Drug-Related Problems Among Ambulatory Heart Failure Patients on Follow-Up at Debre Berhan Comprehensive Specialized Hospital, Ethiopia.

PURPOSE: The purpose of this study was to assess drug-related problems (DRPs) among ambulatory heart failure (HF) patients attending at medical referral clinic of Debre Berhan Comprehensive Specialized Hospital, Ethiopia. MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted among 344 HF patients. Drug-related problems were classified using modified Cipolle's DRP classification schemes and drug-drug interactions were assessed using Micromedex, up-to-date, and drug.com drug-drug interaction checkers. The data was entered into Epidata version 4.2.0 and analyzed using SPSS version 25.0 statistical software. Descriptive statistics were used to summarize patients' characteristics. Univariable and multivariable binary logistic regression analysis was performed to identify associated factors with dependent variables. P < 0.05 was considered statistically significant. RESULTS: The mean age of the study participants was 53.38 ± 18.84 years and nearly half (45%) were in the age group of 31-60 years. Drug-related problems were found in 80.8% of HF patients. A total of 416 DRPs were identified. Adverse drug reaction (35.58%) was the top DRPs identified followed by the need for additional drug therapy (30.53%) and ineffective drug therapy (26.9%), respectively. Diuretics (45%), beta-blockers (BBs) (12.42%), and angiotensin-converting enzyme inhibitors (ACEIs) (10%) were the commonly used drug classes by study participants. The presence of comorbidity (p ˂ 0.001) and level of education of study participants (p = 0.03) had a significant association with the occurrence of DRPs. CONCLUSION: The prevalence of DRPs among ambulatory HF patients was high. The presence of comorbidity and the educational level of study participants had a significant association with the occurrence of DRPs. Checking potential drug-drug interactions before starting a new therapy, monitoring adverse drug reactions, ensuring sustainable availability of medications, and regular education programs are recommended to minimize DRPs.

Galanin Receptors as Drug Target for Novel Antidepressants: Review.

Galanin (GAL) is a 29-amino-acid neuropeptide that serves multiple physiological functions throughout the central and peripheral nervous system. Its role involves in a range of physiological and pathological functions including control of food intake, neuro-protection, neuronal regeneration, energy expenditure, reproduction, water balance, mood, nociception and various neuroendocrine functions. The use of currently available antidepressant drugs raises concerns regarding efficacy and onset of action; therefore, the need for antidepressants with novel mechanisms is increasing. Presently, various studies revealed the link between GAL and depression. Attenuation of depressive symptoms is achieved through inhibition of GalR1 and GalR3 and activation of GalR2. However, lack of receptor selectivity of ligands has limited the complete elucidation of effects of different receptors in depression-like behavior. Studies have suggested that GAL enhances the action of selective serotonin reuptake inhibitors (SSRIs) and promotes availability of transcription proteins. This review addresses the role of GAL, GAL receptors (GALRs) ligands including selective peptides, and the mechanism of ligand receptor interaction in attenuating depressive symptoms.

Antidiabetic Effect of Germinated Lens culinaris Medik Seed Extract in Streptozotocin-Induced Diabetic Mice.

BACKGROUND: Lens culinari s Medik seed has been used in traditional practices to treat various ailments, including diabetes mellitus, in Ethiopia. Previous phytochemical screening studies indicated that germination of the seed of L. culinaris contains more bioactive constituents compared to raw seeds. The aim of this study was to investigate the antidiabetic activity of an aqueous methanol extract of germinated L. culinaris seed extract in streptozotocin (Stz)-induced diabetic mice. METHODS: The antidiabetic effect of germinated L. culinaris seed extract was determined using Stz-induced diabetic mice. An 80% aqueous methanol extract of germinated L. culinaris seed at doses of 100, 200, and 400 mg/kg was used in the treatment group. Glibenclamid (5 mg/kg) and dimethyl sulfoxide 2% were used as positive and negative controls, respectively. The test extract and controls were given daily for 3 weeks. Blood-glucose levels and body-weight changes were measured weekly. Lipid-profile levels were measured at the end of each experiment. Oral glucose-tolerance tests were performed to evaluate the postprandial effect of the extract. RESULTS: The aqueous methanol extract of germinated L. culinaris significantly reduced blood-glucose levels and increased body weight (p<0.05). The extract also improved serum-lipid profiles in diabetic mice after 21 days (p<0.05). The seed extract also resulted in significant reductions in blood-glucose levels after an oral glucose load in normal mice (p<0.05). CONCLUSION: An aqueous methanol extract of germinated L. culinaris seed has both antidiabetic and antihyperlipidemic effects.

Antimalarial Activity of Cordia africana (Lam.) (Boraginaceae) Leaf Extracts and Solvent Fractions in Plasmodium berghei-Infected Mice.

BACKGROUND: Malaria remains a major worldwide public health problem leading to death of millions of people. Spread and emergence of antimalarial drug resistance are the major challenge in malaria control. Medicinal plants are the key source of new effective antimalarial agents. Cordia africana (Lam.) is widely used for traditional management of malaria by local people in different parts of Ethiopia. The present study aimed to evaluate in vivo antimalarial effects of leaf extracts and solvent fractions of Cordia africana on Plasmodium berghei-infected mice. METHODS: The leaf extracts were prepared and tested for oral acute toxicity according to the OECD guideline. In vivo antimalarial effects of various doses of C. africana extracts and solvent fractions were determined using the four-day suppression test (both crude and fractions), as well as curative and chemoprophylactic tests (crude extracts). RESULTS: The acute toxicity test of the plant extract revealed that the medium lethal dose is higher than 2000 mg/kg. The crude extract of the plant exhibited significant parasitemia suppression in the four-day suppression (51.19%), curative (57.14%), and prophylactic (46.48%) tests at 600 mg/kg. The n-butanol fraction exhibited the highest chemosuppression (55.62%) at 400 mg/kg, followed by the chloroform fraction (45.04%) at the same dose. CONCLUSION: Our findings indicated that both the crude leaf extracts and fractions of C. africana possess antimalarial effects, supporting the traditional claim of the plant.

Anti-nociceptive and anti-inflammatory activities of crude root extract and solvent fractions of Cucumis ficifolius in mice model.

Background: Societies in developing countries use traditional medicine as alternatives for management of pain and inflammation. The plant Cucumis ficifolius has been used in Ethiopia to treat many ailments including inflammation and pain. The objective of this study was to evaluate the antinociceptive and anti-inflammatory activities of the crude root extract and solvent fractions of C. ficifolius. Methods: The analgesic activity of crude extract and solvent fractions of C. ficifolius was evaluated with acetic acid-induced writhing, hot plate, and formalin-induced paw licking tests. The anti-inflammatory effect of crude methanolic root extract and solvent fractions of C. ficifolius was evaluated using carrageenan-induced paw edema. The crude extract was given at 200, 400 and 800 mg/kg. Butanol and aqueous fractions were given at 100 and 200 mg/kg doses. The negative control groups were treated with distilled water (10 mL/kg). Standard drugs used were acetylsalicylic acid (ASA) in acetic acid, formalin tests and carrageenan-induced paw edema and morphine (20 mg/kg) in hot plate test. Results: The crude extract, at its maximum dose, produced comparable analgesic activity (72.5%) to ASA in acetic acid writhing test. In the hot plate test, both the crude extract and solvent fractions exhibited a significant prolongation of nociception reaction time. Formalin test result indicated a significant reduction of mean lick time with maximal protection of 64% (early phase) and 83% (late phase). Aqueous and butanol fractions showed good analgesic activity in the three models. Inflammation was decreased by 69% with butanol (200 mg/kg); 71% (800 mg/kg) of crude extract and by 41% and 56% with the use of aqueous fraction at 100 and 200 mg/kg, respectively (p<0.001). Conclusion: The present study indicates that the crude methanolic root extract, as well as butanol and aqueous solvent fractions, showed anti-nociceptive and anti-inflammatory activities.

Reactive Astrocytes as Drug Target in Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disease characterized by deposition of extracellular amyloid-ß, intracellular neurofibrillary tangles, and loss of cortical neurons. However, the mechanism underlying neurodegeneration in Alzheimer's disease (AD) remains to be explored. Many of the researches on AD have been primarily focused on neuronal changes. Current research, however, broadens to give emphasis on the importance of nonneuronal cells, such as astrocytes. Astrocytes play fundamental roles in several cerebral functions and their dysfunctions promote neurodegeneration and, eventually, retraction of neuronal synapses, which leads to cognitive deficits found in AD. Astrocytes become reactive as a result of deposition of Aß, which in turn have detrimental consequences, including decreased glutamate uptake due to reduced expression of uptake transporters, altered energy metabolism, altered ion homeostasis (K+ and Ca+), increased tonic inhibition, and increased release of cytokines and inflammatory mediators. In this review, recent insights on the involvement of, tonic inhibition, astrocytic glutamate transporters and aquaporin in the pathogenesis of Alzheimer's disease are provided. Compounds which increase expression of GLT1 have showed efficacy for AD in preclinical studies. Tonic inhibition mediated by GABA could also be a promising target and drugs that block the GABA synthesizing enzyme, MAO-B, have shown efficacy. However, there are contradictory evidences on the role of AQP4 in AD.

Targeting Renin-Angiotensin System Against Alzheimer's Disease.

Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aß) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aß level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, ß-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.