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Five clerodane diterpenoids have been isolated from the aerial parts of Pulicaria wightiana along with 3'5,6-trihydroxy-3,4',7-trimethoxyflavone and 2-methyl-5-hydroxy-chroman-4-one. The structures and stereochemistry of the compounds were established from spectral (mainly 1D and 2D NMR) studies. The last two compounds were not reported earlier from this plant. The antibacterial activity of the diterpenoids were studied.

This article reviews the recent advances made in the field of human leishmaniasis. Special emphasis is placed upon the application of various molecular tools for accurate and rapid diagnosis, understanding the mechanisms of drug resistance and identification of vaccine candidates. The focus will be on the major role played by recombinant antigens in the immunoserodiagnosis and progress of the Leishmania genome project, which has enabled researchers to design better PCR primers and molecular probes for microarrays. A special interest is placed on the recombinant antigen (rK39) cloned from the Leishmania chagasi kinesin gene and a very recently cloned recombinant antigen (KE16) from the Old World Leishmania donovani species with high sensitivity and specificity. Advances made in the specific PCR primer designed to diagnose and differentiate various species and strains of Leishmania causing visceral and post-kala-azar-dermal leishmaniasis have been covered. Molecular methods (e.g., DNA and protein microarrays) applied to understanding the pathobiology of the parasite, mechanism of host invasion, drug interaction and drug resistance to develop effective therapeutic molecules, gene expression profiling studies that have opened doors to understand many host-parasite relations, effective therapy and vaccine candidates are extensively covered in this review.

An efficient and facile chemoenzymatic synthesis of levamisole by employing lipase-mediated resolution of 3-hydroxy-3-phenylpropanenitrile followed by its conversion to beta-amino alcohol as the key intermediate is described.

High fructose feeding in rats induces insulin resistance, hyperinsulinemia, hyperglycemia and dyslipidemia. The present study was undertaken to determine the hypolipidemic effect of food seasoning spices mixture on fructose-fed insulin resistant rats. Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the spices mixture at three different doses (10 mg, 30 mg or 50 mg/day/rat) orally 15 days later. At the end of 45 days of the experimental period fructose-fed rats displayed elevated plasma glucose and insulin levels and dyslipidemia which included elevated levels of cholesterol, triglycerides, free fatty acids, reduced high density lipoprotein cholesterol and increased very low density lipoprotein cholesterol. Alterations in tissue lipid levels were also observed. Simultaneous treatment with spices mixture along with fructose diet resulted in the normalization of plasma glucose and insulin levels and restoration of lipid levels in plasma and tissues. The insulin potentiating action of the active principles in these spices may contribute to the hypolipidemic effect of spices mixture in high fructose-fed rats.

Leishmaniasis is a parasitic disease caused by a hemoflagellate, Leishmania spp. The parasite is transmitted by the bite of an infected female phlebotomine sandfly. The disease is prevalent throughout the world and in at least 88 countries. Human leishmanial infections may manifest in any of the four most common forms. Depending on the causative species, it can manifest as cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), diffused cutaneous leishmaniasis (DCL), or visceral leishmaniasis (VL). Although there are nearly 25 compounds having antileishmanial effects, only a few are used for humans and most of these are parenteral. The oldest was urea stibamine, developed in India in 1922. The original drug had severe toxic effects, and later on its pentavalent compounds were prepared, which remained the sole treatment modality for several decades and saved millions of lives. However, reports of unresponsiveness to pentavalent sodium antimony gluconate (SAG) started in the 1970s, and in some parts of India about a quarter of kala-azar cases are reported to have developed resistance even to its higher doses. This development led to successful clinical trials of pentamidine and amphotericine B. The latter, an antifungal compound, was also found to be highly nephrotoxic, and to minimize these side effects various colloidal and lipid formulations have been prepared. These preparations are comparatively safe but are exorbitantly costly. In the past two decades, more focus has been given to finding oral drugs to minimize injection-associated complications, including blood-borne infection. Various drugs were reported effective, including antifungal ketoconazole. However, the most promising drug found is an anticancer compound, miltefosine, that belongs to the alkylphosphocholine group. The drug has undergone experimental and clinical trials and found to be 94%-97% effective. However, the drug cannot be given during pregnancy and shows severe gastrointestinal side effects. Moreover, its cost will be another limiting factor. Other drugs such as paromomycin, allopurinol, and sitamaquine have been reported with variable cure rates. Because of these limitations, a combination therapy, preferably coupled with specific parasite enzyme inhibitors, is the only hope.

New pyrrolobenzodiazepine-anthraquinone hybrids have been designed and synthesized, found to effectively bind to DNA and also exhibit cytotoxicity against many cancer cell lines

Background: Identification of basic prognostic indicators of HIV infection is essential before widespread antiretroviral therapy can be implemented in low-technology settings. This study assessed how well body mass index (BMI:kg/m2) predicts survival., Methods: BMI within 3 months of HIV diagnosis was obtained from 1657 patients aged > or = 15 years, recruited in a seroprevalent clinical cohort in The Gambia since 1992 and followed up at least once. Baseline CD4+ counts and clinical assessment at time of diagnosis were done., Results: The mortality hazard ratio (HR) of those with a baseline BMI <18 compared with those with a baseline BMI > or = 18 was 3.4 (95% CI, 3.0-3.9). The median survival time of those presenting with a BMI <16 was 0.8 years, in contrast to a median survival of 8.9 years for those with a baseline BMI > or = 22. Baseline BMI <18 remained a highly significant independent predictor of mortality after adjustment for age, sex, co-trimoxazole prophylaxis, tuberculosis, reported wasting at diagnosis, and baseline CD4+ cell count (adjusted HR = 2.5, 95% CI 2.0-3.0). Sensitivity and specificity of baseline BMI <18 was comparable to that of a CD4+ count <200 in predicting mortality within 6 months of diagnosis., Discussion: BMI at diagnosis is a strong, independent predictor of survival in HIV-infected patients in West Africa. In the absence of sophisticated clinical and laboratory support, BMI may also prove a useful guide for deciding when to initiate antiretroviral therapy.

Background: In sub-Saharan Africa, tuberculosis (TB) is the most frequently diagnosed opportunistic infection and cause of death among HIV-infected patients. HIV-2 has been associated with less immune suppression, slower disease progression and longer survival., Objective: To examine whether the incidence of TB and survival after TB are associated with CD4 cell count rather than HIV type., Methods: Clinical and immunological data were retrospectively evaluated among an open clinic-based cohort of HIV-1- and HIV-2-infected patients to determine incidence of TB (first diagnosis > 28 days after HIV diagnosis) and subsequent mortality. Patients were grouped by CD4 cell count into those with < 200, 200-500 and > 500 x 10 cells/l., Results: Incident TB was diagnosed among 159 of 2012 patients, with 4973 person-years of observation time. In 105/159 (66.0%), the diagnosis was confirmed by direct microscopy or culture. Incidence of TB was highest in the group with < 200 x 10 cells/l (9.1/100 and 8.8/100 person-years in HIV-1 and HIV-2, respectively). Adjusted for CD4 cell count, there was no significant difference in incidence or mortality following TB between HIV-1- and HIV-2-infected patients. Mortality rate was higher in those with incident TB and HIV infection, most markedly in the group with the highest CD4 cell count (hazard ratio, 10.0; 95% confidence interval, 5.1-19.7)., Conclusion: Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.

Three deoxypreussomerins, palmarumycins CP1, JC1 and JC2, have been isolated from a collection of the stems of Jatropha curcas. The second and third compounds are antibacterial constituents which were characterized from spectral evidence. The X-ray crystallographic structure of palmarumycin JC1 was also studied. Deoxypreussomerins have been obtained here from a plant source in appreciable quantities.

Chemical investigation on Jatropha curcas resulted in the isolation of twenty constituents among which four diterpenoids were unknown and six compounds, tetradecyl-(E)-ferulate, 3-O-(Z)-coumaroyl oleanolic acid, heudelotinone, epi-isojatrogrossidione, 2alpha-hydroxy-epi-isojatrogrossidione, and 2-methyanthraquinone had not been reported earlier from this species. The structures of the new compounds were established by extensive studies of their 1D- and 2D-NMR spectra.

Fewer people infected with human immunodeficiency virus (HIV) type 2 progress to acquired immunodeficiency syndrome, compared with those infected with HIV-1. To understand the immune mechanisms leading to slow progression in HIV-2 infection, cell-mediated immune responses were compared between the 2 infections in asymptomatic subjects with a CD4 cell count > or =20%. Interferon- gamma release from T lymphocytes and the cytotoxicity of CD8+ T lymphocytes were measured by ELISPOT and 51Cr release assays. The level of responses and the proportion of responders were similar in the 2 infections, despite a 20-fold difference in their geometric mean plasma virus loads. The proliferation of CD4+ T helper cells, which was evaluated by thymidine incorporation, was not different between the 2 infections. Contrary to widely held views, our results suggest that nonprogression in HIV-2 infection may not be due to more vigorous immune responses.

Background: The risk of mother-to-child transmission (MTCT) of HIV-2 is much lower than that of HIV-1, but the long-term prognosis of perinatally infected HIV-2 children is unknown. We re-visited children who were part of a large MTCT study in The Gambia (conducted during 1993-1997), in order to compare the long-term survival of children perinatally infected with HIV-2 with that of seronegative and of HIV-1 infected children., Methods: Five to eight years' follow-up of a cohort of children born to HIV-negative, HIV-1 positive, and HIV-2 positive mothers., Results: Seven hundred and seventy-four children were followed up for a median of 6.6 years. Of 17 perinatally HIV-1 infected children, three were still alive on 1 July 2001, two had been lost to follow-up, and 12 had died. The median survival was 2.5 years. Of eight HIV-2 infected children five were still alive, none were lost to follow-up and three had died. The mortality hazards ratio of both HIV-1 [9.9; 95% confidence interval (CI), 5.2-19], and of HIV-2 infected children (3.9; CI, 1.2-12) was significantly increased compared with children of seronegative mothers. The mortality hazards ratio of HIV uninfected children of HIV-1 or HIV-2 infected mothers was not significantly increased compared to that of children of seronegative mothers (P = 0.17 and P = 0.5 respectively)., Conclusions: Children with perinatally acquired HIV-2 infection have a higher mortality than children of seronegative mothers. Guidelines for treatment of HIV-1 infected children should be used for treatment of HIV-2 infected children.

Objective: To monitor HIV-1 and HIV-2 trends in The Gambia, West Africa., Methods: In 1993-1995 a nationwide survey among 29 670 pregnant women attending eight antenatal clinics estimated the seroprevalence of HIV-1 at 0.6%, and of HIV-2 at 1.1%. Five years later, sentinel surveillance in pregnant women was established, using unlinked anonymous testing in four clinics. A dried blood spot on filter paper was obtained and tested for HIV antibodies., Results: Between May 2000 and August 2001, 8054 analysable samples were collected at four sites. The prevalence of HIV-1 rose sharply in one rural area from 0.6 to 3.0% (P < 0.0001), but the increase was small and non-significant in two other rural sites and in the urban site. The prevalence of HIV-2 did not change significantly at any of the sites. The overall prevalence of HIV-1 was 1.0% [95% confidence interval (CI) 0.8-1.3%], and of HIV-2 0.8% (CI 0.6-1.0%). Site, nationality and higher age were significantly associated with HIV-1 infection, and higher parity and site were significantly associated with HIV-2 infection., Conclusion: Fifteen years after the first case of HIV-1 was described in The Gambia, the epidemic is still at a low level. There is heterogeneity within the country, with one rural area experiencing a fivefold increase in 6 years. The prevalence of HIV-2 in The Gambia is stable.

Objective: To examine baseline plasma viral loads according to the CD4 cell percentage (CD4%) in HIV-1, HIV-2 and dually infected patients (HIV-D), and to relate these measurements to survival., Patients and Methods: A total of 119 HIV-1, 137 HIV-2 and 81 HIV-D-infected patients attending the Medical Research Council clinic in The Gambia were recruited from 1991 according to baseline CD4%, and followed until death or the end of December 2000. HIV-1 and HIV-2 RNA levels were measured by in-house reverse transcriptase polymerase chain reaction assays., Results: The plasma viral load, which varied inversely with CD4%, was similar in HIV-1 singly and dually infected patients, but was significantly higher in HIV-1 than in HIV-2 singly infected patients, except in those with a CD4% less than 14%. HIV-2 plasma viral load in dually infected patients did not vary significantly with CD4%, but was significantly lower than in HIV-2 singly infected patients with CD4% less than 14%. Multivariate analysis showed that only CD4% was independently associated with survival in HIV-1 and HIV-D infections; whereas both CD4% and plasma viral load were independently associated with survival in HIV-2 infections. The mortality rate of HIV-D-infected patients was not significantly different from that of HIV-1-infected patients, but was significantly higher in the absence of HLA B58., Conclusion: HIV-2 infection does not alter HIV-1 replication or prolong survival in dually infected patients. In a clinical setting in Africa, where many patients present with advanced disease, CD4% may be a more important predictor of prognosis than plasma viral load.

The Clustal series of programs are widely used in molecular biology for the multiple alignment of both nucleic acid and protein sequences and for preparing phylogenetic trees. The popularity of the programs depends on a number of factors, including not only the accuracy of the results, but also the robustness, portability and user-friendliness of the programs. New features include NEXUS and FASTA format output, printing range numbers and faster tree calculation. Although, Clustal was originally developed to run on a local computer, numerous Web servers have been set up, notably at the EBI (European Bioinformatics Institute) (http://www.ebi.ac.uk/clustalw/).

Functional electrical stimulation is used to restore movement and function of paralyzed muscles by activating skeletal muscle artificially. An accurate and predictive mathematical model can facilitate the design of stimulation patterns that produce the desired force. The present study is a first step in developing a mathematical model for non-isometric muscle contractions. The goals of this study were to: (1) identify how our isometric force model's parameters vary with changes in knee joint angle, (2) identify the best knee flexion angle to parameterize this model, and (3) validate the model by comparing experimental data to predictions in response to a wide range of stimulation frequencies and muscle lengths. Results showed that by parabolically varying one of the free parameters with knee joint angle and fixing the other parameters at the values identified at 40 degrees of knee flexion, the model could predict the force responses to a wide range of stimulation frequencies and patterns at different muscle lengths. This work showed that the current isometric force model is capable of predicting the changes in skeletal muscle force at different muscle lengths.