TAFERE MULAW BELETE

Scopus Publications

Diuretic effects of hydromethanolic extract of Rumex nepalensis Spreng. leaves and its solvent fractions in mice
Fasika Argaw Tafesse, Tafere Mulaw Belete, and Assefa Belay Asrie
Elsevier BV

The prevalence of depression and anxiety among cardiovascular patients at University of Gondar specialized hospital using beck's depression inventory II and beck anxiety inventory: A cross-sectional study
Tihitina Sisay, Missaye Mulate, Tewodrose Hailu, and Tafere Mulaw Belete
Elsevier BV

Patient satisfaction with antiretroviral therapy service provided by pharmacists in Dembia district health institutions, Northwest Ethiopia
Tafere Mulaw Belete, Solomon Asmamaw Tadesse, Kidist Atnafu, Minilik Kelemu, and Assefa Belay Asrie
Springer Science and Business Media LLC
Abstract Background The patients’ perception of the health service is a vital tool for measuring health service quality. Besides, Patient satisfaction is an essential feature in assessing the quality of health services. Health institution leaders are considering quantifiable patient satisfaction data as a means to evaluate the health care service. Method An institution-based cross-sectional study was employed from 21/8/2022 to 21/9/2022 among 308 patients attending ART pharmacy services in three health institutions of Dembia distinct. Data were collected by using a questionnaire and reviewing medical charts. Results were calculated and presented in the form of texts, tables, and graphs. Variables with a p-value of 0.05 were considered significant determinants of patient satisfaction. Result A total of 308 HIV patients were recruited with a response rate of 100%. The overall prevalence of satisfaction among respondents was 231(75%). Being unable to read and write [1.21(AOR = 1.07–4.31)] and patient age greater than 48 years 1.9(0.73–2.59) were significantly associated with the level of patient satisfaction. Among the participants 66.9% were satisfied with clear and organized service, and 76% were satisfied with the convenience of a private counseling room. Conclusion The general patient satisfaction at the antiretroviral therapy clinic did not achieve the national target of 85% satisfaction with significant differences among health centers. Being educated to a higher level, absence of signs and directions to ART clinics, and not having the opportunity to ask questions were the factors influencing patient satisfaction with ART service.

Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets
Tafere Mulaw Belete
SAGE Publications
Background Epilepsy is a chronic neurological disorder that affects approximately 50–70 million people worldwide. Epilepsy has a significant economic and social burden on patients as well as on the country. The recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy. The current antiepileptic drugs provide symptomatic relief by restoring the balance of excitatory and inhibitory neurotransmitters. Besides, about 30% of epileptic patients do not achieve seizure control. The prevalence of adverse drug reactions, including aggression, agitation, irritability, and associated comorbidities, is also prevalent. Therefore, researchers should focus on developing more effective, safe, and disease-modifying agents based on new molecular targets and signaling cascades. Summary This review overviews several clinical trials that help identify promising new targets like lactate dehydrogenase inhibitors, c-jun n-terminal kinases, high mobility group box-1 antibodies, astrocyte reactivity inhibitors, cholesterol 24-hydroxylase inhibitors, glycogen synthase kinase-3 beta inhibitors, and glycolytic inhibitors to develop a new antiepileptic drug. Key messages Approximately 30% of epileptic patients do not achieve seizure control. The current anti-seizure drugs are not disease modifying, cure or prevent epilepsy. Lactate dehydrogenase inhibitor, cholesterol 24-hydroxylase inhibitor, glycogen synthase kinase-3 beta inhibitors, and mTOR inhibitors have a promising antiepileptogenic effect.

Prescription pattern and associated factors among pregnant women attending antenatal clinics in University of Gondar, North West Ethiopia
Tafere Mulaw Belete, Gashaw sisay, Esubalew Mengesha, Amanuel Dandena, Wudneh Simegn, Assefa Kebad Mengesha, and Abebe Basazin
Elsevier BV

Recent Updates on the Development of Deuterium-Containing Drugs for the Treatment of Cancer
Tafere Mulaw Belete
Informa UK Limited
Abstract Cancer is one of the deadliest diseases in the world. In 2020, 19.3 million cancer cases and 10 million deaths were reported in the world. It is supposed that the prevalence of cancer cases will rise to 28.4 million by 2040. Chemotherapy-based regimens have a narrow therapeutic index, severe adverse drug reactions, and lack metabolic stability. Besides, the metabolism of anticancer produces several non-active and toxic metabolites that reduce exposure of the target site to the parent drug. Therefore, developing better-tolerated and effective new anticancer drugs and modification of the existing anticancer drugs to minimize toxicity and increase efficacy has become a very urgent need. Deuterium incorporation reduces the metabolism of certain drugs that are breakdown by pathways involving hydrogen-carbon bond scission. For example, CYP450 mediated oxidative metabolism of drugs that involves the breakdown of a hydrogen-carbon bond affected by deuteration. Deuterium incorporation into the drug increases the half-life and reduces the dose, which provides better safety and efficacy. Deutetrabenazine is the first deuterated form of tetrabenazine approved to treat chorea associated with Huntington’s disease and tardive dyskinesia. The study revealed that Deutetrabenazine has fewer neuropsychiatric side effects with favorable safety than tetrabenazine. The current review highlights the deuterium kinetic isotope effect on drug metabolism, deuterated compound pharmacokinetic property, and safety profile. Besides, this review explains the deuterated anticancer drug development update status.

The Immune Response, Safety, and Efficacy of Emergency Use Authorization-Granted COVID-19 Vaccines: A Review
Tafere M. Belete
Bentham Science Publishers Ltd.
COVID-19 has affected millions of people, causing a burden on healthcare systems as well as economies throughout the world. Antiviral drugs do not work well enough for everyone. The mortality rate in the world is still significant. Developing safe, effective, affordable, and fast-acting vaccines for COVID-19 is critical for reducing new viral strains in this pandemic and re-establishing normality in the future. Therefore, several pharmaceutical companies are racing to develop effective vaccines for COVID-19. Scientists have developed different kinds of candidate vaccines with various platforms. By March 2021, thirteen vaccines were approved for emergency use in several countries across the world, whilst over 90 vaccine candidates were under clinical trials. There are also several vaccine candidates in Phase 3 trials awaiting results and approval for their use. These candidate vaccines revealed positive results in the previous phase trials, whereby they can induce an immune response with less adverse reaction in the participants. This review focuses on the development of COVID-19 vaccines and highlights the efficacy and adverse reactions of vaccines authorized for emergency use.

Antidiarrheal Effect of 80% Methanol Extract and Fractions of Clerodendrum myricoides (Hochst.) Vatke (Lamiaceae) Leaf in Swiss Albino Mice
Getaye Tessema Desta, Muluken Adela Alemu, Asegedech Tsegaw, Tafere Mulaw Belete, and Baye Yrga Adugna
Hindawi Limited
Background. Diarrhea is one of the tempting symptoms of diseases in the world. In Ethiopian traditional medicine practices, Clerodendrum myricoides is utilized for the treatment of diarrhea without scientific evidence. Objective. This study was aimed to evaluate the antidiarrheal activity of 80% methanol extract and fractions of the leaf of Clerodendrum myricoides in mice. Methods. The crude extract was prepared by maceration in 80% methanol and then fractionated using hexane, chloroform, and distilled water. Antidiarrheal activity was assessed by castor oil-induced diarrhea, enteropooling, and gastrointestinal motility models using onset of diarrhea, number and weight of feces, volume and weight of intestinal contents, and distance travelled by charcoal meal as main parameters. Negative controls received either distilled water or 2% Tween 80 (10 ml/kg), positive controls received 3 mg/kg loperamide or 1 mg/kg atropine, and the test groups received 100, 200, and 400 mg/kg doses of the extract. Results. The crude extract and chloroform fraction significantly prolonged the onset of diarrhea at 200 and 400 mg/kg and decreased the number of wet, total, and weight of fresh feces at all tested doses. Hexane fraction has a significant antidiarrheal effect on the onset, number, and weight of feces at 400 mg/kg. The crude extract and chloroform fraction at all tested doses, as well as aqueous fraction at 200 mg/kg and 100 mg/kg, produced significant reduction in volume and weight of intestinal contents. Additionally, hexane fraction showed significant reduction of volume and weight of the intestinal content at 400 mg/kg. In the gastrointestinal motility test model, both chloroform fraction and crude extract at all tested doses and aqueous fraction at 200 mg/kg and 400 mg/kg showed a significant antidiarrheal effect as compared to the negative control. Conclusion. The leaf of Clerodendrum myricoides showed antidiarrheal activity which supports the traditional use.

The current status of gene therapy for the treatment of cancer
Tafere Mulaw Belete
Informa UK Limited
Abstract Gene therapy is the administration of foreign genomic material into the host tissue to modify the expression of a gene product or to change the biological properties of cells for therapeutic use. Initially, the major objective of gene therapy was to manage genetic diseases, but now different disorders with several patterns of acquired and inherited disorders are targets of gene therapy. Over three decades, the advancement of Genome engineering technologies facilitated gene therapy for the prevention and management of intractable diseases. Researchers are advancing with cautious optimism that safe and effective treatment will give to patients with single-gene disorders and complex acquired disorders. To date, over 3000 genes associates with disease-causing mutations, and about 2600 gene therapy trials are undergoing for the management of various disorders. This review summarizes the principles of genome-editing approaches, such as zinc finger nucleases, transcription activator-like effector nucleases, meganucleases, and the CRISPR/Cas9 system with the underlying mechanisms. This review also explains the types of gene delivery systems as viral [adenoviral, adeno association, herpes simplex virus] and nonviral delivery systems (physical: DNA bombardment, electroporation) and (chemical: Cationic lipids, cationic polymers). Finally, this review summarizes gene therapy medicines approved to treat cancer in detail, including names, indications, vectors, and mode of gene therapy. Gene therapy becomes an alternative to an existing management for different diseases. Therefore, gene products with safe vectors and better biotechnologies play a significant role in the prophylaxis and management of various disorders in the future.

Review on up-to-date status of candidate vaccines for COVID-19 disease
Tafere Mulaw Belete
Informa UK Limited
Abstract The global pandemic of COVID-19 caused by SARS-CoV-2 continues to spread and poses serious threats to public health and economic stability throughout the world. Thus, to protect the global population, developing safe and effective vaccines is mandatory to control the spread of SARS-CoV-2 pandemic. Since genomic sequences of SARS-CoV-2 and SARS-CoV-1 have similarity and use the same receptor (ACE2), it is important to learn from the development of SARS-CoV-1 vaccines for the development of SARS-CoV-2 vaccines. Normally vaccine development takes 10–15 years but vaccine development against SARS-CoV2 is going on at a very fast pace resulting in almost breakthrough methods of vaccine development by several research institutions. The whole process of vaccine development including clinical trials gets shortened and may be fast tracked to 15–18 months. Global collaborations and increased research efforts among the scientific community have led to more than 214 candidate vaccines globally. The current review highlights the different approaches and technologies used around the world for the design and development of the vaccines and also focuses on the recent status of the SARS-CoV-2 vaccine candidates under development by various institutions to combat the world threat of COVID-19 pandemic.

A review on Promising vaccine development progress for COVID-19 disease
Tafere Mulaw Belete
Elsevier BV

Recent progress in the development of new antimalarial drugs with novel targets
Tafere Mulaw Belete
Informa UK Limited
Abstract Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases, Plasmodium sugar transporter inhibitor, aquaporin-3 inhibitor, choline transport inhibitor, dihydroorotate dehydrogenase inhibitor, isoprenoid biosynthesis inhibitor, farnesyltransferase inhibitor and enzymes are involved in lipid metabolism and DNA replication. This review summarizes the novel molecular targets and their inhibitors for antimalarial drug development approaches.

A recent achievement in the discovery and development of novel targets for the treatment of type-2 diabetes mellitus
Tafere Mulaw Belete
Informa UK Limited
Abstract Type 2 diabetes (T2DM) is a chronic metabolic disorder. Impaired insulin secretion, enhanced hepatic glucose production, and suppressed peripheral glucose use are the main defects responsible for developing the disease. Besides, the pathophysiology of T2DM also includes enhanced glucagon secretion, decreased incretin secretion, increased renal glucose reabsorption, and adipocyte, and brain insulin resistance. The increasing prevalence of T2DM in the world beseeches an urgent need for better treatment options. The antidiabetic drugs focus on control of blood glucose concentration, but the future treatment goal is to delay disease progression and treatment failure, which causes poorer glycemic regulation. Recent treatment approaches target on several novel pathophysiological defects present in T2DM. Some of the promising novel targets being under clinical development include those that increase insulin sensitization (antagonists of glucocorticoids receptor), decreasing hepatic glucose production (glucagon receptor antagonist, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase). This review summarizes studies that are available on novel targets being studied to treat T2DM with an emphasis on the small molecule drug design. The experience gathered from earlier studies and knowledge of T2DM pathways can guide the anti-diabetic drug development toward the discovery of drugs essential to treat T2DM.

Antidiarrheal Activity of Hydromethanolic Root Extract and Solvent Fractions of Clutia abyssinica Jaub. & Spach. (Euphorbiaceae) in Mice
Dessie Zayede, Tafere Mulaw, and Wubayehu Kahaliw
Wiley
Introduction. Diarrheal diseases are associated with an estimated 1.3 million deaths annually, with most occurring in resource‐limited countries; up to 25% of deaths in young children living in Africa and southeast Asia are attributable to acute gastroenteritis. Due to limitations associated with various treatments available, the need for developing newer drugs is imperative. Objective. This study was aimed to evaluate the antidiarrheal activity of root extract and fractions of C. abyssinica Jaub. & Spach. (Euphorbiaceae) in mice. Methods. After plant extraction and subsequent fractionation of the crude extract, the antidiarrheal activity was screened in castor oil induced diarrhea, castor oil induced enteropooling, and gastrointestinal motility test models accordingly. Result. The root extract of C. abyssinica produced neither visible signs of toxicity nor death at a single dose of 2000 mg/kg, suggesting the LD50 > 2000 mg/kg. In the castor oil induced diarrheal model, the highest dose of the extract (400 mg/kg) showed a maximal inhibition in the onset (158.00 ± 14.64, p < 0.01, in minutes) of wet feces as compared to the negative control. In the enteropooling model, 400 mg/kg treated mice showed a significant reduction in volume (0.47 ± 0.02 ml, p < 0.01) and weight (0.50 ± 0.02 g, p < 0.05) of intestinal content as compared to the vehicle treated group. In the gastrointestinal motility test, the hydromethanolic root extract of C. abyssinica significantly inhibited the intestinal transit of charcoal meal at 400 mg/kg. In addition, chloroform and n‐butanol fractions significantly reduced the distance moved by charcoal at doses of 200 mg/kg and 400 mg/kg, whereas aqueous fraction showed a significant effect at all test doses. The highest antidiarrheal index was observed at the maximal dose of extract and each fraction. Conclusion. The results obtained showed that the findings provide scientific support for the folkloric repute of C. abyssinica roots as treatment of diarrhea.

Novel targets to develop new antibacterial agents and novel alternatives to antibacterial agents
Tafere Mulaw Belete
Elsevier BV

Evaluation of Antimalarial Activity of the 80% Methanolic Stem Bark Extract of Combretum molle Against Plasmodium berghei in Mice
Tafere Mulaw, Muluken Wubetu, Bekalu Dessie, Gebreselassie Demeke, and Yalew Molla
SAGE Publications
Background. People are dependent on the traditional use of medicinal plants for the treatment of malaria without scientific validations. Therefore, this study aimed to evaluate the antimalarial activity of methanolic stem bark extract of Combretum molle in mice. Methods. After being infected with Plasmodium berghei, the mice were randomly divided into 5 groups (n = 5). In all cases, group I mice were treated as negative control and received 3% Tween 80; group II mice were treated with 25 mg/kg chloroquine; and groups III, IV, and V mice were treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg of crude extract, respectively. Data were analyzed using one-way analysis of variance followed by Tukey’s post hoc analysis. Results. In the chemosuppressive test, the parasitic suppression effect of the crude extract was found to be significant ( P < 0.05) as compared with the negative control. In the curative experiment, the average parasitic level of those mice treated by the 3 doses of the crude extract was significantly suppressed at days 5, 6, and 7 of treatment ( P < 0.001). Besides, the crude extract had been found to have a chemoprophylactic role as it inhibited the parasite level significantly relative to the negative control ( P < 0.001). Moreover, the crude extract had preventive effects on packed cell volume reduction in the 3 tests ( P < 0.001). Conclusions. The findings of the present study has supported the folklore use of the leaves of Combretum molle in the treatment of malaria. Therefore, further fractionation and characterization of the crude extract is necessary to identify the responsible lead compound(s) responsible for antiplasmodial activity.

TAFERE MULAW BELETE

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