Efficacy of add-on Ayurveda and Yoga intervention in health care workers of tertiary care hospital during COVID-19: Randomized controlled trial.

BACKGROUND: The present study aimed to evaluate the safety and prophylactic efficacy of add-on Comprehensive Ayurveda and mindfulness-based Yoga (CAY) regimen to standard care among HealthCare Workers (HCWs) against COVID-19. MATERIALS AND METHODS: This prospective single-blind (outcome assessor-blinded) RCT was conducted in tertiary care hospital in Delhi during July 2020-April 2021. HCWs of both sexes were randomized to add-on CAY intervention or control group. The primary outcomes were the incidence of confirmed COVID-19 positive cases and influenza-like illness events (ILI). Secondary outcomes were anxiety (GAD-7), depression (PHQ-9), and quality of life (SF-36) at the end of 12 weeks. RESULTS: Three hundred fifty-six participants (181 in intervention and 175 in the control group) were randomized. With the modified intention to treat approach, we analyzed 309 participants. The mean age for the intervention and control group was 39.3 ± 10.1 and 36.6 ± 10 years, respectively. Incidence of COVID-19 event was higher in control group compared to CAY group (16 of 164 [9.8%] vs. 11 of 145 [7.6%]; P = 0.50). The incidence of ILI events was also higher in the control group as compared to the CAY group (14 of 164 [8.5%] vs 9 of 145 [6.2%]). The health change domain of the SF-36 questionnaire showed statistically significant improvement in the CAY group as compared to the control group (P < 0.01). CONCLUSION: Incidence of COVID-19 and ILI events was lower in the CAY group compared with the contr ol group, though the difference is not statistically significant.

Increased metabolic rate and insulin sensitivity in male mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2.

AIMS/HYPOTHESIS: The carcino-embryonic antigen-related cell adhesion molecule (CEACAM)2 is produced in many feeding control centres in the brain, but not in peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin resistance and obesity resulting from hyperphagia and hypometabolism in female Ceacam2 homozygous null mutant mice (Cc2 [also known as Ceacam2](-/-)) mice. Because male mice are not obese, the current study examined their metabolic phenotype. METHODS: The phenotype of male Cc2(-/-) mice was characterised by body fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp analysis and direct recording of sympathetic nerve activity. RESULTS: Despite hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in male Cc2(-/-) mice. In contrast to females, male mice also exhibited insulin sensitivity with elevated ß-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Males and females had increased brown adipogenesis. However, only males had increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity. The mechanisms underlying sexual dimorphism in energy balance with the loss of Ceacam2 remain unknown. CONCLUSIONS/INTERPRETATION: These studies identified a novel role for CEACAM2 in the regulation of metabolic rate and insulin sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle.

Evidence for increased neuropeptide Y synthesis in mediobasal hypothalamus in relation to parental hyperphagia and gonadal activation in breeding ring doves.

Like lactating mammals, male and female ring dove parents increase their food consumption to meet the energetic challenges of provisioning their young. To clarify the neurochemical mechanisms involved, the present study investigated the relationship between parental hyperphagia and changes in activity of the potent orexigen neuropeptide Y (NPY) in the hypothalamus of breeding doves. Changes in NPY-immunoreactive (NPY-ir) cell numbers in the tuberal hypothalamus of male and female doves were examined by immunocytochemistry at six stages of the breeding cycle. Parallel NPY mRNA measurements were recorded in mediobasal hypothalamus (which includes the tuberal hypothalamus) by semiquantitative reverse transcription-polymerase chain reaction using 18S rRNA as the internal standard. NPY mRNA changes were also measured in the mediobasal hypothalamus of nonbreeding doves following intracranial administration of prolactin, an orexigenic hormone that is elevated in the plasma of parent doves, and in response to food deprivation, which mimics the negative energy state that develops in parents as they provision their growing young. NPY-ir cell numbers in the tuberal hypothalamus and NPY mRNA levels in the mediobasal hypothalamus were significantly higher in breeding males and females during the period of parental hyperphagia after hatching than during the late incubation period when food intake remains unchanged. In nonbreeding doves, food deprivation and prolactin treatment increased NPY mRNA in this region by two- to three-fold, which suggests that NPY expression is sensitive to hormonal and metabolic signals associated with parenting. We conclude that NPY synthesis is increased in the mediobasal hypothalamus during the posthatching period, which presumably supports increased NPY release and resulting parental hyperphagia. NPY-ir and mRNA were also high in the mediobasal hypothalamus prior to egg laying when food intake remained unchanged. Several lines of evidence suggest that this elevation in NPY supports the increased gonadal activity that accompanies intense courtship and nest building interactions in breeding doves.

Biochemistry of homocysteine in health and diseases.

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.

Amino acids differentially regulate insulin receptor tyrosine kinase and phosphatidyl inositol-3-OH-kinase activities in human monocytes exposed to high glucose concentration.

Chronic hyperglycemia and insulin resistance are the common factors involved in the development of vascular complications in diabetes mellitus (DM) patients. Since insulin signaling pathway has been shown to be regulated by nutritional supplements, in the present study, we investigated the possible effects of free amino acids, such as lysine, arginine and alanine and their mixture in modulating the insulin receptor tyrosine kinase (IRTK) and phosphatidyl inositol-3-OH-kinase (PI3K) activities and on the changes in actin dynamics in monocytes (MC), exposed to high glucose concentration (25 mM). IRTK and PI3K activities were markedly decreased in MC, incubated with 25 mM glucose. However, on treatment with amino acids, only lysine was effective in augmenting IRTK and PI3K activities in a dose-dependent manner. Arginine had marginal effect in promoting these activities. Equimolar mixture of amino acids showed marginal effect of augmenting only IRTK activity. Alanine had no effect. The F-actin filaments showed grossly diminished organization in the cells treated with 25 mM glucose alone, as assessed by specific binding to phalloidin-FITC, when compared with cells treated with 5 mM glucose. On the other hand, a significant improvement in the F-actin organization was observed in the cells co-incubated with 25 mM glucose and lysine. A possible molecular mechanism is the antiglycating effect of amino acids. The signal transduction starts with binding of ATP to lysine at position 1030 in the beta sub unit of the receptor. This lysine (1030) may be protected by the added lysine or to some extent arginine from glycation and loss of function. In summary, our findings suggest that the amino acids apart from their antiglycating property can also modulate/influence the activities of pivotal enzymes that are upstream in the insulin-mediated signal transduction pathway and bring down glucose.

Determination of carbonyl group content in plasma proteins as a useful marker to assess impairment in antioxidant defense in patients with Eales' disease.

PURPOSE: Formation of protein carbonyl groups is considered an early biomarker for the oxidant/antioxidant barrier impairment in various inflammatory diseases. We evaluated the intensity of free radical reactions in patients with Eales' disease, an idiopathic inflammatory condition of the retina. METHODS: Twenty patients with Eales' disease in active vasculitis stage, 15 patients with Eales' disease in healed vasculitis stage and 20 healthy control subjects were recruited for the study. Plasma protein carbonyl groups,plasma glutathione (GSH) superoxide dismutase (SOD) activity and thiobarbituric acid reactive substances (TBARS) were determined in erythrocytes. RESULTS: Plasma protein carbonyl content was elevated by a factor of 3.5 and 1.8 respectively in active and healed vasculitis stages. The increase of carbonyl group content in active and healed stage of patients with Eales' disease correlated with diminished SOD activity and GSH content. There was also increased accumulation of TBARS in active and healed vasculitis stages of Eales' disease, and this correlated with diminished SOD activity. CONCLUSION: Our results showed that protein carbonyl group content increases with severity of Eales' disease. The increase in carbonyl content correlated with diminished antioxidant status. This confirms an earlier report that free radical mediated tissue damage occurs in Eales' disease. The determination of protein carbonyl content may be used as a simple biomarker to monitor the efficacy of antioxidant supplementation in controlling retinal vasculitis in patients with Eales' disease.

Management of root lesion nematode, Pratylenchus delattrei in crossandra using oil cakes.

Selected oil cakes, neem, castor and mahua, were tried independently and in combination with a chemical nematicide (carbofuran 3G) for the management of Pratylenchus delattrei in crossandra under glass house conditions. The neem oil cake was effective compared to other oil cakes used and there was a synergistic effect when the neemcake was coupled with carbofuran 3G in the management of Pratylenchus delattrei. The treatment resulted in better establishment of seedlings, and with increased plant bio-mass and flower yield.

Insulin receptor tyrosine kinase activity in monocytes of type 2 diabetes mellitus patients receiving oral L-lysine.

The action of lysine as an antidiabetic agent was examined in human volunteers. Eight patients with type 2 DM were orally supplemented with L-lysine hydrochloride 1 g/day in two doses along with antidiabetic tablets (glyciphage or chlorformine), for a period of two months. Periodically their plasma fasting sugar and insulin receptor tyrosine kinase activity was measured in their monocytes. Eight normal healthy volunteers served as controls for comparison of receptor tyrosine kinase activity. Insulin receptor tyrosine kinase was isolated from monocytes by immunoprecipitation and the activity was determined using exogenous substrate poly glu-tyr (4:1) and radioactive ATP. Phosphorylated peptide was separated by electrophoresis and quantified using a liquid scintillation system. The enzyme activity was significantly low (22074 +/- 1728 dpm/ml immunoprecipitate) in subjects with diabetes when compared to non-diabetic control group (50,775 +/- 3597). Lysine treatment enhanced the enzyme activity by 31% in patients with diabetes and decreased their blood sugar by 27%.

Beneficial effect of lysine and amino acids on cataractogenesis in experimental diabetes through possible antiglycation of lens proteins.

Rats were given a single injection of streptozotocin. They became diabetic with a blood sugar of around 300 mg dL-1. They were divided into three groups of six rats each. Group II was the diabetic control. Each one of group III diabetic rats received daily 2 ml of 2% solution of lysine supplement orally. Group IV received daily 2 ml of a 2% solution of a mixture of amino acids supplement for 120 days. In addition there were 6 rats as normal control (Group I). Periodically ophthalmic examination was done by slit lamp. Blood glucose, proteins, hemoglobin, free amino acids, glycosylated hemoglobin and glycated lens proteins were also analysed. Body weight was recorded. The diabetic controls decreased in body weight. The blood sugar levels were lowered from about 295 mg dL-1 to 99 mg dL-1 in the lysine-fed group and from 268 mg dL-1 to 126 mg dL-1 in the amino acids mixture-fed group. The levels of glycosylated hemoglobin and glycated lens proteins increased in diabetic controls while they were normal in other groups. The free amino acid levels in blood were lower in groups receiving lysine or amino acids than in diabetic controls indicating their better utilization. In diabetic control, all the animals developed cataract in 70-90 days; five out of six did not develop cataract in the lysine supplemented group. Four of six did not develop cataract in the amino acid mixture-supplemented group. None developed cataract in normal controls. Lysine and amino acids have anticataractous and antidiabetic effects.

Investigation of the structural requirements of the troponin C central helix for function.

The two globular Ca(2+)-binding domains of troponin C are connected by a three-turn, exposed central helix. The requirements of this helical linker for regulatory function are not fully understood. In the present work we investigated the structural requirement of the linker using a series of insertion mutations that differ in predicted flexibility. TnCinrc has a nine-residue flexible random coil insert, TnCinpp has a nine-residue rigid polyproline insert (three turns), and TnCin alpha h has a seven-residue insert with high potential of forming alpha-helix. TnCinrc and TnCinpp were defective in the activation of the regulated actomyosin ATPase activity in the presence of Ca2+ when compared to wild type or TnCin alpha h, suggesting that altering the flexibility of the central helix impairs the regulatory function of troponin C. TnCin alpha h, TnCinrc, and TnCinpp had 87% +/- 3, 62% +/- 3, and 58% +/- 2 of the wild type activity, respectively (n = 6). All insertions in the central helix resulted in elongation of molecule compared to wild type TnC as determined by Stokes' radius. The Ca(2+)-affinity, the Ca(2+)-dependence of the actomyosin ATPase, and the stability of the insertion mutants were similar to wild type. Deletions of up to two turns of the central helix have little effect on troponin C function [Dobrowolski, Z., Xu, G-Q., & Hitchcock-DeGregori, S. E. (1991) J. Biol. Chem. 266, 5703-5710]. In another mutant (TnCd11) the entire central helix, 87KEDAKGKSEEE97, was deleted. With TnCd11, activation of the actomyosin ATPase activity in the presence of Ca2+ was normal, but inhibition in the absence of Ca2+ was less effective. Interaction of TnCd11 with TnI was altered. There was a 2-fold excess of TnCd11 in reconstituted Tn complex, consistent with another report [Babu, A., Rao, V. G, Su, H., & Gulati, J. (1993) J. Biol. Chem. 268, 19232-19238]. Our results suggest that the native length and structure of the central helix are optimal for normal regulatory function and that connectivity alone is insufficient for TnC function.

Marker rhythmometry with macrophage-colony stimulating factor (M-CSF).

In a patient with a debulked müllerian adenocarcinoma involving the ovary, an elevated serum concentration of macrophage-colony stimulating factor (M-CSF) (5.3 ng/ml) was lowered into the range of the age- and gender-matched controls by a 24-hour infusion of 135 mg/m2 of taxol, as was a Ca125 of 1480 U/ml by three such taxol courses given at 3-week intervals (to 14 U/ml). A downward trend of M-CSF in serum with an about-14-hour ultradian modulation during the first chemotherapy course resembles that of the concomitantly assessed Ca125. A decreasing trend modulated by an about-half-weekly component is found in M-CSF of fractionated urines collected at spontaneous voidings around the clock for 5 days. M-CSF may serve as a chronobiologic marker for optimizing, on an individualized basis, 1) the infradian scheduling of chemotherapy courses and 2) the ultradian-circadian within-course time patterns. Timing based on markers of the anticancer effect aims at teh as-yet unattained transfer from rodent to human of cancer cures that were not previously feasible without chronobiologic considerations. This goal can be pursued with M-CSF as well as Ca125 and UGP as possibly complementary chronobiologic markers in a chronotherapy trial with taxol in humans.

Immunogenicity of three C-terminal synthetic peptides of the beta subunit of human chorionic gonadotropin and properties of the antibodies raised against 45-amino acid C-terminal peptide.

Immunological studies were carried out in rhesus monkeys and rabbits on three C-terminal synthetic peptides of beta-hCG (115-145; 111-145 and 101-145) after conjugating these to tetanus toxoid (TT). The immunogenicity of the peptide conjugates was comparatively poorer with reference to Pr-beta-hCG-TT conjugates at similar doses and immunization schedule. Amongst the three peptides, the best response was obtained with the 45-amino acid c-terminal peptide (45-CTP; 101-145). The anti-45-CTP recognized native hCG and was devoid of cross-reaction with hLH. hCG-induced testosterone production by mouse Leydig cells was inhibited by anti-45-CTP antiserum, although its neutralization capacity decreased more rapidly upon dilution than anti-beta-hCG sera of comparable titres. Immune complexes formed by the anti-45-CTP with hCG had a lower sedimentation value than those formed by anti-beta-hCG antisera with hCG, suggesting the presence of a limited number of immuno-determinant regions in the 45-amino acid C-terminal synthetic peptide.