In vitro and in vivo evaluation of a standardized Curcuma longa Linn formulation in cervical cancer.

BACKGROUND: The anti-cancer activity of phytomolecules present in turmeric or haridra (Curcuma longa Linn) extracts against cancer has been described in various 'in vitro and in vivo' studies. OBJECTIVE: In the present study, in vitro and in vivo anti-cancer and chemo-preventive activity of a new standardized Supercritical Turmeric Oil Extract (SCTOE) NBFR-03 was evaluated in cervical cancer models. METHODS AND MATERIALS: In vitro cytotoxicity of this formulation was assessed at 10, 20, 40, and 80 µg/ml concentrations, in three cervical cancer cell lines (HeLa, SiHa, ME180) using Sulforhodamine B assay. The in vivo anti-cancer activity was evaluated in two groups of female nude mice; the first one was with tumor xenograft implants and at the same time treatment was started with 96 µl/kg/day p.o. and 192 µl/kg/day p.o. NBFR-03 for three months. The second group was kept as chemoprevention group where mice were pre-treated with the formulation (96 µl/kg/day p.o.) for two weeks and injected with cancer cell suspension with continued treatment for three months. RESULTS: No cytotoxicity was seen in any cell line with the extract when compared to positive control (Adriamycin 10 µg/ml). In mice the first treatment group with tumor xenograft implants did not show any significant anti-tumor activity but showed a trend where higher dose group had smaller tumor volumes as compared to lower dose group and controls (p = 0.37 and p = 0.34 respectively). The chemopreventive group with pre-treated mice also showed smaller tumor size as compared to controls (p = 0.163). CONCLUSION: NBFR-03 turmeric oil extract showed a promising trend in mice pre-treated with NBFR-03. There is a scope for further studying the potential of this extract as complementary therapy and as a chemopreventive.

Oral metronomic scheduling of anticancer therapy-based treatment compared to existing standard of care in locally advanced oral squamous cell cancers: A matched-pair analysis.

CONTEXT: Head and neck cancers in developing countries present with advanced disease, compounded by poor access to tertiary care centers. AIM: We evaluated oral metronomic scheduling of anticancer therapy (MSAT) in advanced operable oral cancers, in conjunction with standard therapy. SETTINGS AND DESIGN: This was a retrospective matched-pair analysis carried out in a tertiary referral cancer center. MATERIALS AND METHODS: Advanced operable oral cancer patients having a waiting period for surgery > 3 weeks were administered MSAT. Patients then underwent standard therapy (surgery +/- adjuvant radiation/chemoradiation) as warranted by the disease, followed by MSAT maintenance therapy. Outcomes of the MSAT group were compared with stage-matched controls with similar waiting periods. STATISTICAL ANALYSIS: Survivals were found using the Kaplan-Meier method and compared between groups using the log rank test. RESULTS: Response was seen in 75% of 32 patients. Two-year disease-free survivals (DFS) in MSAT and control groups were 86.5 and 71.6%, respectively. Two-year DFS in MSAT group who received at least three months of MSAT was 94.6% (P = 0.03). CONCLUSIONS: Oral MSAT is an economical, effective, and safe adjuvant therapy for oral cancers. It has the potential for preventing progression of the disease and improving DFS.

Minor salivary gland tumors of the oral cavity: a case series with review of literature.

BACKGROUND: Minor salivary gland tumors (MSGTs) are unusual, accounting for only 15-20% of all salivary gland tumors. The commonest site of MSGTs of the head and neck is oral cavity. AIMS: To describe our experience with MSGTs of oral cavity seen over a period of one decade and elucidate their prognostic factors. MATERIALS AND METHODS: Over a period of 10 years, from 1991 to 2000, all MSGTs of oral cavity were analyzed. All demographic, treatment and survival data were recorded. Kaplan-Meier curves were used to find the survival. Multivariate analysis was performed using Cox regression. RESULTS: We treated 104 patients with curative intent. The commonest site was hard palate, accounting for 54.8% of all sites. The commonest histology was adenoid cystic carcinoma (45.2%). There were 17 (16.34%) pleomorphic adenoma cases, while the remaining 87 (83.66%) were minor salivary gland malignancies. Treatment was surgical in 91.3% of patients. Adjuvant radiotherapy was administered in 38.5% of patients. The median follow-up was 50 months. Recurrences were seen in 22 (25.3%) of the 87 malignant cases. Using Kaplan-Meier analysis, the expected 10-year overall and disease-free survivals were 75.2 and 65.8%, respectively. Survivals were better in non-adenoid cystic tumors (non-ACC). On multivariate analysis, T status, tumor grade and adjuvant therapy were independent prognostic factors for disease-free survival. CONCLUSIONS: MSGTs of oral cavity have good overall survival despite recurrences. T stage, adjuvant radiotherapy and grade are independent prognostic factors for disease-free survival. Adenoid cystic tumors have worse outlook than non-ACC.

Growth inhibition of struvite crystals by the aqueous root extract of Rotula aquatica.

Formation of urinary stone is a serious and debilitating problem throughout the world. In the present study, the inhibitory effect of aqueous extract of root of Rotula aquatica was investigated against struvite crystals (one of the components of urinary stone) grown in vitro using single diffusion gel growth technique. For setting the gel, sodium metasilicate solution (specific gravity 1.05) and 0.5 M aqueous solution of ammonium dihydrogen phosphate were mixed, so that the pH of the mixture could be set at 7.0. Equal amounts of supernatant solution of magnesium acetate (1.0 M) prepared with 0.0%, 0.5% and 1% concentrations of the extract were gently poured on the set gels. It was observed that the number, dimension, total mass, total volume, growth rate and depth of growth of struvite crystals decreased with the increasing extract concentrations in the supernatant solutions. The enhancement of dissolution rate and fragmentation of struvite crystals suggested potential application of the extract for inhibition of struvite type urinary stone.

Growth inhibition of struvite crystals in the presence of herbal extract Commiphora wightii.

Struvite is one of the components of urinary stone. Large number of people is suffering from urinary stones (calculi) problem all over the globe. These stones can grow rapidly forming "staghorn-calculi", which is more painful urological disorder. Therefore, it is of prime importance to study the growth and inhibition of Struvite crystals. This in vitro study has been carried out in the presence of herbal extract of Commiphora wightii by using single diffusion gel growth technique. Sodium metasilicate solution of specific gravity 1.05 and an aqueous solution of ammonium dihydrogen phosphate of 0.5 M concentration were mixed so that the pH value 7.0 could be set. After the gelation, equal amount of supernatant solutions comprising of pure 1.0 M magnesium acetate as well as the mixtures of magnesium acetate and the herbal extract solutions of 0.5 and 1% concentrations of C. wightii were gently poured on the set gels. From the study of growth and inhibition behavior of Struvite crystals, it was found that C. wightii inhibits the growth of the Struvite. This study incorporates multidisciplinary interests and may be used for formulating the strategy for prevention or dissolution of urinary stones.

Plasma levels of genistein following a single dose of soy extract capsule in Indian women.

BACKGROUND & OBJECTIVE: Soy isoflavones are being used as therapy for menopausal syndrome in many countries. Marketed preparations show variability in bioavailability and there are variations in kinetics due to ethnicity and diet. Inspite of soy isoflavone being available in the Indian market there are no studies to show whether the preparation is likely to be effective in women. This study was carried out to determine circulating levels of genistein, a bioactive soy isoflavone, in Indian women after a single dose of soy extract. METHODS: Six healthy vegetarian women volunteers, between 36 and 62 yr and with a mean body mass index (BMI) 25.01+/-2.02 (kg/m2), were enrolled after an informed consent. Women with antibiotic or Soy food intake within 1 month of study were excluded. A single dose of standardized soy extract capsule containing 64.12 mg of total isoflavones (genistein content equivalent to 31.76 mg) was ingested under supervised fasting condition and multiple blood samples were collected at 0, 1, 2, 4, 6, 8 and 24 h. Genistein levels were measured by high performance liquid chromatography (HPLC) method with a detection level of 2.5 ng/100 microl of injection volume. The intra- and inter-assay coefficients of variation were < 5.32 per cent. RESULTS: Genistein was detected (10.3 to 16.2 ng/ml) in 3 volunteers in baseline samples. Within one hour genistein levels rose from 42 ng to 215 ng/ml with a maximum concentration of 117 to 380 ng/ml at 4 to 8 h. A secondary peak suggestive of enterohepatic circulation was seen between 4 and 6 h in 2 out of 6 volunteers. The mean Cmax was 315.5 +/- 57.1 ng/ml. All women had detectable levels from 25.2 to 109.3 ng/ml at 24 h. INTERPRETATION & CONCLUSION: Our study showed adequate circulating levels of genistein in Indian vegetarian women after a single dose of soy extract. Variability in plasma levels of the soy isoflavones may explain differences in responses to therapy.

Hyperhomocysteinemia as a cardiovascular risk factor in Indian women: determinants and directionality.

OBJECTIVE: To assess Homocysteine (Hcy), vitamin B12 and folic acid (FA) concentrations in resident Indian women and to study their correlation with traditional risk factors for coronary artery disease. MATERIAL AND METHODS: The study included 137 consecutive women who attended a health care program (HCP) for women at and above 40 years of age (MAITREYI's HCP). Fasting blood samples for Hcy, B12 and folate were collected on ice, centrifuged within 1/2 hour and stored at -70 degrees C till assayed using a chemiluminescence method. All women underwent a screening for their general health profile including cardiovascular health. RESULTS: Of the 137 women screened 21 were excluded because of presence of factors known to affect Hcy levels (history of existing CAD had hypothyroidism or were on multivitamin supplements). The median Hcy, folic acid and vitamin B12 levels were 9 pmol/L (range 4.2-38.6), 8.8 ng/ml (2.3-31.6 range) and 214 pg/ml (100-2400 range) respectively. The prevalence of hyperhomocysteinemia (>15 pmol/L) was 24.2%. Correlation for continuous variables using spearman's test and for categorical variables with chi-square test showed a highly significant negative correlation with vitamin B12 (p < 0.001) and FA (p<0.002). Both systolic (p < 0.05) and diastolic (p < 0.02) and diastolic blood pressure also showed a significant correlation. However, no correlation was found between plasma Hcy and blood sugars, lipids, age, body mass index and menopausal status. The CAD risk was assessed using Framingham risk scores and this too did not show a correlation with plasma Hcy. CONCLUSIONS: A large number of women from the present study had hyperhomocysteinemia and were deficient in vitamin B12. A significant negative correlation between vitamin B12 and plasma Hcy levels was foundin these older women. Most Indian studies including the present one do not show a positive correlation between elevated Hcy levels and CAD in spite of a large percentage of persons showing elevated homocysteine levels. Since high Hcy levels are recognized as an independent risk factor for CAD, these findings of absence of correlation between Hcy and CAD as reported in various Indian studies need to be explored and explained.

Clinical, endocrine and metabolic studies in the kindred of familial partial lipodystrophy--a syndrome of insulin resistance.

OBJECTIVE: To study clinical, endocrine and metabolic profiles in the kindred of subjects with familial partial lipodystrophy (FPLD, Dunnigan type). MATERIAL AND METHODS: Twenty two relatives (10 males, 12 females), from an extended family with FPLD, were assessed for the phenotypic features, impaired glucose tolerance (IGT)/diabetes mellitus (DM), dyslipidemia and the presence of insulin resistance. Plasma glucose and serum lipids were measured using glucose oxidase and standard colorimetric methods. Serum insulin was estimated by radioimmunoassay. RESULTS: The age was 12 to 67 years, two being adolescents. Two of the 20 adults were overweight and eight were underweight; BMI (adults) was 15.5 to 28.5. Features of FPLD were evident among eight out of 12 women. This typical phenotype was not obvious in all 10 male members. Varying degree of Hirsuitism was observed in four of 12 women, acanthosis nigricans in 11 out of 22 members and skin tags were present in only eight of 22; hypertension in six members and diabetes in four. Eleven members had either impaired glucose tolerance (IGT) (n=7), or DM (n=4). Ten of 20 members showed hyperinsulinemic response on oral glucose tolerance test (OGTT). Dyslipidemia was present in 13 family members. CONCLUSION: The majority (2/3rd) of female members showed typical phenotypic features of FPLD, with a clustering of cardiovascular risk factors and insulin resistance syndrome. More than half the men without phenotypic features of FPLD had either IGT/DM, dyslipidemia, hypertension or cardiovascular disease.

A novel approach to study antibacterial properties of volatile components of selected Indian medicinal herbs.

The aromatic substances of natural origin are used medicinally in Ayurveda, and can have diverse bio-dynamic actions. The existing methods like agar-cup method or disc diffusion method are not adequate to study the exclusive antibacterial effects of the volatile components of aromatic oils due to lack of ideal diffusion and evaporation from the surface. Hence an attempt is made to develop a novel approach to assess the antibacterial activity of few aromatic herbs like Eugenia caryophyllus, Thymus vulgaris, Cinnamonum zeylanium, Cuminum cyminum; these were extracted with hexane filled in tiny sterile tubes and the volatile components were tested for their antibacterial properties using standard strains of gram +ve and gram -ve bacteria grown on agar slants. The results are expressed as a percent of inhibition of the area on the slants, from the top of the extract tube. Of the four herbs selected, volatile components of Thymus vulgaris were most effective againsts all the seven test organisms.