Biodiesel surrogates: Achieving performance demands

Synthesis of surrogate molecules is particularly useful for generating in sight of structural-activity relationships, understanding processes and improving the performance. In order to improve upon the physico-chemical properties of biodiesel, methyl, ethyl, isopropyl and n-butyl esters of β-branched fatty acid have been synthesized, initiating from β-branched alcohols. β-Branched alcohols upon oxidation gave corresponding acids, which were converted to their esters. The synthesized esters have substantially better oxidative stability, exhibited by Rancimat oxidation induction period of more than 24 h. The cloud point of synthesized esters is <−36 °C, pour point is <−42 °C and CFPP is <−21 °C, which is substantially better than fatty acid methyl esters. Besides achieving the objective of better oxidative stability and improved low temperature properties, the synthesized surrogate esters have viscosity in the range of 4.2–4.6 cSt at 40 °C, meeting the international diesel and biodiesel standards. The cetane number of synthesized esters is 62–69, which is much better than diesel and biodiesel. The blends of the synthesized esters in diesel at 5% and 10% meet Indian standards of diesel.     

Impact of Introducing the Line Probe Assay on Time to Treatment Initiation of MDR-TB in Delhi,India

Setting

National Institute of Tuberculosis and Respiratory Diseases (erstwhile Lala Ram Sarup Institute) in Delhi, India.

Objectives

To evaluate before and after the introduction of the line Probe Assay (LPA) a) the overall time to MDR-TB diagnosis and treatment initiation; b) the step-by-step time lapse at each stage of patient management; and c) the lost to follow-up rates.

Methods

A retrospective cohort analysis was done using data on MDR-TB patients diagnosed during 2009–2012 under Revised National Tuberculosis Control Programme at the institute.

Results

Following the introduction of the LPA in 2011, the overall median time from identification of patients suspected for MDR-TB to the initiation of treatment was reduced from 157 days (IQR 127–200) to 38 days (IQR 30–79). This reduction was attributed mainly to a lower diagnosis time at the laboratory. Lost to follow-up rates were also significantly reduced after introduction of the LPA (12% versus 39% pre-PLA).

Conclusion

Introduction of the LPA was associated with a major reduction in the delay between identification of patients suspected for MDR-TB and initiation of treatment, attributed mainly to a reduction in diagnostic time in the laboratory.     

Crystal structure of BinB: A receptor binding component of the binary toxin from Lysinibacillus sphaericus

The binary toxin (Bin), produced by Lysinibacillus sphaericus, is composed of BinA (42 kDa) and BinB (51 kDa) proteins, which are both required for full toxicity against Culex and Anopheles mosquito larvae. Specificity of Bin toxin is determined by the binding of BinB component to a receptor present on the midgut epithelial membranes, while BinA is proposed to be a toxic component. Here, we determined the first crystal structure of the active form of BinB at a resolution of 1.75 Å. BinB possesses two distinct structural domains in its N‐ and C‐termini. The globular N‐terminal domain has a β‐trefoil scaffold which is a highly conserved architecture of some sugar binding proteins or lectins, suggesting a role of this domain in receptor‐binding. The BinB β‐rich C‐terminal domain shares similar three‐dimensional folding with aerolysin type β‐pore forming toxins, despite a low sequence identity. The BinB structure, therefore, is a new member of the aerolysin‐like toxin family, with probably similarities in the cytolytic mechanism that takes place via pore formation. Proteins 2014; 82:2703–2712. © 2014 Wiley Periodicals, Inc.     

Arachidonic acid in postshock mesenteric lymph induces pulmonary synthesis of leukotriene B4.

Mesenteric lymph is the mechanistic link between splanchnic hypoperfusion and acute lung injury (ALI), but the culprit mediator(s) remains elusive. Previous work has shown that administration of a phospholipase A(2) (PLA(2)) inhibitor attenuated postshock ALI and also identified a non-ionic lipid within the postshock mesenteric lymph (PSML) responsible for polymorphonuclear neutrophil (PMN) priming. Consequently, we hypothesized that gut-derived leukotriene B(4) (LTB(4)) is a key mediator in the pathogenesis of ALI. Trauma/hemorrhagic shock (T/HS) was induced in male Sprague-Dawley rats and the mesenteric duct cannulated for lymph collection/diversion. PSML, arachidonic acid (AA), and a LTB(4) receptor antagonist were added to PMNs in vitro. LC/MS/MS was employed to identify bioactive lipids in PSML and the lungs. T/HS increased AA in PSML and increased LTB(4) and PMNs in the lung. Lymph diversion decreased lung LTB(4) by 75% and PMNs by 40%. PSML stimulated PMN priming (11.56 +/- 1.25 vs. 3.95 +/- 0.29 nmol O(2)(-)/min; 3.75 x 10(5) cells/ml; P < 0.01) that was attenuated by LTB(4) receptor blockade (2.64 +/- 0.58; P < 0.01). AA stimulated PMNs to produce LTB(4), and AA-induced PMN priming was attenuated by LTB(4) receptor antagonism. Collectively, these data indicate that splanchnic ischemia/reperfusion activates gut PLA(2)-mediated release of AA into the lymph where it is delivered to the lungs, provoking LTB(4) production and subsequent PMN-mediated lung injury.     

Biochemical characterization of dichlorvos-induced delayed neurotoxicity in rat

In vitro and in vivo studies were carried out to assess the delayed neurotoxicity potential of dichlorvos. In vitro, dichlorvos caused a concentration and time-dependent decrease in the activity of neuropathy target esterase (NTE). The Ki of dichlorvos for NTE was calculated to be 1.28 x 10(3) M-1 min-1. In vitro reactivation and ageing studies revealed that dichlorvos-inhibited NTE became refractory to activation by potassium fluoride after 5 min in the ageing medium, thus indicating the formation of an aged complex between dichlorvos and NTE. In vivo also, dichlorvos (200 mg/kg body wt) given as a single subcutaneous dose inhibited NTE in brain at various intervals after exposure (24 h, 10 days, and 21 days). The delayed neurotoxicity potential of dichlorvos was finally confirmed by the rota rod test, which revealed severe motor deficit in all the exposed animals.     

Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons

Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a neurotrophic and neuroprotective substance against antineoplastic drugs, paclitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons from chick embryos. In this study, 1 in a large quantity, together with a known 17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N-alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the quinone ring and were evaluated for in vitro activity against P19-derived neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1nM) enhanced survival and neurite outgrowth of P19-derived neurons and prevented neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest cytotoxicity and neurotoxicity, is serving as the most promising candidate in neurodegenerative therapy against neurotoxic anticancer drugs.