53 research outputs found
Side effects and discontinuation rate of depot medroxyprogesterone acetate in a tertiary hospital, southern Nigeria
Background: Depot medroxyprogesterone acetate (DMPA) also known as depo provera is a highly effective, safe and long-lasting reversible contraceptive with side effects that may cause discontinuation amongst acceptors. Objective was to determine the prevalence rate, side effects, discontinuation rate and indications for discontinuation of DMPA at Rivers State University Teaching Hospital (RSUTH), Port Harcourt.Methods: This was a retrospective study of 874 clients attending family planning clinic at the RSUTH from 1st January, 2015 to 31st December, 2019. Their records were retrieved from the clinic and reviewed. Data was extracted, coded and analyzed using the statistical package for social sciences (SPSS) IBM version 25.0 (Armonk, NY).Results: One hundred and one clients accepted DMPA out of 874 acceptors of contraceptives within the study period giving a prevalence rate of 11.6%. The modal age group was 25-29 years accounting for 31 (30.7%). Age range was 19-47 years and the modal parity was para 2. Majority of the clients had formal education, 100 (99%), married, 94 (93.1%) and multipara 61 (60.4%). The discontinuation rate was 32.7% and the commonest reasons for discontinuation were secondary amenorrhoea and irregular vaginal bleeding with each contributing 24.2%.Conclusions: The prevalence and discontinuation rates of Depo provera were low. Secondary amenorrhoea and irregular vaginal bleeding were the commonest side effects and reasons for discontinuation
Mechanistic definition of the cardiovascular mPGES-1/COX-2/ADMA axis
Aims: Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of eNOS, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA. Methods and Results: Inhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalisation of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARβ/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors. Conclusions: These data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA
Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine : novel explanation of cardiovascular side effects associated with anti-inflammatory drugs
© 2014 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.BACKGROUND: Cardiovascular side effects associated with cyclooxygenase-2 inhibitor drugs dominate clinical concern. Cyclooxygenase-2 is expressed in the renal medulla where inhibition causes fluid retention and increased blood pressure. However, the mechanisms linking cyclooxygenase-2 inhibition and cardiovascular events are unknown and no biomarkers have been identified.METHODS AND RESULTS: Transcriptome analysis of wild-type and cyclooxygenase-2(-/-) mouse tissues revealed 1 gene altered in the heart and aorta, but >1000 genes altered in the renal medulla, including those regulating the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and monomethyl-l-arginine. Cyclo-oxygenase-2(-/-) mice had increased plasma levels of ADMA and monomethyl-l-arginine and reduced endothelial nitric oxide responses. These genes and methylarginines were not similarly altered in mice lacking prostacyclin receptors. Wild-type mice or human volunteers taking cyclooxygenase-2 inhibitors also showed increased plasma ADMA. Endothelial nitric oxide is cardio-protective, reducing thrombosis and atherosclerosis. Consequently, increased ADMA is associated with cardiovascular disease. Thus, our study identifies ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction with nonsteroidal anti-inflammatory drug usage.CONCLUSIONS: We identify the endogenous endothelial nitric oxide synthase inhibitor ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction.Peer reviewedFinal Published versio
Cloning, expression and characterization of alcohol dehydrogenases in the silkworm Bombyx mori
Alcohol dehydrogenases (ADH) are a class of enzymes that catalyze the reversible oxidation of alcohols to corresponding aldehydes or ketones, by using either nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP), as coenzymes. In this study, a short-chain ADH gene was identified in Bombyx mori by 5′-RACE PCR. This is the first time the coding region of BmADH has been cloned, expressed, purified and then characterized. The cDNA fragment encoding the BmADH protein was amplified from a pool of silkworm cDNAs by PCR, and then cloned into E. coli expression vector pET-30a(+). The recombinant His-tagged BmADH protein was expressed in E. coli BL21 (DE3), and then purified by metal chelating affinity chromatography. The soluble recombinant BmADH, produced at low-growth temperature, was instrumental in catalyzing the ethanol-dependent reduction of NAD+, thereby indicating ethanol as one of the substrates of BmADH
Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing
This work was funded in part by grants from the Wellcome Trust (0852551Z108/Z, to J.A.M.) and British Heart Foundation (FS/16/1/31699, to NSK). SM is a recipient of a PhD award from the King of Saud University, AT is a recipient of a MRC PhD studentship
Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy
Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy
Antimicrobial resistance of Campylobacter isolates from small scale and backyard chicken in Kenya
Background Thermophilic Campylobacter species are a major cause of bacterial
foodborne diarrhoea in humans worldwide. Poultry and their products are the
predominant source for human campylobacteriosis. Resistance of Campylobacter
to antibiotics is increasing worldwide, but little is known about the
antibiotic resistance in Campylobacter isolated from chicken in Kenya. In this
study, 35 suspected Campylobacter strains isolated from faeces and cloacal
swabs of chicken were tested for their susceptibility to seven antibiotics
using a broth microdilution assay and molecular biological investigations.
Results Overall, DNA of thermophilic Campylobacter was identified in 53
samples by PCR (34 C. jejuni, 18 C. coli and one mix of both species) but only
35 Campylobacter isolates (31 C. jejuni and 4 C. coli) could be re-cultivated
after transportation to Germany. Isolates were tested for their susceptibility
to antibiotics using a broth microdilution assay. Additionally, molecular
biological detection of antibiotic resistance genes was carried out. C. jejuni
isolates showed a high rate of resistance to nalidixic acid, tetracycline and
ciprofloxacin of 77.4, 71.0 and 71.0 %, respectively. Low resistance (25.8 %)
was detected for gentamicin and chloramphenicol. Multidrug resistance in C.
jejuni could be detected in 19 (61.3 %) isolates. Resistance pattern of C.
coli isolates was comparable. Resistance to ciprofloxacin was confirmed by
MAMA–PCR and PCR–RFLP in all phenotypically resistant isolates. The tet(O)
gene was detected only in 54.5 % of tetracycline resistant C. jejuni isolates.
The tet(A) gene, which is also responsible for tetracycline resistance, was
found in 90.3 % of C. jejuni and in all C. coli isolates. Thirteen
phenotypically erythromycin-resistant isolates could not be characterised by
using PCR–RFLP and MAMA–PCR. Conclusions To the best of our knowledge, this
study is the first report about resistance to antibiotics in thermophilic
Campylobacter originating from chicken in Kenya. Campylobacter spp. show a
high level of resistance to ciprofloxacin, nalidixic acid and tetracycline but
also a remarkable one to chloramphenicol and gentamicin and they are multidrug
resistant. Resistance to antibiotics is a global public health concern. In
Kenya, resistance surveillance needs further attention in the future. Efforts
to establish at least a National Laboratory with facilities for performing
phenotypic and genotypic characterization of thermophilic Campylobacter is
highly recommended
Genotyping and antibiotic resistance of thermophilic Campylobacter isolated from chicken and pig meat in Vietnam
Background Campylobacter species are recognized as the most common cause of
foodborne bacterial gastroenteritis in humans. In this study nine
Campylobacter strains isolated from chicken meat and pork in Hanoi, Vietnam,
were characterized using molecular methods and tested for antibiotic
resistance. Results The nine isolates (eight C. jejuni and one C. coli) were
identified by multiplex PCR, and tested for the presence or absence of 29 gene
loci associated with virulence, lipooligosaccharide (LOS) biosynthesis and
further functions. flaA typing, multilocus sequence typing and microarray
assay investigation showed a high degree of genetic diversity among these
isolates. In all isolates motility genes (flaA, flaB, flhA, fliM),
colonization associated genes (cadF, docB), toxin production genes (cdtA,
cdtB, secD, secF), and the LOS biosynthesis gene pglB were detected. Eight
gene loci (fliY, virB11, Cje1278, Cj1434c, Cj1138, Cj1438c, Cj1440c, Cj1136)
could not be detected by PCR. A differing presence of the gene loci ciaB (22.2
%), Cje1280 (77.8 %), docC (66.7 %), and cgtB (55.6 %) was found. iamA, cdtC,
and the type 6 secretion system were present in all C. jejuni isolates but not
in C. coli. flaA typing resulted in five different genotypes within C. jejuni,
MLST classified the isolates into seven sequence types (ST-5155, ST-6736,
ST-2837, ST-4395, ST-5799, ST-4099 and ST-860). The microarray assay analysis
showed a high genetic diversity within Vietnamese Campylobacter isolates which
resulted in eight different types for C. jejuni. Antibiotic susceptibility
profiles showed that all isolates were sensitive to gentamicin and most
isolates (88.8 %) were sensitive to chloramphenicol, erythromycin and
streptomycin. Resistance rates to nalidixic acid, tetracycline and
ciprofloxacin were 88.9, 77.8 and 66.7 %, respectively. Conclusions To the
best of our knowledge, this study is the first report that shows high genetic
diversity and remarkable antibiotic resistance of Campylobacter strains
isolated from meat in Vietnam which can be considered of high public health
significance. These preliminary data show that large scale screenings are
justified to assess the relevance of Campylobacter infections on human health
in Vietnam
comprehension: a case study in Turkey
This study has been conducted in order to examine the effects of the stories for thinking on 5th graders' reading comprehension and listening comprehension. A pretest-post test control group quasi-experimental design was used in the study. The sample of the etstudy was composed of 74 5th graders attending public elementary schools. The data have been collected by administering the 'reading comprehension test' and the 'Listening Comprehension Test'. While 'stories for thinking' was applied to the study group, various activities were applied to the control group. The results of the study showed that there was no evidence that the stories for thinking experience added statistically significant value to the students' reading and listening comprehension in relation to the control group
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