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Biomedical subjects

M B Friedman

Publications and source records attributed to M B Friedman.

17 recordsLinked to original sources
PubMed1998

Enhancement of cytotoxicity and clastogenicity of l-DOPA and dopamine by manganese and copper.

It is an increasingly popular hypothesis that the continued degeneration of dopaminergic neurons in Parkinson's disease (PD) may be the consequence of aberrant oxidation of dopamine and resultant generation of DNA reactive species in PD patients receiving levodopa (l-DOPA) therapy. Occupational metal exposure, particularly to manganese, is a risk factor for Parkinsonism and manganese has been shown to be a true catalyst for dopamine oxidation lending support to this hypothesis. In the present studies, we demonstrate that the antiproliferative activity of l-DOPA and dopamine on Chinese Hamster V79 cells is enhanced by at least an order of magnitude by concomitant exposure to manganese chloride or copper sulfate (500 microM), but not to iron(III) or zinc. Moreover, manganese and copper confer strong clastogenic properties to both compounds as detected in an in vitro micronucleus assay in V79 cells. Metal catalyzed oxidation of drug was associated with the development of a brown-black particulate substance presumed to be a melanin precursor formation. The extent of formation of this precursor paralleled clastogenicity. Metal-enhanced effects were completely antagonized by the concurrent addition of cysteine or reduced glutathione to the cultures. These findings are in support of the hypothesis that aberrant oxidation of dopamine resulting from non-physiological levels of catalytic metals may contribute to the death of dopaminergic neurons and further suggest that oxidation-dependent DNA damage may be the basis for this cell death.

Animals↗
PubMed1995

Inhalation toxicity study of a haloalkene degradant of sevoflurane, Compound A (PIFE), in Sprague-Dawley rats.

BACKGROUND: Under certain circumstances in the clinical setting, contact of the anesthetic sevoflurane with a CO2 absorbent (e.g., soda lime, Baralyme) leads to the formation of a degradant designated as pentafluoroisopropenyl fluoromethyl ether (PIFE; Compound A). Previous studies have shown that the kidney is the primary target organ for toxicity in the rat. This study was designed to determine the impact of PIFE on rat renal histology correlated with functional changes. The findings are discussed in terms of probable mechanism of action and relevance to humans. METHODS: Male and female Sprague-Dawley rats were exposed to 0, 30, 61, 114, or 202 ppm PIFE for a single 3-h period via nose-only inhalation. Rats were observed daily for behavioral changes or external physical signs of toxicity (i.e., lacrimation, dyspnea, piloerection, etc.) and body weights were recorded at 6, 4, and 1 day preexposure and 1, 3, 7, and 13 days postexposure. Animals were evaluated for hematologic, clinical chemistry and/or urinalysis changes immediately postexposure and/or at 1, 4, and 14 days postexposure. Rats were killed, subjected to a macroscopic postmortem examination, and evaluated for histopathologic changes in all major tissues and organs at 1, 4, and 14 days postexposure. RESULTS: Labored breathing was observed in 3 of the 20 and 2 of the 20 rats in the 114 ppm and 202 ppm groups, respectively, during the 3-h exposure period. No significant reductions in body weight gain were noted during the 2-week study period. Clinical chemistry evaluations revealed increases in blood urea nitrogen and creatinine 1 day postexposure in males and females exposed to 202 ppm PIFE. Changes in urinary glucose, protein and N-acetyl-beta-glucoaminidase/creatinine were evident one day postexposure in males and females exposed to 202 ppm and in males exposed to 114 ppm PIFE. Most values were within normal ranges by 4 or 14 days postexposure. No drug-related alterations in hematologic parameters were noted. Evidence of olfactory epithelial degeneration and desquamation in the nasal turbinates was noted at 4 days postexposure in male and female rats exposed to 202 ppm PIFE. Concentration-dependent renal tubular necrosis and tubular cell hyperplasia, in the corticomedullary border, were observed in males and females exposed to 114 and 202 ppm PIFE. The severity of tubular necrosis in both males and females was considered minimal to slight at the 114 ppm exposure concentration and slight to moderate at the 202 ppm exposure. Both the numbers of affected animals and severity were reduced over time. The most marked changes in serum and urine chemistry were associated with the animals described as having moderate renal necrosis. Male rats appeared more susceptible to nephropathy than female rats. There were no other PIFE-related histopathologic findings. CONCLUSIONS: The renal histopathologic findings in this study are consistent with those reported in previous acute studies in rats after PIFE administration. Functional changes in the kidney, as evidenced by serum chemistry and urinalyses, were observed at exposure concentrations that induced morphologic alterations.

Anesthetics, Inhalation↗
PubMed1994

Tiagabine inhibits haloperidol-induced oral dyskinesias in rats.

Chronic administration of haloperidol to male Sprague Dawley rats for 6 months at a dosage of 1.5 mg/kg/day produces oral dyskinesias in a significant percent of the treated group. This has been used as an animal model of tardive dyskinesia in several laboratories, because the rat movements display characteristics reminiscent of the human dyskinetic condition. Previously, we have reported a reduction in these haloperidol-induced oral dyskinesias with the coadministration of a direct acting GABA agonist progabide. Here, we have tested an indirect acting GABA agonist, tiagabine, coadministered with haloperidol, for its effect on the oral dyskinesias. At a dosage of 75 mg/kg/day tiagabine significantly inhibited the onset of vacuous chewing movements (VCMs), decreasing the average movement severity from 11.2 +/- 2.0 to 4.4 +/- 1.4, compared with a placebo rate of 1.3 +/- 0.5 (VCMs/5 min). These data support the proposition that an effective, potent GABAmimetic coadministered with haloperidol, will block the onset of rat oral dyskinesias. This conclusion has important implications for the treatment and prevention of tardive dyskinesia in humans.

Animals↗
PubMed1989

Plasmid control of the Pseudomonas aeruginosa and Pseudomonas putida phenotypes and of linalool and p-cymene oxidation.

Two Pseudomonas strains (PpG777 and PaG158) were derived from the parent isolate Pseudomonas incognita (putida). Strain PpG777 resembles the parental culture in growth on linalool as a source of carbon and slight growth on p-cymene, whereas PaG158 grows well on p-cymene, but not on linalool or other terpenes tested, and has a P. aeruginosa phenotype. Curing studies indicate that linalool metabolism is controlled by an extrachromosomal element whose loss forms a stable strain PaG158 with the p-cymene growth and P. aeruginosa phenotype characters. The plasmid can be transferred by PpG777 to both P. putida and P. aeruginosa strains. Surprisingly, the latter assume the P. putida phenotype. We conclude that the genetic potential to oxidize p-cymene is inherent in PpG777 but expression is repressed. Similarly, this observation implies that support of linalool oxidation effectively conceals the P. aeruginosa character.

Acyclic Monoterpenes↗
PubMed1987

Five-month oral (diet) toxicity/infectivity study of Bacillus thuringiensis insecticides in sheep.

Bacillus thuringiensis insecticides (Bt) [Dipel (test substance D or Thuricide-HP (test substance T)] were administered in the diet for 5 months to castrated mixed rambouillet/merino sheep (24-34 kg at the beginning of the study) at a dose of 500 mg/kg/day (approximately 10(12) spores per day). No treatment-related effect was seen on weight gain or clinical chemistry parameters nor were significant gross clinical changes observed. Several blood and tissue samples taken just prior to the time the animals were killed or at necropsy were found to be positive for Bt when cultured. Detailed gross and microscopic pathologic examination of the sheep revealed several incidental lesions. However, the only lesion that may have been associated with the treatment was lymphocytic hyperplasia in Peyer's patches seen in the cecum of three sheep and it was not considered to be clinically significant.

Administration, Oral↗
PubMed1984

Iliofemoral venous thrombosis: real-time ultrasound diagnosis, normal criteria, and clinical application.

We determined the response of the common femoral vein to respiratory maneuvers using high resolution real-time ultrasound in 10 normal subjects, and we evaluated this modality in the diagnosis of iliofemoral venous thrombosis in 36 patients. We developed diagnostic criteria for assessment of the venous system and have confirmed them with phlebography or pathologic findings. An increase in venous diameter of 50-200% on performance of the Valsalva maneuver, with a prompt return to the original configuration, was always associated with a normal iliofemoral venous system. Two patterns of occlusion of the femoral venous system were found: an enlarged circular femoral vein that did not increase in size on deep inspiration or performance of the Valsalva maneuver, and difficulty or inability to detect the common femoral vein. A dampened response, i.e., a 10-50% diameter increase on performance of the Valsalva maneuver, was associated with deep vein thrombosis in four of six patients. The false positive rate of 8% was due to gross congestive cardiac failure in one patient. This technique is simple to perform, relatively inexpensive, expeditious, and has proved useful in confirming or denying the presence of iliofemoral venous thrombosis.

Adult↗
PubMed1980

Acute and chronic effects of barbituartes on depolarization-induced calcium influx into rat synaptosomes.

Depolarization-induced 45Ca2+ influx into synaptosomes isolated from nontreated control and acutely treated rats (given 60 mg/kg phenobarbital i.p.) was significantly depressed (54 and 37%, respectively) by an in vitro challenge with pentobarbital, 0.3 mM (final concentration). However, depolarization-induced 45Ca2+ influx into synaptosomes isolated from tolerant rats (received dietary phenobarbital, 2.5 mg/g of diet, for 13 days) was not significantly altered when the synaptosomes were challenged with 0.3 mM pentobarbital. This suggests that synaptosomal membranes adapt during chronic exposure to barbiturates to allow for an enhanced Ca2+ influx subsequent to depolarization. Our data suggest that sedation may, at least in part, occur as a result of depressed stimulus-secretion coupling and that behavioral tolerance to sedation may occur because of the development of membrane tolerance to allow enhanced calcium influx.

Animals↗
PubMedDate not supplied

Case report: computed tomography of congenital clefts of the atlas.

Congenital clefts of the anterior and posterior arches of the atlas were demonstrated in a cervical spine CT performed in a case of suspected trauma. Intact cortical margins and lack of adjacent soft tissue swelling are CT indices distinguishing congenital clefts from fractures.

Adult↗