Tolerance of bacteria to organic solvents

Organic-solvent-tolerant bacteria are a relatively novel group of extremophilic microorganisms. They overcome the toxic and destructive effects of organic solvents due to the presence of various adaptive mechanisms. Extensive studies done on the toluene tolerance of certain Pseudomonas strains have led to an understanding of the mechanisms of organic solvent tolerance involving novel adaptations such as the toluene efflux pumps, cis-trans isomerisation of membrane fatty acids, rapid membrane repair mechanisms, etc. Organic-solvent-tolerant mutants of Escherichia coli have been constructed and genes enhancing such tolerance characterised. However, there is practically no information available on the tolerance mechanisms of the reported Gram-positive organic-solvent-tolerant bacterial strains like Bacillus, Rhodococcus and Arthrobacter. This review discusses the general aspects of organic-solvent-tolerant bacteria, their history, biodiversity, mechanisms of tolerance and proposes certain probable adaptations of Gram-positive bacteria in tolerance to organic solvents.     

Are <Emphasis Type="Italic">Thymidylate synthase</Emphasis> and <Emphasis Type="Italic">Methylene tetrahydrofolate reductase</Emphasis> genes linked with methotrexate response (efficacy,toxicity) in Indian (Asian) rheumatoid arthritis patients?

Methotrexate (MTX) is among the best-tolerated disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA); major drawbacks of MTX therapy are the large interpatient variability in clinical response and the unpredictable appearance of a large spectrum of side effects. Several studies have demonstrated gene polymorphism that may regulate intracellular methotrexate metabolic pathway enzymes linked to drug efficacy and safety, but the evidence available is not yet conclusive. We decided to run a pilot study to determine the incidence of Methylene tetrahydrofolate (MTHFR; C677T, A1298C) and Thymidylate synthase (TS; 5′ UTR repeat, 3′ UTR deletion) gene polymorphism in rheumatoid arthritis patients in our community (Indian Asian) and further explore its association with MTX response (efficacy, toxicity). Thirty-four naïve RA patients on supervised MTX therapy and 139 healthy controls were genotyped for A1298C and C677T polymorphism of the MTHFR gene and 5′ UTR repeat and 3′ UTR deletion polymorphism of the TYMS gene by polymerase chain reaction-restriction fragment length polymorphism. Association, if any, between gene polymorphism and MTX response in RA patients was analyzed. The MTHFR A1298C ‘C’ allele incidence among RA patients (46%) was significantly higher (χ ²?=?4.24, P?相似文献   

Influence of nitrogen/phosphorus-doped carbon dots on polyamide thin film membranes for water vapor/N2 mixture gas separation

Nanoparticles have been attracting attention because they can significantly improve the performance of membranes when added in small amounts. In this study, the effect of polyamide membranes incorporating hydrophilic nitrogen/phosphorus-doped carbon dots (NP-CDs) to enhance water vapor/N₂ separation has been investigated. NP-CD nanoparticles with many hydrophilic functional groups are synthesized from chitosan by a one-pot green method and introduced to the surface of the polysulfone (PSf) substrates by interfacial polymerization reaction. The mean particle diameter of NP-CDs, estimated from transmission electron microscopy images, is 2.6 nm. By adding NP-CDs (0–1.5 wt%) to the polyamide layer, the contact angles of the membranes dramatically decreased from 65° (PSf) to <9° (thin film nanocomposite (TFN)), which means that the TFN membranes become significantly hydrophilic. From the water vapor separation results, the addition of NP-CDs in the polyamide layer improves the water vapor permeance from 1511 (thin film composite (TFC) without nanoparticles) to 2448 GPU (TFN with 1.0 wt% NP-CD loading, CD-TFN(1.0)) and the water vapor/N₂ selectivity from 73 (TFC) to 854 (CD-TFN(1.0)). To our knowledge, this is the first study of highly functionalized NP-CD-incorporated polyamide membranes to enhance water vapor separation.

Nanoparticles have been attracting attention because they can significantly improve the performance of membranes when added in small amounts.     

Design,synthesis, and PASS-assisted evaluation of novel 2-substituted benzimidazole derivatives as potent anthelmintics

A series of novel 2-substituted benzimidazole analogs has been designed and synthesized by connecting the benzimidazole nucleus with variedly substituted chalcone moieties through an amino linker. The designed analogs were predicted for their biological activity profile through the computer software PASS. The compounds were predicted to have potent anthelmintic activity. These were synthesized and the activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2, and 0.5 % in terms of mortality time and paralysis time for the helminthes. The experimentally observed activity was found to comply with the PASS predicted activity. All compounds showed dose-dependent activities. The compounds with an electron releasing group at the para position on phenyl ring in the chalcone moiety (8 and 9) were the most active in comparison to those bearing electron withdrawing groups. The corresponding ortho analogs (4 and 5) also revealed good paralytic and lethal activities. The higher activities of 8 and 9 may be attributed to the favorable electronic interactions of the electron releasing groups present at para position of the phenyl ring. Comparative analysis of the Lipinski’s parameters and the activities of the compounds revealed all the compounds to comply with the Lipinski’s rule of five. Further an optimum hydrophilicity and total polar surface area in the range of 65–80 of the molecule are required for the potent activity, but Molar refractance is not found to have any significant role in determining the anthelmintic activity.     

Development and Validation of Stability-indicating HPLC Method for Simultaneous Estimation of Cefixime and Linezolid

A stability-indicating reverse phase high performance liquid chromatography method was developed and validated for cefixime and linezolid. The wavelength selected for quantitation was 276 nm. The method has been validated for linearity, accuracy, precision, robustness, limit of detection and limit of quantitation. Linearity was observed in the concentration range of 2-12 μg/ml for cefixime and 6-36 μg/ml for linezolid. For RP-HPLC, the separation was achieved by Phenomenex Luna C₁₈ (250×4.6 mm) 5 μm column using phosphate buffer (pH 7):methanol (60:40 v/v) as mobile phase with flow rate 1 ml/min. The retention time of cefixime and linezolid were found to be 3.127 min and 11.986 min, respectively. During force degradation, drug product was exposed to hydrolysis (acid and base hydrolysis), H₂O₂, thermal degradation and photo degradation. The % degradation was found to be 10 to 20% for both cefixime and linezolid in the given condition. The method specifically estimates both the drugs in presence of all the degradants generated during forced degradation study. The developed methods were simple, specific and economic, which can be used for simultaneous estimation of cefixime and linezolid in tablet dosage form.     

An efficient and environmentally sustainable domino protocol for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO2 nanoparticles as a recyclable and reusable heterogeneous acid catalyst

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines involving a four component reaction of 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamine, cyclic ketones and amino derivatives in the presence of erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst. The present synthetic protocol features mild reaction conditions with operational simplicity, excellent yield with high purity, short reaction time and high atom economy with the use of a recoverable and reusable environmentally sustainable heterogeneous catalyst.

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst.     

Nucleus accumbens dopamine and discriminated approach learning: interactive effects of 6-hydroxydopamine lesions and systemic apomorphine administration

RATIONALE: Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior. OBJECTIVES: To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior. METHODS: Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 microg/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 microl per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA. RESULTS: Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding. CONCLUSIONS: These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.     

Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.     

The tumor microenvironment controls primary effusion lymphoma growth in vivo

Certain lymphomas in AIDS patients, such as primary effusion lymphoma (PEL), are closely associated with the lymphotropic gamma herpes virus Kaposi's sarcoma-associated herpes virus (KSHV), also called human herpesvirus 8. The virus is thought to be essential for tumorigenesis, yet systems to investigate PEL in vivo are rare. Here we describe PEL tumorigenesis in a new xenograft model. Embedded in Matrigel, PEL cells formed rapid, well-organized, and angiogenic tumors after s.c. implantation of C.B.17 SCID mice. Without Matrigel we did not observe comparable tumors, which implies that extracellular support and/or signaling aids PEL. All of the tumors maintained the KSHV genome, and the KSHV latent protein LANA/orf73 was uniformly expressed. However, the expression profile for key lytic mRNAs, as well as LANA-2/vIRF3, differed between tissue culture and sites of implantation. We did not observe a net effect of ganciclovir on PEL growth in culture or as xenograft. These findings underscore the importance of the microenvironment for PEL tumorigenesis and simplify the preclinical evaluation of potential anticancer agents.