Bio-prospecting natural products for the development of Lead molecules.

Healing with medicinal plants is as old as mankind itself. The connection between man and his search for drugs in nature dates from the far past, of which there is ample evidence from various sources. Plants produce an enormous variety of natural products with high structural diversity. Chemical features of medicinal plants serve as an integral determinant of their pharmacological properties and enable their wide use in medical practice. Natural products have been the single most productive source of leads for the drug development. The use of combinatorial chemistry approaches are also based on natural product scaffolds to create screening libraries that closely resemble drug-like compounds. Currently various screening approaches are being taken up to improve the ease with which natural products can be used in drug discovery. In the area of cancer, more than 60% drugs are either natural products or directly derived there from. In other areas, the influence of natural product structures is quite marked, with, the anti-infective area mostly being dependent on natural products and their analogs. It is hoped that the more efficient and effective application of natural products will improve the drug discovery process.Digital copy of Ph.D thesis.University of Kashmir

Phytochemical Investigation of Rhododendron Lepidotum

Throughout the ages, humans have relied on Nature for their basic needs for the production of food-stuffs, shelters, clothing, means of transportation, fertilizers, flavours and fragrances, and, not the least, medicines. Plants have formed the basis of sophisticated traditional medicine systems that have been in existence for thousands of years and continue to provide mankind with new remedies. Although some of the therapeutic properties attributed to plants have proven to be erroneous, medicinal plant therapy is based on the empirical findings of hundreds and thousands of years. The first records, written on clay tablets in cuneiform, are from Mesopotamia and date from about 2600 BC; among the substances that were used were oils of Cedrus species (Cedar) and Cupressus sempervirens (Cypress), Glycyrrhiza glabra (Licorice), Commiphora species (Myrrh) and Papaver somniferum (Poppy juice), all of which are still in use today for the treatment of ailments ranging from coughs and colds to parasitic infections and inflammation

Diffuse duodenal nodular lymphoid hyperplasia: a large cohort of patients etiologically related to Helicobacter pylori infection

Abstract Background Nodular lymphoid hyperplasia of gastrointestinal tract is a rare disorder, often associated with immunodeficiency syndromes. There are no published reports of its association with Helicobacter pylori infection. Methods From March 2005 till February 2010, we prospectively followed all patients with diffuse duodenal nodular lymphoid hyperplasia (DDNLH). Patients underwent esophagogastroduodenoscopy with targeted biopsies, colonoscopy, and small bowel video capsule endoscopy. Duodenal nodular lesions were graded from 0 to 4 based on their size and density. Patients were screened for celiac sprue (IgA endomysial antibody), immunoglobulin abnormalities (immunoglobulin levels & serum protein electrophoresis), small intestine bacterial overgrowth (lactulose hydrogen breath test), and Helicobacter pylori infection (rapid urease test, and histological examination of gastric biopsies). Patients infected with Helicobacter pylori received sequential antibiotic therapy and eradication of infection was evaluated by 14C urea breath test. Follow up duodenoscopies with biopsies were performed to ascertain resolution of nodular lesions. Results Forty patients (Males 23, females 17; mean age ± 1SD 35.6 ± 14.6 years) with DDNLH were studied. Patients presented with epigastric pain, vomiting, and weight loss. Esophagogastroduodenoscopy showed diffuse nodular lesions (size varying from 2 to 5 mm or more) of varying grades (mean score ± 1SD 2.70 ± 0.84) involving postbulbar duodenum. Video capsule endoscopies revealed nodular disease exclusively limited to duodenum. None of the patients had immunoglobulin deficiency or small intestine bacterial overgrowth or positive IgA endomysial antibodies. All patients were infected with Helicobacter pylori infection. Sequential antibiotic therapy eradicated Helicobacter pylori infection in 26 patients. Follow up duodenoscopies in these patients showed significant reduction of duodenal nodular lesions score (2.69 ± 0.79 to 1.50 ± 1.10; p Helicobacter pylori infection showed no significant reduction of nodular lesions score (2.71 ± 0.96 to 2.64 ± 1.15; p = 0.58). Nodules partially regressed in score in 2 patients, showed no interval change in 10 patients and progressed in 2 patients. Conclusions We report on a large cohort of patients with DDNLH, etiologically related to Helicobacter pylori infection.</p

Cystic Echinococcosis: Chronic, Complex, and Still Neglected

Cystic echinococcosis is a most clinically neglected parasitic disease that urgently needs attention. A valuable tool for diagnosing, staging, and following up patients, ultrasound, is readily available. Four management procedures, surgery, percutaneous sterilization techniques, anti-parasitic treatment, and watch & wait, have ‘‘evolved’’ over decades, and been recently summarized, but without adequate comparative evaluation of efficacy, effectiveness, rate of adverse events, relapse rates, and cost. Clinical decision making is on even shakier ground for extrahepatic and extrapulmonary locations, which are rarer and numbers needed to build comparative trials hard to come by. There is an obligation to put at least what we have on an appropriate evidence base by conducting comparative clinical trials at the scale and quality that allow answering these important questions. As one of the expected results, clear criteria for the watch & wait option alone might already save a substantial proportion of patients from unnecessary interventions and save health services money. Difficult chronic diseases clustering in poor rural areas need intelligent, creative approaches, and this one urgently needs operational research incorporating the particularities of resource- poor settings into consideration

Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; A case series 2004 – 2006

<p>Abstract</p> <p>Background</p> <p>Human hepatitis E virus (HEV) infections are considered an emerging disease in industrialized countries. In the Netherlands, Hepatitis E virus (HEV) infections have been associated with travel to high-endemic countries. Non-travel related HEV of genotype 3 has been diagnosed occasionally since 2000. A high homology of HEV from humans and pigs suggests zoonotic transmission but direct molecular and epidemiological links have yet to be established. We conducted a descriptive case series to generate hypotheses about possible risk factors for non-travel related HEV infections and to map the genetic diversity of HEV.</p> <p>Methods</p> <p>A case was defined as a person with HEV infection laboratory confirmed (positive HEV RT-PCR and/or HEV IgM) after 1 January 2004, without travel to a high-endemic country three months prior to onset of illness. For virus identification 148 bp of ORF2 was sequenced and compared with HEV from humans and pigs. We interviewed cases face to face using a structured questionnaire and collected information on clinical and medical history, food preferences, animal and water contact.</p> <p>Results</p> <p>We interviewed 19 cases; 17 were male, median age 50 years (25–84 y), 12 lived in the North-East of the Netherlands and 11 had preexisting disease. Most common symptoms were dark urine (n = 16) and icterus (n = 15). Sixteen ate pork ≥ once/week and six owned dogs. Two cases had received blood transfusions in the incubation period. Seventeen cases were viremic (genotype 3 HEV), two had identical HEV sequences but no identified relation. For one case, HEV with identical sequence was identified from serum and surface water nearby his home.</p> <p>Conclusion</p> <p>The results show that the modes of transmission of genotype-3 HEV infections in the Netherlands remains to be resolved and that host susceptibility may play an important role in development of disease.</p

Hepatitis E Virus Seroprevalence among Blood Donors in Southwest Switzerland

Aim: The aim of this study was to determine the seroprevalence of Hepatitis E virus (HEV) among blood donors in southwest Switzerland.Background: HEV is recognized as a food-borne disease in industrialized countries, transmitted mainly through pork meat. Cases of transmission through blood transfusion have also been reported. Recent studies have revealed seroprevalence rates of 13.5%, 16.6% and 20.6% among blood donors in England, France and Denmark, respectively.Methods: We analyzed 550 consecutive blood donor samples collected in the region of Lausanne, canton of Vaud, Switzerland, for the presence of anti-HEV IgG, using the MP Diagnostics HEV ELISA kit. For each donor, we documented age, sex and alanine aminotransferase (ALT) value.Results: The study panel was composed of 332 men (60.4%) and 218 women (39.6%). Overall, anti-HEV IgG was found in 27 of 550 samples (4.9%). The seroprevalence was 5.4% (18/332) in men and 4.1% (9/218) in women. The presence of anti-HEV IgG was not correlated with age, gender or ALT values. However, we observed a peak in seroprevalence of 5.3% in individuals aged 51 to 70 years old.Conclusions: Compared with other European countries, HEV seroprevalence among blood donors in southwest Switzerland is low. The low seroprevalence may be explained by the sensitivity of commercial tests used and/or the strict regulation of animal and meat imports. Data regarding HEV prevalence in Swiss livestock are lacking and merit exploration

Effects of climate and atmospheric nitrogen deposition on early to mid-term stage litter decomposition across biomes

Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate

Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

<p>Abstract</p> <p>Background</p> <p>The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.</p> <p>Methods</p> <p>Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.</p> <p>Results</p> <p>At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).</p> <p>Conclusions</p> <p>Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.</p