A novel gene THSD7A is associated with obesity.

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

Imbalance of folic acid and vitamin B12 is associated with birth outcome: an Indian pregnant women study.

BACKGROUND/OBJECTIVES: Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid. Along with folic acid, vitamin B12 is also an important determinant of fetal growth and development. During pregnancy, the increased requirement of folic acid is met with supplementation, while vitamin B12 remains untreated and possibly deficient. The objective of our study was to study the combined effect of maternal plasma folate and vitamin B12, and their ratio on birth anthropometrics. SUBJECTS/METHODS: We carried out an observational study on 49 full-term pregnant women at KEM Hospital, Pune, India, during 2006-2008, and measured plasma folate, vitamin B12 and homocysteine in venous blood at 36 weeks of gestation. Neonatal anthropometrics (birth weight, length, head circumference, abdominal circumference, mid arm circumference, chest circumference, triceps skinfold and subscapular skinfold thickness) were measured within 24 h of birth. RESULTS: Maternal plasma folate and vitamin B12 were not correlated to neonatal anthropometrics. The combined association of folate and vitamin B12 expressed as folate to vitamin B12 ratio was correlated to the neonatal anthropometrics. Imbalance in the maternal micronutrients with increasing ratio of folate to vitamin B12 was associated with an increase in plasma homocysteine (P=0.014), lowering of neonatal birth weight (P=0.009), birth length (P=0.034), head circumference (P=0.018) and chest circumference (P=0.009), while no significant association to other anthropometrics was observed. CONCLUSIONS: Supplementation of vitamin B12 in addition to supplementation of folic acid in pregnancy may be important for improving birth weight, birth length, head circumference and chest circumference.

Antiarthritic activity of a standardized, multiherbal, Ayurvedic formulation containing Boswellia serrata: in vitro studies on knee cartilage from osteoarthritis patients.

A validated in vitro model of cartilage damage and published data were used showing that this model measures the chondroprotective and antiinflammatory effects of different antiarthritic drugs. In this report, this model was used to evaluate the effects of a new antiarthritic Ayurvedic formulation containing Zingiber officinale root, Tinospora cordifolia stem, Phyllanthus emblica fruit and oleoresin of Boswellia serrata. Glucosamine sulphate was used as a positive control in the study. Aqueous extracts of each drug were tested on explant cultures of knee cartilage obtained from osteoarthritis patients undergoing knee replacement surgery. The new formulation caused a sustained and statistically significant inhibition in the release of glycosaminoglycans and aggrecan by cartilage explants from these patients. This formulation also induced a transient antiinflammatory effect as measured by a reduction in the levels of nitric oxide released by explants. Furthermore, the data strongly suggest that oleoresin of B. serrata plays a crucial role in the chondroprotective and antiinflammatory activity of this formulation. In summary, this report provides the first, direct, in vitro biochemical evidence of anti-arthritic activity a new Ayurvedic formulation. This formulation significantly reduced damage of articular knee cartilage from chronic osteoarthritis patients.

RAPD Analysis for Determination of Components in Herbal Medicine.

In this study, the RAPD (Random Amplified Polymorphic DNA) technique was employed for determination of the components in an Ayurvedic herbal prescription, Rasayana Churna. One-hundred-and-twenty decamer oligonucleotide primers were screened in the RAPD analysis to identify three Ayurvedic medicines, dried stem of Tinospora cordifolia, dried fruit of Emblica officinalis and dried fruit of Tribulus terestris, the Ayurvedic prescription. Primer OPC-6 simultaneously generated three distinct amplicons, each specific to one component. The marker with 600 bp is specific to Tinospora cordifolia; the marker 500 bp is specific to Emblica officinalis and the remaining marker >1000 bp was present in Tribulus terestris. Presence of three herbal medicines was determined when RAPD reaction with OPC-6 was performed. The technique was proved to contribute to the identification of components in Ayurvedic herbal preparation and thus helping to serve as a complementary tool for quality control.

Immune response modulation to DPT vaccine by aqueous extract of Withania somnifera in experimental system.

Immunopotentiation on oral feeding of standardized aqueous extract of Withania somnifera (Linn. Dunal, Family Solanaceae) was evaluated in laboratory animals immunized with DPT (Diphtheria, Pertussis, Tetanus) vaccine. The immunostimulation was evaluated using serological and hematological parameters. Treatment of immunized animals with test material (100 mg/kg/day) for 15 days resulted in significant increase of antibody titers to B. pertussis (P=0.000007). Immunized animals (treated and untreated) were challenged with B. pertussis 18,323 strain and the animals were observed for 14 days. Results indicate that the treated animals did show significant increase in antibody titers as compared to untreated animals after challenge (P=0.000003). Immunoprotection against intracerebral challenge of live B. pertussis cells was evaluated based on degree of sickness, paralysis and subsequent death. Reduced mortality accompanied with overall improved health status was observed in treated animals after intracerebral challenge of B. pertussis indicating development of protective immune response. Present study indicates application of the test material as potential immunopotentiating agent possible applications in immunochemical industry. The test material also offers direct therapeutic benefits resulting in reduced morbidity and mortality of experimental animals.

Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis.

OBJECTIVE: To evaluate RA-1, a standardized plant extract formulation, traditionally considered a safe, effective antiarthritic in the Asian-Indian Ayurvedic medicinal system. METHODS: One hundred eighty-two patients with active-on-chronic rheumatoid arthritis (RA) participated in a 16 week randomized, double blind, placebo controlled, parallel efficacy clinical drug trial in Pune, India. Tenderness, pain, swelling, and several other efficacy measures were assessed by (1) ACR core set 20% and 50% improvement; (2) ACR 20% improvement response. An intent-to-treat analysis was performed; p<0.05 considered significant. RESULTS: Seventeen patients withdrew (active = 9; placebo = 8); none withdrew due to drug toxicity. An unprecedented placebo response (often p<0.001 in within-group change) was observed. The active RA-1 group remained numerically superior at all evaluation timepoints. RA-1 demonstrated few significant differences: (1) increased proportion with 50% reduction in swollen joint count (95% CI approximately 1.52, 29.90) and swollen joint score (95% CI approximately 0.91, 28.73); (2) reduced rheumatoid factor (95% CI approximately -303.7, -2.72); 39% in the RA-1 group versus 30% placebo showed ACR 20% improvement (95% CI approximately -5.48, 24.59). Only minor side effects were seen, with no significant differences by treatment group. CONCLUSION: In a trial with sufficient power, RA-1 revealed efficacy that was not significantly superior to the strong placebo response, except for improvement in joint swelling. Further, the effect on RF and good safety profile led to an open label phase.

Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation.

The immunomodulatory activities of an Indian Ayurvedic medicinal preparation, i.e. extracts from Ashwagandha, Withania somnifera (L.) Dunal (Solanaceae), namely WST and WS2, were studied in mice for immune inflammation: active paw anaphylaxis and delayed type hypersensitivity (DTH). Immunomodulatory effect was assessed in If IgE-mediated anaphylaxis as reduction of ovalbumin-induced paw edema, in animals treated with WS2 at doses of 150 and 300 mg/kg, and the results were compared with the standard drug disodium chromoglycate. In the DTH model, the modulatory effect was assessed as potentiation or suppression of the reaction, revealing an increase or decrease in mean foot pad thickness, respectively. Potentiation of the DTH reaction was observed in animals treated with cyclophosphamide at a dose of 20 mg/kg, WST at a dose of 1000 mg/kg and WS2 at a dose of 300 mg/kg. On the other hand, cyclophosphamide-induced potentiation of DTH reaction was suppressed in animals treated with WST and WS2. A significant increase in white blood cell counts and platelet counts was observed in animals treated with WST. A protective effect in cyclophosphamide-induced myelosuppression was observed in animals treated with WST and WS2, revealing a significant increase in white blood cell counts and platelet counts. Cyclophosphamide-induced immunosuppression was counteracted by treatment with WS2, revealing significant increase in hemagglutinating antibody responses and hemolytic antibody responses towards sheep red blood cells.

Studies on the immunomodulatory effects of Ashwagandha.

The immunomodulatory activity of an Indian Ayurvedic medicinal preparation, Ashwagandna (Withania somnifera (L. Dunal)) was studied in mice with myelosuppression induced by one or more of the following three compounds: cyclophosphamide, azathioprin, or prednisolone. The assessment of immunomodulatory activity was carried out by hematological and serological tests. A significant modulation of immune reactivity was observed in all the three animal models used. Ashwagandha prevented myelosuppression in mice treated with all three immunosuppressive drugs tested. A significant increase in hemoglobin concentration (P < 0.01), red blood cell count (P < 0.01), white blood cell count (P < 0.05), platelet count (P < 0.01), and body weight (P < 0.05) was observed in Ashwagandha-treated mice as compared with untreated (control) mice. We also report an immunostimulatory activity: treatment with Ashwagandha was accompanied by significant increases in hemolytic antibody responses towards human erythrocytes.

A comparative pharmacological investigation of Ashwagandha and Ginseng.

The aqueous suspensions of roots of an Indian drug Ashwagandha and the Korean drug Ginseng were tested comparatively for 2 pharmacological activities, namely the anti-stress activity by the 'mice swimming endurance test' and anabolic activity by noting gain in body weights and levator ani muscle in rats. A significant increase in mice swimming time was shown by Ginseng (P < 0.001) and Ashwagandha (P < 0.01) as compared to the control group. Significant increase in body weights in the Ashwagandha treated group (P < 0.05) was better than Ginseng (P < 0.5). Gain in wet weights of the levator ani muscle were also significant in Ginseng (P < 0.001) and Ashwagandha (P < 0.01) treated groups, however, the weight gain of dried levator ani muscles showed comparable results for both these drugs (P < 0.01).

Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study.

The clinical efficacy of a herbomineral formulation containing roots of Withania somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc complex (Articulin-F), was evaluated in a randomized, double-blind, placebo controlled, cross-over study in patients with osteoarthritis. After a one-month single blind run-in period, 42 patients with osteoarthritis were randomly allocated to receive either a drug treatment or a matching placebo for a period of three months. After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months. Clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis. Treatment with the herbomineral formulation produced a significant drop in severity of pain (P less than 0.001) and disability score (P less than 0.05). Radiological assessment, however, did not show any significant changes in both the groups. Side effects observed with this formulation did not necessitate withdrawal of treatment.

Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study.

OBJECTIVE: To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension. DESIGN: A double blind, randomised, placebo controlled, crossover trial of 32 weeks' duration. SETTINGS: Cardiology outpatient department, Sassoon General Hospitals, Pune, India. PATIENTS: 37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg). INTERVENTION: Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed. MEASUREMENTS: Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals. RESULTS: Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory. CONCLUSION: Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage.

Ayurvedic treatment of obesity: a randomised double-blind, placebo-controlled clinical trial.

Seventy obese subjects were randomised into four groups. Ayurvedic drug treatments were given for three months while one group received a placebo. Physical, clinical and pathological investigations were carried out at regular intervals. A significant weight loss was observed in drug therapy groups when compared with the placebo. Body measurements such as skin fold thickness and hip and waist circumferences were significantly decreased. Decreases in serum cholesterol and triglyceride levels were observed. No side effects of any kind were observed during the treatment period.

Studies on ayurvedic tablets - part I disintegration time as a preliminary tool for standardisation.

The ayurvedic pharmacy needs to be established on the basis of modern quality standards. A study on ayurvedic Guti-Vati (tablets) was undertaken with this view, revealed that most of the tablets conform to the I P standards for hardness and DT. A few of the tablets showed curious responses similar to that of enteric coated and slow release tablets commonly used in modern medicine.A systematic supporting study is essential so as to establish relationship of such responses to the nature of ingredients and their relevance with the indications and therapeutic utility described in Ayurvedic texts.

Clinical evaluation of terminalia belerica in diarrhoea.

Terminalia belerica (behada) fruit has been evaluated as a promising agent against E. histolytica and a variety of bacteria associated with dysentery and diarrhoea. These in vitro studies were extended further for evaluating clinical efficacy among patients of acute and chronic cases of diarrhoea and dysentery. The Studies were carried out on 25 patients by five medical practitioners practicing at different clinics in the urban areas of Pune. The data was collected as per the protocol given to the concerned clinicians. Inclusion and exclusion criteria were critically followed. Record of patients' history, clinical evaluations and investigations like stool, urine examination were carried out where necessary.The maximum treatment period was 14 days and the dose was 150 mg. tablets of bioactive fraction three times a day. 11 out of 12 patients responded to therapy and required around twelve tablets for recovery. Seven patients having the presence of cyst of amoeba, E. coli etc. became negative at the end of treatment. Improvement started on second day. No side effects of any nature were observed.

Studies on the mechanism of action of Semecarpus anacardium in rheumatoid arthritis.

Semecarpus anacardium nuts are used for variety of disorders in Ayurveda. A chloroform extract of the nut significantly reduced acute carrageenan-induced paw oedema in rats and was active against the secondary lesions of adjuvant-induced arthritis. Delayed hypersensitivity induced in mice by sheep red blood cells as an antigen was potentiated by the extract.

Toxicity of semecarpus anacardium extract.

Toxicity by oral route administration of S. anacardium extract with peanut oil was compared against the same extract emulsified with Tween-80 saline. The traditional way of administration with peanut oil was found to be safe and upto 25 mg/kg/day x9 days, increase in weight, RBCs & haemoglobin % was observed without mortality. Same dose with Tween-80 saline was found to have adverse effects regarding all the pharameters with 16.5% mortality. This study support Ayurvedic method of administration for efficacy without toxicity.

Structural features of cytochalasins responsible for gram-positive bacterial inhibitions.

A study of the relative effectiveness of some eighteen natural and synthetically modified cytochalasins on the uptake of glucose by the Gram-positive bacterium Arthrobacter sialophilus showed that cytochalasins B, C or D and aspochalasins A, C or D were inactive natural congeners. The presence of an alpha,beta-unsaturated carbonyl group in the macrolide moiety of these compounds with appropriate bioisosteric placement, as exemplified by cytochalasin A and aspochalasin B, are requisite molecular features. The transmembrane inhibitory index of active compounds was enhanced by increasing their lipophilicity. Thiol adducts of CA were around 20% as active in solute uptake inhibition as was the free drug. Radioactive 7-O-acetyl CA and its thiol adduct were each rapidly taken up by A. sialophilus and remained firmly bound to cellular components even after denaturant manipulations. These findings provide strong evidence for a stable association between CA and presumptive macromolecular receptors in transport and related processes.