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Biomedical subjects

R M Rai

Publications and source records attributed to R M Rai.

At least 19 recordsLinked to original sources
PubMed1998

Impaired liver regeneration in inducible nitric oxide synthasedeficient mice.

The mechanisms that permit adult tissues to regenerate when injured are not well understood. Initiation of liver regeneration requires the injury-related cytokines, tumor necrosis factor (TNF) alpha and interleukin (IL) 6, and involves the activation of cytokine-regulated transcription factors such as NF-kappabeta and STAT3. During regeneration, TNFalpha and IL-6 promote hepatocyte viability, as well as proliferation, because interventions that inhibit either cytokine not only block hepatocyte DNA synthesis, but also increase liver cell death. These observations suggest that the cytokines induce hepatoprotective factors in the regenerating liver. Given evidence that nitric oxide can prevent TNF-mediated activation of the pro-apoptotic protease caspase 3 and protect hepatocytes from cytokine-mediated death, cytokine-inducible nitric oxide synthase (iNOS) may be an important hepatoprotective factor in the regenerating liver. In support of this hypothesis we report that the hepatocyte proliferative response to partial liver resection is severely inhibited in transgenic mice with targeted disruption of the iNOS gene. Instead, partial hepatectomy is followed by increased caspase 3 activity, hepatocyte death, and liver failure, despite preserved induction of TNFalpha, IL-6, NF-kappabeta, and STAT3. These results suggest that during successful tissue regeneration, injury-related cytokines induce factors, such as iNOS and its product, NO, that protect surviving cells from cytokine-mediated death.

Animals↗
PubMed1997

Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver.

Tumor necrosis factor alpha (TNF), initiates a cytokine cascade that promotes hepatocyte proliferation after 70% partial hepatectomy (PH) but the mechanisms regulating TNF production after PH are unknown. We previously reported that gadolinium chloride (GdCl), an agent that depletes the liver of phagocytically active Kupffer cells, enhances hepatic expression of TNF messenger RNA (mRNA) and promotes liver regeneration after subsequent PH. This suggests that GdCl interferes with Kupffer cell mechanisms that normally constrain TNF production after PH. To evaluate this, the pre- and post-PH expression of TNF, TNF-inducible cytokines (interleukin [IL]-1, IL-6) and cytokines (transforming growth factor [TGF] beta 1 and IL-10) that down-regulate TNF were compared in controls and GdCl-treated rats. In controls, TNF, IL-1, IL-6, and IL-10 increase within 3 hours after PH, whereas TGF-beta 1 is induced much later (> 24 hours after PH). GdCl causes sustained overexpression of TNF mRNA and transient overexpression of circulating TNF protein after PH; both TNF-inducible cytokines are also relatively overexpressed. Cytokines that down-regulate TNF are effected differentially by GdCl. Regenerative induction of IL-10 is abolished but TGF-beta 1 induction is unaltered. Because IL-10 is known to shorten the half-life of TNF mRNA, these results suggest that Kupffer cell production of IL-10 is an important mechanism that down-regulates TNF production during liver regeneration.

Animals↗
PubMed1996

Liver regeneration 3: Regulation of signal transduction during liver regeneration.

The liver has a tremendous capacity to regenerate. For example, after extensive hepatic resection, remaining hepatocytes proliferate to restore the mass of the organ within days to weeks. This proliferative response is fascinating because hepatocytes rarely replicate in the healthy adult liver. Instead, these cells perform highly specialized functions and exemplify mature, terminally differentiated cells. Therefore it is somewhat surprising that the liver can repopulate while performing its many obligate, organ-specific functions. Study of the regenerating liver remnant after partial hepatectomy has helped to delineate mechanisms that regulate proliferation and liver-specific functions in individual hepatocytes, as well as those that coordinate the behaviors of different liver cell populations to balance organ growth and tissue-specific gene expression. Hence, this review will focus on inter- and intracellular signals that regulate the hepatocyte phenotype after PH.

Animals↗
PubMed1996

Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines.

Gadolinium chloride (GdCl3) is commonly used to deplete the liver of Kupffer cells (KC) and has been shown to decrease hepatic phagocytic activity and to abolish hepatic expression of certain KC-specific antigens. However, the exact fate of the KCs after GdCl3 treatment remains unclear. To determine if GdCl3 actually decreases the total number of KCs in the liver, we labeled phagocytically-active KC by administering fluorescent-labeled latex beads to rats treated with either normal saline or GdCl3. Total hepatic fluorescence and the distribution of fluorescence within liver acini were evaluated by intravital microscopy. Hepatic mRNA levels of KCR, a KC-specific gene product, and Pu-1, a ubiquitous monocyte gene product, were assessed by Northern blot analysis, and differences in the expression of pro-inflammatory (tumor necrosis factor (TNF)-alpha) and anti-inflammatory (interleukin (IL)-10) cytokines were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Our results indicate that GdCl3 does not significantly reduce the number of phagocytically active cells in the liver, but alters the acinar distribution of these cells and may provoke a switch in the KC phenotype such that these cells no longer express KCR or IL-10. GdCl3 pretreatment inhibited stress-related induction of IL-10, but failed to down-regulate expression of TNF-alpha. This phenotypic change is likely to have important consequences because it permits relative overexpression of TNF-alpha.

Animals↗
PubMed1996

Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats.

Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl) should inhibit liver regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated and control rats. Functional assays and Northern blot analysis of a Kupffer cell-specific mRNA confirmed that GdCl depleted Kupffer cells. Despite this, semiquantitative reverse transcription-polymerase chain reaction analysis of total hepatic RNA showed six- to eightfold higher levels of TNF transcripts in GdCl-treated rats. In this group, PH caused 12-to 16-fold greater induction of interleukin-6, a TNF-inducible cytokine, and two- to threefold greater induction of several cytokine-regulated genes (c-jun, C/EBP-beta, and C/EBP-delta). GdCl also amplified regeneration-associated increases in the DNA binding activity of AP-1, a growth regulatory transcription factor. Furthermore, hepatic incorporation of [3H]thymidine, expression of the S-phase antigen, proliferating cell nuclear antigen, and the hepatocyte mitotic index were each significantly greater in GdCl-treated rats. Thus, although GdCl causes Kupffer cell depletion, it does not decrease liver TNF and actually enhances liver regeneration after PH.

Animals↗
PubMed1991

Influence of noise spectra on auditory frequencies & degree of temporary threshold shift.

Influence of noise spectra on auditory frequencies of 131 audiometrically normal human volunteers was assessed. Each subject was exposed to four different types of noise on different days for a period of 30 min. Noises utilized in this study were broadband noise (100 dBA), broadband noise (BBN) mixed independently with tones of 0.5, 1.2 and 4 kHz at three intensity levels (85, 95 and 105 dBA) and noises of different bandwidths (100 dBA) around the above tones as centre frequencies. BBN produced maximum TTS2 at 4 kHz (21.42 +/- 0.61 to 26.15 +/- 1.00 dB), while concentration of sound energy around these tones, affected hearing at one-half octave above the point of concentration of sound energy. TTS2 produced by 4 kHz tonal component of 95 and 105 dBA and 2 kHz of 105 dBA were significantly higher than the one produced by BBN at 4 kHz. The single tones of 2 and 4 kHz and noise of 1/3rd octave bandwidth (cf 4 kHz) produced TTS2s which were significantly higher as compared to that of BBN at 4 kHz. At the same centre frequency, noise concentrated in thinner bands was more injurious than that in the thicker bands. Lower frequencies of hearing appears to be more resistant to noise as for the same sound pressure level the TTS2 observed in low frequencies was less as compared to higher frequencies.

Acoustic Stimulation↗
PubMed1990

Therapeutic role of carbogen in impaired hearing.

The therapeutic role of carbogen was evaluated in subjects with sensorineural hearing loss by administering carbogen, a gas mixture of 95 per cent O2 and 5 per cent CO2, for seven consecutive days (30 min/day) and monitoring puretone audiometry before and after the administration. Significant improvement was observed both in air and bone conduction threshold levels on seventh day, indicating that there was some recoverable portion in the hearing level of these subjects. The improvement in hearing may be due to action of CO2 as an otic vasodilator coupled with supplementation of the O2 requirement of degenerating hair cells. Carbogen thus appears to be useful in persons with impaired hearing, involving the inner ear.

Adult↗
PubMed1989

Hydration and tissue solid content of the lean body on prolonged exposure to altitude.

Using densitometric, hydrometric and anthropometric techniques, body fat, tissue solids, water and mineral content were quantitatively measured on two groups each of 26 young and healthy Indian soldiers of mixed ethnic composition. The experimental group was exposed to 3500 m altitude for 2 years and the experiments were carried out after 48 h and 3 weeks rehabilitation in Delhi (300 m). The control group was never exposed to high altidues. Inspite of the experimental group being fed with superior rations at high altitude, this group showed significantly hyperhydrated lean body with reduced tissue solids in comparison to the control group which was fed with identical rations in Delhi. The calculated mean density of the fat free body had declined to 0.092 x 10(3) kg/m3. The 3 week stay at low altitude had little influence on body composition. Hyper-hydration, with reduced tissue solids, would cause reduction in the density of fat free body, and would thus interfere with the estimates of total body fat based on densitometric procedures alone. In the hyperhydrated state, Siri's formula overestimated fat by 22.8% of the true value.

Adipose Tissue↗
PubMed1987

Variations in skinfold thickness during de-acclimatisation and re-acclimatisation to high altitude. Relation to body fat content.

Skinfold thickness, body weight, body water, anthropometric measurements and segment volumes were determined in 28 young and healthy Indian soldiers on return to Delhi (200 m) after staying for more than 24 months at high altitude (3500 m). The measurements were made on the 2nd day and after 3 weeks. Ten subjects were then randomly selected from this group and returned by air to the high-altitude station, and the measurements were repeated on the 3rd and 12th day of their reinduction. Though body weight and total body water increased marginally on transfer to the lower altitude, body density remained more or less unchanged. There were significant increases in the thickness of skinfolds, even when body density had increased. During this period hand and foot volumes decreased significantly. Despite significant increases in thoracic skinfold thickness, the torso volume decreased slightly. On returning to high altitude, the soldiers lost body weight, were hypohydrated and showed reduced skinfold thickness. Fat losses calculated on the basis of reduction in skinfold thickness were far in excess of those calculated from losses in body weight and in total body water. As the reduced skinfold thickness was unrelated to changes in body water content at high altitude, it seems that such reductions are due to redistribution of blood in the skin. From the results of these investigations it is concluded that variations in skinfold thickness during acclimatisation to high altitude do not accurately represent the changes in body fat content.

Acclimatization↗
PubMed1984

Influence of noise on blood coagulation.

A study conducted in rats exposed to a continuous noise of 110 decibels over a period of 3 weeks revealed development of significantly prolonged bleeding time, higher plasma fibrinogen content, and progressively shorter activated partial thromboplastin time in test animals. These changes suggest a coagulopathy induced by noise stress.

Animals↗
PubMed1982

Effect of chronic and acute exposure to noise on physiological functions in man.

Physiological parameters have been compared in 75 normal healthy individuals exposed to occupational noise of 88-107 dB(A) (6-8h/day) for 10-15 years and in 36 normal non-exposed subjects. Blood pressure, both systolic (P less than 0.01) and diastolic (P less than 0.001), and heart rate (P less than 0.05) were found to be significantly higher in the exposed subjects. Irregularity in cardiac rhythm, both in amplitude and duration, was found in 18% of the exposed subjects as against 6% in the non-exposed group. Variation in the heart rate during acute noise exposure of 90 dB(A) has been shown to be related with the preponderance of tonicity of sympathetics and parasympathetics. Measurement of hand blood flow during the same exposure showed a lesser degree of vasoconstriction and a slower recovery rate in the exposed group. Altered observations in the exposed group could be attributed to changes in the mechanical property of blood vessels.

Adult↗