RESUMEN
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.
Asunto(s)
Etnicidad/genética , Obesidad/etnología , Obesidad/genética , Polimorfismo de Nucleótido Simple , Trombospondinas/genética , Población Blanca/genética , Adulto , Índice de Masa Corporal , Femenino , Variación Genética , Genética de Población , Estudio de Asociación del Genoma Completo , Humanos , India/epidemiología , Desequilibrio de Ligamiento , Masculino , Obesidad/epidemiología , Fenotipo , Población Blanca/estadística & datos numéricosRESUMEN
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.
Asunto(s)
Antiinflamatorios/farmacología , Boswellia/química , Cartílago Articular/efectos de los fármacos , Articulación de la Rodilla/efectos de los fármacos , Preparaciones de Plantas/farmacología , Anciano , Agrecanos/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Técnicas In Vitro , Medicina Ayurvédica , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Osteoartritis/tratamiento farmacológico , Extractos Vegetales/farmacologíaRESUMEN
A series of halogenated and related analogues of cytochalasin C (CC) and D (CD) has been synthesized, and the biological activities of the analogues as inhibitors in a cell-free contractility model system obtained from Ehrlich ascites tumor cells were evaluated. The reaction sequence involved treatment of CD with phenyltrimethylammonium perbromide to give 6,12-dibromo-CD (2), dehydrohalogenation of 2 to 12-bromo-CC (3), and the subsequent conversions of 3 to 12-azido- (4), 12-iodo- (5), and 12-cyano-CC (6). The ID50 values for 5, 3, 4, 2, and 6 are 6.0, 7.4, 8.8, 45, and 77 X 10(-7) M, respectively, in comparison to ca. 2.8 X 10(-7) M for the parental compounds. The potential cell and molecular biological applications of these compounds are delineated.
Asunto(s)
Antineoplásicos , Citocalasinas/síntesis química , Animales , Carcinoma de Ehrlich/tratamiento farmacológico , Fenómenos Químicos , Química , Citocalasina D , Citocalasinas/farmacología , Relación Estructura-ActividadRESUMEN
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.
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/farmacología , Factores Inmunológicos/farmacología , Withania/química , Animales , Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/biosíntesis , Recuento de Células Sanguíneas , Cromatografía en Capa Delgada , Femenino , Masculino , Ratones , Extractos Vegetales/farmacología , Raíces de Plantas/química , Agua , Tos Ferina/inmunología , Tos Ferina/mortalidad , Tos Ferina/prevención & controlRESUMEN
A study of the mechanism of action of cytochalasin A (CA) in relation to its structural features and to its selective inhibition of certain contractile processes has been initiated. Quantitative structure-function analyses with several CA-related cytochalasins - including synthetic 21,22-dihydro-CA (DHCA), the 22-beta mercaptoethanol CA-adduct, (CA-2ME), and the 22-dithiothreitol CA-adduct (CA-DTT) - have been carried out in a temperature sensitive gel-sol extract from Ehrlich ascites tumor cells. Each drug congener was purified to homogeneity by HPLC prior to biological testing. The undiminished inhibitory indices of DHCA and CA-2ME (ID50 congruent to 3.7 x 10(-7) M) overrules the prior circumstantial evidence accumulated for the obligatory electrophilic interaction of this drug, at its alpha-beta-unsaturated ketone region, with presumptive receptor nucleophiles.
Asunto(s)
Carcinoma de Ehrlich/fisiopatología , Citocalasinas/farmacología , Ditiotreitol/farmacología , Mercaptoetanol/farmacología , Animales , Colchicina/farmacología , Citocalasina B/farmacología , Relación Dosis-Respuesta a Droga , Ratones , Relación Estructura-ActividadRESUMEN
Treatment of N-acetylneuraminic acid methyl ester with sulfuric acid and acetic anhydride at 50 degrees followed by deacetylation gave 2,3-dehydro-2-deoxy-N-acetylneuraminic acid methyl ester and methyl 5-acetamido-2,6-anhydro-2,3,5-trideoxy-D-glycero-D-talo-non-2-enonate (2,3-dehydro-4-epi-NeuAc methyl ester) in equal yields (approximately 40% each). The structure of the latter was ascertained primarily from analysis of its mass spectrum and 1H- and 13C-nuclear magnetic resonance spectra. The relative proportions of these two glycals in the foregoing reaction was dependent on temperature, as at 0 degrees, the yield of 2,3-dehydro-4-epi-NeuAc was markedly diminished. A minor by-product of this acetylation reaction was 2-methyl-(methyl 7,8,9-tri-O-acetyl-2,6-anhydro-2,3,5-trideoxy-D-glycero-D-talo-non-2-enonate)-[ 4,5-d]-2-oxazoline. Based upon this finding and additional interconversion experiments, a mechanism involving the intermediacy of the latter oxazoline to account for the epimerization is proposed. These glycals and their methyl esters are competitive inhibitors of Arthrobacter sialophilus, neuraminidase, suggesting that the 4-hydroxyl group must be equatorially oriented for maximal enzyme inhibition.
Asunto(s)
Ácido N-Acetilneuramínico/análogos & derivados , Neuraminidasa/antagonistas & inhibidores , Ácidos Siálicos/síntesis química , Arthrobacter/enzimología , Cinética , Espectroscopía de Resonancia Magnética , Ácidos Siálicos/farmacología , Relación Estructura-ActividadRESUMEN
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.
Asunto(s)
Bacterias/efectos de los fármacos , Citocalasinas/farmacología , Arthrobacter/efectos de los fármacos , Arthrobacter/metabolismo , Glucosa/metabolismo , Conformación Molecular , Relación Estructura-ActividadRESUMEN
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.
Asunto(s)
Medicina Ayurvédica , Obesidad/tratamiento farmacológico , Peso Corporal/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , MasculinoRESUMEN
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).
Asunto(s)
Panax , Esfuerzo Físico/efectos de los fármacos , Extractos Vegetales , Plantas Medicinales , Withania , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Cromatografía en Capa Delgada , Masculino , Ratones , Músculos/efectos de los fármacos , Ratas , Estrés Fisiológico/prevención & control , NataciónRESUMEN
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.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Inflamación/terapia , Medicina Ayurvédica , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Extractos Vegetales/farmacología , Withania , Adyuvantes Inmunológicos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Miembro Posterior , Hipersensibilidad Tardía/inmunología , Hipersensibilidad Tardía/terapia , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacología , India , Inflamación/inmunología , Ratones , Ratones Endogámicos , Extractos Vegetales/uso terapéuticoRESUMEN
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.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plantas Medicinales/análisis , Animales , Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/fisiopatología , Artritis Reumatoide/fisiopatología , Edema/inducido químicamente , Edema/tratamiento farmacológico , Hipersensibilidad Tardía/fisiopatología , India , Masculino , RatonesRESUMEN
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.
Asunto(s)
Eritrocitos/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Medicina Ayurvédica , Extractos Vegetales/farmacología , Animales , Anticuerpos/inmunología , Recuento de Células/efectos de los fármacos , Inmunización , Ratones , Ratones EndogámicosRESUMEN
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.
Asunto(s)
Materia Medica/uso terapéutico , Osteoartritis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Zinc/uso terapéutico , Adulto , Método Doble Ciego , Composición de Medicamentos , Femenino , Humanos , India , Masculino , Materia Medica/efectos adversos , Medicina Ayurvédica , Persona de Mediana Edad , Osteoartritis/diagnóstico por imagen , Extractos Vegetales/efectos adversos , Radiografía , Zinc/efectos adversosRESUMEN
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.
Asunto(s)
Hipertensión/tratamiento farmacológico , Cloruro de Magnesio/uso terapéutico , Cloruro de Potasio/uso terapéutico , Adulto , Colesterol/sangre , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/sangre , Cloruro de Magnesio/administración & dosificación , Masculino , Persona de Mediana Edad , Cloruro de Potasio/administración & dosificaciónRESUMEN
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.
Asunto(s)
Peso al Nacer , Tamaño Corporal , Ácido Fólico/administración & dosificación , Complicaciones del Embarazo , Deficiencia de Vitamina B 12/complicaciones , Vitamina B 12/administración & dosificación , Complejo Vitamínico B/administración & dosificación , Antropometría , Suplementos Dietéticos , Femenino , Ácido Fólico/farmacología , Cabeza , Hematínicos , Homocisteína/sangre , Humanos , India , Necesidades Nutricionales , Embarazo , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/prevención & control , Tórax , Vitamina B 12/farmacología , Complejo Vitamínico B/farmacología , Adulto JovenAsunto(s)
Medicina Ayurvédica , Farmacoepidemiología , Fitoterapia , Plantas Medicinales , Humanos , IndiaRESUMEN
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.
RESUMEN
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.