Identifying the core concepts of pharmacology education: A global initiative.

BACKGROUND AND PURPOSE: In recent decades, a focus on the most critical and fundamental concepts has proven highly advantageous to students and educators in many science disciplines. Pharmacology, unlike microbiology, biochemistry, or physiology, lacks a consensus list of such core concepts. EXPERIMENTAL APPROACH: We sought to develop a research-based, globally relevant list of core concepts that all students completing a foundational pharmacology course should master. This two-part project consisted of exploratory and refinement phases. The exploratory phase involved empirical data mining of the introductory sections of five key textbooks, in parallel with an online survey of over 200 pharmacology educators from 17 countries across six continents. The refinement phase involved three Delphi rounds involving 24 experts from 15 countries across six continents. KEY RESULTS: The exploratory phase resulted in a consolidated list of 74 candidate core concepts. In the refinement phase, the expert group produced a consensus list of 25 core concepts of pharmacology. CONCLUSION AND IMPLICATIONS: This list will allow pharmacology educators everywhere to focus their efforts on the conceptual knowledge perceived to matter most by experts within the discipline. Next steps for this project include defining and unpacking each core concept and developing resources to help pharmacology educators globally teach and assess these concepts within their educational contexts.

Comparative Microscopic Assessments of the Effect of Aqueous and Ethanol Extracts of Phoenix dactylifera L. in a Rat Model of Mercury-Triggered Hippocampal Changes.

Mercury is an environmental neurotoxicant that triggers structural and physiological alterations in different brain parts. The hippocampus is associated with learning and memory, and injury to this brain part may lead to behavioural and cognitive changes. Phoenix dactylifera (date palm) has been demonstrated to possess a variety of medical benefits. This study comparatively assessed the neuroprotective property of aqueous and ethanol fruit pulp extracts of P. dactylifera in a rat model of mercury-triggered hippocampal changes using microscopic examinations. Twenty-eight Wistar rats were divided into seven groups (I-VII, n=4). Group I (control) was administered distilled water (2ml/kg); group II was administered mercuric chloride, HgCl2 (5mg/kg); group III was administered vitamin C (100mg/kg) as reference drug +HgCl2; groups IV and V were administered aqueous extract (250mg/kg and 500mg/kg, respectively) +HgCl2, while groups VI and VII were administered ethanol extract (250mg/kg and 500mg/kg, respectively) +HgCl2. Extracts' neuroprotective property were evaluated using histological and histometric assessments of CA1 and CA3 hippocampal sub-regions. Results revealed cytoarchitectural changes including karyopyknosis, basophilic necrosis and remarkably decreased histometric features of hippocampal pyramidal neurons in HgCl2-treated group relative to control. Administration of the extracts remarkably ameliorated mercury-induced degenerative changes by preservation of cytoarchitectural features comparable to reference drug. Comparatively, neuroprotective efficacies of the extracts are relatively similar, especially at doses of 500mg/kg and could be attributed to antioxidant activities of constituent phytochemicals. Results suggest that aqueous and ethanol fruit pulp extracts of P. dactylifera may prove efficacious in ameliorating mercury-triggered microscopic alterations in the hippocampus of Wistar rats.

Sitagliptin-Moringa oleifera coadministration did not delay the progression nor ameliorated functional and morphological anomalies in alloxan-induced diabetic nephropathy.

OBJECTIVE: Sitagliptin (ST) and Moringa oleifera (MO) Lam (Moringaceae) are used concomitantly by diabetic patients, with no study ascertaining for potential favorable or otherwise renal implications. We investigated the effect of coadministration of ST and MO leaf extract on functional and morphological biomarkers of alloxan-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Diabetes was induced with a single dose of 150 mg/kg of alloxan intraperitoneally. Seven groups of eight rats per group were used, with Groups I, II, and VII as normal (NS), diabetic control (DC), and postprandial controls. Groups III, IV, V, and VI were diabetic rats on ST, MO, ST and MO (SM), for 42 days with 2 weeks delayed treatment in a postprandial hyperglycemic group (PPSM), respectively. Serum urea, albumin, electrolyte levels, lipid profile, and kidney tropism were determined in addition to histological examinations. RESULTS: There was a significant increase (P < 0.05) in kidney tropism comparing all drug-treated groups and DC to normal rats. Significant increases in serum urea were observed (P = 0.02) in DC, MO-treated, and SM-treated rats compared to normal rats and also in serum triglyceride (P < 0.05) in MO-treated and SM-treated rats compared to controls and other drug-treated groups. A mild reduction in severity of pathologic lesions was observed (glomerulosclerosis Grade 1) in SM-treated rats compared to a marked necrosis in DC (Grade 3). CONCLUSION: The coadministration of ST-MO did not delay the progression of functional anomalies and renal injury nor ameliorated the lesions associated with chronic DN in Wistar rats.

Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. AIM OF THE STUDY: To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. MATERIALS AND METHOD: Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. RESULTS: A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (p<0.01) to day 28 (38%) (p<0.01) of treatment, compared to day 1. Thereafter, a steady increase of up to 57% on day 42 compared to day 28 was observed. A significant decrease in random blood glucose (RBG) levels, were demonstrated on day 42 (24%) (p<0.001), compared to day 1. No significant difference was seen in mean serum levels of insulin across groups. No significant changes in body weights. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. CONCLUSION: The chronic co-administration of sitagliptin and M. oleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of lenticular opacity (i.e. cataract-like changes) it did not prevent the progression nor ameliorated pathologic lesions in the retina.

PRELIMINARY STUDIES ON THE BEHAVIOURAL EFFECTS OF THE METHANOL EXTRACT OF LEONOTIS NEPETIFOLIA LINN STEM IN MICE.

BACKGROUND: Leonotis nepetifolia Linn (Lamiaceae) is used in traditional medicine for its calming (tranquilizing) effects. The aim of this study was to determine whether there is any scientific justification for this use. To achieve this purpose, we investigated the behavioural effects of the methanol extract of Leonotis nepetifolia stem (37.5, 75 and 150 mg/kg) in mice. METHODS: Acute toxicity studies were carried out on the methanol stem extract of Leonotis nepetifolia to determine the LD50. The behavioural tests employed were diazepam-induced sleep onset and duration, hole board assay for exploratory activity, mouse beam walk assay for motor coordination, and the staircase test for the detection of anxiolytic compounds. Preliminary phytochemical screening was also carried out on the extract. RESULTS: The intraperitoneal LD50 value was found to be 3.8 g/kg. The results showed that the extract significantly prolonged the duration of diazepam-induced sleep at the highest dose (150 mg/kg). There was no observable effect on exploratory activity and motor coordination at the doses tested (37.5, 75 and 150 mg/kg). The extract, however, at 150 mg/kg elicited a significant decrease in the number of rearings in the staircase test, an effect also observed in the group of mice injected with an anxiolytic dose of diazepam. The preliminary phytochemical screening revealed the presence of alkaloids, saponins, glycosides and triterpenoids. CONCLUSION: The results obtained suggest that the crude methanol extract of Leonotis nepetifolia stem possesses some biologically active constituents with potential anxiolytic activity and thus may justify its traditional use as a tranquilizer.

Prevalence and socio-demographic risk factors associated with psychoactive substance use in psychiatric out-patients of a tertiary hospital in Nigeria.

BACKGROUND: The co-morbidity of psychoactive substance use and other mental disorders is a major challenge to the management of both conditions in several parts of the world. There is relative dearth of information on co-morbidity and its predictors in Nigeria. This study determined the prevalence and socio-demographic risk factors associated with psychoactive substance use in the psychiatric out-patients of a tertiary hospital in Nigeria. STUDY DESIGN: A cross-sectional study. MATERIALS AND METHODS: From routine clinic visits over a 4-month period, each consecutive 4(th) adult patients (>18 years) who had previously attended the clinic at least for 1 year, completed a socio-demographic and semi-structured drug use questionnaires and interview with the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) to generate substance use diagnosis. Data was analysed using the statistical package for social sciences (SPSS), version 16. Level of significance was set at P < 0.05. RESULTS: The lifetime prevalence for the use of substance was 29.3%, while that for multiple substances was 17.7%. The most commonly used substances were alcohol, cannabis and tobacco and they were also the ones mostly used in combination with one or the other. A total of 10.1% of the patients had a psychoactive substance use disorder. Being male, married with at least primary education and unemployed were significant risk factors for substance use. CONCLUSION: Psychoactive substance is common among the psychiatric outpatients of the hospital with males, those with formal education, the married and unemployed being at high risk of substance use.

Infectivity of macrophages and the histopathology of cutaneous lesions, liver and spleen is attenuated by leaf extract of Vernonia amygdalina in Leishmania major infected BALB/c mice.

Preliminary investigation of the in vitro and in vivo efficacies of different extracts from the leaves of Vernonia amygdalina (VA), a plant widely used in Nigeria was evaluated in Balb/C mice infected with a laboratory strain of Leishmania major (L. major). The ability of the methanol, hexane and aqueous extracts of the plant to suppress the infection rate and its cytotoxicity on macrophages and L929 cells were determined in the in vitro study. The in vivo study evaluated time course of infection, lesion progression and the histopathology of cutaneous lesions, liver and spleen after inoculation with metacyclic promastigotes. Methanolic extract of VA containing high levels of flavanoids, was the most potent extract as it showed the highest suppression on infectivity and viability of intracellular amastigotes at a concentration lower than that which elicited cytotoxicity on macrophages. Treatment of infected mice with methanolic extract of VA showed delayed onset of disease with a significant reduction in lesion size and attenuation of the histopathological outcome characterised by intact epidermis and less tissue destruction in skin, spleen and liver. In conclusion, these results demonstrate that VA has potent antileishmanial properties which warrants further investigation into the immunological mechanism.

Lamivudine-artesunate co-administration affects glucose metabolism in healthy and diseased wistar rats.

HIV-Malaria co morbidity frequently requires the co administration of Lamivudine and Artesunate, in Malaria endemic areas where HIV is also a problem. This situation is a frequent occurrence in developing countries of the tropics, like Nigeria where the burden of Malaria and HIV is heavy. The co administration of these drugs may result in interactions with possible physiologic and/or therapeutic consequences. This study investigated the effect of Lamivudine-Artesunate co administration on body weight, relative organ weight and glucose tolerance in healthy and diseased (Plasmodium berghei infected and cyclophosphamide immunosuppressed) wistar rats. Animals received a cumulative 21 day treatment with Lamivudine (20 mg/kg) and/or 7 day Artesunate (10 mg/kg), with healthy or disease controls. Results showed that organ weights and body weights were not affected. Oral glucose was however affected in the combination and Artesunate groups in both disease and healthy rats. The study shows that glucose tolerance is altered with Lamivudine-Artesunate co administration, and may be beneficial, as hypoglycaemia is often a complication of Malaria therapy.

Histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult Wistar rats.

BACKGROUND: Lamivudine and artesunate are sometimes co administered in HIV-malaria co morbidity. Both drugs are used concurrently in presumptive malaria treatment and simultaneous HIV post exposure prophylaxis. AIM: The aim of this study was to investigate the effect of lamivudine-artesunate co administration on the histology of the liver of diseased adult Wistar rats. MATERIALS AND METHODS: Five groups of rats of both sexes were used for the study and placed on feed and water ad libitum. Disease state consisted of immunosuppression with cyclophosphamide, and infection with Plasmodium berghei. Group 1 animals served as vehicle control, while group 2 were the diseased controls. Group 3 animals received 20 mg/kg lamivudine for three weeks, while group 4 similarly received 20 mg/kg Lamivudine but also received 10 mg/kg artesunate from day 12. Animals in group 5 received 10 mg/kg artesunate from day 12. All drugs were administered intraperitoneally. The animals were treated for twenty-one days, at the end of which they were sacrificed and their livers fixed in 10% formalin for histological studies. RESULT: Results from the study show the presence of regions of focal necrosis and perivascular cuffing with animals that received artesunate. Hemosiderosis was a common feature in all the parasitized groups, while fatty degeneration was observed in the group that received artesunate alone. CONCLUSION: Concurrent lamivudine-artesunate administration resulted in some histopathological changes in the liver. This study suggests there may be considerable histological changes with repeated occurrence of malaria and immunosuppression that may warrant intermittent lamivudine-artesunate administration, and may require evaluation as well as monitoring of liver function during such therapeutic interventions.

Anti-seizure activity of the aqueous leaf extract of Solanum nigrum linn (solanaceae) in experimental animals.

BACKGROUND: Solanum nigrum is claimed in traditional medical practice, to be useful in the treatment of epilepsy in some parts of Nigeria. OBJECTIVES: To study the anti-convulsant property of the aqueous extract of the leaves of S. nigrum in chicks, mice and rats. METHOD: Aqueous extracts were administered intraperitoneally, at a pre-treatment time of 30 minutes, at graded doses and animals were challenged with different types of proconvulsants. RESULTS: The aqueous leaf extract produced a significantly (P<0.05) dose dependent protection against electrically-induced seizure in chicks and rats, pentylenetetrazole-induced seizure in mice and rats and picrotoxin-induced seizure in mice and rats. The anti-seizure property of the extract was potentiated by amphetamine. CONCLUSION: The result obtained in this study suggests that the leaves of this plant may possess anti-convulsant property in chicks, mice and rats.

Effect of artemether on pentobarbitone sleep and electrical activity in rats.

Artemether (AM), a highly effective treatment for multidrug-resistant malaria and a component of artemisinin combination therapy, has been associated with some neurotoxicity following repeated high doses. This study was aimed at investigating the effect of AM on pentobarbitone sleep and electrical activities in rats. Wistar rats received AM i.p. at 3 dose levels: 1.5, 7.5, and 15 mg/kg, whereas control rats received 0.2 mL of the vehicle (3% v/v Tween 80). AM administered 20 min before pentobarbitone had no significant effect on the onset and duration of sleep. However, after a 7-day pretreatment, AM dose-dependently prolonged pentobarbitone sleep, as did chloramphenicol. Electroencephalogram and electromyogram recordings 20 min after pretreatment showed that AM (15 mg/kg) exhibited inhibitory activity similar to chlorpromazine as opposed to the excitatory effect of amphetamine. When pretreated for 7 days, rats receiving 1.5 mg/kg AM also showed inhibitory activity of the cortical centres, whereas desynchronization of the optic tectum and reticular formation was observed in rats pretreated with 7.5 and 15 mg/kg AM. The present data suggest that although the therapeutic equivalent dose of 1.5 mg/kg AM had no appreciable effects on pentobarbitone sleep but caused reduced electrical activity in rats, higher doses have more profound effects on both indices.

Some pregnancy-related effects of artemether in laboratory animals.

Artemether, highly effective in multi-drug-resistant malaria is not routinely available for use in pregnancy due to the lack of adequate research data in animals and man. This study was therefore aimed at investigating some pregnancy-related effects of artemether. Artemether (1.5, 7.5 and 15 mg/kg i.p. daily for 7 days) did not produce changes in rat oestrous cycle. The drug did not prevent or prolong the rate of conception or parturition, cause pre-term delivery and affect litter size. Birth weight and growth rate of pups from artemether-pretreated dams were within the normal range. Artemether (48-480 microg/ml) had no agonist effect on the isolated uterine smooth muscles of both non-pregnant and pregnant rats and guinea pigs. However, the drug (24- 240 microg/ml) reduced oxytocin-induced contraction of uterine tissues concentration-dependently, particularly in pregnant uteri.