Antiandrogen and Antimicrobial Aspects of Coordination Compounds of Palladium(II), Platinum(II) and Lead(II)

Synthesis, characterization and antimicrobial activities of an interesting class of biologically potent macrocyclic complexes have been carried out. All the complexes have been evaluated for their antimicrobial effects on different species of pathogenic fungi and bacteria. The testicular sperm density, testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trails and biochemical parameters of reproductive organs have been examined and discussed. The resulting biologically active [M(MaLn)(R2)]Cl2 and [Pb(MaLn)(R2)X2] (where, M = PdII or PtII and X = Cl or NO3) type of complexes have been synthesized by the reactions of macrocyclic ligands (MaLn) with metal salts and different diamines in 1:1:1 molar ratio in methanol. Initially the complexes were characterized by elemental analyses, molecular weight determinations and conductivity measurements. The mode of bonding was established on the basis of IR, 1H NMR, 13C NMR, 195Pt NMR, 207Pb NMR, XRD and electronic spectral studies. The macrocyclic ligand coordinates through the four azomethine nitrogen atoms which are bridged by benzil moieties. IR spectra suggest that the pyridine nitrogen is not coordinating. The palladium and platinum complexes exhibit tetracoordinated square-planar geometry, whereas a hexacoordinated octahedral geometry is suggested for lead complexes

Uric acid in men with acute stroke

Abstract Higher levels of uric acid in men as compared to women can be a reason behind greater incidence of stroke in men. The objective of the present study was to evaluate the levels of uric acid in men with acute stroke and correlate with stroke severity.For the purpose of the study ,50 male patients of acute stroke admitted to the hospital and 50 age matched healthy controls were included in the study. Routine biochemical parameters including fasting blood glucose, uric acid and lipid profile were assessed in serum obtained from 5 ml of fasting blood sample. Patients with kidney or liver diseases, malignancies, diuretic use, alcohol intake, on iron or antioxidant therapy were excluded from the study. Initial stroke severity was measured by the National Institute of Health Stroke (NIHS) scale. It was found that , among the 50 cases, 38(76%) had ischemic stroke and 12(24%) had hemorrhagic stroke. Serum uric acid levels were very significantly higher in cases (p<0.001) than controls. There was strong positive correlation between uric acid levels and initial stroke severity (p=0.006, r=0.386). Also, serum uric acid showed a statistically significant correlation with fasting blood glucose, TG and VLDL and an inverse association with HDL in both cases and controls. The conclusion drawn was that the significantly higher levels of uric acid in men with stroke and the positive association of uric acid with stroke severity suggest a possible role of uric acid as a risk factor for stroke in men

Leaching behaviour of pendimethalin causes toxicity towards different cultivars of Brassica juncea and Brassica campestris in sandy loam soil

An experiment was conducted at the farm of Zonal Adaptive Research Station, Uttar Banga Krishi Viswavidhyalaya, Pundibari, Cooch Behar, West Bengal to evaluate the effect of pendimethalin on the yield, weed density and phytotoxicity in different varieties of rai (Brassica juncea) and yellow sarson (B. campestris var. yellow sarson) under higher soil moisture regime in Terai region of West Bengal. Pre-emergence application of pendimethalin at higher dose i.e. 1.0 kg/ha recorded higher plant mortality (30.92%) due to the presence of higher concentration of pendimethalin residue (0.292 µg/g) till the tenth day of crop age and consequently had the reduced yield (12.59 q/ha) than the dose of 0.7 kg/ha (13.33 q/ha) where plant mortality was only 12.62% due to comparatively lower level of pendimethalin residue (0.192 µg/g). Although the application of pendimethalin at the rate of 1.0 kg/ha was able to control weed more efficiently (18.96/m2) than the dose of 0.7 kg/ha (30.41/m2) and subsequent lower doses. The herbicide leached down to the root zone resulting in phytotoxicity towards crop. Yellow sarson group (Brassica campestris) showed more susceptibility than rai (Brassica juncea) group against pendimethalin application at higher doses

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

Resistance to antimonials has emerged as a major hurdle to the treatment and control of VL and led to the introduction of Miltefosine as first line treatment in the Indian subcontinent. MIL is an oral drug with a long half-life, and it is feared that resistance may emerge rapidly, threatening control efforts under the VL elimination program. There is an urgent need for monitoring treatment efficacy and emergence of drug resistance in the field. In a set of VL/PKDL cases recruited for MIL treatment, we observed comparable drug susceptibility in pre- and post-treatment isolates from cured VL patients while MIL susceptibility was significantly reduced in isolates from VL relapse and PKDL cases. The PKDL isolates showed higher tolerance to MIL as compared to VL isolates. Both VL and PKDL isolates were uniformly susceptible to PMM. MIL transporter genes LdMT/LdRos3 were previously reported as potential resistance markers in strains in which MIL resistance was experimentally induced. The point mutations and the down-regulated expression of these transporters observed in vitro could, however, not be verified in natural populations of parasites. LdMT/LdRos3 genes therefore, do not appear to be suitable markers so far for monitoring drug susceptibility in clinical leishmanial isolates

Solisluumurtumien konservatiivinen ja operatiivinen hoito : Systemaattinen kirjallisuuskatsaus 1190 potilaasta

Peer reviewe

Variation in structure and properties of poly(glycerol adipate) via control of chain branching during enzymatic synthesis

Poly (glycerol adipate) (PGA) can be produced from divinyl adipate and unprotected glycerol by an enzymatic route to generate a polymer with relatively low molar mass (12 kDa). PGA bears a pendant hydroxyl group which imparts a hydrophilic character to this water insoluble polymer. We have examined the effect of synthesis temperature on polymer characteristics through various techniques including FT-IR, 1H and 13C NMR, surface and thermal analysis, both to expand the data already present in the literature about this material and to understand better its properties for potential pharmaceutical applications. The use of a lipase (Novozym 435) as a catalyst suppresses cross-linking at the pendant glyceryl hydroxyl through steric hindrance at the active site, thus producing polymers with low degrees of branching (5–30%), and removes the need for any pre- or post-polymerization protection/deprotection reactions. Careful temperature control during synthesis can give polymers with reproducible molecular weights and reduced amounts of polymer branching compared to synthesis at higher temperatures. Due to the ability of the synthetic route to produce a range of structures, PGA generated by enzymatic routes may emerge as a useful biodegradable polymer platform to engineer solid dispersions or nanoparticles for healthcare applications

Purification and Characterization of a Novel Chlorpyrifos Hydrolase from Cladosporium cladosporioides Hu-01

Chlorpyrifos is of great environmental concern due to its widespread use in the past several decades and its potential toxic effects on human health. Thus, the degradation study of chlorpyrifos has become increasing important in recent years. A fungus capable of using chlorpyrifos as the sole carbon source was isolated from organophosphate-contaminated soil and characterized as Cladosporium cladosporioides Hu-01 (collection number: CCTCC M 20711). A novel chlorpyrifos hydrolase from cell extract was purified 35.6-fold to apparent homogeneity with 38.5% overall recovery by ammoniumsulfate precipitation, gel filtration chromatography and anion-exchange chromatography. It is a monomeric structure with a molecular mass of 38.3 kDa. The pI value was estimated to be 5.2. The optimal pH and temperature of the purified enzyme were 6.5 and 40°C, respectively. No cofactors were required for the chlorpyrifos-hydrolysis activity. The enzyme was strongly inhibited by Hg2+, Fe3+, DTT, β-mercaptoethanol and SDS, whereas slight inhibitory effects (5–10% inhibition) were observed in the presence of Mn2+, Zn2+, Cu2+, Mg2+, and EDTA. The purified enzyme hydrolyzed various organophosphorus insecticides with P-O and P-S bond. Chlorpyrifos was the preferred substrate. The Km and Vmax values of the enzyme for chlorpyrifos were 6.7974 μM and 2.6473 μmol·min−1, respectively. Both NH2-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometer (MALDI-TOF-MS) identified an amino acid sequence MEPDGELSALTQGANS, which shared no similarity with any reported organophosphate-hydrolyzing enzymes. These results suggested that the purified enzyme was a novel hydrolase and might conceivably be developed to fulfill the practical requirements to enable its use in situ for detoxification of chlorpyrifos. Finally, this is the first described chlorpyrifos hydrolase from fungus

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes