Tadalafil-associated anterior ischaemic optic neuropathy.
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Biomedical subjects
Publications and source records attributed to M V Singh.
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BACKGROUND: This study mainly focused on renal blood flow, hematological parameters, blood gases, and blood pH, which are affected on exposure to moderate (3500 m) and extreme altitudes (5800 m) in sea level residents. HYPOTHESIS: Acute and prolonged exposure to high or extreme altitude may cause pathophysiological changes in kidney and renal plasma/blood flow, leading to retention of fluids in the tissues. Combined with the decreased availability of oxygen to the tissues, these may be responsible for high altitude maladies. METHOD: Fifteen male sea level (SL) volunteers, 22-25 yr old, were studied for blood gases, blood viscosity, hematocrit, hemoglobin concentration, and effective renal blood/plasma flow at Delhi (260 m), 3500 m (60 d stay), 5800 m (70 d stay), and 7 d after return to SL. RESULTS: Compared with SL, a significant increase from 7.34 to 7.43 (p < 0.01) in blood pH was observed at 3500 m that remained significantly increased at 5800 m. PO2 was about 39% less at 5800 m than at SL. PCO2 reduced significantly from 42.07 to 28.05 mm Hg on return from 5800 m to SL. The blood viscosity increased significantly (38%) at 5800 m and decreased significantly by 38% (p < 0.01) after return to SL. The effective renal plasma flow reduced significantly (p < 0.01) from 615.6 at SL to 381.5 ml x min(-1) x 1.73 m(-2) at 5800 m. CONCLUSION: The study suggests a crucial role of renal function in the acclimatization process; renal function also appears to be one factor by which the body protects itself against severe hypoxia.
On-farm field experiments were carried out at two sites having 38- and 10-year-old orchard cropping systems under sub-tropical climatic regions to evaluate changes in organic carbon accumulation and chemical and microbiological properties of the soils. Under a system of different intercropped fruit trees, the cultivation of coconut (Cocos nucifera L.) intercropped with guava (Psidium guajava L.) enhanced the soil microbial activity approximately 2-fold after 38 yrs over 10 yrs of the same intercropped system. Soil organic carbon increased from 3.4 to 7.8 and 2.4 to 6.2 g kg-1 after 38 and 10 yrs, respectively, following the establishment of orchards. The increase was attributed to greater recycling of bio-litters. Levels of dehydrogenase, phosphatase and soil microbial biomass under field conditions generally depended more on the nature of the cropping system than on soil types. Similarly, average carbon inputs of bio-litter to the soil in monocrop (0.98 Mg ha-1 yr-1) was less than intercropped fruit trees (2.07 Mg ha-1 yr-1). The average level of soil microbial biomass carbon was 1158 kg ha-1 (0-0.15 m depth) and the organic carbon turnover rate was 8.5 yr-1 after 38 yrs of intercropped fruit trees, which resulted in a lower ratio (1.81) of carbon inputs to soil microbial biomass carbon.
BACKGROUND: The objective of this study is to evaluate the efficacy of oral glutamic acid supplementation in promoting hypoxic tolerance. METHODS: The experiments were conducted in albino rats by exposing them to three levels of hypoxia in a simulated environment for varying periods of time. The parameters studied include: gasping time at 35,000 ft (10,668 m), food and water intake, and heart to body weight (b.w.) ratio at 25,000 ft (7620 m), tolerance to composite stress at 15,000 ft (4572 m) and biodistribution of glutamate (glu). RESULTS: Supplementation of Glu (27 mg x kg(-1) b.w.) as glutamic acid dissolved in normal saline resulted in 4.8 times enhanced hypoxic tolerance (time taken for appearance of first gasp), 23% body weight gain and 24% increase in food consumption over control during hypoxia. When animals were subjected to composite stress of cold, hypoxia and restraint (CHR), the Glu fed animals showed higher resistance to fall in rectal temperature than the control group. Hypoxia significantly enhanced heart to body weight ratio compared with control, and Glu supplementation reduced and brought it down to that of control. CONCLUSION: The study reveals that Glu in optimal doses may be a conditionally essential amino acid resulting in enhanced tolerance to hypoxia and cold.
BACKGROUND: Research has focused mainly on the relationship of zinc and copper contents and physical stresses like running, cycling, etc. It has also been reported that other forms of stresses change the concentration of these trace elements in humans. However,there are no reports on the effects of high altitude induced hypoxic stress on the plasma levels of these metals. Since hypoxia is one of the important stresses, we considered it appropriate to observe the changes in the levels of zinc and copper concentrations and in certain related zinc and copper enzymes and hormones in the plasma of human volunteers on acute induction to high altitude. From these findings, we intended to ascertain whether supplementation of these trace elements would be required for optimal health under such conditions. HYPOTHESIS: On acute induction to hypoxia, contents of these trace elements may change as the requirements of stressed organs and tissue may increase. Hence, further supplementation may be beneficial under hypoxic stress for better adaptability. METHOD: Volunteers were divided into two groups: with and without zinc and copper salt supplementation. Blood samples were collected at sea level and on induction to acute hypoxia on days 3 and 10. Trace mineral contents and their related enzyme (alkaline phosphatase) and hormone (ceruloplasmin) levels were determined in plasma samples. RESULTS: Plasma zinc contents were significantly reduced upon induction to high altitude in the non-supplemented group, but not in the zinc-supplemented group. Alkaline phosphatase activity increased significantly upon induction to the high altitude stress. The enzyme activity remained elevated up to day 10 of the stress. Plasma copper contents and ceruloplasmin activity did not change upon induction to high altitude. CONCLUSION: Under hypoxic stress, circulating levels of zinc and alkaline phosphatase in plasma changed appreciably as plasma zinc was transported into the organs and tissues. However, circulating levels of copper and ceruloplasmin in plasma did not change, indicating no extra supplementation of copper is required under hypoxic stress.
Stearoyl CoA desaturase gene 1 (SCD1) is a delta 9 desaturase that is transcriptionally activated during the differentiation of 3T3-L1 preadipocytes into adipocytes. We have demonstrated that a SCD1/BP region in SCD1 proximal promoter (-114 to -86 bp) is essential for the transcriptional activation of this gene during differentiation. Mutation in this region abolished the basal activity of the proximal promoter of SCD1, and also failed to induce transcription in response to the differentiation cocktail in transfected cells. The SCD1/BP region contains a TGGCA sequence at -90 bp from the transcription start site. Using competitor oligonucleotides and nuclear factor 1 (NF1)-specific antibodies in gel shift assays, we have shown that in preadipocytes, a NF1 protein binds to this TGGCA sequence. On MDI-induced differentiation of preadipocyte into adipocyte, an additional DNA-protein complex appeared. The appearance of a new NF1 complex is related to the differentiation-specific transcriptional activation of the SCD1 gene. This is the first report to show a differentiation-related change in NF1 protein binding during preadipocyte differentiation.
Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector. Stable transfectants were selected by their resistance to the antibiotic G418. More than a dozen G418-resistant clones were isolated and were screened for tyrosinase expression using dopa-oxidase activity. The clone with the highest tyrosinase activity was selected and expanded for further studies. Northern blot analyses of total RNA from cells showed that the transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human melanotic melanoma cells. The melanin content of the transfected cells was dependent on the concentration of L-tyrosine in the culture medium. In addition, the growth of transfected cells was inhibited when grown in a medium containing high concentrations of L-tyrosine. These results suggest that tyrosinase activity is cytotoxic in a substrate-dependent manner. This may have far reaching therapeutic use for glioma tumours.
The study was conducted on human volunteers as controls as well as after administration of vanadyl sulphate on induction to high altitude (HA) at 3500 m. The plasma vanadium contents were significantly reduced in the control group on abrupt induction to HA on days 3 and 10, indicating redistribution to other organs/tissues under the stressful situation. In the vanadium salt-treated group, plasma vanadium contents were similar to those obtained at sea-level. Administration of vanadyl sulphate did not act as a diuretic. Moreover the vanadium supplemented group drank more water and also excrete less urine than the control group.
The relationship between growth properties and gap junctional communication properties of two glioma cell lines, 9L and C6, was compared. Using microinjection of a gap junction permeable fluorescent dye, it was demonstrated that 9L cells were extensively dye coupled through gap junctions, whereas C6 cells had low levels of dye coupling between the cells. More gap junctions were observed between 9L cells than between C6 cells both by electron microscopy and immunofluorescent labelling with specific antibodies. Immunoblotting and immunofluorescence labelling of cellular proteins from 9L and C6 cells also showed differences in the Cx43 connexin contents of these cells, reflecting the differences in their gap junctional communication. Northern blot analyses confirmed that the level of Cx43 mRNA was higher in 9L than in C6 cells. In spite of these differences in gap junctions, the two cell lines did not differ in their growth rates in cultures. These results suggest a lack of direct correlation between gap junctional communication and cell growth regulation in these two glioma cell lines.
The 9L rat glioma cells communicate via gap junctions which are formed of connexin 43. The gap junctional communication was inhibited in these cells by transfecting them with an antisense Cx43 DNA construct, and its effect on their growth rate was investigated. This construct was induced by a Zn(2+)-inducible metallothionein promoter. Results showed that the induction of antisense RNA expression in rat 9L glioma cells produced the loss of gap junctions which was reflected in the loss of gap junctional communication. By inducing the antisense construct with zinc acetate, and using specific antibodies to connexin 43, the synthesis of this connexin was inhibited in the transfected cells and gap junctions were lost on the cell-cell appositions. There was no such effect on the untransfected cells. The loss of gap junctions at cell-cell appositions also correlated with the loss of Lucifer yellow fluorescent dye transfer between the cells. The effect of loss of gap junctions on the growth rate of the cells was assessed. In spite of the drastic decrease in the number of gap junctions between cells, their growth rate was only approximately 20% less than that of the transfected but non-induced cells. Therefore, gap junction communication is not negatively related to the rate of growth of these cells.
In this investigation 9L rat glioma cells were grown on coverslips in culture, and when subjected to mechanical trauma, they were capable of mounting an astroglial response, without interaction with neurons, as evidenced by cell hypertrophy and increased immunostaining for glial fibrillary acidic protein and J1-31 antigen. It is of particular interest that this neoplastically transformed cell line is capable of mounting an astroglial response when subjected to mechanical trauma in vitro. The advantages of this model over in vivo models of central nervous system injury include the ease of reproducibility of results, and the ability to investigate molecular mechanisms under controlled conditions.
Using radioactive iodine, the effect of 1 month's yogic exercises has been investigated on the thyroid function of subjects resident at sea level (SL) specially after their exposure to high altitude (HA). The results have been compared with a group of SL subjects who underwent physical training (PT) exercises for the same duration. Ten healthy male volunteers in the age range of 20-30 years were used as test subjects in this study with each serving as his own control. The subjects were randomly divided into two groups of 5 each. One group practised hatha yogic exercises, while the other group performed the regular PT exercises. The thyroidal accumulation and release of radioactive iodine have been measured in each of the subjects of both groups before and after 1 month of their respective exercises at SL. One month of yogic exercises at SL has been observed to cause a significant reduction in the trans-thyroidal availability of radioiodine. The thyroid radioactivity in this group of subjects was always below normal levels with the exception of two peaks of radioactive iodine uptake, when the levels of radioactivity in the thyroid were similar to the control values of pre-yogic exercises. The release of radiolabel at 24-48 h was significantly increased after yogic exercises. In contrast, the subjects performing PT exercises for the same duration at SL showed significant thyroid uptake of radioactive iodine at 24 h. Subsequently their 131I uptake continued to rise slowly until 72 h without any demonstrable thyroidal release of radiolabel. This indicated that increased thyroid activity was induced by conventional PT exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
In the present investigation thyroidal accumulation of radioiodine and its release were assessed by direct testing of thyroid function using radioactive iodine, in vivo, in sea level residents intermittently exposed to hypobaric hypoxia. Thyroidal accumulation of radioiodine and its turnover were examined daily for 14 days. Twelve healthy human male volunteers were divided into three groups, with an equal number of individuals in each group. A decompression chamber was used to expose each group of subjects to hypoxic conditions at a simulated altitude of 3810 m for 8 h/day for 14 days. An oral dose of 25 mu Ci iodine-131 was administered to each individual of the first group immediately before the initiation of intermittent hypoxia. The second group of subjects received a tracer dose at the beginning of the 4th day of the 14 days, intermittent exposure to hypoxia, while the third group received the tracer dose 1 week after the completion of the exposure. Control studies were carried out on the subjects before they were subjected to the experimental conditions. Thyroidal accumulation of 131I in experimental subjects during the hypoxic state and in the post-hypoxic state was higher than in the control studies. The pattern of accumulation during exposure to hypoxia and in the post-hypoxic state showed multiple peaks of radioactive iodine uptake (PRAIU), a unique feature. The multiple PRAIU by the thyroid in experimental subjects were sharp and of short duration, reflecting an increased rate of 13I release from the thyroid. Control subjects had a single PRAIU by the thyroid 24 h after the administration of tracer.
Body fluid compartments at different levels of graded hypohydration and partial rehydration were determined using radiotracers in 28 heat-acclimated, male volunteers from tropical regions of India, in hot dry conditions in a climatic chamber. These subjects were hypohydrated to varying degrees (i.e., 1%, 2%, 3%, and 4% body mass deficit) by moderate work in hot conditions in a climatic chamber maintained at 45 degrees C dry bulb temperature and 30% relative humidity. Rehydration study was carried out only in those subjects who were hypohydrated to 3% and 4% body mass and who were brought back to 2% level of hypohydration by receiving a calculated amount of water. Up to the 2% level of hypohydration, a major contribution towards sweat loss was observed from the interstitial fluid (ISF) compartment. At higher levels of hypohydration, no further significant loss from ISF was seen, though significant losses in intracellular fluid (ICF) and plasma volume (PV) were apparent. The present study also found that at the 4% hypohydration level, a maximum fluid contribution was met by the ICF compartment. Significant increases observed in sweat K+ at 3 and 4% also indicate the ICF mobilization, which is rich in K+ ions. On partial rehydration, the ISF compartment held the repletion fluid in excess, and was found to be enough to restore sweat rate to euhydration level. This study clearly indicates that sudorific gain is achieved with partial restoration alone in subjects hypohydrated to 3 and 4% levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma volume (PV) at different levels of hypohydration was determined using radio-iodinated serum albumin-125 in 28 heat acclimated male volunteers in hot dry condition in a climatic chamber. The heat acclimated subjects were hypohydrated to varying degrees i.e. 1%, 2%, 3% and 4% body mass deficit by moderate work in hot conditions in a climatic chamber maintained at 45 degrees C dry bulb temperature and 30% relative humidity. A rehydration study was carried out in only those subjects who were hypohydrated to 3% and 4% body mass and they were brought back to a 2% level of hypohydration by giving a calculated amount of water. A significant decrease in PV was observed at 3% and 4% hypohydration only. The magnitude of the decrease was the same in both the groups and not related to the level of hypohydration. With partial rehydration in the 3% hypohydrated group PV was restored fully, while in the 4% hypohydrated group restoration was incomplete, indicating that at this hypohydration level some of the replenished water that entered in plasma may have moved to the intracellular compartment which may have contributed more at 4% hypohydration. It is suggested that with higher levels of thermal hypohydration significant reduction in the intracellular compartment may result in accentuated physiological strain during work in the heat.
Studies on adaptation to high altitude (HA) of 3500 m in the Himalayas were conducted in three phases, each including 10 normal and healthy males normally resident at sea-level. Phase I subjects had no previous experience of HA, phase II subjects after 4-6 months at HA were airlifted to sea-level and phase III subjects stayed continuously for 6 months at 3500 m. Body fluid compartments and blood gases were determined in all three groups. Plasma volume was highly elevated in the phase II subjects on reinduction to sea-level from HA. In comparison to phase I subjects, the retention of fluid in extracellular compartment was increased at HA leading to increased susceptibility to high altitude illness. Phase III subjects were hyperhydrated with decreased plasma volume and increased PO2 in comparison to the other two groups.
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.
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