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41.
Acylation of Pseudomonas cepacia lipase with Pyromellitic dianhydride to modify 72% of total amino groups was carried out. Different organic solvents were screened for precipitation of modified lipase. It was found that 1,2-dimethoxyethane was the best precipitant which precipitated 97% protein and complete activity. PCMC (protein coated microcrystals), CLPCMC (crosslinked protein coated microcrystals), EPROS (enzyme precipitated and rinsed with organic solvents) and pH tuned preparations of modified and unmodified lipase were prepared and used for carrying out transesterification reaction with n-octane and dimethyl formamide (DMF) as reaction medium. In n-octane, among all the preparations, CLPCMC of modified lipase gave highest rate (1970 nmol min−1 mg−1) as compared to unmodified pH tuned lipase (128 nmol min−1 mg−1). In DMF, with both 1% (v/v) and 5% (v/v) water content, CLPCMC showed highest initial rate of 0.72 and 7.2 nmol min−1 mg−1, respectively. Unmodified pH tuned lipase showed no activity at all in DMF with both 1% and 5% (v/v) water content. 相似文献
42.
43.
Kangwana BP Kedenge SV Noor AM Alegana VA Nyandigisi AJ Pandit J Fegan GW Todd JE Brooker S Snow RW Goodman CA 《PLoS medicine》2011,8(5):e1000437
Background
It has been proposed that artemisinin-based combination therapy (ACT) be subsidised in the private sector in order to improve affordability and access. This study in western Kenya aimed to evaluate the impact of providing subsidized artemether–lumefantrine (AL) through retail providers on the coverage of prompt, effective antimalarial treatment for febrile children aged 3–59 months.Methods and Findings
We used a cluster-randomized, controlled design with nine control and nine intervention sublocations, equally distributed across three districts in western Kenya. Cross-sectional household surveys were conducted before and after the delivery of the intervention. The intervention comprised provision of subsidized packs of paediatric ACT to retail outlets, training of retail outlet staff, and community awareness activities. The primary outcome was defined as the proportion of children aged 3–59 months reporting fever in the past 2 weeks who started treatment with AL on the same day or following day of fever onset. Data were collected using structured questionnaires and analyzed based on cluster-level summaries, comparing control to intervention arms, while adjusting for other covariates. Data were collected on 2,749 children in the target age group at baseline and 2,662 at follow-up. 29% of children experienced fever within 2 weeks before the interview. At follow-up, the percentage of children receiving AL on the day of fever or the following day had risen by 14.6% points in the control arm (from 5.3% [standard deviation (SD): 3.2%] to 19.9% [SD: 10.0%]) and 40.2% points in the intervention arm (from 4.7% [SD: 3.4%] to 44.9% [SD: 11.7%]). The percentage of children receiving AL was significantly greater in the intervention arm at follow-up, with a difference between the arms of 25.0% points (95% confidence interval [CI]: 14.1%, 35.9%; unadjusted p = 0.0002, adjusted p = 0.0001). No significant differences were observed between arms in the proportion of caregivers who sought treatment for their child''s fever by source, or in the child''s adherence to AL.Conclusions
Subsidizing ACT in the retail sector can significantly increase ACT coverage for reported fevers in rural areas. Further research is needed on the impact and cost-effectiveness of such subsidy programmes at a national scale.Trial Registration
Current Controlled Trials ISRCTN59275137 and Kenya Pharmacy and Poisons Board Ethical Committee for Clinical Trials PPB/ECCT/08/07. Please see later in the article for the Editors'' Summary 相似文献44.
45.
Blagg JA Noe MC Wolf-Gouveia LA Reiter LA Laird ER Chang SP Danley DE Downs JT Elliott NC Eskra JD Griffiths RJ Hardink JR Haugeto AI Jones CS Liras JL Lopresti-Morrow LL Mitchell PG Pandit J Robinson RP Subramanyam C Vaughn-Bowser ML Yocum SA 《Bioorganic & medicinal chemistry letters》2005,15(7):1807-1810
Through the use of computational modeling, a series of pyrimidinetrione-based inhibitors of MMP-13 was designed based on a lead inhibitor identified through file screening. Incorporation of a biaryl ether moiety at the C-5 position of the pyrimidinetrione ring resulted in a dramatic enhancement of MMP-13 potency. Protein crystallography revealed that this moiety binds in the S(1)(') pocket of the enzyme. Optimization of the C-4 substituent of the terminal aromatic ring led to incorporation of selectivity versus MMP-14 (MT-1 MMP). Structure activity relationships of the biaryl ether substituent are presented as is pharmacokinetic data for a compound that meets our in vitro potency and selectivity goals. 相似文献
46.
Awasthi V Pandit S Misra PC 《Journal of enzyme inhibition and medicinal chemistry》2005,20(2):205-209
Plasma membrane (PM) vesicles isolated from the yeast Saccharomyces cerevisiae (wild-type NCIM 3078, and a MG 21290 mutant pma 1-1) were used to monitor the effect of the detergents, 3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate (Chaps) and Triton X-100, on (H+)-ATPase (E.C. 3.6.1.35), NADH oxidase and NADH-hexacynoferrate (III)[HCF (III)] oxidoreductase (E.C. 1.6.99.3) activities. The results obtained show that Triton X-100 inhibited both membrane bound and solubilized NADH-dependent redox activities. The nature of this inhibition as determined for NADH-HCF(III) oxidoreductase was non-competitive and the Ki values for wild and mutant enzymes were 1.2 x 10(-5) M and 8.0 x 10(-6) M, respectively. The findings are interpreted, in view of the established reports, that the active site architecture of PM bound NADH-dependent oxidoreductase in yeast is likely to be different than in other eukaryotes. 相似文献
47.
Anil A Pandit R Indap M Lali A 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,818(1):83-87
Tubulin, a potential target for anti-cancer drugs, has been purified in one step and obtained as flow-through fraction directly from an extract of a mammalian brain tissue by adsorption chromatography on H-CELBEADS, an indigenously developed rigid, superporous cross-linked cellulose based weakly hydrophobic adsorbent. The fibrous polymerized tubulin mass passed through the H-CELBEADS bed while the associated proteins were separated by adsorption. The final tubulin preparation was obtained free from other proteins as seen on SDS-PAGE. Purified tubulin was obtained in a yield of about 29 mg/100 g brain, and its bioactivity, evaluated through its ability to bind colchicine, was found to be preserved. 相似文献
48.
OBJECTIVE: To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). STUDY DESIGN: Papanicolaou- and May-Grünwald-Giemsa-stained smears of aspirates from 26 cases of HBL were analyzed by 2 observers. Histologic material, available in 15 cases, was correlated. A cytology grouping system was proposed on the basis of which all cases were classified. RESULTS: The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was < or = 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of > or = 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respectively). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in 1 case. CONCLUSION: Epithelial HBL can be easily diagnosed in aspirates further classified into fetal and embryonal subtypes, which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes. 相似文献
49.
Boehme SA Lio FM Sikora L Pandit TS Lavrador K Rao SP Sriramarao P 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(6):3599-3603
Elevated levels of serotonin (5-hydroxytryptamine, 5-HT) are observed in the serum of asthmatics. Herein, we demonstrate that 5-HT functions independently as an eosinophil chemoattractant that acts additively with eotaxin. 5-HT2A receptor antagonists (including MDL-100907 and cyproheptadine (CYP)) were found to inhibit 5-HT-induced, but not eotaxin-induced migration. Intravital microscopy studies revealed that eosinophils roll in response to 5-HT in venules under conditions of physiological shear stress, which could be blocked by pretreating eosinophils with CYP. OVA-induced pulmonary eosinophilia in wild-type mice was significantly inhibited using CYP alone and maximally in combination with a CCR3 receptor antagonist. Interestingly, OVA-induced pulmonary eosinophilia in eotaxin-knockout (Eot-/-) mice was inhibited by treatment with the 5-HT2A but not CCR3 receptor antagonist. These results suggest that 5-HT is a potent eosinophil-active chemoattractant that can function additively with eotaxin and a dual CCR3/5-HT2A receptor antagonist may be more effective in blocking allergen-induced eosinophil recruitment. 相似文献
50.
The present study examines the role of cerebroventricular administered (IIIrd ventricle) galanin on LHRH and LH release in adult and immature male rats. In both age groups, galanin stimulated LHRH synthesis and release from the hypothalamus, leading to a higher release of pituitary LH which in turn increased plasma LH levels. Galantide, a galanin receptor blocker, on the other hand, drastically reduced hypothalamic LHRH and plasma LH while increasing pituitary LH. In vitro incubation of anterior pituitary cells with galanin followed by LHRH resulted in increased release of pituitary LH but not by galanin alone. Galantide exhibited no such effect either alone or with LHRH. These results indicate that galanin is an important regulator for both hypothalamic LHRH and hypophysial LH and its role is independent of age in the case of male rats. 相似文献