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In order to achieve the goal of developing extracorporeal liver support devices, it is necessary to optimise bioprocess environment
such that viability and function are maximised. Optimising culture medium composition and controlling the constitution of
the cellular microenvironment within the bioreactor have for many years been considered vital to achieving these aims. Coupled
to this is the need to understand apoptosis, the prime suspect in the demise of animal cultures, including those of hepatocytes.
Results presented here show that absent nutrients including glucose and amino acids play a substantial part in the induction
of apoptosis. The use of chemical apoptosis inhibitors was utilised to investigate key components of hepatic apoptosis where
caspases, predominantly caspase 8, were implicated in staurosporine (STS)-induced HepZ apoptosis. Caspase 9 and 3 activation
although recorded was of less significance. Interestingly, these results were not consistent with those of mitochondrial membrane
depolarisation where inhibition of caspase activation appeared to drive depolarisation. Inhibition of mitochondrial permeability
transition and use of anti-oxidants was unsuccessful in reducing apoptosis, caspase activation and mitochondrial membrane
depolarisation. In further studies, the anti-apoptotic gene bcl-2 was over-expressed in HepZ, resulting in a cell line that was more robust and resistant to death induced by glucose and cystine
deprivation and treatment with STS. Bcl-2 did not however show significant cytoprotectivity where apoptosis was stimulated
by deprivation of glutamine and serum. Overall, results indicated that although apoptosis can be curbed by use of chemical
inhibitors and genetic manipulation, their success is dependent on apoptotic stimuli. 相似文献
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Wadzanai P. Samaneka Gibson Mandozana Willard Tinago Nehemiah Nhando Nyaradzo M. Mgodi Mutsawashe F. Bwakura-Dangarembizi Marshall W. Munjoma Zvenyika A. R. Gomo Zvavahera M. Chirenje James G. Hakim 《PloS one》2016,11(11)
BackgroundLaboratory reference ranges used for clinical care and clinical trials in various laboratories in Zimbabwe were derived from textbooks and research studies conducted more than ten years ago. Periodic verification of these ranges is essential to track changes over time. The purpose of this study was to establish hematology and chemistry laboratory reference ranges using more rigorous methods.MethodsA community-based cross-sectional study was carried out in Harare, Chitungwiza, and Mutoko. A multistage sampling technique was used. Samples were transported from the field for analysis at the ISO15189 certified University of Zimbabwe-University of California San Francisco Central Research Laboratory. Hematology and clinical chemistry reference ranges lower and upper reference limits were estimated at the 2.5th and 97.5th percentiles respectively.ResultsA total of 769 adults (54% males) aged 18 to 55 years were included in the analysis. Median age was 28 [IQR: 23–35] years. Males had significantly higher red cell counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin compared to females. Females had higher white cell counts, platelets, absolute neutrophil counts, and absolute lymphocyte counts compared to males. There were no gender differences in eosinophils, monocytes, and absolute basophil count. Males had significantly higher levels of urea, sodium, potassium, calcium, creatinine, amylase, total protein, albumin and liver enzymes levels compared to females. Females had higher cholesterol and lipase compared with males. There are notable differences in the white cell counts, neutrophils, cholesterol, and creatinine kinase when compared with the currently used reference ranges.ConclusionData from this study provides new country specific reference ranges which should be immediately adopted for routine clinical care and accurate monitoring of adverse events in research studies. 相似文献
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Thesla Palanee-Phillips Katie Schwartz Elizabeth R. Brown Vaneshree Govender Nyaradzo Mgodi Flavia Matovu Kiweewa Gonasagrie Nair Felix Mhlanga Samantha Siva Linda-Gail Bekker Nitesha Jeenarain Zakir Gaffoor Francis Martinson Bonus Makanani Sarita Naidoo Arendevi Pather Jessica Phillip Marla J. Husnik Ariane van der Straten Lydia Soto-Torres Jared Baeten 《PloS one》2015,10(6)
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Lipase-catalysed synthesis of esters of ferulic acid with natural compounds and evaluation of their antioxidant properties 总被引:1,自引:0,他引:1
Nyaradzo T.L. Chigorimbo-Murefu Sergio Riva Stephanie G. Burton 《Journal of Molecular Catalysis .B, Enzymatic》2009,56(4):277-282
Lipases from Candida antarctica (Novozyme 435®), Candida rugosa, Chromobacterium viscosum and Pseudomonas sp. were used to perform transesterifications of vinyl ferulate with hydroxyl-steroids and p-arbutin. The antioxidant activity of the products was evaluated using the free radical 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radical quenching antioxidant assays, and inhibition of the oxidation of low-density lipoprotein, LDL. Arbutin ferulate was found to possess a 19% higher antiradical activity against the ABTS free radical than its precursor ferulic acid, and it also inhibited the oxidation of LDL more efficiently (by 10%) than its precursors. All of the biocatalytically synthesised products exhibited higher antioxidant activity than Trolox, the well known commercial benchmark antioxidant, and their precursor, ferulic acid. 相似文献
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Connie Celum Sybil Hosek Mandisa Tsholwana Sheetal Kassim Shorai Mukaka Bonnie J. Dye Subash Pathak Nyaradzo Mgodi Linda-Gail Bekker Deborah J. Donnell Ethan Wilson Krista Yuha Peter L. Anderson Yaw Agyei Heather Noble Scott M. Rose Jared M. Baeten Jessica M. Fogel Adeola Adeyeye Lubbe Wiesner James Rooney Sinead Delany-Moretlwe 《PLoS medicine》2021,18(6)
BackgroundPre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study.Methods and findingsHIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted.ConclusionsIn this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population.Trial registrationClinicalTrials.gov .Connie Celum and co-workers report on use of pre-exposure prophylaxis by young women in Southern Africa. NCT02732730相似文献
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