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Biomedical subjects

A B Shah

Publications and source records attributed to A B Shah.

36 records · Page 2Linked to original sources
PubMed1990

Distribution and excretion of 1,8-dinitro[14C]pyrene in the mouse.

The disposition of the environmental pollutant and potent mutagen and carcinogen, 1,8-dinitropyrene (DNP) in female BALB/c mice was investigated. In the first 48 h after oral administration of 1,8-dinitro[4,5,9,10-14C]pyrene ([14C]DNP), 42% of the dose was eliminated in the faeces and 12% in the urine. Faeces was the major pathway of excretion with 45% of the dose being eliminated by this route in 9 days. Distribution of DNP in various tissues (blood, liver, spleen, lungs, kidneys, stomach, small and large intestine) was studied over 9 days. There was a linear increase in the concentration of radioactive material in the blood, liver and kidneys up to 6 h after [14C]DNP administration, representing 0.27, 2.9 and 0.21% of the radioactive dose, respectively. The corresponding figures after 24 h decreased to 0.1, 1.6 and 0.12%, respectively. In comparison, radioactivity present in the spleen and lungs was low and did not significantly change with time. In studies with ligated sections of the gastrointestinal tract, DNP absorption was from the small and large intestine and there was none from the stomach. The rate of absorption of DNP from the small intestine was greater than that from the large intestine, although overall uptake of the compound was poor (more than 80% of the original dose was recovered from the ligated small intestine after 120 min). The data from these studies suggest that although absorption of orally administered DNP is slow, the compound or its metabolites persist in the body for long periods and the liver should be considered as the major target organ.

Administration, Oral↗
PubMed1990

Activation and detoxification of 1,8-dinitropyrene by mammalian hepatic fractions in the Salmonella mutagenicity assay.

1,8-Dinitropyrene (DNP) is a potent, direct-acting mutagen to Salmonella typhimurium TA98 due to activation by bacterial metabolism. We have studied the effects of uninduced and Aroclor-induced rodent liver post-mitochondrial supernatant (S9), microsomes or cytosolic preparations on its activity. With the plate incorporation protocol, the reported S9-mediated inhibition of mutagenicity was confirmed and shown to be greater after induction when equivalent levels of protein were plated. Cytosol increased mutagenicity considerably whereas the inhibitory effect of S9 could be attributed to the microsomal fraction. The activating and detoxifying capacities of the various hepatic fractions derived from male Sprague-Dawley rats and female BALB/c mice were similar. In the absence of hepatic preparations, DNP mutagenicity was much lower in TA98/1,8DNP6 (deficient in transacetylase) than in TA98, although mutagenic activity could be still increased in the former strain by addition of uninduced cytosol. When DNP was pre-incubated in a liquid assay with S9 before addition of TA98, inhibition occurred and was time dependent. Thus the overall detoxifying effect of S9 is independent of bacterial metabolism. Furthermore, inhibition occurred under conditions where cytosol and microsomal components of S9 were kept together, indicating that the detoxifying effect of the microsomes predominates. The data therefore suggest that the microsomal-mediated detoxification by S9 may be due to the presence of an inhibitory component, enzymatic or otherwise, whose concentration is increased after Aroclor-induction. Nitro-reductase activities detected in TA98 and TA98/1,8-DNP6 were 10-fold higher than those in the mammalian fractions, although the activities in the latter increased to the bacterial enzyme levels after incubation of induced S9 or microsomes, but not cytosol, with an NADPH-generating system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Osteogenic sarcoma producing human chorionic gonadotrophin. Case report with immunohistochemical studies.

An osteogenic sarcoma occurring in a 22-year-old woman was found to be associated with production of a large amount of beta human chorionic gonadotrophin (B-hCG). Pregnancy was excluded on the basis of a normal ultrasonogram and a proliferative type endometrium obtained by curettage. A homogenate of the tumor was strongly positive for B-hCG while immunohistochemical staining of the tumor cells was strongly positive for B-hCG and negative for pregnancy associated glycoprotein. These results indicate ectopic production of hCG by the osteosarcoma.

Adult↗
PubMed1984

Prostacyclin infusion in acute cerebral infarction.

We gave prostacyclin infusions to seven patients with acute cerebral infarction. Patients without CT evidence of infarction improved, but those who already had hypodensities on CT did not benefit. Increased platelet activity, measured by plasma beta-thromboglobulin, decreased significantly (p less than 0.01) during prostacyclin administration to normal levels, but rose again after the infusion. These results indicate that prostacyclin can be given safely in doses adequate to suppress platelet function. Our findings encouraged us to proceed with a controlled trial of its clinical efficacy.

Acute Disease↗
PubMed1984

Age-dependent alterations in the accumulation of l-methadone in the brain synaptosomes and other subcellular fractions.

Albino Sprague-Dawley rats (1, 8, 12 and 20 days old) were injected intraperitoneally with l-[3H-1]-methadone (5 mg/kg containing 50 muCi/kg), and sacrificed at 15 min, 1 h and 3 h. Whole brain was homogenized in 0.32 M sucrose-Tris buffer and the homogenates were subjected to differential centrifugation to separate nuclei, mitochondria, microsomes, soluble cytosol, myelin, membrane and synaptosomes. Methadone levels in each fraction were examined. The methadone contents in the whole brain (sum of all fractions) of 1- and 8-day-old rats were significantly higher relative to those of 12- and 20-day-old rats at all time intervals. The most striking finding in this study was that during development, the percentage of methadone content in the synaptosomal fraction progressively increased relative to other subcellular fractions; interestingly, there was an associated decrease in the percent levels in the soluble cytosol suggesting a shift of methadone from cytosol to synaptosomes. These alterations in brain synaptosomal accumulation of methadone could result from the progressive increase in the affinity of methadone for synaptosomes as these particles become enriched in the protein and lipid contents and possibly increase in opiate receptor density during the neuronal maturation and the synaptogenesis of the developing brain.

Aging↗
PubMed1983

Regional localization of [14C] methylphenidate in rabbit brain.

1. Neuroanatomical distribution of [14C] methylphenidate has been examined in rabbit brain following intracerebroventricular administration. 2. After about a week of implantation of cannula, in lateral ventricle, in albino rabbits, [14C] methylphenidate was injected through the cannula. The distribution of [14C] methylphenidate was examined at 15, 60 and 180 min after the injection in twelve brain regions. 3. The highest levels were observed at the first sampling time (15 min), in medulla and cervical spinal cord. Pons, caudate, tegmentum and hypothalamus also showed significant uptake of [14C] methylphenidate. Cerebral cortex and thalamus showed very low uptake. 4. The uneven distribution suggests a special affinity of methylphenidate for certain brain regions. The implications of this finding for the central actions of methylphenidate are discussed.

Animals↗
PubMed1983

The influence of nisoldipine--a "calcium entry blocker" on drug induced stereotyped behavior in rats.

In view of potential ability of calcium entry blockers to affect Ca2+ fluxes in neurons, the effects of nisoldipine on phencyclidine (PCP) and apomorphine (APO) induced stereotyped behavior have been examined in 3 and 4 week old rats. The rats (3 and 4 weeks old) were pretreated with either 0.2 ml of saline + ethanol mixture (10:1 v/v) or nisoldipine (25 mg/kg) i.p., 5 min before the i.p. administration of PCP (5 mg/kg) or APO (10 mg/kg). While nisoldipine pretreatment significantly blocked the PCP induced stereotypy in 3 and 4 week old rats, the APO induced stereotypy was not altered. These preliminary data suggest that nisoldipine specifically blocks PCP induced stereotypy probably by antagonizing it effects at the presynaptic level. The significance of this finding in relation to mechanism of action of PCP and calcium entry blockers is discussed.

Age Factors↗
PubMedDate not supplied

Squash preparation and frozen section in intraoperative diagnosis of central nervous system tumors.

OBJECTIVE: To investigate the diagnostic accuracy of squash preparation (smears) and frozen section (FS) in the rapid intraoperative diagnosis of central nervous system (CNS) tumors. STUDY DESIGN: One hundred eighty-three CNS tumors were examined over a period of 18 months (January 1995-June 1996). All these were open biopsies, and the smear interpretation was compared with FS findings and paraffin section diagnosis. RESULTS: In 183 tumors, squash preparation was satisfactory in 156 cases (85.2%), and the diagnostic accuracy was 89.7% (140/156). The accuracy of FS diagnosis was 90.4% (141/156). CONCLUSION: The squash smear preparation is a fairly accurate and reliable tool in the rapid intraoperative diagnosis of CNS tumors. The accuracy of this technique is nearly as good as that of FS (P value = .9877). With the advent of stereotactic biopsies, the pathologist may have to depend entirely upon cytologic features for a definitive diagnosis.

Astrocytoma↗
PubMedDate not supplied

Enhanced in vivo platelet activation in subtypes of ischemic stroke.

It remains uncertain whether platelet activation in ischemic stroke is contributory or secondary to brain ischemia. The efficacy of aspirin (ASA) in stroke prevention suggests that platelet activation contributes to the occurrence of stroke. On the other hand, platelet activation may be simply a generalized consequence of cerebral ischemic damage. To examine this issue, plasma levels of the platelet specific proteins beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured in fifty-eight patients with various defined types of acute ischemic strokes. beta-TG was a broader indicator of platelet activation than PF4. Compared with an age-matched control group, thromboembolic and cardioembolic stroke patients had significantly elevated beta-TG levels (p less than 0.001). Also, beta-TG levels in these stroke categories were significantly higher in samples drawn within the first week after the event than in those drawn later (p less than 0.001). In contrast, beta-TG levels in lacunar stroke patients and in most TIA patients were normal. beta-TG levels did not correlate with the volume of cerebral infarction as measured by planimetry from CT scans. Moreover, beta-TG levels in patients on chronic ASA therapy at the time of stroke did not differ from those in patients of the same diagnostic categories not taking aspirin. These data indicate that platelet activation may be important in some, but not all, subtypes of ischemic stroke and that platelet activation can occur in stroke even though the platelet cyclooxygenase pathway is suppressed.

Adult↗