Association of Mycobacterium infections in patients with Mendelian susceptibility to mycobacterial disease with venous thromboembolism

An association between a hypercoagulable state and Mendelian susceptibility to mycobacterial disease (MSMD) has been established in a few studies; resultant thrombosis is considered rare. In a case‐control study, the prevalence of factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C mutations were investigated in mycobacterium‐infected patients. The study comprised 30 patients with mycobacterial infections (invasive, disseminated and/or recurrent infections with Bacille Calmette–Guerin or non‐tuberculosis mycobacteria and Mycobacterium Tuberculosis with positive results for acid‐fast bacilli and tuberculin skin tests) and 30 normal healthy controls. Forty female (66.7%) and 20 male subjects (33.3%) aged from 3 to 70 years were recruited into this study. Genotyping of targeted genes was performed by RT‐PCR and cytokine TNF‐α concentrations were quantified using a commercially available ELISA kit. Significant associations between mycobacterial infection and TNF‐α production after stimulating peripheral blood mononuclear cells with LPS alone and with IFN‐γ plus LPS were identified. Moreover, genotyping analysis in the studied population revealed a significant association between MTHFR c.677C>T (OR, 3.28; 95% CI, 1.35–7.92; P < 0.05), MTHFR c.1298A>C (OR, 2.33; 95% CI, 1.10–4.93; P < 0.05) and mycobacterial infection in affected patients, indicating susceptibility to venous thromboembolism according to previous studies. Additionally, mycobacterium‐infected patients had a significantly greater prevalence of MTHFR C677T and A1298C mutations than controls.     

2-Hydroxyphenacyl azoles and related azolium derivatives as antifungal agents

2-Hydroxyphenacyl azole and 2-hydroxyphenacyl azolium compounds have been described as a new class of azole antifungals. Most target compounds showed significant in vitro antifungal activities against tested fungi (Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum) with low MICs values included in the range of 0.25-32 microg/mL comparable to reference drug fluconazole. The most active compounds were also assessed for their cytotoxicity using MTT colorimetric assay on normal mouse fibroblast (NIH/3T3) cells. The results of antifungal activity and toxicity tests indicated that these compounds display antifungal activity at non-cytotoxic concentrations.     

Rumen and post-abomasal disappearance in lactating cows of amino acids and other components of barley grain treated with sodium hydroxide, formaldehyde or urea

Four rumen and duodenum cannulated, Holstein lactating cows were used in a change-over design to determine the effects of NaOH, formaldehyde (HCHO) or urea treated barley on disappearance of dry matter (DM), crude protein (CP), amino acids (AA), NDF, ADF and starch of barley in the rumen, post-abomasal (PAT) and total tract by the mobile nylon bag technique. Experimental treatments were coarse milled barley, barley treated with 35 g NaOH/kg, barley treated with 4 g formaldehyde/kg and barley treated with 35 g urea/kg, in which all chemical treated barley was milled coarse before feeding.

NaOH treatment reduced concentrations of lysine and cystine in the barley grain. All chemical treatments decreased rumen disappearances of barley CP but only NaOH and formaldehyde treatments also decreased total AA and some of the AA disappearances in the rumen. All chemical treatments increased DM, OM, CP, starch, NDF and ADF disappearance of barley in the PAT, but only NaOH and formaldehyde treatments increased total AA and most individual AA disappearances in the PAT. Chemical treatments increased disappearance of starch, methionine and glycine in the total tract (P<0.05).

Rumen disappearance of TAA was lower than for CP but PAT disappearance of TAA was more than for CP and finally total tract disappearance of TAA was more than for CP. Individual AA in barley disappeared at different rates in the rumen and PAT. Consequently, the proportion of digesta CP and AAs of barley, entering the intestine were changed by the chemical treatments. We concluded that, appropriate treatment of barley with NaOH or HCHO were provided substantial protection of CP and individual AA from rumen digestion and increased disappearance of most of barley nutrients in PAT, but, NaOH treatment reduced the AA quality of barley. Consequently, formaldehyde can therefore be considered better than NaOH and urea for treatment of barley grain.     

Synthesis and antibacterial activity of N-[2-[5-(methylthio)thiophen-2-yl]-2-oxoethyl] and N-[2-[5-(methylthio)thiophen-2-yl]-2-(oxyimino)ethyl]piperazinylquinolone derivatives

A number of N-substituted piperazinylquinolone derivatives were synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative bacteria. Preliminary results indicated that most compounds tested in this study demonstrated comparable or better activity against Staphylococcus aureus and Staphylococcus epidermidis than their parent piperazinylquinolones as reference drugs. Among these derivatives, ciprofloxacin derivative 5a, containing N-[2-[5-(methylthio)thiophen-2-yl]-2-oxoethyl] residue, showed significant improvement of potency against staphylococci, maintaining Gram-negative coverage.     

Regulation of the xylan-degrading apparatus of Cellvibrio japonicus by a novel two-component system

The microbial degradation of lignocellulose biomass is not only an important biological process but is of increasing industrial significance in the bioenergy sector. The mechanism by which the plant cell wall, an insoluble composite structure, activates the extensive repertoire of microbial hydrolytic enzymes required to catalyze its degradation is poorly understood. Here we have used a transposon mutagenesis strategy to identify a genetic locus, consisting of two genes that modulate the expression of xylan side chain-degrading enzymes in the saprophytic bacterium Cellvibrio japonicus. Significantly, the locus encodes a two-component signaling system, designated AbfS (sensor histidine kinase) and AbfR (response regulator). The AbfR/S two-component system is required to activate the expression of the suite of enzymes that remove the numerous side chains from xylan, but not the xylanases that hydrolyze the beta1,4-linked xylose polymeric backbone of this polysaccharide. Studies on the recombinant sensor domain of AbfS (AbfS(SD)) showed that it bound to decorated xylans and arabinoxylo-oligosaccharides, but not to undecorated xylo-oligosaccharides or other plant structural polysaccharides/oligosaccharides. The crystal structure of AbfS(SD) was determined to a resolution of 2.6A(.) The overall fold of AbfS(SD) is that of a classical Per Arndt Sim domain with a central antiparallel four-stranded beta-sheet flanked by alpha-helices. Our data expand the number of molecules known to bind to the sensor domain of two-component histidine kinases to include complex carbohydrates. The biological rationale for a regulatory system that induces enzymes that remove the side chains of xylan, but not the hydrolases that cleave the backbone of the polysaccharide, is discussed.     

Vasoactive intestinal peptide receptor activity in human fetal enterocytes

Functional and specific receptors for vasoactive intestinal peptide (VIP) (determined by their capacity to bind ¹²⁵I-VIP and activate adenylate cyclase) and cyclic AMP-dependent phosphodiesterase activities were characterized in enterocytes of human fetal small intestine between 18 and 23 weeks of gestation. Half-maximal stimulation of the cyclase and inhibition of ¹²⁵I-VIP binding in membrane preparations were respectively observed at 1.4 and 5 × 10⁻¹⁰ M VIP. The peptides structurally related to VIP activated the cyclic AMP generating system at pharmacological doses (10⁻⁷M and above) in the following order of potency: VIP> PHI> GRF> secretin. Other peptides or test substances, including GIP, pancreatic glucagon, somatostatin-14, gastrin, CCK, neurotensin, pancreatic polypeptide, PYY, substance P, histamine and isoproterenol are inactive in this system, while the ubiquitous adenylate cyclase activators NaF, forskolin and prostaglandins were effective. These results, combined with the appearance of intestinal VIP in nerve fibers at 8 weeks and with the morphological and enzymatic maturation at 9–12 weeks of the intestinal mucosa, indicate that this neuropeptide may regulate either the differentiation or function of enterocytes during the early development of human intestinal mucosa.     

Field evaluation of two biorational compounds in the control of pear psylla,Cacopsylla pyricola (Förster), on pear trees

Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) is an important pest of commercial pear in all pear-growing regions of Iran. In the scope of an integrated pest management, a research was carried out on the impact of treatment with biorational compounds in comparison with conventional chemical insecticides for controlling the pear psyllid. The experiments were done with five treatments consisted of diflubenzuron and lufenuron as biorational insecticides and thiacloprid and diazinon as conventional chemical insecticides and untreated check. The trials were set up in a randomised complete block design. The treatments were replicated four times. Samplings were carried out one day before spraying and 3, 7, 15, 30 and 45 days after spraying through clipping 15 leaves in each replicate and counting the number of pear psyllid live nymphs. Mortality percentage was calculated using Henderson–Tilton formula. The data were subjected to analysis of variance (ANOVA) and the means comparison was performed using Duncan’s multiple range test. The results indicated that the highest mortality in diflubenzuron and lufenuron treatments occurred after 15 days, with 82.09% and 71.01% mortality, respectively. In comparison with conventional chemical insecticides, the efficacy of biorational compounds was higher or not significantly different. The results of the trials are discussed in terms of improving management of the populations of pear psylla.