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Biomedical subjects

S B Singh

Publications and source records attributed to S B Singh.

At least 19 recordsLinked to original sources
PubMed2007

Hypobaric hypoxia-induced dendritic atrophy of hippocampal neurons is associated with cognitive impairment in adult rats.

Simulated hypobaric hypoxia (HBH), resembling high altitude hypoxia severely affects the CNS and results in several physiological changes. The hippocampus is closely associated with learning and memory and an insult to this region affects cognition. Previous studies suggest that rapid or prolonged exposures to HBH are associated with psychomotor and cognitive impairments. The defense personnel, mountain climbers and rescue teams are exposed to such harsh environment and thus it demands a systematic study emphasizing the subtle effects of such extreme environments on cognitive function. Accordingly, this study evaluated the effect of hypobaric hypoxia on structural changes in the principal neurons of the hippocampus and learning in eight-arm radial maze. Adult male Wistar rats, subjected to simulated hypobaric hypoxia equivalent to an altitude of 6000 m for a period of 2 or 7 days, in a hypoxic chamber served as hypoxic group (HY). Rats housed in a similar chamber for the same period of time, without hypoxic exposure served as sham control (SC), while normal control (NC) group of rats were housed in standard laboratory conditions. The dendritic morphology of neurons in cornu ammonis region 1 (CA1) and cornu ammonis region 3 (CA3) was studied in Golgi-impregnated hippocampal sections. Exposure for 2 days to hypobaric hypoxia had minimal deleterious effects on the CA1 pyramidal neurons, while exposure for 7 days resulted in a significant decrease in the number of branching points, intersections and dendritic length. Unlike the CA1 pyramidal neurons, the CA3 neurons exhibited dendritic atrophy following both 2 and 7 days of hypoxic exposure. Further, hippocampal-dependent spatial learning was affected marginally following 2 day exposure, while 7 day exposure severely affected learning of the partially baited radial arm maze task. Our study suggests that dendritic atrophy in the hippocampus on exposure to HBH could be one of the bases for the cognitive deficits exhibited under such conditions.

Animals↗
PubMed2005

Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture.

Hippocampus has received a considerable attention in the recent past due to its role in a number of important functions such as learning and memory. The effect of hypoxia on neuronal cell injury especially on hippocampal cells is not well known. The aim of the present study was to characterize the biochemical changes in primary cultured hippocampal neurons during hypoxic exposure and the protective effect of N-acetyl cysteine on hypoxia-induced cytotoxicity. The hippocampal culture grown in 24-well plates was exposed to hypoxia for 3 h in a dessicator in 95% N(2), 5% CO(2) atmosphere at 37 degrees C. Later, the cells were allowed to recover for 1 h under normoxia. It was observed that there is an appreciable increase in cytotoxicity in cells exposed to hypoxia. Further, there was a significant decrease in mitochondrial membrane potential and appreciable increase in reactive oxygen species and single-strand DNA breaks in cells exposed to hypoxia compared to control. There is a significant fall in glutathione peroxidase, glutathione reductase, reduced glutathione levels, and nitric oxide in the cells exposed to hypoxia. Significant elevation in the intracellular calcium level in the cells on exposure to hypoxia was observed. Supplementation with NAC (50 microM) resulted in a significant cytoprotection, fall in ROS generation, and higher antioxidant levels similar to that of control cells. NAC also inhibited DNA strand breaks induced by hypoxia. The study indicates that NAC has significant neuroprotective activity during hypoxia in primary hippocampal culture.

Acetylcysteine↗
PubMed2005

Appetite regulatory peptides in Indian Antarctic expeditioners.

Antarctica presents an inhospitable environment due to extreme low temperature, high wind velocity, low humidity, snowstorms, long polar days and nights, high level of UV radiations, magnetic storms and increased ionisation along with social isolation and sexual deprivation. Acclimatisation to any new condition is associated with certain metabolic changes along with alteration in nutritional requirements. There are reports of increased food intake and gain in body weight during past Indian Antarctic expeditions. Therefore, the present study was undertaken with the aim to assess the changes in appetite regulatory peptides i.e. leptin and neuropeptide Y in relation to energy intake and expenditure of the Antarctic expeditioners. The study was conducted in three phases viz. Phase I at Goa (basal), Phase II 48 h after reaching Antarctica and Phase III after one month of stay at Antarctica. Energy and nutrient intake were analysed from the duplicate plate samples of the expeditioners. Energy expenditure was computed using 24 h activity records for 7 days. Blood samples were collected in each phase for biochemical estimations. After reaching Antarctica, the expeditioners were active and the total energy expenditure (mean +/- SEM, n = 10) was found to be 3120 +/- 474 kcal/day. The actual energy intake was found to be 3911 +/- 310 kcal/day. This indicates that the Antarctic expeditioners had very active life and weight gain during expedition could be due to positive energy balance. After 48 h of stay at Antarctica plasma leptin levels (mean +/- SEM, n = 22) decreased from normal basal values 5.66 (+/- 0.59) ng/ml (Phase I) to 4.40 (+/- 0.37) ng/ml (Phase II), even though there was an increase in body fat. Increased level of plasma leptin was observed in Phase III as compared to phase I and II. Concomitantly there was increase in plasma neuropeptide Y levels from 0.303 (+/- 0.004) ng/ml to 1.211 (+/- 0. 27) ng/ml (p < 0.001) in Phase II and decrease in Phase III. The decrease in plasma leptin levels and increase in neuropeptide Y levels in Phase II may be responsible for increase in appetite and gain in body weight at Antarctica.

Adult↗
PubMed2005

Effect of hypobaric hypoxia on visual evoked potential at high altitude.

The effect of hypobaric hypoxia on visual evoked potential (VEP) was studied in 27 male volunteers at sea level (SL), during the 1st and 3rd weeks of their stay at high altitude (HA) of 3,500 m and in the 1st week of their return to the sea level (RSL). Exposure to high altitude (HA) led to significant changes in VEP. The N1 wave latency of both right and left eye was significantly increased (P<0.05) during 3rd week of stay at the altitude which persisted even after the return to the sea level. The latency of P1 wave of both right and left eye was higher in 3rd week at high altitude but not significant statistically. But the delay in P1 latency persisted in 1st week of their return to sea level which was significant (p<0.05) statistically as compared to sea level. The latency of N2 wave was significantly decreased (P<0.05) during the 1st week of stay at HA and returned back to basal value in the 3rd week of stay at HA in both right and left eye. However, the changes observed in NPN complex in terms of wave latencies were within the physiological limits. The amplitude of wave N1-P1 of both the right and left eye did not show any change. The changes observed reflect the process of acclimatisation to 3500m high altitude.

Adult↗
PubMed2004

Effect of chronic hypobaric hypoxia on components of the human event related potential.

BACKGROUND & OBJECTIVES: Induction to high altitude (HA) leads to deterioration in cognitive functions. The event related potentials (ERPs) like P300 are reported to be affected by hypoxia and bring about impairments in cognitive performance. The aim of the study was to investigate the effect of hypobaric hypoxia on event related potentials at two different altitudes i.e., 3200 m (HA I) and 4300 m (HA II) in ascending order to see how ERPs change with increasing altitude. METHODS: The study was carried out on 20 healthy male volunteers at sea level (SL) and thereafter at high altitude (HA) in Eastern Himalayas and on return to sea level (RSL). The P300 was recorded by using standard auditory odd ball paradigm with compact -4 (Nicolet, USA). RESULTS: The N1, N2 and P2 latencies were not significantly affected at HA I and HA II in comparison with SL indicating no effect of hypobaric hypoxia on sensory conduction. However, at HA II, most of the subjects showed an increase in latency of P3 component reflecting sensory discrimination and delay in evaluation process at 4300 m. At HA I, only 10 out of 20 subjects showed an increase in P3 wave latency and 3 did not show any change in N2-P3 components. INTERPRETATION & CONCLUSION: The results of the present study showed an increase in P300 wave latency at 3200 and 4300 m of high altitude. The observations suggest that hypoxia causes slowing of the signal processing at 4300 m, and magnitudes of the effects are altitude dependent with higher level of decline observed with increasing altitude.

Adult↗
PubMed2004

Effect of high altitude on human auditory brainstem responses.

The effect of hypobaric hypoxia on Brain Stem Auditory evoked potentials (BAERs) were studied. BAERs were recorded in 30 volunteers at sea level (SL) and then at high altitude (HA) of 3200 m (HA I) and 4300 m (HA II) in Eastern Himalayas and on return to sea level (RSL). The BAERs were recorded using Nicolet Compact - 4 (USA) in response to monaural auditory stimuli consisting of clicks of 100 ps square pulse at a rate of 15/sec. The BAERs were recorded on day 4 of their stay at 3200 m and 4300 m respectively. Findings indicated an increase in absolute peak latencies of wave V at 3200 m, which was statistically significant. On further ascent to 4300 m there was an increase in absolute peak latencies of wave I and III indicating delay in sensory conduction at the medullo-pontine auditory pathways.

Adult↗
PubMed2004

Changes in visual evoked potentials on acute induction to high altitude.

BACKGROUND & OBJECTIVES: Induction to high altitude leads to altered central nervous system (CNS) functions induced by hypobaric hypoxia. The sensory systems like visual and auditory systems are reported to be affected by hypoxia. The present study was undertaken to assess the effects of hypobaric hypoxia on visual evoked potentials (VEPs) at 3200 m and 4300 m. METHODS: The VEP of 30 human volunteers were recorded at sea level (SL) and then at high altitude (HA) of 3200 m (HA I) and 4300 m (HA II) in eastern Himalayas and on return to sea level (RSL). The absolute latencies and amplitude of positive and negative waves were recorded. RESULTS: High altitude of 3200 m did not alter the latency of major wave N1, P1 and N2 of the VEPs. At HA II (4300 m), there was a statistically significant increase (P < 0.01) in the latency of NI wave as compared to the SL value and HA I (3200 m) in both left and right eye. There was a slight increase in latenty of P1 wave in both left and right eye at HA II. INTERPRETATION & CONCLUSION: From these results it may be concluded that induction to HA causes increase in latency of N1 wave at 4300 m which is still within physiological limits. This increase in wave latency of N1 wave in both eyes may be due to synaptic delay and/or altered neuronal processing at HA.

Adult↗
PubMed2003

Effect of vitamin C and E supplementation in modulating the peripheral nerve conduction following cold exposure in humans.

Exposure to an extremely cold environment without proper protection leading to hypothermia is an emergency, one of the several complications of which is impairment in nerve conduction. Our previous work in the rat model has shown the beneficial effect of vitamin C in modulating the effect of hypothermia on nerve conduction. The present study aimed to evaluate the effect of vitamins C and E, administered alone or in combination, in modulating the effect of mild hypothermia on human ulnar nerve conduction. The study was carried out on 26 volunteers divided into three groups: group I received vitamin C supplementation (2000 mg/day in a single dose and 1,000 mg/day for the next 6 days), group II received vitamins C and E in combination (1,000 mg and 800 mg respectively in a single dose and 500 mg and 400 mg respectively for the next 6 days) and group III received vitamin E (800 mg in a single dose and the same for the next 6 days). The recordings were carried out before and after single and weekly supplementation in each group. There was a fall in ulnar nerve conduction velocity with a reduction in the oral temperature of 2-2.5 degrees C. Vitamin C administered alone and in combination with vitamin E reduced the fall in ulnar nerve conduction velocity. Prior supplementation with vitamin C and E could help ameliorate the impairment in human ulnar nerve conduction due to hypothermia.

Adult↗
PubMed2003

Isolation and insecticidal activity of mellamide from Aspergillus melleus.

Mellamide, a novel indole amide, was isolated from a fermentation of Aspergillus melleus using silica gel and high-performance liquid chromatographic methods. This allowed its separation from three known antiparasitic compounds (ochratoxin A, viomellin and xanthomegnin) also present in the potent extract. The structure was elucidated by (1)H, (13)C, COSY, DEPT, HMQC and HMBC NMR experiments. HR-FTMS aided in the molecular weight and formula determination. Mellamide showed in vitro insecticidal activity in bioassays against larvae of Lucilia sericata and Aedes egypti with LD(90) of 1,000 and 50 micro g/ml, respectively.

Amides↗
PubMed2003

Effect of high altitude (HA) on event related brain potentials.

Event Related brain potentials (ERPs) were recorded in 15 subjects using standard auditory odd ball paradigm, in which subjects were presented a sequence of two distinguishable sound stimuli of that occurred frequently (frequently (frequent stimulus-non target) and the other infrequently (rare stimulus-target). These recordings were made at sea level (SL) and then the subjects were air lifted to 3500 m altitude (HA), where they stayed for 3 weeks. Their ERPs were recorded during the first and third week of stay at HA and on return to sea level (RSL). Data indicated impairment in cognitive function as a result of exposure to HA as depicted by increase in the latency of P3 which was significant during the 1st week of stay at HA compared to sea level. The P3 wave latency during the 3rd week of stay at HA showed an increase compared to SL but was not statistically significant. From the results it may be concluded that high altitude hypoxia induced slow processing of stimulus evaluation, may be responsible for increase in P3 latency. The difference in the latent period of P3 waves during the first and third week of stay at HA may be due to continuous stay at HA which might lead to the time dependent adaptive processes occurring with increasing duration of exposure to HA which may induce learning effects.

Acoustic Stimulation↗
PubMed2002

Effect of a carbohydrate supplement on feeding behaviour and exercise in rats exposed to hypobaric hypoxia.

The effect of a carbohydrate supplement, offered as a diet option, on feeding behaviour, body weight gain, and endurance exercise was studied in rats exposed to hypobaric hypoxia. Male albino rats (n = 35) were randomly divided into 5 groups; hypoxic supplemented and control groups; normoxic supplemented and control groups, and an untreated control group. After treadmill training for 5 days, the hypoxic groups were exposed to simulated high altitude equivalent to 6960 m for 18 days continuously. Food and water intakes, body weight and endurance exercise were recorded before and during the exposure period. Blood glucose, insulin, muscle and liver glycogen were assayed at the end of the exposure period. Hypobaric hypoxia resulted in a significant decrease in food and water intake, and body weight, and reduced endurance exercise capacity compared to the basal and normoxic group values. The carbohydrate supplement did not ameliorate the hypoxia-induced loss in body weight, but however, significantly delayed the onset of fatigue during exercise in the supplemented rats compared to the hypoxic control group.

Altitude↗
PubMed2001

Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure-activity relationships of 2-methoxystypandrone and its analogues.

2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC(50) value of 4.6 microM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% overall yield using a Diels-Alder approach. Several analogues of this compound were prepared. Isolation, synthesis and HRV 3C-protease structure-activity relationships of these compounds have been described.

3C Viral Proteases↗
PubMed2001

Structure, histone deacetylase, and antiprotozoal activities of apicidins B and C, congeners of apicidin with proline and valine substitutions.

[structure: see text]. Isolation and structure elucidation of two novel cyclic tetrapeptides that show a variety of potent antiprotozoal activities by reversibly inhibiting HDAC have been reported. These are the new members of a unique family of cyclic tetrapeptides that do not require the electrophilic alpha-epoxyketone moiety of HC-toxin, trapoxin A, or chlamydocin for their potent activities against HDAC and the malarial parasite.

Amino Acid Substitution↗
PubMed2001

Synthesis of natural flutimide and analogous fully substituted pyrazine-2,6-diones, endonuclease inhibitors of influenza virus.

Flutimide, a fully substituted 1-hydroxy-3H-pyrazine-2,6-dione, is a fungal metabolite isolated from a new species of Delitschia cofertaspora. It has been shown to selectively inhibit cap-dependent endonuclease activity of influenza virus A. The inhibition of this activity is a target for the potential development of a therapeutic agent to treat influenza infections. A convergent total synthesis of flutimide starting from L-leucine has been described. The synthetic methodology has been extended to include the synthesis of specifically designed aromatic analogues of flutimide, some of which exhibited greater than 7-fold improvement in activity. The most potent compounds were those with p-fluorobenzylidene or p-methoxybenzylidene substitutions at C-5 of 3H-pyrazine-2,6-dione and showed IC(50) values of 0.9 and 0.8 microM, respectively. The details of the rationale for the synthetic design, syntheses, and biological activities of these analogues are described.

Antiviral Agents↗
PubMed2001

Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes.

B cell linker protein (BLNK) is a SLP-76-related adaptor protein essential for signal transduction from the BCR. To identify components of BLNK-associated signaling pathways, we performed a phosphorylation-dependent yeast two-hybrid analysis using BLNK probes. Here we report that the serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1), which is activated upon antigen-receptor stimulation and which has been implicated in the regulation of MAP kinase pathways, interacts physically and functionally with BLNK in B cells and with SLP-76 in T cells. This interaction requires Tyr(379) of HPK1 and the Src homology 2 (SH2) domain of BLNK/SLP-76. Via homology modeling, we defined a consensus binding site within ligands for SLP family SH2 domains. We further demonstrate that the SH2 domain of SLP-76 participates in the regulation of AP-1 and NFAT activation in response to T cell receptor (TCR) stimulation and that HPK1 inhibits AP-1 activation in a manner partially dependent on its interaction with SLP-76. Our data are consistent with a model in which full activation of HPK1 requires its own phosphorylation on tyrosine and subsequent interaction with adaptors of the SLP family, providing a mechanistic basis for the integration of this kinase into antigen receptor signaling cascades.

Adaptor Proteins, Signal Transducing↗