A kinetic study on the Novozyme 435‐catalyzed esterification of free fatty acids with octanol to produce octyl esters

Octyl esters can serve as an important class of biolubricant components replacing their mineral oil counterparts. The purpose of the current work was to investigate the enzymatic esterification reaction of free fatty acids (FFA, from waste cooking oil) with octanol in a solvent‐free system using a commercial lipase Novozyme 435. It was found that the esterificaton reaction followed the Ping‐pong bi‐bi kinetics with no inhibition by substrates or products within the studied concentration range. The maximum reaction rate was estimated to be 0.041 mol L^?1 g^?1 h^?1. Additionally, the stability of Novozyme 435 in the current reaction system was studied by determining its activity and final conversion of FFA to esters after 12 successive utilizations. Novozyme 435 exhibited almost 100% enzyme activity up to 7 cycles of reaction and gradually decreased (by 5%) thereafter. The kinetic parameters evaluated from the study shall assist in the design of reactors for large‐scale production of octyl esters from a cheap biomass source. The enzyme reusability data can further facilitate mass production by curtailing the cost of expensive enzyme consumption. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1494–1499, 2015     

Assessing Community Based Improved Maternal Neonatal Child Survival (IMNCS) Program in Rural Bangladesh

Objectives

A community based approach before, during and after child birth has been proven effective address the burden of maternal, neonatal and child morbidity and mortality in the low and middle income countries. We aimed to examine the overall change in maternal and newborn health outcomes due the “Improved Maternal Newborn and Child Survival” (IMNCS) project, which was implemented by BRAC in rural communities of Bangladesh.

Methods

The intervention was implemented in four districts for duration of 5-years, while two districts served as comparison areas. The intervention was delivered by community health workers who were trained on essential maternal, neonatal and child health care services. A baseline survey was conducted in 2008 among 7, 200 women with pregnancy outcome in last year or having a currently alive child of 12–59 months. A follow-up survey was administered in 2012–13 among 4, 800 women of similar characteristics in the same villages.

Findings

We observed significant improvements in maternal and essential newborn care in intervention areas over time, especially in health care seeking behaviors. The proportion of births taking place at home declined in the intervention districts from 84.3% at baseline to 71.2% at end line (P<0.001). Proportion of deliveries with skilled attendant was higher in intervention districts (28%) compared to comparison districts (27.4%). The number of deliveries was almost doubled at public sector facility comparing with baseline (P<0.001). Significant improvement was also observed in healthy cord care practice, delayed bathing of the new-born and reduction of infant mortality in intervention districts compared to that of comparison districts.

Conclusions

This study demonstrates that community-based efforts offer encouraging evidence and value for combining maternal, neonatal and child health care package. This approach might be considered at larger scale in similar settings with limited resources.     

Mechanical loading modulates chondrocyte primary cilia incidence and length

The pathways by which chondrocytes of articular cartilage sense their mechanical environment are unclear. Compelling structural evidence suggests that chondrocyte primary cilia are mechanosensory organelles. This study used a 3D agarose culture model to examine the effect of compressive strain on chondrocyte cilia. Chondrocyte/agarose constructs were subjected to cyclic compression (0–15%; 1 Hz) for 0.5–48 h. Additional constructs were compressed for 48 h and allowed to recover for 72 h in uncompressed free‐swelling conditions. Incidence and length of cilia labelled with anti‐acetylated α‐tubulin were examined using confocal microscopy. In free‐swelling chondrocytes, these parameters increased progressively, but showed a significant decrease following 24 or 48 h compression. A 72 h recovery partially reversed this effect. The reduced cilia incidence and length were not due to increased cell division. We therefore propose that control of primary cilia length is an adaptive signalling mechanism in response to varying levels and duration of mechanical loads during joint activity.     

Synthesis, cytotoxicity, and structure-activity relationship (SAR) studies of andrographolide analogues as anti-cancer agent

A series of analogues of andrographolide, prepared through chemo-selective functionalization at C14 hydroxy, have been evaluated for in vitro cytotoxicities against human leukemic cell lines. Two of the analogues (6a, 9b) exhibited significant potency. Preliminary studies on structure-activity relationship (SAR) revealed that the α-alkylidene-γ-butyrolactone moiety of andrographolide played a major role in the activity profile. The structures of the analogues were established through spectroscopic and analytical data.     

Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents

A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC²), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.     

The development of benzimidazoles as selective rho kinase inhibitors

Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC₅₀ <10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).     

Celecoxib analogs possessing a N-(4-nitrooxybutyl)piperidin-4-yl or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridin-4-yl nitric oxide donor moiety: Synthesis,biological evaluation and nitric oxide release studies

A new group of hybrid nitric oxide (NO) releasing anti-inflammatory (AI) coxib prodrugs (NO-coxibs) wherein the para-tolyl moiety present in celecoxib was replaced by a N-(4-nitrooxybutyl)piperidyl 15a–b, or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridyl 17a–b, NO-donor moiety was synthesized. All compounds released a low amount of NO upon incubation with phosphate buffered saline (PBS) at pH 7.4 (2.4–5.8% range). In comparison, the percentage NO released was higher (3.1–8.4% range) when these nitrate prodrugs were incubated in the presence of l-cysteine. In vitro COX-1/COX-2 isozyme inhibition studies showed this group of compounds are moderately more potent, and hence selective, inhibitors of the COX-2 relative to the COX-1 enzyme. AI structure–activity relationship data acquired showed that compounds having a MeSO₂ COX-2 pharmacophore exhibited superior AI activity compared to analogs having a H₂NSO₂ substituent. Compounds having a MeSO₂ COX-2 pharmacophore in conjunction with a N-(4-nitrooxybutyl)piperidyl (ED₅₀ = 132.4 mg/kg po), or a N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridyl (ED₅₀ = 118.4 mg/kg po), moiety exhibited an AI potency profile that is similar to aspirin (ED₅₀ = 128.7 mg/kg po) but lower than ibuprofen (ED₅₀ = 67.4 mg/kg po).     

Efficient CNS gene delivery by intravenous injection

We administered recombinant SV40-derived viral vectors (rSV40s) intravenously to mice with or without prior intraperitoneal injection of mannitol to deliver transgenes to the central nervous system (CNS). We detected transgene-expressing cells (mainly neurons) most prominently in the cortex and spinal cord; prior intraperitoneal mannitol injection increased CNS gene delivery tenfold. Intravenous injection of rSV40s, particularly with mannitol pretreatment, resulted in extensive expression of multiple transgenes throughout the CNS.     

DNA binding and nuclease activity of a one-dimensional heterometallic nitrosyl complex

The interaction of a structurally characterized Sr–Fe nitrosyl complex with DNA has been studied by UV–vis and fluorescence spectroscopy, viscometric, and gel electrophoresis techniques. From the absorption titration studies the intrinsic binding constant of the complex with DNA was calculated to be 1.6 × 10⁴ M⁻¹. Fluorimetric studies indicate that the complex compete with EB in binding to DNA. The complex shows nuclease activity on pUC19 supercoiled DNA in presence of H₂O₂.