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Biomedical subjects

R Mehta

Publications and source records attributed to R Mehta.

At least 91 records · Page 5Linked to original sources

Portacaval anastomosis disrupts circadian locomotor activity and pineal melatonin rhythms in rats.

To determine whether hepatic encephalopathy may be associated with a disruption of circadian function, the circadian rhythms of locomotor activity and pineal melatonin content were examined in an animal model of complete portal-systemic shunting, rats with a portacaval anastomosis (PCA). The locomotor activity rhythm of all sham-operated animals entrained normally to a light/dark cycle and exhibited a normal free-running period during exposure to constant light. In contrast, PCA led to a dampening of the locomotor activity rhythm in all animals and the abolishment of a circadian periodicity in the activity rhythm of approximately 50% of rats during exposure to either a light/dark cycle or constant light. While normal diurnal variations of pineal melatonin content were seen in sham-operated rats, the amplitude of this variation appeared to be decreased in PCA animals. The similar effects of PCA on both a behavioral and an endocrine circadian rhythm, known to be regulated by a common neural pacemaker, coupled with studies indicating that a variety of other circadian rhythms may be disrupted in both animals and humans with hepatic dysfunction, suggests that this circadian disturbance originates within the pacemaker or on one of its afferent/efferent pathways.

Animals↗

Amsacrine is safe and effective therapy for patients with myocardial dysfunction and acute leukemia.

The role of amsacrine in inducing remission in patients with cardiac disease and acute leukemia was evaluated. There were 17 patients with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL), and one with biphenotypic leukemia. In this series of 24 patients whose disease had relapsed and who had reduced left ventricular ejection fraction, nine had a complete remission, seven with AML and two with ALL. In addition, four of six with newly diagnosed acute leukemia and reduced left ventricular ejection fraction also responded. Among nine patients who underwent endomyocardial biopsy, none had morphologic changes of sufficient degree to account for drug-induced heart failure. Patients with preexisting arrhythmias received amsacrine without incident if their serum potassium level was higher than 4.0 mEq/l at the time of drug administration. Amsacrine is safe and effective therapy for patients with acute leukemia and cardiac disease.

Amsacrine↗

Age-related effects of chronic ethanol intake on vitamin A status in Fisher 344 rats.

The present study was designed to investigate the interaction of age and ethanol on vitamin A status in rats. Rats aged 2 and 19 mo were fed a liquid diet containing 36% of total energy as ethanol or pair-fed a diet containing isoenergetic carbohydrate in place of ethanol. After 3 wk older rats had lower serum retinol (P = 0.04) and higher vitamin A concentrations in liver (P = 0.0001), esophagus (P = 0.0001) and the proximal (P = 0.03) and distal (P = 0.0001) colon than younger animals. Hepatic microsomal cytochrome P-450, retinyl ester hydrolase (REH) and cellular retinol-binding protein (cRBP) were significantly reduced; acyl coenzyme A: retinol acyltransferase (ARAT) was increased; and alcohol (retinol) dehydrogenase (ADH) activity was unchanged with age. Ethanol ingestion increased serum retinol as well as esophageal and colonic vitamin A levels in both age groups. Hepatic cRBP decreased further in the older rats with ethanol feeding, but no change was noted in the percentage of hepatic vitamin A as retinol or retinyl esters. Ethanol ingestion decreased REH (P = 0.0001) and ARAT activities (P = 0.02) and increased cytochrome P-450 (P = 0.04) but had no effect on the activity of ADH in either age group. These data indicate that, regardless of age, chronic ethanol ingestion significantly alters the tissue distribution of vitamin A; however, ethanol reduced cRBP levels only in older rats.

Acyltransferases↗

Antifungal activity of HWA-138 and amphotericin B in experimental systemic candidiasis.

HWA-138, a pentoxifylline analog, has been shown to increase yeast urinary clearance and to reduce yeast counts in the kidneys of rats infected with Candida albicans. Furthermore, HWA-138 has also been shown to prevent amphotericin B-induced acute renal failure in rats. We report here on the effects of HWA-138 alone and in combination with amphotericin B in the treatment of systemic candidiasis in mice. When single doses of HWA-138 were administered intravenously (10, 25, or 50 mg/kg of body weight) into infected mice, no significant improvement in survival was observed. In infected mice treated intravenously with multiple doses of HWA-138 (10, 25, or 50 mg/kg once daily for 5 consecutive days), a significant increase in survival time was seen only in animals also receiving 25 mg of HWA-138 per kg (14 +/- 3 days test versus 9 +/- 1 days control; P less than 0.05). The coadministration of subtherapeutic doses of amphotericin B and HWA-138 resulted in increased survival time. Combination therapy with amphotericin B (0.1-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) resulted in a significant increase in survival time over controls (19 +/- 4, 19 +/- 5, and 21 +/- 9 days, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P < 0.05). Variance analysis of these findings indicate synergistic activity between amphotericin B and HWA-138 in the treatment of experimental candidiasis in mice.

Amphotericin B↗

Sucking on the 'emptied' breast: non-nutritive sucking with a difference.

A simple method to promote the use of human milk and subsequent breast feeding in low birthweight infants was evaluated in 32 babies. In the 'intervention' group (n = 16; mean (SD) weight 1559 (228) g and length of gestation 33.2 (1.8) weeks), infants were allowed to suckle at the breast when their general condition permitted after as much milk as possible had been expressed, and were then given the full required feeds by tube. Full breast feeding was started as soon as the infant could suck adequately. Sixteen control infants (mean (SD) weight 1605 (198) g and length of gestation 34.1 (2.4) weeks), were breast fed in the conventional manner only after it had been established that they could suck well; until then they received all their feeds by tube. After discharge the mean (SD) periods of exclusive and total breast feeding were longer in the group that had received the intervention (3.7 (1.3) and 5.1 (2.2) months, respectively) than among the controls (1.9 (0.6) and 3.3 (1.9) months, respectively). This 'intervention' method helps to promote milk formation, provides sucking experience for low birthweight infants without interfering with their nutritional intake and consequent weight gain, and encourages subsequent breast feeding with its well recognised advantages.

Breast Feeding↗

Comparison of four different ovarian stimulation protocols in an in vitro fertilisation & embryo transfer programme.

Four different ovarian stimulation protocols were evaluated in an in vitro fertilisation and embryo transfer programme in 208 women (228 treatment cycles). In the rigid protocol (RP), 100 mg of clomiphene citrate (CC) was given from day 3 to day 7 of the menstrual cycle and 300 IU of human menopausal gonadotropin (hMG) was given from day 5 of the menstrual cycle. In the individualised protocol (IP) the same drugs and doses were used as in RP, but the day of initiation of CC depended on the length of the individual's menstrual cycle and hMG was administered from the last day of CC. In the programmed protocol (PP), ovarian function was suppressed with oral contraceptive pills (ethinyl estradiol 30 micrograms and norethisterone 1 mg) started on day 5 of the menstrual cycle for 45 to 70 days. Considering the last day of pill intake as day 0, CC was given for 5 days from day 5 and hMG (300 IU) from day 7. In the alternate day protocol (ADP), 100 mg of CC was administered from day 2 to day 6 and hMG (300 IU) was given on alternate days from day 2 to day 8 or day 10 of the cycle. In all the women, hCG (5000 IU) was administered when the diameter of at least 2 follicles was greater than or equal to 16 mm and estradiol levels were 300 pg/ml/dominant follicle. Patients not showing such a response were not treated further. The cardinal events of IVF-ET such as number of good responders, incidence of oocytes harvested, fertilised and embryos transferred per cycle were compared and it was concluded that the pregnancy rates were highest in women treated by the PP.

Adult↗

Endotoxin and the hyperdynamic circulation of portal vein-ligated rats.

Humoral factors may be responsible for the hyperdynamic circulation seen in portal hypertension. Endotoxin, a peripheral arteriolar vasodilator, has been proposed to mediate this hemodynamic picture. We examined the pathogenic role of endotoxin in portal vein-ligated rats, a prehepatic portal hypertensive model with a well-developed hyperdynamic circulation. To this end, we (a) administered oral neomycin, a poorly absorbable antibiotic, at doses of 50 and 100 mg/day for 7 days and found no evident splanchnic hemodynamic effects of a 2-log-fold reduction of cecal aerobic bacterial flora as assessed by the radioactive microsphere technique in portal vein-ligated rats studied in the postanesthesia awake state; (b) assayed endotoxin in arterial samples using a quantitative limulus assay and found no evidence of endotoxinemia in PVL rats; (c) induced a state of endotoxin tolerance by repeated daily intraperitoneal injections of low-dose endotoxin and found no amelioration of the hyperdynamic state in portal vein-ligated rats. Our results do not support the hypothesis that endotoxin plays a major pathogenic role in the hyperdynamic circulation of this experimental model.

Ammonia↗

A simple method of evaluation of jaundice in the newborn.

This paper evaluates a simple tool, the icterometer, in assessing jaundice in the newborn. The instrument consists of a perspex scale with yellow stripes of increasing intensity, numbered 1-5, alternating with transparent areas through which the infant's blanched skin colour can be seen and compared with the coloured stripes. The scale was found to be useful for more objective screening of neonatal jaundice, particularly in decreasing the number of blood samples to be taken for serum bilirubin. The present study suggests that serum bilirubin estimation can be avoided when the icterometer readings on the face are 3 or less, unless there is a rapid rise in jaundice within 24-36 h. However, a reading on the sole of even 1 is significant and requires assessment by trained staff for blood sampling and/or phototherapy. The instrument may also be useful to peripheral staff in developing countries when deciding on referral to specialist centres and to staff in specialist centres for screening cases of neonatal jaundice and decreasing the number of blood samples.

Bilirubin↗

Screening tests for intrauterine growth retardation: a comparison of umbilical artery Doppler to real-time ultrasound.

In a study designed to compare Doppler umbilical artery velocimetry to ultrasound morphometric measurements in the prediction of intrauterine growth retardation, 636 paired ultrasound and Doppler umbilical artery examinations were performed between 24 and 40 weeks gestational age. Intrauterine growth retardation was defined as birth weight less than the tenth percentile per gestational age and 25 (9.2%) of the infants born in our study met this criteria. In general, when the gestational age was limited to less than 30 weeks, none of the tests were highly predictive of intrauterine growth retardation. Doppler umbilical artery systolic-to-diastolic ratios of greater than 3 had the highest sensitivity. However, due to inclusion of a large number of false-positives, it was considered a poor test. After 30 weeks, fetal abdominal circumference less than the tenth percentile had a greater sensitivity (45%) and positive predictive value (28%) than Doppler systolic-to-diastolic ratios greater than 3 (36% and 18%, respectively). Doppler ultrasound umbilical artery systolic-to-diastolic ratios are not more predictive of intrauterine growth retardation than ultrasound morphometric measurements.

Birth Weight↗

Inhibition of heterochromatin condensation of human Y chromosome by distamycin-A.

Distamycin-A, an oligopeptide antibiotic with a N-methylpyrrole ring system and propionamide side chain, preferentially forms stable bonds with AT rich double stranded DNA. When introduced to cell cultures, it inhibits condensation of the heterochromatic region of the Y chromosome. The frequency of metaphases showing inhibition of heterochromatin condensation of the Y chromosome was found to be dependent on the treatment time and concentration of distamycin-A in the culture medium. When distamycin-A was added to a concentration of 100 micrograms/ml at the start of the culture (72 hours), the frequency of Y heterochromatin decondensation was found to be 48%, 30% and 6% in amniotic fluid, lymphocyte and fibroblast cultures respectively. The highest frequency of metaphases with decondensed Y heterochromatin were observed when distamycin-A treatment was carried out for the last 24 hours prior to harvest, the frequencies being 94%, 72% and 59% in amniotic fluid, lymphocyte and fibroblast cultures respectively. Increase in the concentration of distamycin-A from 25 micrograms/ml to 50 micrograms/ml during the last 24 hours of culture increased the incidence of metaphases with Y heterochromatin decondensation from 51% to 69% in amniotic fluid, 40 to 49% in lymphocyte and 29% to 31% in fibroblast cultures. Highest frequency of metaphases with Y heterochromatin decondensation were observed when the cultures were exposed to distamycin-A at a concentration of 100 micrograms/ml for the last 24 hours of culture.

Cells, Cultured↗

Effect of Mycobacterium leprae-infected Schwann cells and their supernatant on lymphocyte neuroglia interaction.

Since the resolution of neural lesions and subsequent nerve damage in leprosy must inevitably involve the participation of immune cells sensitized to Mycobacteria, we have used the dissociated Schwann cell culture model to study the relationship between M. leprae-infected Schwann cells and sensitized immune cells. Our earlier study on light and ultrastructural observations showed that on infection with M. leprae, the cytomorphology of Schwann cells remains unaffected, while degenerative changes suggestive of apoptosis are seen in extraneous lymphocytes which are subsequently phagocytosed by the Schwann cells. We now present additional evidence confirming that the phagocytosis of splenic cells by Schwann cells is indeed a two-step process. The first involves M. leprae-dependent cytotoxicity to splenic cells. This is followed by phagocytosis of these cells, which is a secondary and M. leprae-independent phenomenon. This finding has implications particularly on the weak inflammatory response observed in nerve lesions of a majority of lepromatous patients.

Animals↗

DOT-enzyme linked immunosorbent assay for detection of Clostridium perfringens type A enterotoxin.

A procedure, which we have termed DOT-ELISA, to detect Clostridium perfringens type A enterotoxin on nitrocellulose paper is described. Seventy eight preparations from 39 cultures of C. perfringens type A were tested simultaneously by this and by Plate-ELISA methods. The results were comparable. DOT-ELISA detected as little as 0.02 micrograms of purified enterotoxin and 0.13 micrograms of enterotoxin in cell-free culture supernatant. As little as 0.02 micrograms purified enterotoxin mixed with human faeces could be detected specifically. The method is simple and does not require an ELISA reader.

Clostridium perfringens↗

Cytotoxicity of N6-cycloalkylated adenine and adenosine analogs to mouse hepatoma cells.

Cytotoxic effect(s) of N6-cycloalkylated adenine and adenosine derivatives, upon the viability of mouse hepatoma cells, were studied in vitro. N6-Cyclopropyl- and N6-cyclobutyladenine and adenosine derivatives (33 micrograms/ml; 24-48 h) exerted significant cytotoxic effects upon the cells. N6-Cyclopentyl- and N6-cyclohexyladenines exerted similar effects under different experimental conditions (133-166 micrograms/ml; 48-72 h), while no significant cytotoxic effect(s) were observed with the corresponding adenosine derivatives under these conditions. Observed physical changes in the treated cells included cell elongation, short stubby filaments, wide intracellular spaces and ruptured cell membranes. N6-Cycloalkylated nucleosides were usually more cytotoxic than the cycloalkylated bases.

Adenine↗

In vitro interaction of M. leprae-infected Schwann cells and splenic cells.

The interaction between M. leprae-infected cultured Schwann cells and sensitized splenic cells was noted both under light and electron microscopy. No evidence of cytomorphological changes in infected Schwann cells was obtained. However, sensitized splenic cells were noted to undergo degenerative changes suggestive of the phenomenon of apoptosis. Subsequently a large number of these degenerated cells were observed within the Schwann cell. Such a process has not been hitherto reported in the histopathology of leprous nerves. Nevertheless, these findings indicate an aberrant metabolic function in M. leprae-infected Schwann cells.

Animals↗

The L protein of vesicular stomatitis virus modulates the response of the polyadenylic acid polymerase to S-adenosylhomocysteine.

TsG16(I) is a temperature-sensitive (ts) mutant of vesicular stomatitis virus, Indiana serotype, which overproduces polyadenylic acid [poly(A)] in an in vitro transcription system due to a mutation in the L protein. Others have reported that L-S-adenosylhomocysteine (S-Ado-Hcy) causes wild-type (wt) virus to overproduce poly(A) in vitro. The possibility that tsG16(I) constitutively expresses a property induced by S-Ado-Hcy in the case of wt virus was found not to be so since polyadenylation by the mutant was still sensitive to S-Ado-Hcy. Indeed, S-Ado-Hcy caused tsG16(I) to overproduce poly(A) in vitro to a greater extent than its parental wt virus. The increase in polyadenylation observed in response to saturating levels of S-Ado-Hcy differed for tsG16(I), for its parental wt virus and for another wt strain. To characterize which viral protein modulated the polyadenylation response to S-Ado-Hcy, purified virions were fractionated and their phenotypes in homologous and heterologous reconstitution assays were examined. The results indicated that the viral L protein modulated the response in all three stocks of virus. These data provide further evidence to suggest that the L protein of vesicular stomatitis virus plays a role in polyadenylation of the viral mRNA.

Adenosine Monophosphate↗