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Biomedical subjects

M Marr

Publications and source records attributed to M Marr.

8 recordsLinked to original sources

Inflammatory response on injection of chitosan/GP to the brain.

Chitosan is a well-known biomaterial that, with the addition of glycerophosphate salt (GP), gels at physiological temperatures and therefore is useful for tissue engineering purposes. This study examines the procedure of injecting chitosan/ GP to the brain in order to form a gel track. The gel system and surgical technique were successful in this endeavour; however, on examining the inflammatory response to the material it was found that the chitosan/GP was wholly engulfed by macrophages within 7 days. This was determined by staining for both the gel and the macrophages, an important technique for localising injected material. The chitosan/GP-containing macrophages formed a neat tract at the lesion site, but after 45 days no chitosan/GP was found. It was concluded that, although chitosan/GP is present after implantation, it is not available for direct scaffolding in the brain.

Animals↗

Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats.

Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day.

Animals↗

Domain organization of the Escherichia coli RNA polymerase sigma 70 subunit.

We used limited trypsin digestion to determine the domain organization of the Escherichia coli RNA polymerase sigma 70 subunit. Trypsin-resistant fragments containing sigma 70 conserved region 2 (sigma 70(2)), and carboxy-terminal fragments containing conserved regions 3 and 4 (sigma 70(3-4)) were identified by a combination of amino acid sequencing and mass spectrometry. The domains were studied for partial biochemical functions of sigma 70.sigma 70(2) bound core RNA polymerase competitively with intact sigma 70. In contrast to sigma 70(2) alone, the RNA polymerase holoenzyme formed with sigma 70(2) specifically bound a single-stranded DNA oligomer with a sequence corresponding to the non-template strand of the -10 promoter element (the Pribnow box). Sigma 70(2) also forms crystals that are suitable for X-ray analysis. Sigma 70(3-4) bound the T4 AsiA protein with high affinity. The epitope for T4 AsiA on sigma 70 was further localized to within sigma 70[551-608], comprising sigma conserved region 4.2.

Amino Acid Sequence↗

Determination of sertraline and desmethylsertraline in human serum using copolymeric bonded-phase extraction, liquid chromatography and gas chromatography-mass spectrometry.

The determination of the new antidepressant drug sertraline and its main metabolite, desmethylsertraline, in human serum is described. A new solid-phase extraction method employing the dual functionality Clean Screen cartridge is presented followed by reversed-phase liquid chromatographic (LC) analysis. The sample preparation yielded extremely clean extracts and absolute recoveries in excess of 90% for both drugs from human serum. The response of the LC system was linear over the concentration range 0.01-2.5 mg/l for both sertraline and desmethylsertraline with a limit of detection of 0.01 mg/l. A gas chromatographic-mass spectrometric (GC-MS) system is also described should confirmation of the drugs be necessary.

1-Naphthylamine↗

Confirmation of benzodiazepines in urine as trimethylsilyl derivatives using gas chromatography-mass spectrometry.

A confirmation procedure for the identification and quantitation of various benzodiazepines in urine is presented. The urine sample is first hydrolyzed enzymatically because of the glucuronide conjugation of some benzodiazepine metabolites, then extracted using bonded-phase columns. After elution into an organic solvent, the samples are evaporated, converted to the trimethylsilyl ether derivatives and analyzed by electron ionization GC-MS. Quantitation was performed using selected-ion monitoring for each benzodiazepine using prazepam as the internal standard. The method provides excellent linearity and sensitivity for the trimethylsilyl derivatives.

Benzodiazepines↗

Lack of teratogenicity of microcystin-LR in the mouse and toad.

Microcystin-LR (MC-LR) is a cyanobacterial toxin generated by the organism Microcystis aeruginosa. Although the hepatotoxicity of this chemical has been characterized, the potential developmental toxicity in vertebrates has not been well studied. The purpose of this study was to elucidate the effects of this toxin on the in vivo and in vitro development of mammals and the development of an Anuran (toad). Initial acute toxicity experiments with female CD-1 mice were accomplished with MC-LR administered i.p. in saline. Lethality occurred at 128 and 160 microg kg (-1) and histopathology revealed massive hepatic necrosis with diffuse hemorrhage. Developmental toxicity studies were done with MC-LR administered i.p. for 2-day periods: gestation days 7-8, 9-10 or 11-12. Doses used ranged from 2 to 128 microg kg(-1). On gestation day 17, fetuses were weighed and analyzed for gross morphological and skeletal defects. No treatment-related differences were seen in litter size, viability, weight or the incidence of anomalies. Groups of dams dosed with 32-128 microg kg(-1) on gestation days 7-8, 9-10 or 11-12 were allowed to give birth and the growth and development of their pups were followed postnatally. There were no significant effects noted in the offspring of the treated dams. Neurulation-staged CD-1 mouse conceptuses were exposed to 50-1000 nM MC-LR in whole embryo culture for 24 h. No significant increase in abnormalities or developmental delays was observed. Finally, exposure of the developing toad. Bufo arenarum was done from stage 17 (tail bud) for 10 days at concentrations of 1-20 mg l(-1). No effect on morphological development or survival was noted in any exposed groups. These data indicate that microcystin does not appear to affect development adversely in the mouse (in vivo or in vitro) or the toad at the doses and exposure parameters used.

Animals↗