Acute Oral Toxicological Profile of Croton membranaceus Mull. Arg. Aqueous Stem Extract, a Herbal Treatment for Benign Prostate Hyperplasia, in Male Sprague-Dawley Rats.

Croton membranaceus Mull. Arg. is a traditional medicinal plant frequently employed in Ghana for the treatment of benign prostatic hyperplasia and prostate cancer. The objective of this study was to determine the acute oral toxicity of the aqueous stem extract of Croton membranaceus (CMASE) in male Sprague-Dawley (S-D) rats. The acute toxicity of CMASE was evaluated using S-D rats randomly divided into four groups of five animals each. Three groups (low dose, median dose, and high dose) of rats received single oral doses of CMASE (1000, 2500, and 5000 mg/kg body weight, respectively) using an oral gavage. The control group was given distilled water. After 14 days of daily observations, hematological, biochemical, and histopathological analyses were conducted on the rats. From the results obtained, doses of CMASE up to 5000 mg/kg did not cause death or induce any clinical indications of toxicity during the study period. Also, the mean body weight and the hematological indices assessed were not significantly affected by the various doses of CMASE compared to the control group. However, serum uric acid and creatinine levels decreased significantly (p < 0.001) 14 days after the extract administration. Serum liver function enzyme levels, including alkaline phosphatase (ALP), alanine aminotransferases (ALT), and aspartate aminotransferases (AST), and serum proteins (total proteins and albumin) exhibited significant (p < 0.001) non dose-dependent changes (increases and decreases) in treated groups compared to the controls. Other biochemical indices, however, did not differ significantly between the treated groups and the controls. The gross pathological and histological analysis of the heart, liver, and kidney tissues did not reveal any significant changes in histoarchitecture. The oral LD50 of CMASE in rats was greater than 5000 mg/kg, indicating that the extract was relatively safe. It must, however, be used with care as a substitute for the roots.

Comparative Determination of Glomerular Filtration Rate Estimation Formulae in Type 2 Diabetic Patients: An Observational Study.

Assessing glomerular filtration rate (GFR) involves collecting timed urine samples for 24 hours, requiring significant time and resources in the clinical setting. Using predictive GFR formulae to assess renal function may be a better alternative. Our goal was to determine which predictive GFR formula had the highest level of concordance with the GFR that has been measured in a resource-poor setting. This is an observational study. We selected fifty (50) individuals diagnosed with type 2 diabetes (T2DM) in Kumasi, Ghana. The sociodemographic and clinical characteristics were obtained using a structured questionnaire. Urine was obtained from each subject over 24 hours. The levels of glucose (FBG) and creatinine in patients' blood, as well as the levels of creatinine in their urine, were measured after the patients had fasted overnight. Participants had a mean age of 57.4 ± 10.7 (years), BMI of 27.8 ± 4.1 (kg/m2), FBG of 9.0 ± 3.1 (mmol/L), and creatinine concentrations of 95.6 ± 29.1 (µmol/L). A Krouwer plot was used to compare the measured GFR with three formulae: Chronic Kidney Disease Epidemiology (CKD-EPI), Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault (CG) for GFR prediction. Among the 3 estimates, CG showed nonsignificance (p > 0.05) with the measured GFR. The primary finding was that the GFR calculated using the CG formula was not different from the GFR measured, suggesting that CG is the most appropriate alternative GFR estimate among a cross-section of T2DM patients in Ghana.

Medication errors at a diabetes management center in a resource-poor setting.

BACKGROUND: Medication errors are known to cause adverse drug reactions, hospital admissions and mortality. In most resource-poor settings, medication errors occur but are undocumented. OBJECTIVE: This study sought to investigate medication errors in a diabetic clinic at Komfo Anokye Teaching Hospital (KATH), Ghana. METHODS: The research combined both qualitative and quantitative data collection methods. The quantitative aspect involved retrospectively reviewing patient folders over two years (1st January 2019 to 31st December 2021). Patients' folders were reviewed to identify possible medication errors. The qualitative arm explored underlying factors and experiences related to medication errors through interviews with healthcare workers. Ten healthcare professionals at KATH were interviewed using an interview guide. RESULTS: A total of 264 patients' folders were retrieved. The majority (23.11%) of the patients were between 18 and 25 y.o., and there were more females (52.27%) than males. About 60% of the patients had diabetes and hypertension comorbidity. The overall prevalence of medication errors was 18.18%. The most prevalent type of medication error identified was wrong drug formulation (n = 19, 39.58%). About 47.92% of the medication errors resulted in adverse events and this was predominantly caused by antidiabetic drugs (47.83%) and anti-hypertensive drugs (34.78%). Patients in the age category of 26-35 y.o. [aOR: 0.31, CI: 0.11-0.90] had reduced odds of medication errors whilst patients with comorbidity of diabetes and hypertension [aOR: 5.95, CI: 2.43-14.60] had an increased odds of medication errors. Large patient population, low staff numbers and inadequate knowledge of drugs by healthcare workers were factors that contributed to medication errors. CONCLUSION: Medication errors was moderately high in this diabetic clinic, and the errors led to a number of adverse events. Age, diabetes and hypertension comorbidity, large patient population, low staff numbers, and inadequate knowledge about drugs were identified as factors that influenced medication errors.

Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria.

Introduction: Limited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM). Methods: A prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR). Results: Among SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (-5.38 to 58.57) vs. no-HU -0.34 (-3.19 to 4.44), p = 0.024]; bilirubin [HU+, -4.44 (-16.36 to 20.74) vs. no-HU -18.37 (-108.79 to -7.16)]; and alanine aminotransferase, [HU+, -4.00 (-48.55 to 6.00) vs. no-HU, 7.00 (-22.00 to 22.00)] were observed during follow up. Conclusion: Parasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies.

Biochemical markers of nephrotic syndrome: An observational, cross-sectional study.

Background: Blood protein leakage, especially albumin, into the urine is the hallmark of nephrotic syndrome (NS), which poses a serious public health problem. The absence of albumin prompts the liver to produce more proteins to make up the difference. The therapeutic significance of these additional proteins in NS is not yet fully understood. Methods: In total, 99 patients with NS and 47 persons without NS (control group) were included in this cross-sectional study. Socio-demographic and clinical information were obtained from recruits utilizing a standard questionnaire and a check of the lab order forms for individuals. Each participant had a 6-mL (6 mL) sample of venous blood taken and levels of calcium, C-reactive protein (CRP), albumin, and other proteins in the serum were assayed. The proteins in serum were separated using the electrophoresis technique, and the various fractions were then measured by a densitometer. Calculations were made for the oncotic pressure. Results: The NS group had significantly greater levels of serum CRP, urea, alpha-2-globulin, gamma globulins, and M component than the control group (p < 0.05 respectively). Transferrin, total proteins, albumin, beta-1-globulins, calcium, and oncotic pressure were significantly higher in persons without NS compared to the NS group (p < 0.05 respectively). In addition, levels of CRP (odds ratio = 1.41, p = 0.005) and gamma globulin (odds ratio = 4.12, p = 0.005) in the blood were observed to be independent predictors in the occurrence of NS. These two factors increased the likelihood of developing NS by approximately 1.5 and 4 times, respectively. Conclusion: Among the proteins assayed, CRP and gamma globulin were found to be predictors of NS. Nonetheless, further studies are required to understand the mechanisms associated with these serum proteins in NS.

Increased Brain-Derived Neurotrophic Factor and Hippocampal Dendritic Spine Density Are Associated with the Rapid Antidepressant-like Effect of Iron-citalopram and Iron-Imipramine Combinations in Mice.

Iron supplementation previously demonstrated antidepressant-like effects in post-partum rats. The present study evaluates the possible synergistic antidepressant effect of sub-therapeutic dose of iron co-administered with citalopram or imipramine in female Institute of Cancer Research mice. Depression-like symptoms were induced in the forced swim (FST), tail suspension (TST), and open space swim (OSST) tests while open field test (OFT) was used to assess locomotor activity. Mice (n = 8) received iron (0.8-7.2 mg/kg), citalopram (3-30 mg/kg), imipramine (3-30 mg/kg), desferrioxamine (50 mg/kg) or saline in the single treatment phase of each model and subsequently a sub-therapeutic dose of iron co-administered with citalopram or imipramine. Assessment of serum brain derived neurotrophic factor (BDNF) and dendritic spine density was done using ELISA and Golgi staining techniques respectively. Iron, citalopram and imipramine, unlike desferrioxamine, reduced immobility score in the TST, FST and OSST without affecting locomotor activity, suggesting antidepressant-like effect. Sub-therapeutic dose of iron in combination with citalopram or imipramine further enhanced the antidepressant-like effect, producing a more rapid effect when compared to the iron, citalopram or imipramine alone. Iron, citalopram and imipramine or their combinations increased serum BDNF concentration, hippocampal neuronal count and dendritic spine densities. Our study provides experimental evidence that iron has antidepressant-like effect and sub-therapeutic dose of iron combined with citalopram or imipramine produces more rapid antidepressant-like effect. We further show that iron alone or its combination with citalopram or imipramine attenuates the neuronal loss associated with depressive conditions, increases dendritic spines density and BDNF levels. These finding suggest iron-induced neuronal plasticity in the mice brain.

Pharmaceutical and pharmacokinetic evaluation of a newly formulated multiparticulate matrix of levodopa and carbidopa.

Levodopa is routinely co-administered with carbidopa in the management of Parkinson's disease. Although the aforementioned combination therapy is effective, there may be fluctuating plasma levels of levodopa after oral administration. We formulated and evaluated the kinetic characteristics of the chitosan-pectin-based multiparticulate matrix of levodopa and carbidopa. Pectin was extracted from the cocoa husk, and the chitosan-pectin-based matrix was prepared by wet granulation. Formulations were evaluated for drug-excipient compatibility, drug content, precompression properties and in vitro release. For pharmacokinetic evaluation, rats were put into groups and administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet® CR or levodopa/carbidopa immediate release powder. Rats were administered the different formulations of levodopa/carbidopa (20/5 mg/kg) per os every 12 hours. The pharmacokinetic parameters of levodopa were estimated for the various treatment groups. The percentage content of levodopa and carbidopa in the various formulations was within the acceptance criteria. The AUC0-24 for levodopa/carbidopa multiparticulate matrix (Formulation 3: 484.98 ± 18.70 µg.hr/mL); Formulation 4: 535.60 ± 33.04 µg.hr/mL), and Cmax (Formulation 3: 36.28 ± 1.52 µg/mL; Formulation 4: 34.80 ± 2.19 µg/mL) were higher than Sinemet® CR (AUC0-24 262.84 ± 16.73 µg.hr/mL and Cmax 30.62 ± 3.37 µg/mL). The t 1/2 of the new formulation was longer compared to Sinemet® CR.

Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review.

Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.

Neonatal Sepsis in a Resource-Limited Setting: Causative Microorganisms and Antimicrobial Susceptibility Profile.

Background: Empiric treatment of suspected neonatal sepsis must be based on data on setting-specific causative pathogens and their respective susceptibilities to antimicrobials, as well as universal treatment guidelines. This approach will ensure better therapeutic outcomes and reduce mortality. Objectives: The objectives of this study were to determine the bacteriological profile and antibiotic susceptibility pattern of isolated microorganisms responsible for neonatal sepsis in a regional hospital in Ghana. Methods: This was a retrospective study that assessed causative microorganisms and antimicrobial susceptibility profiles of neonates suspected of sepsis at the Greater Accra Regional Hospital from January 2018 to December 2019. Blood culture was done using a fully automated BACTEC 9240 blood culture system. Bacteria isolates were identified by Gram staining and conventional biochemical methods. Antimicrobial susceptibility testing was done by Kirby-Bauer's disc diffusion method, and interpretations were carried out according to clinical and laboratory standards. Culture and antibiotic sensitivity reports were obtained and the data subsequently analyzed. Results: Of 2514 blood samples collected from neonates suspected of neonatal sepsis, 528 (21.0%) of the samples were found to be culture-positive. The majority of these positive cultures were from male neonates (68.9%). A total of 11 different pathogens were isolated, of which Gram-positive organisms had a preponderance of 72.0% over Gram-negative organisms (28.0%). Staphylococcus epidermidis was the most common pathogen identified, accounting for 60.0% of isolates. The most prevalent Gram-negative bacteria were Klebsiella spp. (13.6%). Most Gram-positive microorganisms showed sensitivity to amikacin, meropenem, vancomycin, and piperacillin/tazobactam. Gram-positive isolates were found to be resistant to ampicillin and penicillin, but moderately susceptible to flucloxacillin. Most Gram-negative isolates were sensitive to meropenem. Conclusion: The prevalence of culture-proven sepsis was 21.0%. The most prevalent Gram-negative bacteria were Klebsiella spp. As there is some level of antibiotic resistance observed in the current study, it is necessary for routine microbial analysis of samples and their antibiogram.

Gestational iron supplementation reverses depressive-like behavior in post-partum Sprague Dawley rats: Evidence from behavioral and neurohistological studies.

Background: Postpartum depression is a mood disorder that affects about 9-20% of women after child birth. Reports suggest that gestational iron deficiency can cause a deficit in behavioral, cognitive and affective functions and can precipitate depressive symptoms in mothers during the postpartum period. The present study examined the effect of iron supplementation on depressive behavior during postpartum period in a rat model. Method: Female Sprague-Dawley rats were crossed. Pregnant rats received iron, fluoxetine, desferrioxamine or vehicle throughout the period of gestation. During the postpartum period, mothers from all groups were taken through the open field test (OFT), forced swim test (FST), novelty-induced hypophagia (NIH) and sacrificed for histological examination of the brains. Results: Results showed that rats treated with iron-chelating agent, desferrioxamine, and vehicle during gestation exhibited increased immobility scores in the FST, increased latency to feed and reduced feeding in the NIH with corresponding decreased number of neurons and dendritic branches in the cortex of the brain. These depression-related effects were attenuated by perinatal iron supplementation which showed decreased immobility scores in the FST comparable to rats treated with fluoxetine, a clinically effective antidepressant. Iron treatment also decreased latency to feeding while increasing feeding behavior in the NIH. Iron-treated dams had a higher number of neurons with dendritic connections in the frontal cortex compared to vehicle- and desferrioxamine-treated groups. Conclusion: The results suggest that, iron supplementation during gestation exerts an antidepressant-like effect in postpartum Sprague-Dawley rats, attenuates neuronal loss associated with depression and increases dendritic spine density.

Extract of Xylopia aethiopica and its kaurene diterpene, xylopic acid, improve learning and memory in mice.

Background: Cognitive dysfunction, presenting as learning and memory impairment, is a common manifestation in many chronic diseases of the nervous system. Some of these diseases include depression, epilepsy, and Alzheimer's disease. To date, few drugs or medicinal products have shown ability to improve learning and memory deficits. Neuroprotection is one of the mechanisms by which memory could be improved. The extract of Xylopia aethiopica and its kaurene derivative, xylopic acid, have previously demonstrated neuroprotective effects in animal models. The aim of the present study was to investigate the effect of an extract of Xylopia aethiopica fruit and xylopic acid, on learning and memory using murine models. Materials and methods: Unripe Xylopia aethiopica fruits were collected, dried, and extracted using 70% v/v ethanol. Xylopic acid was isolated from the fruits using petroleum ether, concentrated with ethyl acetate and then recrystallized with petroleum ether before purifying with ethanol (96%v/v). Institute of Cancer Research (ICR) mice received oral doses of the extract of Xylopia aethiopica (XAE; 30, 100 and 300 mg/kg), xylopic acid (XA; 30, 100 and mg/kg), citicoline (300 mg/kg), piracetam (300 mg/kg) or ketamine (30 mg/kg) and saline (vehicle). The animals were then taken through the Morris water maze test (MWM), spontaneous alternation Y-maze test (Y-maze), and novel object recognition test (NOR), to assess learning and memory. Results: In the NOR test, XAE (30, 100 and 300 mg/kg) and XA (30, 100 and 300 mg/kg) increased the percentage exploration and recognition index (p = 0.0005 and p < 0.0001, respectively) when compared to both vehicle and ketamine groups. Similarly, doses of XAE and XA as used in the NOR test increased the percentage alternation in the Y-maze test. Although XAE and XA treatments decreased the latencies to find hidden platform in the MWM test, it was not significantly different from the vehicle group. However, this decrease in latency differed significantly when compared to the ketamine group. Interestingly, both XAE and XA treatments increased the percentage frequency to the target quadrant in the probe trial of the MWM. It is noteworthy that in all the three models used, both the extract and xylopic acid performed better than piracetam and citicoline, the reference drugs. Conclusion: The ethanolic extract of Xylopia aethiopica fruit and xylopic acid improved exploratory learning and recognition memory, spatial working, recognition, and reference memories in the behavioral tests.

A comparative analysis of pattern and attitude towards self-medication among pharmacy and non-pharmacy students in University of Ghana.

Introduction: self-medication involves the use of medicines without the input of health professionals. Available studies are not entirely conclusive on self-medication among health science versus non-health science university students. The current study therefore sought to investigate relevant aspects of self-medication among pharmacy and non-pharmacy students. Methods: this quantitative cross-sectional research was conducted among undergraduate pharmacy and non-pharmacy students of the University of Ghana from October 1st 2019 to December 6th 2019. Using a questionnaire, interviews were conducted to assess the pattern and attitude towards self-medication among respondents within the last 2 months. Results: a total of 337 (163 pharmacy and 174 non-pharmacy) students filled and completed questionnaires. The prevalence of self-medication was 55.2% for pharmacy and 51.1% for non-pharmacy students. Both pharmacy and non-pharmacy students were either accepting or ambivalent towards self-medication. Painkillers were the major class of medications that were self-medicated by both pharmacy (38.5%) and non-pharmacy students (30.7%). The most common reason for self-medication among pharmacy (62.2%) and non-pharmacy (56.2%) students was the need for rapid relief from an illness. Majority of the participants who were self-medicated (27.6% among non-pharmacy and 36.8% among pharmacy students) demonstrated ambivalent attitude towards self-medication. An increase in the study level reduced the likelihood of self-medication in both pharmacy and non-pharmacy students: OR=0.442, CI = 0.266-0.736 for pharmacy students and OR=0.671, CI = 0.456-0.987 for non-pharmacy students. Conclusion: self-medication is common students of the University of Ghana. Prevalence of self-medication was higher among pharmacy students than non-pharmacy students. This study provides data for targeted education and sensitisation of self-medication among university students.

Effect of Metaswitch® dietary supplement on anthropometric parameters, serum lipids, glucose level, oxidative stress and in vivo antioxidant properties in high fat diet-induced overweight Sprague Dawley rats.

PURPOSE: Obesity and overweight are metabolic disorders associated with oxidative stress, and risk factors for many chronic diseases. We sought to investigate the effects of Metaswitch dietary supplement on weight gain and associated acute metabolic alterations in a high-fat diet-induced overweight rat model. METHODS: Female Sprague Dawley (SD) rats were put into 6 groups. Control groups were fed normal (NCD) or high-fat diet (HFD). Treatment groups on HFD receieved 3 different daily doses of Metaswitch for 3 weeks. Another group on HFD received Slimrite® (phenylpropanolamine), a standard drug. Rats on HFD also received cyproheptadine to stimulate appetite. Food consumption and anthropometric parameters were determined weekly. Serum lipids, glucose level, hepatic lipid peroxidation, and antioxidant activity were used to assess overweight in rats. RESULTS: Food intake remained relatively constant among groups. Rats on HFD had significantly increased body weight compared to rats fed NCD. Metaswitch significantly prevented weight gain; this effect was greater or similar to rats administered Slimrite, but was not dose-dependant. No significant changes occurred in the levels of serum lipids and glucose among the groups. However, serum triglyceride (TG) was significantly increased. The TG/HDL-C ratio revealed significant metabolic alterations which was prevented by Metaswitch. Catalase activity was significantly decreased in the HFD untreated group but was restored in Metaswitch-treated groups. CONCLUSIONS: A 3-week HFD regimen with cyproheptadine supplementation in female SD rats resulted in a significant increase in body weight and acute metabolic alterations. The aforementioned changes were found to have been prevented with the administration of Metaswitch.

Genotoxicity, nitric oxide level modulation and cardio-protective potential of Kalanchoe Integra Var. Crenata (Andr.) Cuf Leaves in murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Advancement in cancer therapy has improved survival among patients. However, use of anticancer drugs like anthracyclines (e.g., doxorubicin) is not without adverse effects. Notable among adverse effects of doxorubicin (DOX) is cardiotoxicity, which ranges from mild transient blood pressure changes to potentially serious heart failure. Anecdotal reports suggest that Kalanchoe integra (KI) may have cardio-protective potential. AIMS OF THE STUDY: This study sought to determine the cardio-protective potential of KI against doxorubicin-induced cardiotoxicity and also examined any possible genotoxic potential of KI in selected organs. Additionally, the nitric oxide modulatory potential of KI was assessed. MATERIALS AND METHODS: The leaves of KI were collected, air-dried, pulverised and extracted using 70% ethanol. High-performance liquid chromatography (HPLC) fingerprinting was done for KI. Also, the single-cell gel electrophoresis assay (Comet assay) was employed to ascertain the genotoxic potential of KI. In assessment of cardio-protective potential of KI against doxorubicin-induced cardiotoxicity, a total of 42 female Sprague-Dawley rats were put into 7 groups (n = 6). Group I: vehicle control, received normal saline (1 mL/kg p.o) for 30 days. Group II: toxic control, received DOX (20 mg/kg i.p.) once on the 29th day. Group III: KI control, received KI (300 mg/kg p.o) for 30 days. Group IV: vitamin E control, received vitamin E (100 mg/kg p.o) for 30 days. Group V: KI treated-1, received KI (300 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VI: KI treated-2, received KI (600 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VII: vitamin E treated, received vitamin E (100 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Thirty-six (36) hours after last administration, rats were sacrificed. Blood samples were taken via cardiac puncture to determine levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), lactate dehydrogenase (LDH), enzymatic antioxidants such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Nitric oxide level was also determined. Hearts of rats in each group were excised and taken through histopathological examination. RESULTS: In the HPLC fingerprint analysis, 13 peaks were identified, and peak with retention time of 24.0 min had the highest peak area (3.223 x104 mAU). Comet assay showed that the KI extract was non-genotoxic. Pretreatment with KI protected rats against doxorubicin-induced cardiotoxicity as evidenced by the low levels of AST, ALT, ALP, CK and LDH compared with the controls (p < 0.05). SOD, CAT and GPX levels were also high for rats administered KI extracts, further showing that KI protected rats against doxorubicin-induced cardiotoxicity. KI also inhibited nitric oxide levels at 300 mg/kg and 600 mg/kg effective doses. Histological examination revealed that rats pretreated with KI showed no signs of abnormal myocardial fibres (shape, size and configuration). CONCLUSION: Ethanolic (70%) leaf extract of KI showed no genotoxic potential and possessed cardioprotective effects against doxorubicin-induced cardiotoxicity in Sprague-Dawley rats. KI also inhibited nitric oxide production, thus, a potential nitric oxide scavenger.

Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha.

INTRODUCTION: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. METHODS: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30-300 mg/kg, orally [PO]), imipramine (3-30 mg/kg, PO), fluoxetine (3-30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. RESULTS: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. CONCLUSION: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Possible future trajectory of COVID-19: emphasis on Africa.

Coronavirus disease 2019 (COVID-19) has caused morbidity and mortality in many countries. COVID-19 has also negatively affected the economy of several nations. The dynamics of interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host, and possible evolution of the virus into more virulent strains pose a threat to global eradication. With the advent of vaccination in most countries, vaccine hesitancy, especially in Africa, is expected to reduce. We also believe that the COVID-19 vaccine would have substantial impact on reducing incidence, hospitalizations, and deaths. A predictor model for COVID-19 infection pattern through to 2025 suggests that recurrent outbreaks are likely to occur. There is a prediction that Africa would not fully recover from the economic crises posed by the pandemic; nonetheless, we expect that economic activities on the continent will improve as countries undertake mass vaccinations and populace attain herd immunity. The growth of e-commerce has been remarkable during the pandemic and we don´t expect trend to decline anytime soon. The pandemic has led to technology and digital platform utilization and/or improvement, which invariably has the tendency to improve quality of lives in the future. These include effective big data monitoring, online shopping, among others. Our future trajectory for recurrent waves of COVID-19 is that these may occur in winter months in temperate climates. We believe that COVID-19 has strengthened Africa´s resilience to future pandemics.

Assessment of prescribing patterns of antibiotics using National Treatment Guidelines and World Health Organization prescribing indicators at the Ghana Police Hospital: a pilot study.

INTRODUCTION: irrational or inappropriate prescribing of antibiotics is a major problem in healthcare and leads to antibiotic resistance. There is the need to understand the prescribing patterns and antibiotic stewardship in health facilities to support appropriate antibiotic use. A study was carried out to evaluate prescribing pattern of antibiotics at the Ghana Police Hospital using National Standard Treatment Guidelines (STG) and World Health Organization (WHO) prescribing indicators. METHODS: a cross-sectional descriptive study was conducted at the Ghana Police Hospital. Data on prescriptions of antibiotics for both out-patients and in-patients was collected between December 2019 and March 2020. A pretested self-designed tool was used for data collection. All sampled prescriptions were assessed for appropriateness using the STG of 2017 and WHO "AWaRe" classification. The criteria used in assessment included dose, frequency, duration of treatment and choice of antibiotic prescribed for disease condition. Descriptive statistics were used in data analysis. RESULTS: a total of 184 patient prescriptions (286 antibiotics) were included in this study. Results showed that antibiotics were mostly prescribed for dental and dental-related conditions (20.7%) and obstetric post-delivery prophylaxis (18.1%). Appropriateness of indicators for antibiotics prescribed assessed ranged between 89.2% to 97.6%. The most frequently prescribed antibiotics were metronidazole (25.9%), amoxicillin with clavulanic acid (22.0%), amoxicillin (16.4%) and ciprofloxacin (10.1%). Based on WHO "AWaRe" classification, the "access" group of antibiotics (74%) was the most prescribed, followed by "watch" group (24%). There were no antibiotics prescribed from the "reserve" group of antibiotics and another 2% that was not part of AwaRe classification. CONCLUSION: study revealed that the level of appropriateness for prescribing indicators assessed was relatively high and majority of prescribed antibiotics were from the "access" and "watch" group. These observations suggest responsible prescribing of antibiotics at the Ghana Police Hospital and effective antibiotic stewardship should be sustained and improved.

One year after first case of COVID-19 in Ghana: epidemiology, challenges and accomplishments.

Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus, has affected many lives, health systems and economies across the globe. Countries in both resource-rich and poor have equally been affected. In Ghana, COVID-19 has caused morbidity and mortality among the populace. The first two cases of COVID-19 were reported in Ghana in March 2020. At the onset of the pandemic in Ghana, there were challenges in securing isolation centers and quarantine facilities. Nonetheless, the government of Ghana put in place a number of measures in line with World Health Organization (WHO) guidelines, to halt the spread of the virus. Some measures taken by the government included partial lockdown of areas deemed hotspots for the spread of the virus. In April 2020, Ghana was ranked number one among African countries in administering tests per million people, because of the effective "trace and test" approach. The government of Ghana also encouraged local manufacturing of personal protective equipment, antivirals and hand sanitizers to help meet the demand of the nation. There were also restrictions on public gathering within the early parts of 2020, and these were eased with time. In February 2021, Ghana became the first country to receive vaccines through the COVAX initiative with a delivery of 600,000 doses of Oxford-AstraZeneca vaccines. The efforts by Ghana to deal with the COVID-19 pandemic have been commendable. Not withstanding, the adverse impact of the COVID-19 on public health in Ghana has been significant, and there is still a lot to learn from other countries in the sub-region, and the world as whole.

A Pharmacokinetic Evaluation of a Pectin-Based Oral Multiparticulate Matrix Carrier of Carbamazepine.

BACKGROUND: Carbamazepine is a drug used in the treatment of neurological disorders such as epilepsy. However, due to its erratic absorption, oral bioavailability is often poor. There is, therefore, the need to develop alternative formulations for carbamazepine with better pharmacokinetic characteristics. AIM: The aim of this study was to formulate an oral modified-release multiparticulate matrix of carbamazepine from cocoa pod husk (CPH) pectin and evaluate the pharmacokinetic profile of this formulation using in vitro and in vivo models. METHODS: CPH pectin was extracted from cocoa pod husks with hot aqueous and citric acid solutions. Oral multiparticulate carbamazepine matrices were formulated from CPH pectin cross-linked with calcium. The formulation was evaluated for carbamazepine content and release profile in vitro. For in vivo pharmacokinetic profile estimation, rats were put into 4 groups of 5 animals each to receive carbamazepine multiparticulate matrix formulations A and B, carbamazepine powder, and Tegretol CR®. Animals in each group received 200 mg/kg of each drug via the oral route. Maximum plasma concentration (C max), area under the concentration-time curve (AUC), elimination rate constant (K e ), and terminal half-life (t 1/2) of the formulations were estimated by noncompartmental analysis. RESULTS: The pectin extraction from fresh cocoa pod husks using hot aqueous and citric acid solutions gave pectin yields of 9.63% and 11.54%, respectively. The drug content of carbamazepine in CPH pectin formulations A and B was 95% and 96%, respectively. There was controlled and sustained release of carbamazepine for both formulations A and B in vitro. AUC0⟶36 (176.20 ± 7.97 µg.h/mL), C max (8.45 ± 0.71 µg/mL), T max (12 ± 1.28 h), and t 1/2 (13.75 ± 3.28 h) of formulation A showed a moderately enhanced and comparable pharmacokinetic profile to Tegretol CR® (AUC0⟶36: 155 ± 7.15 µg.h/mL, C max: 8.24 ± 0.45 µg/mL, T max: 8.0 ± 2.23 h, and t 1/2: 13.51 ± 2.87 h). CONCLUSION: Findings from the study suggest that formulations of CPH pectin had the potential to control and maintain therapeutic concentrations of carbamazepine in circulation over a period of time in the rat model.

Toxicity, mutagenicity and trace metal constituent of Termitomyces schimperi (Pat.) R. Heim (Lyophyllaceae) and kaolin, a recipe used traditionally in cancer management in Cote d'Ivoire.

ETHNOPHARMACOLOGICAL RELEVANCE: Some local communities in Cote d'Ivoire use the mushroom Termitomyces schimperi combined with kaolin (TSK) to manage various cancers in patients. However, there is a paucity of data on toxicity, mutagenicity and trace metal constituent of TSK. AIM OF THE STUDY: We sought to investigate the acute and sub-chronic toxicities, mutagenic potential, and trace metal constituents of TSK. MATERIALS AND METHODS: To assess acute toxicity, single doses (1000, 3000 and 5000 mg/kg) of aqueous extract of TSK were administrated per os to Sprague Dawley (SD) rats on Day 1. The rats were then monitored for 13 consecutive days. Sub-chronic toxicity was evaluated by daily administration of 200 and 500 mg/kg of the extract per os for 90 consecutive days. SD rats used as control received distilled water. Signs of toxicity, changes in body weight and mortality were monitored. After the aforementioned monitoring processes, rats were sacrificed and blood collected for full blood count and biochemistry analysis. Animal organs were also collected for histopathological examination. The mutagenic potential of the aqueous extract of TSK (10000 µg/mL) on TA98 Salmonella typhimurium was estimated. Additionally, energy-dispersive X-ray fluorescence (ED-XRF) method was employed to determine trace metal constituents of TSK. RESULTS: Single-dose administration of 5000 mg/kg of TSK did not cause any death in the SD rats; thus, LD50 was above 5000 mg/kg. Administration of 1000 and 3000 mg/kg of the aqueous extract of TSK did not cause any significant change in behaviour and body weight of SD rats during the 14-day monitoring period. However, the mean corpuscular volume and the mean corpuscular haemoglobin concentration increased significantly (p < 0.01) among rats administered 1000 and 3000 mg/kg of TSK. There was a significant increase (p < 0.0001) in alanine transaminase levels in rats administered 1000 and 3000 mg/kg of TSK extract compared with control. Conversely, there was a significant decrease (p=0.0122) in serum creatine level among rats administered 1000 and 3000 mg/kg of TSK extract compared with control. After 14 days, there were minimal changes with isolated organs of TSK-treated and control rats. Furthermore, 90-day treatment with extract of TSK caused no significant change in parameters assessed. TSK induced frameshift gene mutation in S. typhimurium before (p < 0.05) and after metabolic activation (p < 0.001). Elemental analysis of TSK revealed the presence of toxic (aluminium) or potentially toxic (silver, rabidium, titanium and zirconium) elements. CONCLUSIONS: The aqueous extract of TSK showed no toxicity (acute and sub-chronic) at doses tested. These findings are consistent with the absence of heavy metals (i.e., cadmium) and potentially toxic elements (i.e., uranium) in TSK samples analysed. TSK showed some level of mutagenic potential. Further mutagenic and chronic toxicity studies on TSK are required.