Safety of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials.

BACKGROUND: The efficacies of artemisinin based combinations have been excellent in Africa, but also comprehensive evidence regarding their safety would be important. The aim of this review was to synthesize available evidence on the safety of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa. METHODS: A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL) for retrieving randomized control trials comparing safety of DHA-PQ and AL for treatment of uncomplicated P. falciparum malaria among children in Africa. The search was performed from August 2020 to 30 April 2021. Using Rev-Man software (V5.4.1), the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI). RESULTS: In this review, 18 studies were included, which involved 10,498 participants were included. Compared to AL, DHA-PQ was associated with a slightly higher frequency of early vomiting (RR 2.26, 95% CI 1.46 to 3.50; participants = 7796; studies = 10; I2 = 0%, high quality of evidence), cough (RR 1.06, 95% CI 1.01 to 1.11; participants = 8013; studies = 13; I2 = 0%, high quality of evidence), and diarrhoea (RR 1.16, 95% CI 1.03 to 1.31; participants = 6841; studies = 11; I2 = 8%, high quality of evidence) were more frequent in DHA-PQ treatment arm. CONCLUSION: From this review, it can be concluded that early vomiting, diarrhoea, and cough were common were significantly more frequent in patients who were treated with the DHA-PQ than that of AL, and both drugs are well tolerated. More studies comparing AL with DHA-PQ are needed to determine the comparative safety of these drugs.

Characteristics of recent clinical investigations into systemic therapy against cervical cancer: systematic analysis of trial details from Clinicaltrials.gov.

A review that systematically assessed the current state of clinical research into systematic therapy-based interventions against invasive cervical cancer. It analysed registry details of 59 systemic therapy-based cervical cancer trials on ClinicalTrials.gov with study start dates between January 2010 and June 2018. The review characterised the present cervical cancer trial landscape in terms of trial design features, systemic therapy (chemotherapy, targeted therapy, immunotherapy, and repurposed therapy), and disease stages of interest. It also made an attempt to qualitatively synthesise the trial landscape in terms of the nature and trend of research focus, alignment with existing clinical needs, novelty of treatments or concepts pursued, and promise of new treatments.

Adherence to COVID -19 protective practices in Ethiopia: Use and predictors of face mask-wearing.

Introduction: The Ethiopian Ministry of Health strongly recommends that anyone, regardless of vaccination status, wears a standard face mask consistently when in public. This study aimed to assess the self-reported use and predictors of wearing face masks in the general population in Ethiopia. Methods: This was a population-based cross-sectional study using a telephone survey. Adults living in Ethiopia were randomly selected from the Ethio Telecom list of mobile phone numbers and interviewed about their mask-wearing practice and individual and household-level factors that could impact on the use of face masking. Multivariable logistic regression was used to measure associations. Results: A total of 614 participants were interviewed from September to November 2021. The prevalence of self-reported face mask use when in public was 81.1%. Living outside Addis Ababa, including Oromia [adjusted odds ratio [(AOR) 0.30, 95% confidence interval (CI) (0.14, 0.63)], Amhara [AOR 0.11, 95% CI (0.05, 0.23)], and Southern Nations, Nationalities and People's Region [AOR 0.31, 95% CI (0.12-0.79)] and being divorced or widowed [AOR 0.18, 95% CI (0.06, 0.62)] were found to be inversely associated with face mask use. Female gender [AOR 1.91, 95% CI (1.02, 3.58)] and older age [age ≥ 50, AOR 2.96, 95% CI (1.09-7.97)] were positively associated with the use of face masks. Attending social events [AOR 0.51, 95% CI (0.31-0.82)], was negatively associated with the use of face masks. Conclusion: Self-reported use of face masks was relatively high nationally, but inconsistent among different regions and demographics. The findings imply that policies and messaging campaigns may need to focus on specific populations and behaviors in this ongoing pandemic.

Impact of COVID-19 on population health and economic wellbeing in Ethiopia: A national pilot survey.

Introduction: The COVD-19 pandemic has resulted in unprecedented global health and economic crisis, particularly in countries struggling with poverty. We conducted a national survey to understand the economic and health impacts of COVID-19 in Ethiopia. Methods: A pilot, population-based, cross-sectional survey was conducted among adults randomly selected from the Ethio Telecom list of mobile phone numbers. Participants underwent a comprehensive phone interview about the impact of COVID-19 on their economic well-being and the health-related risks associated with COVID-19. Results: Of 4,180 calls attempted, 1194 were answered, of which a successful interview was made with 614 participants. COVID-19 affected the family income of 343 [55.9%] participants, 56 [9.1%] lost their job, 105 [17.1%] perceived high stress in their household, and 7 [1.14%] reported death in their family in the past month. The odds of having a decreased income due to COVID-19 were 2.4 times higher among self-employed [adjusted odds ratio (AOR) 2.4, 95% CI (1.58-3.77)] and 2.8 times higher among unemployed [AOR 2.8, 95% CI (1.35-5.85)] participants. Two-hundred twenty-one [36%] participants had comorbidity in their household with hypertension, 72 [11.7%], diabetes,50 [8.1%], asthma, 48 [7.8%], and other chronic diseases, 51 [8.4%]. Forty-six [7.5%] participants had COVID-like symptoms in the previous month, where cough, headache, and fatigue were the most common. Conclusion: COVID-19 posed serious economic pressure on households. Self-employed and unemployed were the most affected. Continuous surveillance is needed to actively monitor the impact of COVID-19 in the community and safeguard the economic and health well-being of individuals and households.

Efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials.

BACKGROUND: Emergence of Plasmodium falciparum resistance to artemisinin and its derivatives poses a threat to the global effort to control malaria. The emergence of anti-malarial resistance has become a great public health challenge and continues to be a leading threat to ongoing malaria control efforts. The aim of this review was to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria among children in Africa. METHODS: A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Central Register of Controlled Trials' database (CENTRAL) for retrieving randomized control trials comparing efficacy of DHA-PQ and AL for treatment of uncomplicated falciparum malaria in African children. The search was performed from August 2020 to April 2021. Using Rev-Man software (V5.4.1), R-studio and Comprehensive Meta-analysis software version 3, the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI). RESULTS: In this review, 25 studies which involved a total of 13,198 participants were included. PCR-unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in the DHA-PQ treatment arm on day 28 than that of AL (RR 0.14, 95% CI 0.08-0.26; participants = 1302; studies = 4; I2 = 0%, high quality of evidence). Consistently, the PCR-adjusted treatment failure was significantly lower with DHA-PQ treatment group on day 28 (RR 0.45, 95% CI 0.29-0.68; participants = 8508; studies = 16; I2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47-0.78; participants = 5959; studies = 17; I2 = 0%, high quality of evidence). However, the efficacy was ≥ 95% in both treatment groups on day 28. CONCLUSION: From this review, it can be concluded that DHA-PQ reduces new infection and recrudescence on days 28 and 42 more than AL. This may trigger DHA-PQ to become a first-line treatment option.

Efficacy and safety of azithromycin and amoxicillin/clavulanate for otitis media in children: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Resistance, prolonged therapy, and more adverse reactions made amoxicillin less preferred for treating otitis media. This study aimed to compare the efficacy and safety of azithromycin and amoxicillin/clavulanate for the treatment of otitis media in children. METHODOLOGY: This study was a systematic review and meta-analysis. PubMed, Cochrane library, and Google scholar databases were searched. Comparative randomized clinical trial studies between azithromycin and amoxicillin/clavulanate to treat otitis media in children published up to 30 September 2019 were included. The risk of bias was assessed and Data was extracted by the first author and checked by the second author. Meta-analysis was performed by STATA software version 16, and Mantel-Haenszel statistical method with effect measure odds ratio was employed for analysis. RESULT: 751 records were identified and 14 studies were eligible for analysis. In 12 studies azithromycin had equivalent clinical efficacy and 2 had less to amoxicillin/clavulanate. Meta-analysis results showed no statistically significant difference in efficacy in favor of amoxicillin/clavulanate after completion of treatment OR 0.75, 95% CI (0.62-0.91). On subgroup analysis for children less than 2 years (OR 0.96 95% CI (0.49-2.29), and greater than 2 years (OR 1.40 95% CI (0.93-2.11) and also efficacy on follow up (OR 0.97 95% CI (0.83-1.15) there is no statistically significant difference. The clinical adverse events are more in the amoxicillin/clavulanate group than in the azithromycin with a statistical significant difference OR 0.46 95% CI (0.43-0.56). CONCLUSION: Azithromycin is comparable to amoxicillin/clavulanate to treat otitis media in children, and it is safer and more tolerable.

Understanding the key processes of excellence as a prerequisite to establishing academic centres of excellence in Africa.

BACKGROUND: Africa's economic transformation relies on a radical transformation of its higher education institutions. The establishment of regional higher education Centres of Excellence (CoE) across Africa through a World Bank support aims to stimulate the needed transformation in education and research. However, excellence is a vague, and often indiscriminately used concept in academic circles. More importantly, the manner in which aspiring institutions can achieve academic excellence is described inadequately. The main objective of this paper is to describe the core processes of excellence as a prerequisite to establishing academic CoE in Africa. METHODS: The paper relies on our collaborative discussions and real-world insight into the pursuit of academic excellence, a narrative review using Pubmed search for a contextual understanding of CoEs in Africa supplemented by a Google search for definitions of CoEs in academic contexts. RESULTS: We identified three key, synergistic processes of excellence central to institutionalizing academic CoEs: participatory leadership, knowledge management, and inter-disciplinary collaboration. (1) Participatory leadership encourages innovations to originate from the different parts of the organization, and facilitates ownership as well as a culture of excellence. (2) Centers of Excellence are future-oriented in that they are constantly seeking to achieve best practices, informed by the most up-to-date and cutting-edge research and information available. As such, the process by which centres facilitate the flow of knowledge within and outside the organization, or knowledge management, is critical to their success. (3) Such centres also rely on expertise from different disciplines and 'engaged' scholarship. This multidisciplinarity leads to improved research productivity and enhances the production of problem-solving innovations. CONCLUSION: Participatory leadership, knowledge management, and inter-disciplinary collaborations are prerequisites to establishing academic CoEs in Africa. Future studies need to extend our findings to understand the processes key to productivity, competitiveness, institutionalization, and sustainability of academic CoEs in Africa.

N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians.

BACKGROUND AND OBJECTIVES: N-acetyltransferase 2 (NAT2) metabolize several drugs including isoniazid. We investigated the effect of genotype, geographical difference, and smoking habit on NAT2 phenotype in Ethiopians. METHODS: Genotyping for NAT2 191G > A, 341 T > C, 590G > A, and 857G > A was performed in 163 unrelated healthy Ethiopians (85 living in Ethiopia and 78 living in Sweden). The NAT2 phenotype was determined using caffeine as a probe and log AFMU/(AFMU + 1X + 1 U) urinary metabolic ratio (MR) as an index. RESULTS: The frequencies of NAT2*4, *5, *6, *7, and *14 haplotypes were 14.1, 48.5, 30.1, 5.5, and 1.8%, respectively. The frequencies of rapid (NAT2*4/*4), intermediate (heterozygous *4), and slow (no *4 allele) acetylator genotypes were 1.8, 24.6, and 73.6%, respectively. The distribution NAT2 MR was bimodal with 70% being phenotypically slow acetylators. NAT2 genotype (p < 0.0001) and country of residence (p = 0.004) independently predicted NAT2 phenotype. Controlling for the effect of genotype, ethnic Ethiopians living in Ethiopia had significantly higher NAT2 MR than those living in Sweden (p = 0.006). NAT2 genotype-phenotype concordance rate was 75%. Distinct country-of-residence-based genotype-phenotype discordance was observed. The proportion of phenotypically determined rapid acetylators was significantly higher and slow acetylators was lower in Ethiopians living in Ethiopia (39% rapid, 61% slow) than in Sweden (20% rapid, 80% slow). Sex and smoking had no significant effect on NAT2 MR. CONCLUSIONS: We report a high prevalence of NAT 2 slow acetylators in Ethiopians and a conditional NAT2 genotype-phenotype discordance implicating a partial phenotype conversion and metabolic adaptation. Gene-environment interactions regulate NAT2 phenotype.

The Next Generation Scientist program: capacity-building for future scientific leaders in low- and middle-income countries.

BACKGROUND: Scientific and professional development opportunities for early career scientists in low- and middle- income countries (LMICs) are limited and not consistent. There is a disproportionately low number of biomedical and clinical researchers in LMIC's relative to their high burden of disease, a disparity that is aggravated by emigration of up to 70% of scientists from their countries of birth for education and employment elsewhere. To help address this need, a novel University-accredited, immersive fellowship program was established by a large public-academic-private network. We sought to describe the program and summarize progress and lessons learned over its first 7-years. METHODS: Hallmarks of the program are a structured learning curriculum and bespoke research activities tailored to the needs of each fellow. Research projects expose the scientists to state-of-the-art methodologies and leading experts in their fields while also ensuring that learnings are implementable within their home infrastructure. Fellows run seminars on drug discovery and development that reinforce themes of scientific leadership and teamwork together with practical modules on addressing healthcare challenges within their local systems. Industry mentors achieve mutual learning to better understand healthcare needs in traditionally underserved settings. We evaluated the impact of the program through an online survey of participants and by assessing research output. RESULTS: More than 140 scientists and clinicians from 25 countries participated over the 7-year period. Evaluation revealed strong evidence of knowledge and skills transfer, and beneficial self-reported impact on fellow's research output and career trajectories. Examples of program impact included completion of post-graduate qualifications; establishment and implementation of good laboratory- and clinical- practice mechanisms; and becoming lead investigators in local programs. There was a high retention of fellows in their home countries (> 75%) and an enduring professional network among the fellows and their mentors. CONCLUSIONS: Our experience demonstrates an example for how multi-sectoral partners can contribute to scientific and professional development of researchers in LMICs and supports the idea that capacity-building efforts should be tailored to the specific needs of beneficiaries to be maximally effective. Lessons learned may be applied to the design and conduct of other programs to strengthen science ecosystems in LMICs.

Population Pharmacokinetic Model Linking Plasma and Peripheral Blood Mononuclear Cell Concentrations of Efavirenz and Its Metabolite, 8-Hydroxy-Efavirenz, in HIV Patients.

The objectives of this study were to characterize the population pharmacokinetics (PK) of efavirenz (EFV) and 8-hydroxy-efavirenz (8OHEFV) in plasma and peripheral blood mononuclear cells (PBMCs) and to explore covariates affecting the PK parameters. Fifty-one patients had steady-state 0-to-24-h concentrations of EFV and 8OHEFV in plasma with corresponding concentrations in PBMCs, while 261 patients had one or two sparse concentrations at 16 ± 1 h postdose at weeks 4 and/or 16. The pharmacogenetic markers CYP2B6*6, CYP3A5*3, CYP3A5*6, UGT2B7*2, ABCB1 (3435C→T, 3842A→G), OATP1B1*1B, and OATP1B1*5, the presence of a rifampin-based antituberculosis (anti-TB) regimen, baseline body weight and organ function values, and demographic factors were explored as covariates. EFV concentration data were well described by a two-compartment model with first-order absorption (Ka ) and absorption lag time (Alag) (Ka = 0.2 h-1; Alag = 0.83 h; central compartment clearance [CLc/F] for CYP2B6*1/*1 = 18 liters/h, for CYP2B6*1/*6 = 14 liters/h, and for CYP2B6*6/*6 = 8.6 liters/h) and PBMCs as a peripheral compartment. EFV transfer from plasma to PBMCs was first order (CLp/F = 32 liters/h), followed by capacity-limited return (Vmax = 4,400 ng/ml/h; Km = 710 ng/ml). Similarly, 8OHEFV displayed a first-order elimination and distribution to PBMCs, with a capacity-limited return to plasma. No covariate relationships resulted in a significant explanation of interindividual variability (IIV) on the estimated PK parameters of EFV and 8OHEFV, except for CYP2B6*6 genotypes, which were consistent with prior evidence. Both EFV and 8OHEFV accumulated to higher concentrations in PBMCs than in plasma and were well described by first-order input and Michaelis-Menten kinetics removal from PBMCs. CYP2B6*6 genotype polymorphisms were associated with decreased EFV and 8OHEFV clearance.

Elevated levels of circulating CDH5 and FABP1 in association with human drug-induced liver injury.

BACKGROUND & AIMS: The occurrence of drug-induced liver injury (DILI) is a major issue in all phases of drug development. To identify novel biomarker candidates associated with DILI, we utilised an affinity proteomics strategy, where antibody suspension bead arrays were applied to profile plasma and serum samples from human DILI cases and controls. METHODS: An initial screening was performed using 4594 randomly selected antibodies, representing 3450 human proteins. Resulting candidate proteins together with proposed DILI biomarker candidates generated a DILI array of 251 proteins for subsequent target analysis and verifications. In total, 1196 samples from 241 individuals across four independent cohorts were profiled: healthy volunteers receiving acetaminophen, patients with human immunodeficiency virus and/or tuberculosis receiving treatment, DILI cases originating from a wide spectrum of drugs, and healthy volunteers receiving heparins. RESULTS: We observed elevated levels of cadherin 5, type 2 (CDH5) and fatty acid-binding protein 1 (FABP1) in DILI cases. In the two longitudinal cohorts, CDH5 was elevated already at baseline. FABP1 was elevated after treatment initiation and seemed to respond more rapidly than alanine aminotransferase (ALT). The elevations were verified in the DILI cases treated with various drugs. In the heparin cohort, CDH5 was stable over time whereas FABP1 was elevated. CONCLUSIONS: These results suggest that CDH5 may have value as a susceptibility marker for DILI. FABP1 was identified as a biomarker candidate with superior characteristics regarding tissue distribution and kinetics compared to ALT but likely with limited predictive value for the development of severe DILI. Further studies are needed to determine the clinical utility of the proposed markers.

In vivo antiplasmodial activity and toxicological assessment of hydroethanolic crude extract of Ajuga remota.

BACKGROUND: Malaria is one of the most life-threatening health problems worldwide and treatment has been compromised by drug resistance. Identifying lead molecules from natural products might help to find better anti-malarial drugs, since those obtained from natural sources are still effective against malarial parasites. This study aimed at investigating the in vivo antiplasmodial activity of crude extract of the leaves of Ajuga remota together with its safety in mice models. METHODS: In vivo parasite growth inhibitory effect of crude extract was assessed in mice inoculated with Plasmodium berghei (ANKA strain). The in vivo antiplasmodial activity of the test extract was performed against early infection (4-day suppressive test), curative effect against established infection and prophylactic effect against residual infection. Acute and sub-acute toxicity were carried out according to OECD guidelines. RESULTS: In vivo parasite growth inhibition effect of hydroethanolic crude extract of A. remota was evaluated at 30, 50 and 100 mg/kg dose levels. It suppressed parasitaemia by 77.34% at 100 mg/kg dose level in the 4-day test. In curative and prophylactic potential tests, it suppressed parasitaemia by 66.67 and 59.66% at 100 mg/kg dose level, respectively. In vivo toxicity tests revealed no toxicity. All parasitaemia suppressions were statistically significant at P < 0.05 as compared to the vehicle-treated group. The crude extract also prolonged survival time in a dose dependent manner. CONCLUSIONS: The investigation results suggest that the leave extract of Ajuga remota possesses antimalarial activity.

In vivo antimalarial activity of crude extracts and solvent fractions of leaves of Strychnos mitis in Plasmodium berghei infected mice.

BACKGROUND: Malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-Saharan Africa. Today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. Medicinal plants are the unquestionable source of effective antimalarials. The present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant Strychnos mitis in Plasmodium berghei infected mice. METHODS: Standard procedures were employed to investigate acute toxicity and 4-day suppressive effect of crude aqueous and hydro-methanolic extracts of the leaves of Strychnos mitis against P. berghei in Swiss albino mice. Water, n-hexane and chloroform fractions, obtained from crude hydro-methanolic extract, were also tested for their suppressive effect against P. berghei. RESULTS: All crude extracts revealed no obvious acute toxicity in mice up to the highest dose administered (2000 mg/kg). All crude and solvent fractions of the leaves of Strychnos mitis inhibited parasitaemia significantly (p < 0.01). At the highest dose of 600 mg/kg, both aqueous and hydro-methanolic extracts demonstrated higher performance with 95.5 and 93.97% parasitaemia suppression, respectively. All doses of crude extracts and fractions of leaves of Strychnos mitis prolonged survival time of infected mice dose dependently. The highest two doses of the crude aqueous and hydro-methanolic extracts, and chloroform and aqueous fractions prevented weight loss in a dose dependent manner. Whereas, all doses of n-hexane fraction prevented loss of body weight but not in a dose dependent manner. The crude aqueous extract at the doses of 400 mg/kg and 600 mg/kg and hydro-methanolic extract at all dose levels significantly (p < 0.01) prevented packed cell volume reduction. Crude aqueous extract at a dose of 600 mg/kg and hydro-methanolic extract at all dose levels significantly prevented temperature reduction. Phytochemical screening of the crude aqueous and hydro-methanolic extracts revealed the presence of alkaloids, anthraquinones, glycosides, terpenoids, saponins, tannins and phenols. CONCLUSION: The results of this study provide support the traditional therapeutic use of Strychnos mitis for treatment of malaria. However, further in-depth study is needed to evaluate the potential of the plant towards the development of new antimalarial agent.

Genome-wide association and replication study of anti-tuberculosis drugs-induced liver toxicity.

BACKGROUND: Drug-induced liver injury (DILI) is a well-recognized adverse event of anti tuberculosis drugs (ATD) possibly associated with genetic variations. The objective of this study was to perform genome-wide association study (GWAS) to identify genetic variants associated with the risk for ATD induced liver toxicity in Ethiopian patients. RESULT: Treatment-naïve newly diagnosed tuberculosis patients (n = 646) were enrolled prospectively and treated with rifampicin based short course anti-tuberculosis therapy. Whole genome genotyping was done using Illumina Omni Express Exome Bead Chip genotyping array with 951,117 single nucleotide polymorphisms (SNPs) on 48 DILI cases and 354 ATD tolerants. Replication study was carried out for 50 SNPs with the lowest P-values (top SNPs) using an independent cohort consisting of 27 DILI cases and 217 ATD tolerants. In the combined analysis, the top SNP identified was rs10946737 (P = 4.4 × 10-6, OR = 3.4, 95 % confidence interval = 2.2-5.3) in the intron of FAM65B in chromosome 6. In addition, we identified a cluster of SNPs with suggestive genome-wide significance in the intron of ATP/GTP binding protein-like 4 (AGBL4). CONCLUSION: We identified genetic variants that are potentially associated with ATD induced liver toxicity. Further studies with larger sample sizes are essential to confirm the findings.

Effect of Rumex Abyssinicus on preneoplastic lesions in dimethylhydrazine induced colon carcinogenesis in rats.

BACKGROUND: Cancer as a multistage process can be reversed or blocked by using chemopreventive agents. Colon cancer chemoprevention has been widely investigated using cyclooxygenase inhibitors and many other chemicals of synthetic or natural origin. This particular study was carried out to assess the colon cancer chemopreventive effect of hydro-methanol extract of Rumex abyssinicus rhizome on rats. METHOD: Colon cancer chemopreventive potential of hydro-methanol extract of Rumex abyssinicus rhizome was determined based on the number and multiplicity of aberrant crypt foci (ACF). Fifteen DMH (1, 2-dimethylhydrazine) treated and five untreated Wistar female rats were used. DMH was administered subcutaneously 30 mg/kg, after its pH was adjusted to 6.5-7. Treatment groups started receiving extract after six weeks of weekly DMH injections. The rats were divided in to four groups: Group 1 received only oral normal saline, Group 2 received DMH and normal saline, Group 3 and 4 received DMH plus 250 mg/kg and 500 mg/kg extract, respectively. Specific phytoconstituents of the plant, which were reviewed from original articles, were virtually evaluated for cyclooxygenase-2 (COX-2) inhibition. The binding energies and interactions of the phytochemicals from Rumex abyssinicus against COX-2 were determined by Autodock4.2. RESULTS: There was a statistically significant reduction (p-value < 0.05) in the number of aberrant crypt (AC) and aberrant crypt foci (ACF) at both administered doses. However, significant association (p-value > 0.05) was not observed in reducing crypt multiplicity. The docking process resulted in estimated binding energies [-6.83 kcal/mol to -7.9 kcal/mol] which are closer to the positive controls or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [-4.55 kcal/mol to -10.84 kcal/mol]. The phytochemical-COX-2 interaction indicated the involvement of key amino acid residues in inhibition of cyclooxygenase like ARG120, TYR355, TYR385, SER530 and GLY526. CONCLUSIONS: Rumex abyssinicus had demonstrated a chemopreventive potential at post-initiation stage. As the virtual screening data suggested, COX-2 inhibition by the anthraquinones in the extract could be one mechanism for the observed chemopreventive effect.

Antidiabetic activities of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin-induced diabetic rats.

BACKGROUND: Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. The aim of this study was to investigate the antidiabetic activity of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin (STZ) induced diabetic rats. METHODS: The aqueous ethanol extract and n-butanol fraction of Moringa stenopetala leaves hydroalcoholic (500 mg/kg body weight) and metformin (150 mg/kg body weight) were administered to diabetic rats. Blood glucose, lipid profiles, liver and kidney function were examined after 14 days of experiment. Histopathological profile of the pancreas was also observed in diabetic rats at the end of study. An oral sucrose challenge test was also carried out to assess the post prandial effect of the extract. RESULTS: Oral administration of the aqueous ethanol and n-butanol extracts of Moringa stenopetala leaves (500 mg/kg body weight) and metformin (150 mg/kg) significantly reduced blood glucose level (P<0.05), improved serum lipid profiles, liver enzymes and kidney functions in diabetic rats after 14 days. The extracts also improved damage of islet of Langerhan's in diabetic rats. The plant material reduced the post-prandial glucose level (P<0.001) at the dose of 750 mg/kg. CONCLUSION: These findings revealed that both the aqueous ethanol and n-butanol extracts of Moringa stenopetala leaves possess antihyperglycemic and antihyperlipidemic properties, and alleviate STZ-induced pancreatic damage in diabetic rats. The beneficial effects of plant material in inhibition of diabetes-induced complications are being investigated.

Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

BACKGROUND & AIMS: There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. METHODS: Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. RESULTS: In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. CONCLUSIONS: M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.

Intestinal α-glucosidase and some pancreatic enzymes inhibitory effect of hydroalcholic extract of Moringa stenopetala leaves.

BACKGROUND: Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. One of the successful methods to prevent of the onset of diabetes is to control postprandial hyperglycemia by the inhibition of α-glucosidase and pancreatic α-amylase activities, resulting in the aggressive delay of the carbohydrate digestion of absorbable monosaccharides. The aim of the present study is to investigate the effect of the extract of the leaves of Moringa stenopetala on α-glucosidase, pancreatic α-amylase, pancreatic lipase, and pancreatic cholesterol esterase activities, and, therefore find out the relevance of the plant in controlling blood sugar and lipid levels. METHODS: The dried leaves of Moringa stenopetala were extracted with hydroalcoholic solvent and dried using rotary vapor under reduced pressure. The dried extracts were determined for the total phenolic compounds, flavonoid content and condensed tannins content by using Folin-Ciocateu's reagent, AlCl3 and vanillin assay, respectively. The dried extract of plant-based food was further quantified with respect to intestinal α-glucosidase (maltase and sucrase) inhibition and pancreatic α-amylase inhibition by glucose oxidase method and dinitrosalicylic (DNS) reagent, respectively. RESULTS: The phytochemical analysis indicated that flavonoid, total phenolic, and condensed tannin contents in the extract were 71.73 ± 2.48 mg quercetin equivalent/g of crude extract, 79.81 ± 2.85 mg of gallic acid equivalent/g of crude extract, 8.82 ± 0.77 mg catechin equivalent/g of crude extract, respectively. The extract inhibited intestinal sucrase more than intestinal maltase with IC50 value of 1.47 ± 0.19 mg/ml. It also slightly inhibited pancreatic α-amylase, pancreatic lipase and pancreatic cholesterol esterase. CONCLUSION: The result demonstrated the beneficial biochemical effects of Moringa stenopetala by inhibiting intestinal α-glucosidase, pancreatic cholesterol esterase and pancreatic lipase activities. A daily supplement intake of the leaves of Moringa stenopetala may help in reducing hyperglycemia and hyperlipidemia.

Evaluation of Statin Indication and Dose Intensification Among Type 2 Diabetic Patients at a Tertiary Hospital.

Background: Diabetes mellitus (DM) increases cardiovascular disease (CVD) incidence and mortality. While guidelines endorse statin use in type 2 DM (T2DM) to mitigate cardiovascular risks and mortality, challenges like statin initiation and prompt treatment adjustments affect patient outcomes. This study aimed to assess the appropriateness of indications for and dose intensification of statin therapy among T2DM patients at Tikur Anbessa Specialized Hospital (TASH). Methodology: A hospital-based cross-sectional study was conducted from April 1 to June 30 2020. In total, 405 T2DM patients were selected using a systematic random sampling technique. The data were analyzed using SPSS version 26.0. An adjusted odds ratio (OR) was used and a 95% confidence interval (CI) and p-values of <0.05 were utilized to determine statistical significance. Results: Of the total 405 participants, 346 (85.4%) started taking statins for primary or secondary prevention purposes. Indication for statin use was appropriate in 96.2% patients, while for 216 (62.4%) patients their doses were appropriately intensified. Predictors of the inappropriateness of statin use were an atherosclerotic cardiovascular disease (ASCVD) score of ≥7.5% (AOR=0.28; 95% CI: 0.102-0.738, p=0.01), the presence of dyslipidemia (AOR=4.48; 95% CI: 1.85-10.84; p=0.001), initiation of aspirin therapy (AOR=3.7; 95% CI: 1.522-9.144; p=0.004), and an LDL-cholesterol level of 70-189 mg/dL (AOR=0.124; 95% CI: 0.042-0.365; p=0.001). DM duration of ≥10 years (AOR=2.51; 95% CI: 1.35-4.66, p=0.004), male gender (AOR=2.04; 95% CI: 1.16-3.58, p=0.013), age ≥65 years (AOR=2.15; 95% CI: 1.23-3.75, p=0.007) and uncontrolled blood pressure (AOR=2.09; 95% CI: 1.07-4.08, p=0.031) were associated with inappropriate statin intensification. Conclusion: The study found that indication of statins was optimal and about two-thirds of patients had their doses appropriately intensified. Monitoring is needed to avoid inappropriate intensification of statin therapy, particularly in patients with longer diabetes duration, those of male gender and advanced age, and those with uncontrolled blood pressure.