Ascent to high-altitude results in decreased inspired partial pressure of oxygen because of a decrease in barometric pressure. Altitude acclimatization requires physiological and metabolic changes to improve tolerance to altitude hypoxia. Cellular response to hypoxia results into changes in the profile of gene expression and the present study explored the same in murine model. Liver being the largest metabolic organ, the molecular details of acute hypobaric hypoxia (AHH) induced transcriptional changes in the tissue were investigated. Swiss albino mice were exposed to hypobaric hypoxia (∼426mmHg) in a decompression chamber and cDNA microarray was used to study the transcriptional profile in liver. Notably, by the tenth hour several of the genes involved in sterol metabolism such as SREBF1, INSIG1, HMGCS1, FDFT1, SQLE, and HSD3B4 were downregulated more than 2-fold suggesting that AHH suppresses sterol biosynthesis in the liver. Real-time PCR helped validate the downregulation of SREBF1, HMGCS1, FDFT1, and HSD3B4 genes. However, no significant change was observed in the serum cholesterol levels throughout the AHH exposure. The findings are indicative of transcriptional downregulation of SREBP target genes as a part of acclimatization response to hypoxia. The study highlights the significance of SREBP in the regulation of sterol metabolism under the acute hypoxic response.

In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C)–hypoxia (428 mmHg)–restraint (C-H-R) animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C) during C-H-R exposure and its recovery to Trec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining Trec 23°C and Trec 37°C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining Trec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA), blood lactate dehydrogenase (LDH) and a decrease in blood catalase (CAT) and plasma testosterone levels. On recovery (Trec 37°C) of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD), CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2%) on attaining Trec 23°C during C-H-R exposure and on recovery to Trec 37°C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.

People who visit high-altitude areas are exposed to a stressful environment and a good percentage of them suffer from high-altitude-induced diseases, including systemic hypertension. Identification of genetic markers for high-altitude-induced diseases would help to reduce the rate of morbidity/mortality from such diseases. The development of systemic hypertension on exposure to high altitude (3,500 m) for 30 days in otherwise normotensive natives of low-altitudes was investigated. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotypes and renin-angiotensin-aldosterone system were simultaneously studied. In the hypertensives during their stay at high altitude, the ACE D allele frequency was significantly higher than in the normotensives (0.67 versus 0.32 χ21 = 10.6, P < 0.05). In the normotensives during their stay at high altitude, there was no significant increase in plasma aldosterone levels despite increased plasma renin activity. Results of the present study suggest that environmental changes and pre-existing genetic factors, namely the ACE D allele, might be two of the factors predisposing natives of low altitudes to systemic hypertension, a polygenic disease, at high altitude.

Per cent oxygen saturation of arterial haemoglobin levels (SaO 2 ), a measure of hypoxemia has been analysed in the permanent residents of Ladakh. The population recognized as high-altitude controls (HAC) and high-altitudemonks (HAM), resided at the same altitude of 3600 m but differed in their routines. SaO 2 was measured with a Finger-Pulse Oximeter. The HAM had 3.08% higher SaO 2 (P < 0.001) compared to the HAC, with mean SaO 2 of 91.8 ′ 6.1% and 89.0 ′ 2.6%, respectively. Furthermore, the younger HAM also revealed an elevation of 4.55% SaO 2 than the HAC of identical age (P < 0.001). The HAM, who are less hypoxemic than their counterparts are physically more active, which may be a selective advantage in the extreme environment of higher altitudes.

Angiotensin converting enzyme (ACE) gene I/D polymorphism has been associated with high altitude (HA) disorders as well as physical performance. We, however, envisage that the polymorphism may be associated with adaptation to the hypobaric hypoxia of altitude, thus facilitating physical performance. For this purpose, three unrelated adult male groups, namely (1) the Ladakhis (HLs), who reside at and above a height of 3600 m, (2) lowlanders, who migrated to Ladakh (MLLs), and (3) resident lowlanders (LLs), have been investigated. The HLs had significantly (p & 0.001) greater numbers of the II homozygotes and the ID heterozygotes than the DD homozygotes, the genotype distribution being 0.46, 0.43 and 0.11 for II, ID and DD genotypes respectively. The MLLs comprised 60% II homozygotes, which was higher (p & 0.001) than the HLs (46%). In the LLs, the heterozygotes were greater (p & 0.001) in number than the II and DD homozygotes. The I allele frequency was 0.72 in the MLLs, 0.67 in the HLs and 0.55 in the LLs. Polymorphism study suggested that the II genotype could be associated with altitude adaptation, which might influence physical efficiency.

The isoflavanoids 7-hydroxyisoflavanone 4a, 7-hydroxy-3', 4'-dimethoxyisoflavanone 4b, 5, 7-dihydroxy-3', 4'-dimethoxylsoflavanone 4c, 5, 7-dihydroxy-2'-methoxyisoflavanone 4d, 5, 7-dihydroxy-3', 4'-dimethoxyisoflavanone 4e and 5, 7-dihydroxy-4'-methoxyisoflavanone 4f have been conveniently prepared by using paraforomaldehyde and diethylamine as a base.

Conference Abstract| October 01 2000 Angiotensin-Converting Enzyme Gene Polymorphism in Relation to High Altitude Physical Performance M. A. Qadar Pasha; M. A. Qadar Pasha 1Functional Genomics unit, Centre for Biochemical Technology, Mall road, Delhi-110007, India Search for other works by this author on: This Site PubMed Google Scholar A. P. Khan; A. P. Khan 1Functional Genomics unit, Centre for Biochemical Technology, Mall road, Delhi-110007, India Search for other works by this author on: This Site PubMed Google Scholar R. Kumar; R. Kumar *Biochemistry Department, Defence Institute of Physiology and Allied Sciences, Delhi-110054, India Search for other works by this author on: This Site PubMed Google Scholar S. K. Grover; S. K. Grover *Biochemistry Department, Defence Institute of Physiology and Allied Sciences, Delhi-110054, India Search for other works by this author on: This Site PubMed Google Scholar S. K. Brahmachari S. K. Brahmachari 1Functional Genomics unit, Centre for Biochemical Technology, Mall road, Delhi-110007, India Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (2000) 28 (5): A230. https://doi.org/10.1042/bst028a230 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation M. A. Qadar Pasha, A. P. Khan, R. Kumar, S. K. Grover, S. K. Brahmachari; Angiotensin-Converting Enzyme Gene Polymorphism in Relation to High Altitude Physical Performance. Biochem Soc Trans 1 October 2000; 28 (5): A230. doi: https://doi.org/10.1042/bst028a230 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2000 Biochemical Society2000 Article PDF first page preview Close Modal You do not currently have access to this content.

OBJECTIVE:A composite Indian herbal preparation-I (CIHP-I) containing ingredients derived from 7 different plants and asphalt was tested for its adaptogenic activity and its mechanism of action was investigated.DESIGN:CIHP-I was tested using the cold-hypoxia-restraint (C-H-R) animal model in which the restrained rats were exposed to 5 degrees C at 428 mm Hg atmospheric pressure. Rectal temperature (Trec) of the rats was continuously monitored during the exposure and the recovery periods. The time for fall of Trec to 23 degrees C and its recovery to 37 degrees C were used as indices of endurance and the adaptogenic activity. Carbohydrate and lipid parameters were investigated to find out the nature of fuel being used during thermogenesis.RESULTS:After 12 weeks of administration of an oral dose of 7.5 mg/kg(-1)/day(-1), CIHP-I was found to possess significant adaptogenic activity. CIHP-I helped improve resistance to C-H-R induced hypothermia (Trec 23 degrees C) in animals by increased mobilization of free fatty acids (FFA) from adipose tissue. Blood glucose and muscle glycogen levels were maintained. CIHP-I treatment restricted the release of creatine phosphokinase (CPK) into the circulation during C-H-R exposure.CONCLUSIONS:The results suggested that CIHP-I is a strong adaptogen. It improved cold resistance during C-H-R exposure and enhanced recovery from hypothermia. The energy-dependent cell membrane permeability was maintained. Stored lipids were mobilised and possibly used for thermogenesis in preference to carbohydrates.

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.

Benzylation of chelated phenolic groups in different classes of polyphenolics 1-5 has been carried out, in quantitative yields efficiently by making use of tetra-n-butylammonium iodide as a catalyst in the presence of benzyl chloride-acetone-potassium carbonate. The procedure for working up the reaction mixture has also been improved by avoiding the step involving steam distillation required for removal of benzyl chloride after the reaction is over.

Hypoxia results in body weight loss due to anorexia and hypophagia and reduced human performance. The present study was undertaken to evaluate the role of oral glutamate administration with food and water in improvement in hypoxic tolerance, if any. The placebo controlled study revealed that supplementation of optimal dose of glutamate (Glu) promoted hypoxic tolerance in male Sprague Dawley Albino rats fed one dose daily for 5 days and exposed to continuous intermittent hypoxia of 6 hrs per day at 10,668m in an animal exposure chamber. Effect of varying dose of Glu on body weight (bw),food intake and water uptake were studied which revealed the optimal dose of Glu to be 27mgKg bw. Oral feeding of Glu resulted in improved tolerance of combined stress of cold and hypoxia as measured by fall in rectal temperature from 37’C to 23’C and faster rewarming. It enhanced 5.8 times hypoxic tolerance 36% bw gain and 24% food intake in hypoxia possibly by acting as a conditionally essential amino acid under hypoxia.

2'-Hydroxychalcones 1 possessing different substitution patterns in rings A and B, have been found to undergo efficient isomerization to the corresponding flavanones 2 when heated in ethanol with hydrochloric acid and tetra-n-butylammonium iodide.

Substances which enhance endurance for physical and mental work and increase non-specific resistance to stress during a prolonged stay in physiologically adverse habitats are called 'adaptogens'. Panax ginseng is well known for its anti-stress and adaptogenic properties. In the present study, adaptogenic activity by the intake of a herbo-vitamin-mineral preparation (HVMP) containing P. ginseng and multivitamin-mineral preparation (MVMP) was evaluated using the cold-hypoxia-restrained (C-H-R) animal model. The aim was to determine whether the cold tolerance and recovery from acute hypothermia mediated by P. ginseng was modified by simultaneous intake of additional vitamins and minerals. Results suggest that the adaptogenic effect of HVMP was more or less the sum total of its two components P. ginseng and MVMP. In HVMP, P. ginseng was found to be effective for developing resistance to cooling and MVMP helped in stimulating faster recovery from acute hypothermia.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

o-Hydroxy-omega-cinnamylideneacetophenones (1) have been found to undergo oxidative cyclization to the corresponding 2-styrylchromones (2) in satisfactory yields by heating them with potassium iodate in dimethyl sulphoxide.

2'-Hydroxychalcones have been found to undergo smooth conversion to flavones when heated with sodium periodate in dimethyl sulphoxide.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Chalcones have been found to undergo facile reduction on treatment with sodium borohydride-nickel chloride system in dioxan-methanol medium to afford dihydrochalcones.