A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

Effect of Vitamin D Supplementation on Thyroid Autoimmunity among Subjects of Autoimmune Thyroid Disease in a Coastal Province of India: A Randomized Open-label Trial.

OBJECTIVE: Hashimoto's thyroiditis (HT) is a variant of autoimmune thyroid disorders (AITD) which has been associated with vitamin D (vit-D) deficiency. However, whether vit-D supplementation is linked to reduction of thyroid autoantibodies and improvement of thyroid function is not well characterized. The present study was planned to evaluate the effect of vit-D supplementation on possible improvement of thyroid autoantibody titer and thyroid hormone profile in patients with AITD subjects. METHODS: Twenty-three patients of HT were given weekly supplementation of 60,000 IU vit-D for 8 weeks followed by once a month for another 4 months. After 6 months of vit-D supplementation, thyroid autoantibody titer (TPO antibody) and thyroid hormone profile was rechecked. RESULTS: Mean serum vit-D was increased significantly from 15.33 ± 5.71 to 41.22 ± 12.24 ng/mL (normal levels) after supplementation. There was significant increase in thyroid autoantibody titre (from 746.8 ± 332.2 to 954.1 ±4 59.8 IU/ml; P = 0.006) and TSH level (7.23 ± 3.16 to 3.04 ± 2.62 (mIU/L); P = 0.01) following 6 months of vit-D supplementation. CONCLUSION: Vitamin-D levels were low in AITD patients in eastern India and, its supplementation in HT patients increased thyroid antibody titer and there was significant reduction in serum TSH and increased in free T4.

Assessment of clinical outcomes and prescribing behavior among inpatients with severe preeclampsia and eclampsia: an Indian experience.

OBJECTIVES: The study aims to evaluate the management, maternal-fetal outcomes, and prescription behavior among inpatients with severe preeclampsia and eclampsia. MATERIALS AND METHODS: This prospective cohort study in a tertiary referral center was conducted in 164 inpatient pregnant women who fulfilled the inclusion criteria. The study was conducted between November 2005 and February 2007. The patients were followed-up till delivery. Antepartum and intrapartum care and maternal and perinatal outcome were noted. Chief outcome measures were maternal and perinatal mortality and drug use indicators. RESULTS: Median age at delivery of the women was 25 (22-28) years. Majority were suffering from antepartum eclampsia (52.5%), followed by preeclampsia (31%) and postpartum eclampsia (16.5%). Nulliparity (61.6%) was more common in eclampsia, while multiparity in preclamptic group. A total of 48% had preterm delivery. Most presented with headache (50%) and hyperreflexia (29%). Only 15% presented with all three prodromal symptoms and 86% had hypertension. There was increased morbidity, operative intervention, and admission to intensive care unit. Most babies (67%) weighed <2.5 kg and had poor outcome. The maternal mortality was 0.4/1000. Average number of drugs prescribed in patients of preeclampsia, antepartum eclampsia, and postpartum eclampsia were 13.2, 14.9, and 14.2, respectively. Antibiotics (24.6%) were the most common class of the drugs prescribed in all the groups, followed by vitamin and calcium supplements (22.7%) and antihypertensives (13.5%). Most common antihypertensive used were calcium channel blockers and anticonvulsant magnesium sulphate. CONCLUSIONS: There was increased maternal and perinatal morbidity. Protocols for the management of eclampsia, including antihypertensive and anticonvulsant therapies, should be available and reviewed regularly to improve the standard of care and reduce the prevalence of this dangerous condition.

Low plasma levels of cholecalciferol and 13-cis-retinoic acid in tuberculosis: implications in host-based chemotherapy.

OBJECTIVE: The aim of this study was to estimate the concentration of cholecalciferol and 13-cis-retinoic acid (RA) in the plasma and pleural fluid of patients with tuberculosis (TB) against controls. METHODS: Plasma levels of cholecalciferol and 13-cis-RA were measured in 22 patients with TB and healthy controls and their pleural fluids levels were measured in 6 TB patients and diseased controls by established high-performance liquid chromatography-based procedure. RESULTS: Cholecalciferol levels in plasma and pleural fluid of patients with TB and healthy controls were 67.45 (10.71) nmol/L and 21.40 (8.58) nmol/L compared with 117.43 (18.40) nmol/L (P < 0.001) and 94.73 (33.34) nmol/L (P = 0.0049), respectively. 13-cis-RA level in the plasma of patients with TB and healthy controls were 1.51 (0.72) nmol/L and 6.67 (0.81) nmol/L (P < 0.001), respectively. 13-cis-RA was not detectable in pleural fluid. The levels of both the agents were lower in patients with TB than in controls. CONCLUSION: It was observed that in patients with TB there is a combined deficiency of cholecalciferol and 13-cis-RA compared with healthy volunteers. Because cholecalciferol and 13-cis-RA are in equilibrium with active ingredients of vitamins A and D, we feel that there is a combined deficiency of these vitamins in patients with TB. There is an evidence that concomitant vitamin A and D supplementation can kill intracellular Mycobacterium tuberculosis in vitro. Therefore, the observations made in this study can pave the path for a trial of combined supplementation of available formulations of vitamin A and D (cholecalciferol and 13-cis-RA) for novel anti-tubercular drug therapy. Because such an approach is host-based it has potential to treat even multidrug-resistant and extensively drug-resistant forms of TB.

Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients.

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability-enhancer. The present study aimed at evaluating the effect of piperine on the steady-state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t-test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC(0-12hr) (p < 0.001), average C(ss) (p < 0.001), t(1\2el) (p < 0.05) and a decrease in K(el) (p < 0.05), in both the dose groups, whereas changes in K(a) and t(1\2a) were not significant. Cmax (p < 0.01) and t(max) (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption.

Evaluation of antihyperalgesic effect of curcumin on formalin-induced orofacial pain in rat.

The present study was planned to evaluate the role of curcumin in the formalin-induced orofacial pain in rats that mimics typical human orofacial pain. Adult Wistar rats of either sex received an injection of 50 microL of 5% v/v subcutaneous formalin injection into one vibrissal pad and consequent facial grooming behavior was monitored. Animals exhibited two distinct periods of nocifensive grooming: (a) an acute phase lasting 0-6 min; and (b) a tonic phase lasting 6-45 min. The analgesic response of curcumin was observed at doses of 25, 50, 100, 200, 400 and 600 mg/kg i.p., administered 15 min prior to formalin injection. Another group received subanalgesic dose of diclofenac (0.2 mg/kg) and curcumin 25 mg/kg. Curcumin and diclofenac were administered 15 and 5 min prior to formalin injection respectively. Curcumin produced a dose-dependent inhibition of facial grooming in both acute and tonic phases compared to vehicle and potentiated the subanalgesic dose of diclofenac. The study results for the first time demonstrated the per se antinocifensive effect of curcumin and also exhibited a synergistic interaction with the subanalgesic dose of an NSAID in the facial pain model. More studies are necessary to elucidate the mechanisms of curcumin in this model of pain.

Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy.

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.