregnant groups. These data indicate that total hepatic metabolism of these three compounds is not altered in pregnancy despite a decrease in specific activity for parathion activation.

Animals↗
PubMed1983

Influence of pregnancy on parathion toxicity and disposition.

The effects of pregnancy and lactation on the toxicity and distribution of parathion and paraoxon were examined. Signs of cholinergic stimulation were more intense in pregnant mice when compared to virgin controls after administration of parathion or its active metabolite, paraoxon. Cholinesterase activity and tissue levels of parathion and paraoxon were determined in mice at 19 days of gestation or Day 19 postpartum after administration of a single dose of 5 mg/kg parathion or 0.58 mg/kg paraoxon. Plasma (pseudo) cholinesterase activity was consistently lower in treated pregnant mice. Total brain cholinesterase was also suppressed to a greater degree in pregnant mice after treatment with parathion or paraoxon when compared with virgin animals treated similarly. In addition, when equal quantities of paraoxon (32 micrograms) were administered to both pregnant and virgin animals, total brain cholinesterase was significantly less in pregnant mice. Administration of parathion to lactating mice on Day 19 postpartum did not result in any significant differences in plasma or brain cholinesterase activity when compared to that in virgin animals. Pregnant mice treated with 5 mg/kg parathion demonstrated higher concentrations of both parathion and paraoxon in blood and brain than similarly treated virgin controls which correlated with the enhanced cholinesterase inhibition. Decreased ability to detoxify paraoxon was also demonstrated by a significant reduction in serum paraoxonase activity during pregnancy.

Animals↗
PubMedDate not supplied

Pharmacokinetic evaluation of a new oral cyclosporine formulation.

STUDY OBJECTIVE: To compare the pharmacokinetics of a new oral cyclosporine preparation with those of cyclosporine solution diluted in Isocal and the intravenous formulation. DESIGN: Randomized, crossover trial. SETTING: Tertiary care referral center. PATIENTS: Seven pediatric liver transplant recipients who were receiving oral cyclosporine as part of their immunosuppressive regimen. All patients completed the study. INTERVENTIONS: Pharmacokinetic studies were performed with the intravenous and oral dosage forms. Patients received one dose of intravenous cyclosporine, and then were randomized to receive their usual oral cyclosporine dose incorporated into a chocolate wafer or mixed with Isocal. After a minimum of 3 days, the alternative preparation was administered. Serial cyclosporine blood samples were collected at predetermined intervals for 12 hours after the third dose for each regimen. Concentrations were determined by high-performance liquid chromatography. The data for the three dosage forms were fit simultaneously with a two-compartment model. MEASUREMENTS AND MAIN RESULTS: No difference was seen in F, ka, Cmax, and tmax between the two oral cyclosporine preparations (p > 0.05). No new rejection episodes occurred during the study period. CONCLUSIONS: We conclude there is no difference in the bioavailability of the oral solution and the chocolate formulation. We believe the new preparation may increase patient compliance and ensure administration of a complete dose compared with the currently marketed solution.

Administration, Oral↗
PubMedDate not supplied

Hepatocellular carcinoma in children associated with Gardner syndrome or familial adenomatous polyposis.

PURPOSE: Gardner syndrome, a variant of familial adenomatous polyposis, is characterized by colonic polyps that undergo malignant change and benign and malignant extracolonic lesions. Tumors frequently associated with Gardner syndrome include carcinoma of the ampulla of Vater, papillary carcinoma of the thyroid, and, in children, hepatoblastoma. The childhood malignancies often precede the appearance of other manifestations by several years. PATIENTS AND METHODS: Two patients are described. Gardner syndrome was diagnosed in a 15-year-old girl with fibrolamellar hepatocellular carcinoma after desmoid tumors and colonic polyposis developed. Classic hepatocellular carcinoma was also diagnosed in a 9 1/2-year-old boy with familial adenomatous polyposis. RESULTS: In patient 1, the diagnosis of fibrolamellar hepatocellular carcinoma preceded the diagnosis of Gardner syndrome by almost 2 years. The diagnosis was confirmed by identifying a germline mutation of the adenomatous polyposis coli (APC) gene. This is the first patient reported with fibrolamellar hepatocellular carcinoma associated with Gardner syndrome. Patient 2 had a strong family history of familial adenomatous polyposis but no manifestations of Gardner syndrome. He was not tested for the APC mutation. The current literature and previously reported cases of hepatocellular carcinoma in patients with Gardner syndrome or familial adenomatous polyposis are reviewed. CONCLUSIONS: Because hepatocellular carcinoma is uncommon in the pediatric and adolescent population, it is important to consider the possibility of Gardner syndrome or familial adenomatous polyposis in these patients.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Fosfomycin--friend or foe?

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Antineoplastic Combined Chemotherapy Protocols↗