Current Status of Endoplasmic Reticulum Stress in Type II Diabetes.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Guessability of standard pharmaceutical pictograms in members of the Nigerian public.

Background: Pharmaceutical pictograms are standardized images used to visually convey medication instructions. Very little is known about the ability of Africans to interpret these images. Objectives: Thus, the aim of this study was to assess the guessability (ability to correctly guess meaning) of selected International Pharmaceutical Federation (FIP) and United States Pharmacopoeia (USP) pictograms in members of the Nigerian public. Methods: A cross-sectional survey was carried out between May and August 2021 on 400 randomly sampled members of Nigerian public. Selected pictograms (24 FIP and 22 USP pictograms) were grouped and printed on A3 sheets of paper which were used to interview members of the public who fulfilled the study's' eligibility criteria. Respondents were asked to guess the meanings of either the FIP or USP pictograms, and their answers written down verbatim. Descriptive and inferential statistics were used to report the data collected. Results: Four hundred respondents were interviewed, with 200 respondents each assessing the guessability of the FIP and USP pictograms. The guessability of assessed FIP pictograms ranged between 3.5 and 95%, while that for the USP pictograms was 27.5-97%. Eleven FIP and Thirteen USP pictograms respectively achieved the International Organization for Standardization (ISO) comprehensibility cutoff point of 67%. Guessing performance (the total number of pictograms correctly guessed by an individual) of respondents that assessed the FIP pictograms was significantly associated with their age (p = 0.044) and highest level of education completed (p = 0.003). For the USP pictograms, guessing performance was only significantly associated with the highest educational level completed (p < 0.001). Conclusions: Guessability of both pictogram types varied widely, but the guessability of the USP pictograms was generally better than that for the FIP pictograms. Many of the tested pictograms may however need to be redesigned before they can be correctly interpreted by members of the Nigerian public.

Investigating Knowledge of Antibiotics, Antimicrobial Resistance and Antimicrobial Stewardship Concepts Among Final Year Undergraduate Pharmacy Students in Northern Nigeria.

Introduction: Well trained, knowledgeable and competent pharmacists are indispensable in the fight against antimicrobial resistance (AMR), which is a current global public health problem. The aim of this work was to assess knowledge of antibiotics, antimicrobial resistance and antimicrobial stewardship of fifth year pharmacy students at three universities in Northern Nigeria. Methods: A descriptive cross-sectional study that used a paper-based questionnaire to collect data from July to September 2021 was conducted. The questionnaire was self-administered and divided into four sections. The first section collected information about the demographic data of respondents, while section B explored their knowledge of antibiotics and AMR. Section C contained six questions assessing knowledge of various aspects of antimicrobial stewardship (AMS), while the final part assessed respondents' preparedness to work with antibiotics and perceptions of their current knowledge of these concepts. Descriptive statistics were used to report the results obtained. Results: A total of 164 questionnaires were retrieved. Majority of respondents were male (58.3%) and aged between 21 and 25 years (53.4%). Most of them had some knowledge of antibiotics and AMR, however several misconceptions with respect to these concepts were identified. Only 80 (48.8%) of respondents indicated that they knew what AMS was, although most of these students were correctly knowledgeable about the goals and scope of AMS and composition of the AMS team. Generally, less than half of respondents agreed that their current knowledge of antibiotics, AMR or AMS was adequate for their future careers, and over 90% of them agreed that they would like more education about these topics. Conclusion: Many of the study's' respondents were somewhat knowledgeable about these concepts, although several knowledge gaps were also observed. Improving undergraduate pharmacy education with respect to these concepts is recommended.

Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity.

The role of the endoplasmic reticulum (ER) has evolved from protein synthesis, processing, and other secretory pathways to forming a foundation for lipid biosynthesis and other metabolic functions. Maintaining ER homeostasis is essential for normal cellular function and survival. An imbalance in the ER implied stressful conditions such as metabolic distress, which activates a protective process called unfolded protein response (UPR). This response is activated through some canonical branches of ER stress, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6). Therefore, chronic hyperglycemia, hyperinsulinemia, increased proinflammatory cytokines, and free fatty acids (FFAs) found in diabesity (a pathophysiological link between obesity and diabetes) could lead to ER stress. However, limited data exist regarding ER stress and its association with diabesity, particularly the implicated proteins and molecular mechanisms. Thus, this review highlights the role of ER stress in relation to some proteins involved in diabesity pathogenesis and provides insight into possible pathways that could serve as novel targets for therapeutic intervention.

Ameliorative effect of methanol stem extract of Parquetina nigrescens (Afzel) bullock on scopolamine-induced sub-chronic cognitive deficit in mice.

Background Parquetina nigrescens (Afzel) Bullock is a commonly used medicinal plant in African traditional medicine. The powdered roots and stems of the plant are taken with pap as a memory enhancer among the Yorubas of southwestern Nigeria. The mechanism by which scopolamine induces cognitive deficit mimics the pathogenesis of neurodegeneration in cognitive impairment. This study therefore, aimed at investigating the effect of the methanol stem extract of P. nigrescens on sub-chronically scopolamine-induced cognitive deficit in mice. Method Phytochemical screening was carried out on the extract using standard protocols. The oral median lethal dose (LD50) was estimated according to the Organisation for Economic Cooperation and Development (OECD) 425 limit test guideline. Doses of 250, 500, and 1000 mg/kg of the extract were used for the study. The elevated plus maze (EPM) and novel object recognition tests (NORT) were used to assess cognitive function. The brain tissue was assayed for the level of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activity. Results The plant extract contains phenolics, carbohydrates, tannins, saponins, and unsaturated sterols.The extract decreased the transfer latencies on days 7 and 8 against the scopolamine group in EPM and increased the discrimination index decreased by scopolamine in NORT. The methanol stem extract of P. nigrescens significantly (p ≤ 0.01) reduced MDA level;  significantly  (p ≤ 0.01) increased SOD activity;  non-significantly increased GSH activity and the activity of AChE apeared not altered. Conclusion The methanol stem extract of P. nigrescens ameliorated sub-chronically scopolamine-induced cognitive deficit via antioxidant mechanism.

Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways.

Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. digitata (MEAD) on chronic unpredictable mild stress (CUMS) and the possible mechanism responsible for its antidepressant activity. Methods Acute toxicity of MEAD was determined using the OECD guideline 420. The CUMS model was used to induce depression, and behavioral tests such as sucrose preference test (SPT), open field test (OFT), novel-object recognition test (NORT), and tail suspension test (TST) were carried out in mice. The concentrations of plasma cortisol and brain-derived neurotrophic factor (BDNF) protein in the brain were assessed using enzyme-linked immunosorbent assay kits. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed using colorimetric methods. Results The LD50 was established to be ≥5000 mg/kg. On CUMS-induced depression, MEAD significantly (p ≤ 0.05) and dose dependently reversed the weight loss, increased the line-crossing activity in OFT, increased sucrose consumption in SPT, decreased the duration of immobility in TST, and increased the novelty exploration time in NORT. The MEAD extract significantly (p ≤ 0.05) and dose dependently increased the levels of BDNF, decreased the levels of plasma cortisol, increased the levels of total SOD activity, and decreased the levels of plasma MDA. Conclusion Our findings show that MEAD ameliorates CUMS-induced depressive-like behavior and its effect is possibly mediated via the neuroendocrine, neurotrophic, and oxidative stress pathways.

Management of musculoskeletal pain in retail drug outlets within a Nigerian community: a descriptive study.

OBJECTIVE: This work aimed to describe attitudes and practices of both community pharmacies and patent and proprietary medicine vendor (PPMV) outlets towards over-the-counter (OTC) analgesic use for musculoskeletal pain states within Zaria, Nigeria. METHODS: The study was carried out in 2 phases from May to August 2016. Phase one was a cross-sectional survey of 40 retail drug outlets (10 community pharmacies and 30 PPMVs). A simulated patient scenario of a young adult male complaining of acute onset back pain was used to collect data on the type and quality of analgesic recommended, duration of consultation, as well as nature of information provided during the drug dispensing process. The second phase involved semi structured interviews with 7 drug vendors (4 pharmacists and 3 patent medicine vendors). The interviewees were asked questions to assess their knowledge of analgesics as well as what type of analgesic they would recommend in three hypothetical patient scenarios. RESULTS: A wide variety of therapeutic agents were recommended for the simulated patient. Majority of these drugs were oral analgesics and contained NSAIDS either alone or in combination. Less than half of both patent medicine outlets and pharmacies (26.7% and 40% respectively) provided the simulated patient with information on duration of therapy, and asked the patient questions about their past medical and medication history (30% and 33.3% respectively). All analgesics purchased from the pharmacies were registered with the Nigerian drug regulatory agency and had expiry dates compared to only 66.7% and 90% of those bought from patent medicine outlets. Interviewed drug vendors admitted to obtaining a large amount of their knowledge on analgesics from drug information leaflets and prior learning. They also showed some knowledge deficits when questioned on side effects of analgesics and appropriate drug selection in the hypothetical scenarios. CONCLUSIONS: There are problems with both the OTC analgesics recommended, and the counselling provided for these medicines by drug vendors within the Zaria community. While both pharmacies and patent medicine outlets had shortcomings in several of the areas assessed by the simulated patient, the pharmacies performed better.