The impact of adherence and instillation proficiency of topical glaucoma medications on intraocular pressure

Background: The possible sequel of poorly controlled intraocular pressure (IOP) includes treatment failure, unnecessary medication use, and economic burden on patients with glaucoma.Objective: To assess the impact of adherence and instillation technique on IOP control.Methods: A cross-sectional study was conducted on 359 glaucoma patients in Menelik II Hospital from June 1 to July 31, 2015. After conducting a Q-Q analysis, multiple binary logistic analyses, linear regression analyses, and two-tailed paired t-test were conducted to compare IOP in the baseline versus current measurements.Results: Intraocular pressure was controlled in 59.6% of the patients and was relatively well controlled during the study period (mean (M) = 17.911 mmHg, standard deviation (S) = 0.323) compared to the baseline (M = 20.866 mmHg, S = 0.383, t (358) = -6.70, p p = 0.03). Moreover, primary angle-closure glaucoma (adjusted odds ratio (AOR) = 0.347, 95% confidence interval (CI): 0.144-0.836) and two medications (AOR = 1.869, 95% CI: 1.259-9.379) were factors affecting IOP.Conclusion: Good instillation technique of the medications was correlated with a reduction in IOP. Consequently, regular assessment of the instillation technique and IOP should be done for better management of the disease

Vortex formation and recirculation zones in left anterior descending artery stenoses: computational fluid dynamics analysis

Flow patterns may affect the potential of thrombus formation following plaque rupture. Computational fluid dynamics (CFD) were employed to assess hemodynamic conditions, and particularly flow recirculation and vortex formation in reconstructed arterial models associated with ST-elevation myocardial infraction (STEMI) or stable coronary stenosis (SCS) in the left anterior descending coronary artery (LAD). Results indicate that in the arterial models associated with STEMI, a 50% diameter stenosis immediately before or after a bifurcation creates a recirculation zone and vortex formation at the orifice of the bifurcation branch, for most of the cardiac cycle, thus allowing the creation of stagnating flow. These flow patterns are not seen in the SCS model with an identical stenosis. Post-stenotic recirculation in the presence of a 90% stenosis was evident at both the STEMI and SCS models. The presence of 90% diameter stenosis resulted in flow reduction in the LAD of 51.5% and 35.9% in the STEMI models and 37.6% in the SCS model, for a 10 mmHg pressure drop. CFD simulations in a reconstructed model of stenotic LAD segments indicate that specific anatomic characteristics create zones of vortices and flow recirculation that promote thrombus formation and potentially myocardial infarction

Genetic and non-genetic parameter estimates for growth traits and Kleiber ratios in Dorper × indigenous sheep

Genetic improvement programme will only be successful when accompanied by a good understanding of the influence of different environmental factors, knowledge of the genetic parameters and the genetic relationships between the traits of interest. This study aimed to evaluate the influence of non-genetic fac- tors on growth traits and Kleiber ratios and to estimate genetic parameters for early growth traits in Dorper indigenous crossbred sheep. The effects of fixed factors were analysed by the general linear model procedure of statistical analysis system, while the genetic parameters were estimated using a WOMBAT computer program fitted animal model. The overall least-square mean for birth weight (BRW), weaning weight (3MW), six-month weight, nine-month weight, and yearling weight were 3.03 ± 0.02, 14.5 ± 0.18, 20.4 ± 0.26, 24.8 ± 0.31, and 28.3 ± 0.40 kg, respectively. The overall least- square mean for Kleiber ratio from birth to weaning (KR1), weaning to six months, six to nine months and nine months to yearling age were 16.8 ± 0.10, 6.41 ± 0.17, 4.55 ± 0.21 and 3.38 ± 0.20 g/kg of meta- bolic weight, respectively. The inclusion of maternal genetic effect had a significant influence on BRW, and it explains 20% of the phenotypic variation. The total heritability estimates for BRW, 3MW, birth to weaning average daily weight gain and KR1 were 0.10, 0.14, 0.16 and 0.12, respectively. The pheno- typic correlation varied from 0.11 ± 0.05 to 0.98 ± 0.02, whereas the direct genetic correlation ranged from 0.32 ± 0.40 to 0.98 ± 0.17. The mean inbreeding coefficient was 0.105% with an annual rate of 0.02%. The heritability estimates for growth traits and Kleiber ratio suggest that slow genetic progress would be expected from the selection. However, the integration of selection with crossbreeding pro- gramme can enhance genetic gain. Therefore, selection should be conducted based on breeding values estimated from multiple information sources to increase the selection response

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide

In Vivo Antimalarial Activity of Solvent Fractions of the Leaves of Justicia schimperiana Hochst. Ex Nees Against Plasmodium berghei in Mice

Increasing resistance of Plasmodium falciparum to almost all the available antimalarial drugs urges a search for newer antimalarial drugs. Justicia schimperiana Hochst. Ex Nees is traditionally used for the treatment of malaria and a study conducted previously on the crude leaf extract confirmed that the plant is endowed with antimalarial activity. The present study was therefore aimed to evaluate antimalarial activities of chloroform, methanol and aqueous fractions of the leaves of J. schimperiana against Plasmodium berghei in mice. A rodent malaria parasite, P. berghei, was used to inoculate healthy male Swiss Albino mice. The extraction was conducted following successive soxhlet extraction and maceration. The resulting fractions were evaluated at doses of 200, 400 and 600 mg/kg. Parameters, such as parasitaemia, survival time, body weight, temperature, and packed cell volume were determined using the 4-day suppressive, curative and prophylactic tests. All the three fractions had shown significant suppression of parasitaemia in the 4-day suppressive test, of which the methanol fraction exerted the highest chemosuppression (65.2%, p<0.001) at 600 mg/kg followed by the aqueous fraction (40.93%, p<0.001) at the same dose. The methanol fraction also showed significant suppression of parasitaemia in both curative (67.44%, p< 0.001) and prophylactic (35.02%, p<0.01) tests at 600 mg/kg dose. All doses of the methanol fraction significantly (p<0.05) prevented the reduction in rectal temperature in the 4-day suppressive and curative tests. In conclusion, the results of the studies demonstrated high antimalarial activities of methanol and aqueous fractions against P. berghei in mice. These findings substantiated the previous activity of crude extract and traditional use of the plant. Therefore, the plant could be potentially utilized as a source of templates for the development of new antimalarial agent.Keywords: Justicia schimperiana, in vivo, anti-malarial activity, Plasmodium berghei, solvent fraction

Phytochemical Screening and In Vitro Antitrypanosomal Activity of the Aerial Parts of Artemisia abyssinica Against Trypanosoma congolense Field Isolate

African trypanosomiasis is a major public health problem having serious economic implications affecting both human and agricultural development. The present work dealt with phytochemical screening and in vitro antitrypanosomal activity testing of the hydromethanolic and dichloromethane (DCM) extracts of the aerial parts of Artemisia abyssinica Sch.Bip. ex A.Rich. against Trypanosoma congolense field isolate. The in vitro assay was conducted by incubating a mixture of infected blood and extracts at concentrations of 4, 2 and 0.4 mg/ml coupled with infectivity test in which a mixture of infected blood was inoculated to healthy mice. Phytochemical screening showed the presence of alkaloids, flavonoids, tannins, polyphenols, and cardiac glycosides in the hydromethanolic extract, and terpenoids, polyphenols and phytosteroids in the DCM extract. The result evidenced that the DCM extract had immobilized trypanosomes after 18 and 40 min of incubation at 4 and 2 mg/ml, respectively, while the hydromethanolic extract ceased the motility of the parasites after 35 min only at a concentration of 4 mg/ml. In the infectivity test, only 4 mg/ml of  the DCM extract caused loss of infectivity of the parasites to mice. In conclusion, the result obtained from this preliminary investigation renders the plant to be a potential candidate for development of new lead against African trypanosomiasis.Keywords: Artemisia abyssinica, phytochemical screening, in vitro antitrypanosomal activity, Trypanosoma congolense, crude extract

Prevalence and Characteristics of Polypharmacy and Drug-Drug Interaction in Afincho Ber Health Centre, Addis Ababa, Ethiopia

Polypharmacy is the prescription of multiple medications for a patient which is a common problem worldwide. The aim of this study was to identify the extent of polypharmacy and occurrence of drug–drug interaction in Afincho Ber Health Centre, Addis Ababa. The study was conducted by retrospective crosssectional review of prescriptions of all adult outpatients for a period of 6 months at Afincho Ber Health Centre. In this study, polypharmacy was defined as prescription of 4 or more drugs. All the statistical calculations were performed using SPSS® software version 20. Drug-drug interactions were identified using computer based Micromedex2® software. Among the total of 271 prescriptions analyzed, 113 (41.70%) were identified as polypharmacy. At least one drug-drug interaction was detected in 106 (39.1%) prescriptions of which 17 (16.04%) were severe drug interactions. In conclusion, polypharmacy and drug-drug interaction were both identified to be commonly encountered problems among the outpatients.Keywords: Polypharmacy, Drug-drug Interactions, Health Centre, Retrospective Cross-sectional Review, Ethiopi

Experimental Evaluation of Analgesic and Anti-inflammatory Activity of 80% Methanolic Leaf Extract of Moringa stenopetala Bak. F. in Mice

Moringa stenopetala Bak F. is commonly used in folk medicine as a remedy to treat various ailments like hypertension, headache, stomach disorders, asthma, diabetes and malaria. However, the use of the herb for treatment of pain and inflammation has not been scientifically investigated. Thus, in this experiment 80% methanol crude extract of the leaves of M. stenopetala was evaluated for its analgesic and antiinflammatory activities using established animal models. Swiss albino mice of either sex were randomly divided into five groups (n = 6). The negative control group was orally given 0.5 ml of distilled water. The positive control received standard drug based on the respective model (morphine 10 mg//kg, acetyl salicylic acid 81 mg/kg, indomethacin 25 mg/kg). The rest of the groups were treated with 80% methanol extract of M. stenopetala leaves at doses of 200, 400 and 600 mg/kg. Animals were then subjected to a battery of tests including hot plate, tail flick, acetic acid induced writhing, and carrageenan induced paw oedema tests. The results indicate that M. stenopetala extract showed a dose-dependent significant reduction of pain in analgesia models (p<0.001) with 600 mg/kg dose producing the highest reduction. The extract significantly reduced carrageenan-induced inflammation in a dose independent manner, in which the highest reduction of inflammation was observed at 400 mg/kg. The data collectively indicate that the 80% methanol extract of M. stenopetala leaves have potential analgesic and anti-inflammatory activities against stimuli in tested animals and can be recommended for further studies.Keywords: Moringa stenopetala, Leaves, Crude Extract, Analgesic Activity, Anti-inflammatory Activit

Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis

Atopic dermatitis (AD) is a common, complex inflammatory skin disorder where a defect skin barrier is central in the pathogenesis. Mutations in the filaggrin gene cause ichthyosis vulgaris (IV). IV is one of several keratinization disorders named ichthyoses where mutations in skin barrier genes are a common underlying genetic factor. Furthermore, filaggrin mutations are a major risk factor for moderate to severe AD. The aim of the work reported in this thesis is to improve the understanding of the genetic mechanisms of skin barrier defects associated with AD, and to identify whether AD and other common disorders of keratinisation may share genetic susceptibility factors related to skin barrier dysfunction. Paper I presents data suggesting that filaggrin mutations may be rare in Ethiopian AD and IV patients, implying other mechanisms should be more important in the pathogenesis of IV and AD in this ethnic group. Paper II presents a novel mutation in the steroid sulfatase gene in a patient with clinical signs of common ichthyosis type. In paper III association between filaggrin mutations and childhood onset of psoriasis was tested. No association to any prevalent filaggrin mutations was found, and no novel mutations. This indicates that filaggrin loss-of- function variants do not have a strong effect on the onset of psoriasis in childhood. In paper IV it is demonstrated that functional parameters and gene expression in molecular pathways in vivo is altered in patients suffering from AD and IV and depend on filaggrin genotype. Patients with filaggrin mutations displayed a severe phenotype with impaired barrier function measured as increased trans-epidermal water loss, and significantly altered pH levels. Furthermore, the numbers of genes with altered expression were significantly higher in patients with low or absent filaggrin expression. These pathways include many genes involved in inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion. Paper V represents a candidate gene study where expression analysis links the epidermal transglutaminases 1 and 3 to the manifestation of AD and genetic analysis suggests that genetic variation at the transglutaminase 1 locus could be involved in the development of the disease. The results of the work reported in this thesis provides additional descriptive information and further elucidates the pathogenesis underlying AD and other disorders of keratinization, in particular in relation to filaggrin deficiency. Better understanding of the genetic factors and molecular and functional consequences should hopefully enable future individually designed barrier restoring therapy