Metabolic syndrome and central obesity in depression: A cross-sectional study.

INTRODUCTION: The current epidemiological data and meta-analyses indicate a bidirectional association between depression and metabolic syndrome (MetS). AIMS: To assess the prevalence of metabolic syndrome and obesity in drug naïve patients (in current episode) having Recurrent Major Depressive Disorder and Bipolar Depression. METHOD: This was a single point cross sectional observational study that involved administration of diagnostic and assessment tools and blood investigations. Recruitment for the study was done from a period of September 2008 to august 2009. RESULTS: The prevalence of MetS was significantly more in the depression group when compared to healthy controls. The Bipolar depression group had 24% prevalence and recurrent depression group had 26% prevalence as opposed to none in the control group. The prevalence of MetS did not differ significantly amongst the both depression groups. Presence of central obesity was significantly more in the recurrent depression (30%) and Bipolar depression (24%) as compared to controls (8%). There was no statistically significant difference between the two depression subgroups. DISCUSSION: Our study adds to the mounting evidence that links the presence of depression and metabolic syndrome. As we had ensured a drug free period of at least 3 months, the findings in our study indicate that the metabolic syndrome observed in our study is independent of drug exposure. CONCLUSIONS: This study demonstrated significantly more incidence of metabolic syndrome and central obesity in patients of depression than age and sex matched controls.

Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug.

Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T 1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85 ± 1.94 h, 13.77 ± 2.05 h, and 878.74 ± 133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment.

BACKGROUND: Brahmi (Bacopa monniera) is a traditional Indian medicinal plant which causes multiple effects on the central nervous system. The standardized extract of this plant has shown enhanced behavioural learning in preclinical studies and enhanced information processing in healthy volunteers. AIM: To study the efficacy of standardized Bacopa monniera extract (SBME) in subjects with age-associated memory impairment (AAMI) without any evidence of dementia or psychiatric disorder. METHODS: A double-blind, placebo-controlled randomized study design was employed. The subjects received either 125 mg of SBME or placebo twice a day for a period of 12 weeks followed by a placebo period of another 4 weeks (total duration of the trial 16 weeks). Each subject was evaluated for cognition on a battery of tests comprising mental control, logical memory, digit forward, digit backward, visual reproduction and paired associate learning. RESULTS: SBME produced significant improvement on mental control, logical memory and paired associated learning during the 12-week drug therapy. CONCLUSION: SBME is efficacious in subjects with age-associated memory impairment.

Antifungal Activity of a Phytoterpenoid (AOS-A) Isolated from Artabotrytis odoratissimus on Spore Germination of Some Fungi.

Phytoterpenoid isolated from Artabotrytis odoratissimus inhibited spore germination of some plant pathogenic as well as saprophytic fungi e.g. Alternaria alternata, A. solani, Cercospora sp., Curvularia maculans, C. pennisetti, Fusarium udum, Helminthosporium echinochlova, H. frumentacie, H. penniseti and Ustilago cynodontis. In Curvularia maculans and H. frumentacie, spore germination was completely inhibited at 2000 ppm. However, Curvularia maculans and C. pennisetti showed considerable sensitivity to this chemical even at 500 ppm.

Characterization of phenolic compounds in some Indian mango cultivars.

Mangoes (Mangifera indica) are rich in phenolic acids as detected by high-performance liquid chromatography. The phenolics have prominent medicinal properties. Among six important commercial mango cultivars (Deshi, Langra, Chausa, Mallika, Dashahari and Amrapali) tannic acid was maximal in Mallika, while gallic acid was maximal in Chausa and all other varieties. Caffeic acid was maximal in Langra followed by Chausa and Amrapali. Many of the pharmacological properties attributed to mango might be due to the presence of phenolic acids in fairly significant amounts.

Post-marketing surveillance of arteether in malaria.

OBJECTIVE: To undertake post-marketing surveillance (PMS) of arteether (E-Mal) with the aim of obtaining feedback from clinicians regarding its safety, tolerability, efficacy and adverse event profile in patients of P. falciparum malaria. METHOD: Post-marketing surveillance proforma to collect data from clinicians using arteether (E-Mal) was provided to institutions/nursing homes and hospitals where Arteether (E-Mal) was available for use in treatment of P. falciparum malaria. These clinicians were informed about the need and relevance of providing this feedback regarding their reexperience on E-Mal therapy on predesigned proforma. Duly filled proformas were received by Central Drug Research Institute, Lucknow for data analysis, documentation and conclusions regarding E-Mal therapy. RESULT: A total of 300 reports were received for analysis from states of Bihar, Gujarat, Madhya Pradesh, Maharashtra, Rajasthan and Uttar Pradesh. The results show that 294 cases (98%) were cured, five cases improved and one patient did not show any change in the clinical status. The side effects (headache, nausea, vomiting and giddiness) reported in the proforma of 14 cases were mild in nature and no causal relationship with arteether could be ascertained. CONCLUSION: An indepth analysis of these 300 reports confirmed the safety, highlighted excellent tolerability and further proved the efficacy of three-day schedule of arteether (IMI) for treatment of malaria. Arteether should not be used in P. Vivax malaria (E-Mal) except when smear is positive for both (P. falciparum and P. vivax). In such a situation risk-benefit should be carefully evaluated before advocating the use of E-Mal therapy. The post-marketing surveillance is continuing and it is hoped that with more feedback from the clinicians from various parts of the country PMS data on this novel antimalarial drug (E-Mal) would further be documented.

Efficacy of alkaloid (-)-corypalmine against spore germination of some fungi.

Inhibition activity of the alkaloid (-)-corypalmine on spore germination of plant pathogenic and saprophytic fungi (Alternaria solani, A brassicicola, A. brassicae, A. melongenae, Curvularia pallescens, C. lunata, C. maculans, Curvularisa sp., Colletotrichum sp., Helminthosporium speciferum, H. frumentacei, H. pennisetti, Heterosporium sp., Penicillum sp., Ustilago cynodontis) was determined. Spore germination of all the tested fungi was inhibited, Heterosporium sp. and Ustilago cynodontis being the most sensitive (complete inhibition of spore germination was observed at the very low concentration of 200 ppm). Curvularia palliscens, C. maculans and Curvularia sp. were less sensitive; complete inhibition of spore germination occurred at 400 ppm.

Comparative efficacy of centbutindole & risperidone in schizophrenia.

Centbutindole is a new antipsychotic agent related to butyrophenone group. The drug is dopamine antagonist but it also blocks 5HT(2) receptors. Clinically the drug has passed through phase I, II & III clinical trials successfully and it has shown effective antipsychotic activity in schizophrenic patients. In the present study the drug was compared with risperidone in a double blind manner for a period of 8 weeks to assess the efficacy in schizophrenic patients. Patients of schizophrenia evaluated on PANSS, CGI & UKU side effect rating scale weekly Out of 44 patients included in study, 38 completed the trial. The intergroup comparison of two drugs showed that centbudindole and risperidone have similar onset of antipsychotic action as both the drugs showed significant decrease in the total PANSS score as well as positive syndrome score, negative syndrome score and general psychopathology score from 2nd week onwards. The scores in both the groups showed a steady and significant decline from 2nd week to 8th week of study. The present study showed that centbutindole has similar improvement on clinical global impression with risperidone. The side effect profile was similar in the two drugs except dystonia (5 patients in centbutindole vs 1 patient in risperidone group). The findings of present study shows that Centbutindole could be used as a promising new drug for treatment of schizophrenia in place of a typical antipsychotics as it has shown improvement on negative symptoms similar to risperidone.

A multicentric study with arteether in patients of uncomplicated falciparum malaria.

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.

Individual and combined effects of berberine and santonin on spore germination of some fungi.

Berberine and santonin were isolated from rhizomes of Berberis aristata and unexpanded flower buds of Artemisia maritima, respectively. Efficacy of these two chemicals individually as well as of their mixtures, was tested against spore germination of some saprophytic and obligate fungi. While berberine individually was effective against most of the fungi, Helminthosporium spp. were least affected even at the highest dose (1500 ppm). Santonin was equally effective against several fungi. Mixture of both alkaloids found to be more effective than individual ones. Keeping the dose of berberine constant and santonin at two different concentrations (viz. 250 and 500 ppm) the spore germination of Helminthosporium oryzae was stimulated. Increasing concentration of santonin inhibited the spore germination of all other fungi tested, Colletotrichum capsici being affected only by 20 and 5% (at berberine concentration of 250 and 500 ppm, respectively). On the other hand, santonin being constant and berberine at different concentrations, the mixture was effective against all the fungi.

Multicentric clinical trials for safety and efficacy evaluation of alpha;beta arteether in complicated P. falciparum malaria.

OBJECTIVE: To evaluate efficacy of alpha;beta arteether in patients of P. falciparum malaria presenting with complications was undertaken in a multicentric clinical trial. METHOD: Each patient who consented to undergo clinical trial with parenteral Arteether was treated with a fixed dose schedule of Arteether given intramuscularly in a dose of 150 mg once a day on three consecutive days. Every patient was followed upto 28 days with clinical, haematological and parasitological monitoring every day upto one week and thereafter at 14, 21 and 28 days. The response was assessed in terms of fever clearance time, parasite clearance time, cure rate and parasite reappearance rate. RESULTS: A total of 211 patients of P. falciparum malaria were included in the study from four centres (Bhilai, Guwahati, Jamshedpur and Rourkela). Results of this study showed that fever clearance time ranged between 24-168 hours, parasite clearance time ranged between 24-120 hours and overall mortality ranged between 4-8.5%. Out of 211, only 14 patients expired during the study, of these, 10 patients expired within first two days i.e. before completing the three day schedule of arteether therapy. Tolerability to arteether injection was good in all these patients and no untoward effects were experienced or reported during the study. Overall cure rate observed in these studies was 93%. CONCLUSION: This study shows a rapid parasite and fever clearance in patients of complicated P. falciparum malaria.

Serum lipid profile in suicide attempters.

Practical difficulties associated with assessment of central parameters necessitates the development of peripheral markers of suicidal risk. Recent research suggest that serum lipid profile may be a useful indicator of suicidal behaviour. Serum lipid profiles of forty suicide attempters were compared with forty age, sex and BMI matched controls.Total serum cholesterol, serum Triglyceride, LDL levels and HDL levels were found to be lower in suicide attempters but were not statistically significant. Statistically significant negative con-elation was seen between risk-rescue score and above mentioned parameters. No statitically significant difference was observed when various diagnostic break-up groups of patients were compared.

A comparative efficacy study of centbutindole and haloperidol in schizophrenia.

A double blind study was undertaken to compare the efficacy between centbutindole and haloperidol. A total of 44 patients suffering from schizophrenia diagnosed in accordance to ICD-10 criteria were included. They were randomly assigned into two groups receiving centbutindole (4.5 mg) or haloperidol (15 mg) in two divided doses per day for six weeks. Each patient was evaluated on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI-S) and UKU side effect scale every week. Five patients (1 patient in centbutindole group, 4 patients in haloperidol group) dropped out due to various reasons. A total of 39 patients (21 patients in centbutindole group and 18 patients in haloperidol group) completed the study. The results revealed an early onset of therapeutic effect with centbutindole for both positive and negative symptoms. However, the efficacy was comparable between centibutindole and haloperidol from 3rd week onwards.

Multicentric efficacy study of centpropazine and imipramine in depressed patients.

Centpropazine is a new antidepressant with minimal anticholinergic effects in preclinical animal models. In this study centpropazine has been compared with imipramine in a double blind randomized multicentric study. A total of 159 patients of major depressive disorder (79 in centpropazine group and 80 in imipramine group) from four centres were included in this trial. Each patient was randomised to receive either centpropazine in a dose of 40 to 120 mg per day or imipramine in a dose of 50 to 150 mg per day for a period of six weeks. The antidepressant efficacy of centpropazine was comparable to imipramine but anticholinergic side effects were four times less than imipramine. This establishes centpropazine as an effective antidepressant with remarkably safer tolerability profile.

Serum lipids : new biological markers in depression ?

Several studies suggest that a low cholesterol concentration is associated with depression. The authors sought to determine whether an association exists between serum lipid concentrations and depression. 28 drug-naive patients of major depression diagnosed according to DSMlll- R criteria were included in the study and severity of depression was measured on Hamilton Rating Scale for Depression. Suicidal intent was assessed on Suicidal Intent Questionnaire. 28 normal healthy controls were selected and matched for age, sex and body-mass index with the depressives. Serum lipid estimations were done in each subject after 12 hours overnight fasting. The main finding of the study is that total serum cholesterol, serum triglycerides and serum LDL cholesterol are decreased while serum HDL cholesterol is increased in depression and these changes were more marked in depressed subjects with definite suicidal intent. On regression analysis, total serum cholesterol was the most important predictive variable of the severity of depression.

Effectiveness of alpha,beta-arteether in acute falciparum malaria.

With the emergence of widespread chloroquine resistance and a world-wide scarcity of quinine, a search for newer antimalarial drugs has become imperative. Different derivatives of qinghaosu have been successfully tried. alpha,beta-Arteether, an ethyl derivative of qinghaosu, was administered to 51 patients with Plasmodium falciparum malaria, in a dose of 150 mg intramuscularly once a day on 3 consecutive days. Complete parasite clearance from the peripheral blood was observed in 80% of the patients at 48 h and in 98% at 72 h. The median parasite clearance time was 2 d (range 1-4 d). 65% of the patients became afebrile within 48 h and 81% by 72 h. The mean fever clearance time was 52.04 h (standard deviation 27.09). No side effect was seen. Patients were followed-up for 4 weeks; 7 were readmitted with P. falciparum infection but it could not be ascertained definitely whether these cases were reinfections or recrudescences. alpha-beta Arteether was a safe, effective and convenient drug for treating P. falciparum malaria. This is the first clinical study with arteether in falciparum malaria.

Clinical efficacy of centporpazine-a new antidepressant.

Efficacy of centpropazine, a new antidepressant, has been evaluated in forty two patients of endogenous depression. The 4 week open trial was carried out in a dose-range of 40 to 120mg per day. A significant lowering of Hamilton Depression Rating Scale (HDRS) score was observed in 34 patient. The antidepressant effect could be detected in 9 patients within one week, in 28 cases in two weeks and in all the 34 patients by third week. Giddiness, headache, dryness of mouth and weakness were reported by 11 patients.

High performance liquid chromatographic (HPLC) determination of centchroman in human serum and application to single-dose pharmacokinetics.

A simple and sensitive (2 ng/ml) HPLC method with fluorescence detection has been developed to measure serum concentrations of centchroman, a new nonsteroidal antifertility agent. The method was sufficiently sensitive to follow the drug over 21 days in human volunteers. Pharmacokinetic parameters of centchroman were determined after a single oral dose of 60 mg (2 x 30-mg tablets) in two healthy female volunteers. Centchroman is slowly eliminated from serum, showing a biexponential disappearance curve from serum. The terminal half-life of centchroman in the two volunteers was 168 and 175 hr, respectively.