Regression of coronary atherosclerosis through healthy lifestyle in coronary artery disease patients--Mount Abu Open Heart Trial.

AIMS: To evaluate the efficacy of a unique healthy and happy lifestyle (HLS) program in regression of coronary atherosclerosis and reduction in cardiac events in an open trial. METHODS: One hundred and twenty three angiographically documented moderate to severe coronary artery disease (CAD) patients were administered HLS comprising of low-fat, high-fiber vegetarian diet, moderate aerobic exercise and stress-management through Rajyoga meditation. Its most salient feature was training in self-responsibility (heal+thy) and self-empowerment through inner-self consciousness (swasth; swa=innerself, sth=consciousness) approach using Rajyoga meditation. Following a seven day in-house sojourn, patients were invited for six month follow-up for reassessment and advanced training. At the end of two years, all patients were asked to undergo repeat angiography. RESULTS: Three hundred and sixty coronary lesions were analysed by two independent angiographers. In CAD patients with most adherence, percent diameter stenosis regressed by 18.23 +/- 12.04 absolute percentage points. 91% patients showed a trend towards regression and 51.4% lesions regressed by more than 10 absolute percentage points. The cardiac events in coronary artery disease patients were: 11 in most adherence, and 38 in least adherence over a follow-up period of 6.48 yrs. (risk ratio; most vs least adherence: 4.32; 95% CI: 1.69-11.705; P < 0.002). CONCLUSION: Overall healthy changes in cardiovascular, metabolic and psychological parameters, decline in absolute percent diameter coronary stenosis and cardiac events in patients of CAD were closely related to HLS adherence. However, more than 50% adherence is essential to achieve a significant change.

Effect of high-altitude hypoxia on feeding responses and hedonic matrix in rats.

Albino male rats (n = 78) were exposed to a simulated high altitude (HA) equivalent to 7,620 m for 6 h daily, contiguously for a period of 21 days, to study their feeding behavior and gustatory responses. Their food, water intake, and body weight were recorded daily, and blood sugar and blood insulin were estimated once a week. All the parameters were recorded for a period of 3 wk each before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intakes and body weight and mild hyperglycemia and hyperinsulinemia during hypoxic exposure. The 1-h single-bottle taste solution test showed a preference for sweet solutions (13% glucose and 0.2% saccharine) over citric acid (0.16%), sodium chloride (0.9%), and quinine sulfate (0.001%) during exposure to simulated HA. The 1-h two-bottle test containing glucose (calories plus taste) and saccharine (taste but no calories) administration showed a preference for the glucose solution over the saccharine solution. The trend of the 1-h intake of all test solutions also showed a reversal to preexposure levels after termination of HA hypoxia. It would appear that high-altitude stress influences food intake in a manner that sensory cues (e.g., preference for sweet substances) become more important.

Acclimatization at high altitude in gradual and acute induction.

The study assessed physiological responses to induction to high altitude first to 3,500 m and then to 4,200 m and compared the time course of altitude acclimatization in two groups of male volunteers. The acutely inducted group was transported by aircraft (AI) to 3,500 m in 1 h, whereas the gradually inducted group was transported by road (RI) in 4 days. Baseline recordings of basal cardiovascular, respiratory, and blood gas variables were monitored at sea level as well as at 3,500 m on days 1, 3, 5, and 7. Blood gases were measured on day 10 also. After 15 days at 3,500 m, the subjects were inducted to 4,200 m by road, and measurements were repeated on days 1, 3, and 5, except blood gas variables, which were done on day 10 only. Acute mountain sickness symptoms were recorded throughout. The responses of RI were stable by day 3 of induction at 3,500 m, whereas it took 5 days for AI. Four days in transit for RI appear equivalent to 2 days at 3,500 m for AI. Acclimatization schedules of 3 and 5 days, respectively, for RI and AI are essential to avoid malacclimatization and/or high-altitude illness. Both groups took 3 days at 4,200 m to attain stability for achieving acclimatization.

Acute toxicity of methyl isocyanate, administered subcutaneously in rabbits: changes in physiological, clinico-chemical and histological parameters.

Subcutaneous administration of methyl isocyanate (MIC) in 0.5 LD50 and 1 LD50 doses in female rabbits resulted in significant changes in physiological, clinico-chemical and histological parameters. There was a fall in arterial blood pressure and cardioacceleration in both the 0.5 LD50 and 1 LD50 groups, while the respiration showed a differential response in these groups with the former showing hyperpnoea and the latter showing respiratory inhibition. A significant increase in the arterial blood lactic acid, lactate/pyruvate ratio and 2,3-diphosphoglycerate levels, and the significant changes in acid-base status of both arterial and venous blood indicated tissue hypoxia of a stagnant type. Histopathological observations revealed a mild to moderate degree of congestion, focal lymphocytic infiltrations and necrosis in all visceral organs examined. These findings suggest that acute toxicity of MIC in vivo may be mediated by its effects on vascular beds.

Immunomodulatory effects of agents of plant origin.

The immunomodulatory properties of amla (Emblica officinalis) and shankhpushpi (Evolvulus alsinoides) were evaluated in adjuvant induced arthritic (AIA) rat model. Injecting Complete Freund's Adjuvant (CFA) in right hind paw of the animals induced inflammation. The crude extracts of both the herbs were administered intraperitonially following a repeated treatment profile. The anti-inflammatory response of both the extracts was determined by lymphocyte proliferation activity and histopathological severity of synovial hyperplasia. Both the extracts showed a marked reduction in inflammation and edema. At cellular level immunosuppression occurred during the early phase of the disease. There was mild synovial hyperplasia and infiltration of few mononuclear cells in amla or shankhpushpi treated animals. The induction of nitric oxide synthase (NOS) was significantly decreased in treated animals as compared to controls. These observations suggest that both the herbal extracts caused immunosuppression in AIA rats, indicating that they may provide an alternative approach to the treatment of arthritis.

Mechanism of action of NIM-76: a novel vaginal contraceptive from neem oil.

The present study was undertaken to elucidate the mechanism of spermicidal action of NIM-76, a fraction isolated from neem oil. The spermicidal activity of NIM-76 was confirmed using a fluorescent staining technique. NIM-76 was found to affect the motility of the sperm in a dose-dependent manner. Supplementation of pentoxifylline, which is known to enhance the motility of the sperm, could not prevent the spermicidal action of NIM-76. There was a gradual leakage of cytosolic LDH from the sperm in the presence of NIM-76. Electron microscopic studies revealed the formation of pores and vesicles over the sperm head, indicating the damage to the cell membrane. Membrane fluidization studies did not reveal any significant change in the fluidity of sperm cell membrane structure.

PIP: Neem oil, an extract of a native plant of India, has been demonstrated to have anti-fertility, anti-implantation, and abortifacient properties. An active fraction, termed NIM-76, was extracted that eliminates its abortifacient properties while retaining spermicidal activity. This fraction kills all human sperm in vitro in under 20 seconds at a concentration of 25 mg/ml. With increases in NIM-76 concentrations from 10 to 1000 mcg/ml, there was a linear decrease in percentages of motile as well as progressively motile sperm with time; also recorded were decreases in percentages of rapid, medium, and slow moving sperm, mean track speed, progressive velocity, mean linearity, and lateral head displacement and an increase in the percentage of static sperm. Electron microscopy revealed the formation of pores and vesicles over the sperm head, indicating damage to the cell membrane. Membrane fluidization studies did not reveal any significant change in the fluidity of sperm cell membrane structure. Since calcium supplementation did not relieve the sperm from the spermicidal action, it was determined that NIM-76 does not cause any depletion of intracellular calcium. The capability of NIM-76 to selectively kill sperm without affecting normal cells makes it a highly desirable potential vaginal contraceptive agent.

In vivo experimental model to evaluate the insect repellent N-N, diethylphenylacetamide in Periplaneta americana Linn.

The responsiveness of insect antennae to bornyl acetate (BA), a sex pheromone mimic and N,N-diethyl phenylacetamide (DEPA), a multi-insect repellent has been studied. Electrical activity from the antennal lobe was quantified to observe the alterations in power and frequency spectrum in P. americana Linn. following exposure to these chemicals. Two distinct patterns of responses were exhibited on exposure to BA and DEPA, the former producing a marked excitation and the latter inhibition of electrical discharge during the exposure to these compounds at a concentration of 200 micrograms.

Role of xanthinol nicotinate in the revival of monkeys subjected to acute haemorrhagic shock.

The therapeutic potential of xanthinol nicotinate in the revival of anaesthetised monkeys subjected to acute blood loss was investigated. The arterial pressure was lowered to 40 +/- 5 mmHg by rapid arterial bleeding and was maintained at this level for 2 h. Shed blood was then returned through infusion, to the animals. Animals alive at the end of 72 h observation period were considered as survivors. The test drug was infused 1/2 h prior to and 1/2 h, 1 h, 1 1/2 h and 2 h after the onset of oligaemic hypotension. The animals which received normal saline instead of test drug were treated as control. The physiological and biochemical parameters recorded prior to and after the onset of oligaemic hypotension were heart rate, pulse pressure, electrocardiogram, electroencephalogram (EEG), lactic acid, creatine phosphokinase, urea and glucose. The results showed tachycardia, narrowing of pulse pressure, depression of ST segment with occasional T inversion, slowing of EEG with increase in amplitude, rise in blood lactic acid, creatine phosphokinase, urea and glucose. The magnitude of these responses were proportional to the duration and severity of shock. These changes were markedly attenuated in the drug treated group. Enhancement of survival was observed in drug treated groups as compared to control. It was 10 per cent in control as against 60, 86, 71, 57 and 50 per cent in the groups which received the test drug 1/2 h prior to and 1/2 h, 1 h, 1 1/2 h and 2 h after the onset of oligaemic hypotension. It is concluded that the beneficial effect of the drug in the revival of monkeys subjected to acute haemorrhagic shock may be due to better maintenance of tissue perfusion.

Seizure susceptibility & intra rectal sodium valproate induced recovery in developing undernourished rats.

The seizure threshold and therapeutic potential of intrarectal sodium valproate were studied in young developing normal and undernourished rats, using the penicillin model. Undernourished rats were highly susceptible to seizure discharge. They exhibited generalised electrocortical inhibition and repeated episodes of epileptic discharges even after temporary neuronal recovery. Delayed spontaneous and drug induced neuronal recovery, low spike frequency and amplitude (P less than 0.001) reduced background EEG and marked electrocortical silence in response to intrarectal (25 mg/kg) sodium valproate treatment, was observed in the undernourished animals. Rehabilitated animals exhibited partial neuronal recovery which was related to the improvement in body weight. Analysis of spike frequency, spike amplitude and neuronal recovery time showed that both normal and undernourished animals behaved in a similar fashion at lower doses of penicillin (2.5 to 15 IU). Significant differences in the electrophysiological parameters were observed between the two groups at higher doses of penicillin (20 to 30 IU).

Experimental studies on the treatment of frostbite in rats.

The effect of treatment by high dose of vitamin C, rapid rewarming by 37 degrees C water alone and with vitamin C, rapid rewarming by 37 degrees C decoction of Indian black tea alone and with vitamin C for experimentally produced frostbite was evaluated in 6 groups (25 each) of rats. Frostbite was produced experimentally in the hind limbs by exposing the animals at -15 degrees C for 1h using the harness technique. The degree of injury was assessed and classified on the basis of tissue necrosis at the end of 15 days. Administration of high dose of vitamin C for prolonged period and rapid rewarming at 37 degrees C water bath immediately after cold exposure apparently reduced the tissue damage. High dose of vitamin C therapy preceded by rapid rewarming in plain water showed additional benefit. Rapid rewarming in decoction of Indian tea resulted in identical beneficial effect. The degree of tissue preservation was highest with rapid rewarming in tea decoction followed by high dose of vitamin C.

Kainic acid induced epileptogenesis in developing normal & undernourished rats--a computerised EEG analysis.

Experimental epilepsy was induced in developing normal, undernourished and subsequently rehabilitated rats by locally injecting graded doses of Kainic acid (KA) in the right frontal cortex. Frequency and power spectral analysis of EEG was carried out to assess the progressive changes in EEG during KA-epileptogenesis. Undernourished animals were highly susceptible to seizure discharge. They exhibited generalized tonic-clonic discharge and had episodes of clinical seizures even after temporary neuronal recovery. Increase in power of delta, theta and decrease in alpha power was observed in the compressed spectral array (CSA) of undernourished animals. Delayed neuronal recovery with reduced background EEG and marked electrosilence in response to intra-rectal sodium valproate was observed in undernourished animals. Rehabilitated animals exhibited partial recovery which was related to the body weight gain. Spike frequency, spike amplitude and neuronal recovery time were not significantly differet between normal and undernourished animals at lower doses of KA (7.5-60 ng) whereas at higher doses (120-500 ng) marked differences were observed in these parameters. In KA treated undernourished rats 3H-glycine incorporation was significantly higher than normal in the hippocampus and spinal cord and lower in the cerebellum.

Auditory evoked response in patients of diabetes mellitus.

Brainstem auditory evoked response (BAER) and the mid latency response (MLR) were recorded in 25 diabetic men and compared with a group of 25 control subjects. The threshold of hearing was higher (P less than 0.001) in the patients. The BAER peak latencies were also significantly prolonged in both the ears; however, the degree of prolongation was more prominent in the right ear. The interpeak latencies of waves I-III were also prolonged (P less than 0.01) in the left ear, with non significant increase noticed in the right ear also. The wave V amplitude was lower (P less than 0.05) in diabetics. The MLR, on the other hand, was not affected in patients. These findings suggest functional impairment in the auditory pathway in patients of diabetes mellitus.

Aerobic capacity & perceived exertion after practice of Hatha yogic exercises.

BACKGROUND & OBJECTIVES: Reports on the effect of yogic exercises on aerobic capacity are few. There is also no literature available on the effect of yogic exercise on perceived exertion (PE) after maximal exercise. In this study the effect of training in Hatha yogic exercises on aerobic capacity and PE after maximal exercise was observed. METHODS: Forty men from the Indian army (aged 19-23 yr) were administered maximal exercise on a bicycle ergometer in a graded work load protocol. The oxygen consumption, carbon dioxide output, pulmonary ventilation, respiratory rate, heart rate (HR) etc., at maximal exercise and PE score immediately thereafter were recorded. The subjects were divided into two equal groups. Twelve subjects dropped out during the course of study. One group (yoga, n = 17) practiced Hatha yogic exercises for 1 h every morning (6 days in a week) for six months. The other group (PT, n = 11) underwent conventional physical exercise training during the same period. Both groups participated daily in different games for 1 h in the afternoon. In the 7th month, tests for maximal oxygen consumption (VO2Max) and PE were repeated on both groups of subjects. RESULTS: Absolute value of VO2Max increased significantly (P < 0.05) in the yoga group after 6 months of training. The PE score after maximal exercise decreased significantly (P < 0.001) in the yoga group after 6 months but the PT group showed no change. INTERPRETATION & CONCLUSION: The practice of Hatha yogic exercises along with games helps to improve aerobic capacity like the practice of conventional exercises (PT) along with games. The yoga group performed better than the PT group in terms of lower PE after exhaustive exercise.

Immediate treatment of frostbite using rapid rewarming in tea decoction followed by combined therapy of pentoxifylline, aspirin & vitamin C.

BACKGROUND & OBJECTIVES: Frostbite, the severest form of cold injury is a serious medical problem for our Armed Forces operating in the snow bound areas at high altitude. Effects of treatment by rapid rewarming in tea decoction followed by combined therapy of pentoxifylline, aspirin and vitamin C were evaluated in amelioration of tissue damage due to experimentally induced frostbite in rats. METHODS: Experiments were conducted in 2 groups (25 each) of albino rats (control i.e., untreated and experimental i.e., treated). Frostbite was produced experimentally in all the animals by exposing one of the hind limbs at -12 +/- 1 degree C with wind flow 25-30 lit/min for 30 min in a freezing-machine, with simultaneous recordings of rectal and ambient temperatures. The degree of tissue damage was assessed after 10 days. Following cold exposure, neither external thawing nor any medication was given to the animals of the control group; while the exposed limb of the experimental animals was rewarmed in tea decoction maintained at 37-39 degrees C for 30 min immediately after cold exposure, with simultaneous oral ingestion of warm tea decoction. These animals were also given pentoxifylline (40 mg/kg), aspirin (5 mg/kg) and vitamin C (50 mg/kg) twice daily orally for the next 7 days. RESULTS: In the control group, 68 per cent animals suffered from severe (56%) to very severe (12%) frostbite, while the remaining 32 per cent had moderate frostbite. No animals of this group could escape injury or suffered anything less than moderate frostbite; whereas 52 per cent of experimental animals escaped injury (no frostbite) and 32 and 16 per cent suffered only with primary and moderate degree of injury, respectively. None from this group suffered from severe or very severe frostbite. INTERPRETATION & CONCLUSION: It is evident from the study that this combined therapy resulted in significant improvement in the degree of tissue preservation and proved to be highly beneficial as an immediate treatment of frostbite in rats. The combined pharmacological properties of these drugs might have altered the haemorrheologic status of blood and produced curative beneficial effect in improving tissue survival. Clinical studies are required for confirmation of these beneficial effects in humans, which has already been taken up.

Effect of Sahaja yoga practice on seizure control & EEG changes in patients of epilepsy.

The effect of Sahaja yoga meditation on seizure control and electroencephalographic alterations was assessed in 32 patients of idiopathic epilepsy. The subjects were randomly divided into 3 groups. Group I (n = 10) practised Sahaja yoga for 6 months, Group II (n = 10) practised exercises mimicking Sahaja yoga for 6 months and Group III (n = 12) served as the epileptic control group. Group I subjects reported a 62 per cent decrease in seizure frequency at 3 months and a further decrease of 86 per cent at 6 months of intervention. Power spectral analysis of EEG showed a shift in frequency from 0-8 Hz towards 8-20 Hz. The ratios of EEG powers in delta (D), theta (T), alpha (A) and beta (B) bands i.e., A/D, A/D + T, A/T and A + B/D + T were increased. Per cent D power decreased and per cent A increased. No significant changes in any of the parameters were found in Groups II and III, indicating that Sahaja yoga practice brings about seizure reduction and EEG changes. Sahaja yoga could prove to be beneficial in the management of patients of epilepsy.

Efficacy of pentoxifylline with aspirin in the treatment of frostbite in rats.

The efficacy of pentoxifylline--a haemorrheologic agent along with aspirin--an analgesic agent was evaluated in the amelioration of the tissue damage due to experimentally induced frostbite in 5 groups (20 each) of rats with body weights ranging between 175 and 200 g. Frostbite was produced experimentally in the hind limbs by exposing the animals to -15 +/- 1 degrees C for 1 h using the harness technique, with simultaneous recording of rectal and environmental temperatures. The degree of tissue damage was assessed on the basis of tissue necrosis after 15 days. Administration of pentoxifylline (40 mg/kg bw) 30 min before and 30 min after the cold exposure followed by two doses of the same daily for the next 5 days along with aspirin (5 mg/kg bw) twice daily for the same duration only after cold exposure, resulted in significant improvement in the degree of tissue preservation. The findings of this preliminary study have brought to light the potential usefulness of these drugs in the treatment of frostbite. The combined pharmacological properties of these two drugs might have altered the haemorrheologic status of blood and produced the curative beneficial effect in improving tissue survival following experimentally induced frostbite in rats.

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.

Peripheral vascular response to local cold stress of tropical men during sojourn in the Arctic cold region.

Peripheral vascular response to local cold stress was studied on 4 groups of volunteers by eliciting cold-induced vasodilatation (CIVD) response during immersion of right hand in cold water (4 degrees C) for 30 min, to examine whether tropical men can get acclimatized to local cold compared to temperate zone people, during Arctic cold exposure. Group A and B (10 each) were drawn from tropical region of India, while Group C and D (6 each) from temperate zone of Russia and natives of Arctic, respectively. Initial study was conducted on control Group A at Delhi. Group B was airlifted to the Arctic (70 degrees N, 38 degrees E), where measurements were done on them during the seventh week of acclimatization, then they were flown back to Delhi and retested. For comparison, study was done at the Arctic on six migrants (Group C) from temperate zone of Russia and 6 natives (Group D) of the Arctic. There was a significant improvement of CIVD response and peripheral blood flow of tropical men due to acclimatization to Arctic environment, which was similar to that of the migrants but lower than the natives. Thus local cold acclimatization is possible even in tropical men as in those of the temperate zone people.

Effect of vitamin C in modulating the hypothermic influence on nerve conduction.

The study was carried out to evaluate the effect of different degrees of hypothermia on nerve conduction and the possible beneficial effect of vitamin C in the amelioration of the impairment in nerve conduction due to hypothermia. Sixty male Wistar rats, 225-250 g, were randomly divided into two equal groups of untreated controls and vitamin C treated experimental groups. Sciatic nerve conduction and nerve temperature (Tn) were recorded at different degrees of hypothermia by step-wise lowering of rectal temperature (Tr) from 38 to 20 degrees C. A regression analysis showed a positive linear relationship of Tr with nerve conduction velocity (NCV) and with Tn in both groups (p < 0.001). There was also a positive linear relationship between Tn and NCV in both groups: control, p < 0.001; experimental, p < 0.05. Comparisons between the regression equations of Tr with NCV, Tr with Tn, and Tn with NCV showed significant differences between the two groups (p < 0.001). There was no significant relationship between Tr and the amplitude of the action potential. Vitamin C may have a protective effect against the impairment of NCV due to hypothermia.

Effect of vitamin C and E in modulating peripheral vascular response to local cold stimulus in man at high altitude.

At high altitude (HA), cold stress is aggravated by hypoxia, perhaps due to the increased formation of free radicals which trigger oxidative stress. This may be one of the contributing factors for adverse effects including disturbances in microcirculation and capillary permeability resulting in decreased peripheral blood flow. This leads to altered cold-induced-vasodilatation (CIVD) response on exposure to HA. The present study was conducted on 40 male volunteers (4 groups of 10 each) to evaluate the utility of supplementation of vitamin C (500 mg/d)and vitamin E (400 mg/d) singly, as well as in combination, in modulating peripheral vascular response by assessing CIVD response under local cold stimulus both at Delhi (200 m) and at HA (3,700 m). On exposure to 3,700 m, decreased CIVD response was observed in all the groups. The responses were better in vitamin supplemented groups, in general, as compared to the placebo group. The best CIVD response was seen in the vitamin C (singly)-treated group. Administration of vitamin C and E together did not result in any additional benefit. Facilitation of CIVD response due to supplementation of vitamin C may be attributed to its (a) antioxidant effect, and (b) major physiological functions of increased metabolism and thermogenic properties, facilitation of collagen synthesis, restoration of intercellular substances and better maintenance of the rheological status of the blood. Hence, vitamin C is effective for improving peripheral blood flow and thereby reduces the incidence of cold injuries during acclimatization or outdoor duties at HA.