Ephrem Engidawork

Association of multicellular behaviour and drug resistance in Salmonella enterica serovars isolated from animals and humans in Ethiopia.

To determine the association between multicellular behaviour, integron status and antibiotic resistance among 87 Ethiopian Salmonella enterica isolates of animal and human origin.

Pharmacological and Toxicological Effects of Catha edulis F. (Khat)

Khat chewing is deeply rooted in the culture and tradition of communities in khat belt countries, and its consumption is spread to other countries through the suitcase trade. The aim of this article is to review current knowledge on the chemistry, social, pharmacology and toxicology of khat and its use. Khat produces effect invariably in every system, which is harmful or beneficial in some instances. Harmful effects are observed in heavy users, although firm evidence is lacking. Chewing khat acutely elicits states of euphoria, which is followed by low mood. Khat contains alkaloids with psychostimulant properties, but the effect cannot be totally explained by these alkaloids. It is also not clear whether the effect produced in some organs like liver could be attributed to khat or pesticides sprayed during farming. Although the evidence indicates that khat has adverse effects in most organs, our understanding of the complex interaction between use and effect is incomplete, and causal relationships have not yet been described. Moreover, khat has positioned itself well in the social, economic and political arena. Thus, a multidisciplinary research is required to understand the different dimensions and come up with ways that maximize the benefit while minimizing the risk. Copyright

Individual Differences in Male Rats in a Behavioral Test Battery: A Multivariate Statistical Approach

Animal models for anxiety, depressive-like and cognitive diseases or aging often involve testing of subjects in behavioral test batteries. The large number of test variables with different mean variations and within and between test correlations often constitute a significant problem in determining essential variables to assess behavioral patterns and their variation in individual animals as well as appropriate statistical treatment. Therefore, we applied a multivariate approach (principal component analysis) to analyse the behavioral data of 162 male adult Sprague-Dawley rats that underwent a behavioral test battery including commonly used tests for spatial learning and memory (holeboard) and different behavioral patterns (open field, elevated plus maze, forced swim test) as well as for motor abilities (Rota rod). The high dimensional behavioral results were reduced to fewer components associated with spatial cognition, general activity, anxiety-, and depression-like behavior and motor ability. The loading scores of individual rats on these different components allow an assessment and the distribution of individual features in a population of animals. The reduced number of components can be used also for statistical calculations like appropriate sample sizes for valid discriminations between experimental groups, which otherwise have to be done on each variable. Because the animals were intact, untreated and experimentally naïve the results reflect trait patterns of behavior and thus individuality. The distribution of animals with high or low levels of anxiety, depressive-like behavior, general activity and cognitive features in a local population provides information of the probability of their appeareance in experimental samples and thus may help to avoid biases. However, such an analysis initially requires a large cohort of animals in order to gain a valid assessment.

Current status, challenges and the way forward for clinical pharmacy service in Ethiopian public hospitals

BackgroundClinical pharmacy service has evolved steadily over the past few decades and is now contributing to the ‘patient care journey’ at all stages. It is improving the safety and effectiveness of medicines and has made a significant contribution to the avoidance of medication errors. In Ethiopia, clinical pharmacy service is in its initial phase, being started in July 2013. This study therefore aimed at assessing the status, challenges and way forward of clinical pharmacy service in the country.MethodsA cross-sectional survey was conducted in six regional states and one city- administration in September 2014. A total of 51 hospitals were included in the study. Both qualitative and quantitative methods were employed for data collection.ResultsA total of 160 pharmacy graduates, and 51 pharmacy heads participated in the study. Internal Medicine and Pediatric wards were the major wards where the graduates provide clinical pharmacy service. Almost 94% of the new graduates were found to be involved in clinical pharmacy service, but 47% of them rated their service as poor. The overall satisfaction of the graduates was close to 36%. Thirteen hospitals discontinued and two hospitals not even initiated the service largely due to shortage of pharmacists and lack of management support. About 44% of the surveyed hospitals documented the clinical pharmacy service provided using either developed or adopted formats. Lack of awareness by the medical fraternity, high attrition rate, lack of support from the management as well as from the health care team, readiness of the graduates to deliver the service, and shortage of pharmacists were identified by the key informants as the major stumbling block to deliver clinical pharmacy service.ConclusionClinical pharmacy service is initiated in most of the surveyed hospitals and a large proportion of the graduates were involved in the service. Although there is a great enthusiasm to promote clinical pharmacy service in the surveyed hospitals, efforts made to institutionalize the service is minimal. Thus, concerted efforts need to be exerted to promote the service through organizing awareness forums as well as revisiting the curriculum.

Antihypertensive activity of 80% methanol seed extract of Calpurnia aurea (Ait.) Benth. subsp. aurea (Fabaceae) is mediated through calcium antagonism induced vasodilation

ETHNOPHARMACOLOGICAL RELEVANCE Calpurnia aurea (Ait.) Benth. subsp. aurea (CASA) (Fabaceae) seeds are used to treat hypertension in Ethiopian folklore medicine, particularly by Shinasha, Agew-awi and Amhara people in northwest Ethiopia. However, the claim has so far not been substantiated scientifically. AIM OF THE STUDY The study was conducted to evaluate the antihypertensive activity of 80% methanol extract of CASA in animal model of hypertension as well as its vasorelaxant effect and possible underlying mechanisms in isolated guinea pig aorta. MATERIAL AND METHODS Hypotensive and antihypertensive effect of CASA extract was determined in vivo through the intravenous (iv) route in normotensive and hypertensive anesthetized rats using 2-kidney-1-clip (2K1C) rat model. Ex vivo, guinea pig thoracic aortic rings were isolated and suspended in organ bath, and the vasodepressor effects as well as the mechanism of action of the extract were studied by means of isometric tension recording experiments. RESULTS The blood pressure fell dose-dependently and significantly in renal hypertensive and normotensive rats following i.v. administration, suggesting that the hydroalcoholic extract possesses hypotensive and antihypertensive effects. The extract also caused a dose-dependent relaxation of aorta pre-contracted with KCl at a concentration of 5-250mg/L, with a maximum relaxation of 92.1% achieved at 250mg/L. The relaxation mechanism was found to be independent of the muscarinic receptors, histamine receptors, ATP dependent K(+) channels, cyclooxygenase enzymes, cGMP/NO pathway and the endothelium system. The extract caused rightward shift of the Ca(++) dose-response curves, similar to that caused by verapamil, indicating that it produced vasorelaxation by inhibiting extracellular Ca(2+) influx. CONCLUSIONS The findings demonstrate that the plant is endowed with antihypertensive effect, providing evidence for its traditional use. The effect may be, at least in part, due to dilation of blood vessels through blockage of Ca(2+) channels.

Assessment of inhaled corticosteroids use and associated factors among asthmatic patients attending Tikur Anbessa Specialized Hospital, Ethiopia

BackgroundInhaled corticosteroids (ICSs) are cornerstone therapy for persistent asthma. However, underutilization of ICSs is common and little is known about factors contributing toward this undesirable use.MethodsA cross-sectional study was conducted through interview and chart review among persistent asthmatic patients attending chest clinic of Tikur Anbessa Specialized Hospital from 1 May to 31 September 2014. A total of 131 eligible patients who attended the clinic during study period were included in the study. A multivariate logistic regression was used to examine the association between independent and dependent variables.ResultsOverall, extent of underutilization of ICSs was found to be 68%. Monthly income, comorbidity and types of ICSs products prescribed showed significant association with reported underutilization. Patients’ reported reasons for underutilization includes; unaffordability (44%), using only when symptoms exacerbate (21%), fear of side effects (10%), practitioners’ recommendation (10%) and unavailability of ICSs in the local market (7%). Physicians also stated unaffordability, fear of side effects and dependency, lack of local guideline for asthma management and unavailability of ICSs as the contributing factors.ConclusionIn this setting, extent of underutilization of ICSs was found to be high and seems the result of complex interaction of various factors. Financial problem combined with inconsistent availability of ICSs in the local market, patients’ poor knowledge of asthma and ICSs, negative attitude toward ICSs, absence of local guidelines for asthma management are found to be essential elements dictating an extent of ICSs use.

Mouse hippocampal GABAB1 but not GABAB2 subunit-containing receptor complex levels are paralleling retrieval in the multiple-T-maze

GABAB receptors are heterodimeric G-protein coupled receptors known to be involved in learning and memory. Although a role for GABAB receptors in cognitive processes is evident, there is no information on hippocampal GABAB receptor complexes in a multiple T maze (MTM) task, a robust paradigm for evaluation of spatial learning. Trained or untrained (yoked control) C57BL/6J male mice (n = 10/group) were subjected to the MTM task and sacrificed 6 h following their performance. Hippocampi were taken, membrane proteins extracted and run on blue native PAGE followed by immunoblotting with specific antibodies against GABAB1, GABAB1a, and GABAB2. Immunoprecipitation with subsequent mass spectrometric identification of co-precipitates was carried out to show if GABAB1 and GABAB2 as well as other interacting proteins co-precipitate. An antibody shift assay (ASA) and a proximity ligation assay (PLA) were also used to see if the two GABAB subunits are present in the receptor complex. Single bands were observed on Western blots, each representing GABAB1, GABAB1a, or GABAB2 at an apparent molecular weight of approximately 100 kDa. Subsequently, densitometric analysis revealed that levels of GABAB1 and GABAB1a but not GABAB2- containing receptor complexes were significantly higher in trained than untrained groups. Immunoprecipitation followed by mass spectrometric studies confirmed the presence of GABAB1, GABAB2, calcium calmodulin kinases I and II, GluA1 and GluA2 as constituents of the complex. ASA and PLA also showed the presence of the two subunits of GABAB receptor within the complex. It is shown that increased levels of GABAB1 subunit-containing complexes are paralleling performance in a land maze.

Evaluation of the reversibility and possible mechanisms of antifertility of Catha edulis F. (khat) extract following subacute administration in rodents

The study of antifertility mechanisms of khat can be used to counteract the possible toxicities during pregnancy as abuse of khat is common in all segments of female population. The present study was initiated to assess the reversibility of antifertility effect and to evaluate the possible mechanisms of antifertility of the chloroform diethyl ether extract of Catha edulis. K300 exhibited significant decrease in the mean number of litters and mean birth weight of live litters compared to K100 and control group (CON) (p<0.01 in both cases). The anti-implantation and antifertility effects were reversible after a 21 day washout period. Post-implantation losses for K200 and K400 were 27% (p<0.01) and 30% (p<0.01), respectively. Maternal mortality in pregnant mice and morphological changes like massive leukocyte infiltration, necrosis and haemorrhage in rat uterus were observed in K400. No morphological changes were shown in ovary at all doses of the extract. Khat has antifertility effect with possibility of complete sterility in higher dose treated groups. The possible mechanisms include decreased serum estradiol concentration and massive leukocyte infiltration in uterus stroma cells. Khat use should be discouraged in female population especially during pregnancy.

Phenotypic and genotypic characterization of temporally related nontyphoidal Salmonella strains isolated from humans and food animals in central Ethiopia

Salmonella is one of the common causes of food‐borne bacterial illnesses. The primary sources of human nontyphoidal Salmonella (NTS) infection are food animals. This study characterized temporally and spatially related Salmonella isolated during April 2013 to March 2014 from faeces of diarrhoeic human patients in Addis Ababa (n = 68) and food animals (n = 84) in Addis Ababa and surrounding districts (dairy cattle, n = 30; slaughtered cattle, n = 20; poultry, n = 26; swine n = 8). Isolates were serotyped, page typed and tested for antimicrobial susceptibility using Kirby–Bauer disc diffusion method, and genotyped by pulsed‐field gel electrophoresis (PFGE). The dominant Salmonella serovars isolated from food animals were S. Saintpaul (38.1%), S. Typhimurium (17.9%) and S. Kentucky (9.5%), whereas in humans, S. Typhimurium (39.7%), S. Virchow (30.9%) and S. Kottbus (10.3%) were frequently isolated. Resistance to streptomycin, sulfisoxazole, tetracycline, ampicillin and cephalothin was higher in animal isolates than human isolates, and mean number of antimicrobials to which isolates were resistant was significantly higher in isolates from cattle and poultry compared to those from humans (p < 0.05). All S. Kentucky isolated from animals and humans were multidrug resistant (MDR) with shared resistance phenotype (AmpCfCipTeSuSNa). Although this study involved small sample size and was not able to show clear epidemiological linkage among isolates from various sources, genotyping by PFGE analysis demonstrated circulation of closely related genotypes of S. Virchow, S. Typhimurium and S. Kentucky among humans and food animals. Detection of related Salmonella isolates from humans and animals, the high MDR status of isolates from animals and close proximity of farms and human residential areas in the absence of appropriate biosecurity present major public health problem. Integrated surveillance of Salmonella serovars in humans and animals and implementation of appropriate hazard analysis and pathogen control strategies along critical points of the food chain from farm to table is recommended.

Management Practice, and Adherence and Its Contributing Factors among Patients with Chronic Kidney Disease at Tikur Anbessa Specialized Hospital: A Hospital Based Cross-Sectional Study

The objective of this study was to assess the management practice, medication adherence, and factors affecting medication adherence in CKD patients at Tikur Anbessa Specialized Hospital (TASH). Methods. A cross-sectional study was conducted at the nephrology clinic of TASH. A total of 256 CKD (stages 1 and 2=50, stage 3=88, stage 4=55, and stage 5=63) patients were recruited through systematic random sampling. Data were collected from medical records and interviewing patients. The rate of adherence was determined using 8-item Morisky medication adherence scale. The data were analyzed using SPSS version 20.0 statistical software. Univariate and multivariate binary logistic regression were used to investigate the potential predictors of medication nonadherence. Results. About 57.3% of diabetes mellitus with hypertension were treated with combination of insulin and ACEI based regimens. Other cardiovascular comorbidities were predominantly treated with Acetyl Salicylic Acid in combination with β-blocker. Only 61.3% (stages 1 and 2=70%, stage 3=73.9%, stage 4=54.5%, and stage 5=43%) of the study population were adherent to their treatment regimens. Forgetfulness (79.8%) was the major reason for medication nonadherence. Patients who had an average and high monthly income were 4.14 (AOR=4.14, 95% CI: 1.45-11.84, p=0.008) and 6.17 times (AOR=6.17, 95% CI: 1.02-37.46, p=0.048) more likely to adhere as compared to those who had very low income. Patients who were prescribed with ≥5 drugs were 0.46 times (AOR= 0.54, 95% CI: 0.27-1.10, p=0.049) less likely to adhere compared to their counterpart. Patients who were students, drivers, or teachers working in private school were about 7.46 times (AOR=7.46, 95% CI: 1.49-37.26, p=0.014) more likely to adhere compared with patients who were farmers. Conclusion. Insulin and ACEIs based regimens were the most frequently used regimens in the treatment of diabetes mellitus and hypertension comorbidities. Very low income, increased number of prescribed medications, and being a farmer were the predictors of medication nonadherence.