A protein restricted diet induces a stable increased fat storage phenotype in flies.

Background: Scientific evidence has revealed possible confounders in diet induced obesity models of Drosophila melanogaster. High Sugar Diet (HSD) induction of obesity in flies has been associated with fly hyperosmolarity and glucotoxicity, while High Fat Diet (HFD) induction has been associated with lipotoxicity. The objective of this study was to assess for a healthy obesity phenotype by comparison of fly survival, physio-chemical and biochemical changes associated with HSD, HFD and Protein Restricted Diet (PRD) obesity induction models of male Drosophila melanogaster. Here, we provide information on a PRD as the plausible option in obesity research not involving cancer, diabetes, glucotoxicity and lipotoxicity studies. Methods: Obesity was induced by exposing Drosophila melanogaster white mutant w1118 to four experimental diets for four weeks. Group 1 was fed regular food (control), group 2 was fed a 0.5% less yeast than in regular feed (PRD), group 3 was fed a 30% w/v sucrose to regular cornmeal food (HSD) and group 4 was fed a 10% w/v food-grade coconut oil to regular cornmeal food (HFD). Peristaltic waves were measured on 3rd instar larvae of all experimental groups. Negative geotaxis, fly survival, body mass, catalase activity, triglycerides (TG/TP), sterol, and total protein were measured in adult Drosophila melanogaster after four weeks. Results: Triglycerides (TG/TP) and total protein levels were significantly higher in HSD phenotype. Sterols were higher in HFD phenotype. Though catalase enzyme activity was highest in PRD phenotype, this activity was not statistically significant when compared to that of HSD and HFD phenotypes. However, PRD phenotype had the lowest mass, highest survival rate and the highest negative geotaxis, thus demonstrating a balanced, stable and more viable metabolic status in the experimental model. Conclusion: A protein restricted diet induces a stable increased fat storage phenotype in Drosophila melanogaster.

Nanodelivery of antiretroviral drugs to nervous tissues.

Despite the development of effective combined antiretroviral therapy (cART), the neurocognitive impairments associated with human immunodeficiency virus (HIV) remain challenging. The presence of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCFB) impedes the adequate penetration of certain antiretroviral drugs into the brain. In addition, reports have shown that some antiretroviral drugs cause neurotoxicity resulting from their interaction with nervous tissues due to long-term systemic exposure. Therefore, the research into the effective therapeutic modality that would cater for the HIV-associated neurocognitive disorders (HAND) and ART toxicity is now receiving broad research attention. Thus, this review explores the latest information in managing HAND using a nanoparticle drug delivery system (NDDS). We discussed the neurotoxicity profile of various approved ART. Also, we explained the applications of silver nanoparticles (AgNPs) in medicine, their different synthesis methods and their interaction with nervous tissues. Lastly, while proposing AgNPs as useful nanoparticles in properly delivering ART to enhance effectiveness and minimize neurocognitive disorders, we hypothesize that the perceived toxicity of AgNPs could be minimized by taking appropriate precautions. One such precaution is using appropriate reducing and stabilizing agents such as trisodium citrate to reduce silver ion Ag + to ground state Ag0 during the synthesis. Also, the usage of medium-sized, spherical-shaped AgNPs is encouraged in AgNPs-based drug delivery to the brain due to their ability to deliver therapeutic agents across BBB. In addition, characterization and functionalization of the synthesized AgNPs are required during the drug delivery approach. Putting all these factors in place would minimize toxicity and enhance the usage of AgNPs in delivering therapeutic agents across the BBB to the targeted brain tissue and could cater for the HIV-associated neurocognitive disorders and neurotoxic effects of antiretroviral drugs (ARDs).

Cerebral Cortical Activity During Academic Stress Amongst Undergraduate Medical Students at Kampala International University (Uganda).

Background: Stress among medical students is related to their academic lifespan; however, information on brain health among medical students from developing countries continues to be scarce. The objective of this study was to establish perceived academic stress levels, assess the ability to cope with stress, and investigate its effects on the visual reaction time (VRT), audio reaction time (ART), and tactile reaction time (TRT) in the somatosensory cortex among medical students of Uganda. Methods: This was a cross-sectional study conducted among preclinical (n = 88) and clinical (n = 96) undergraduate medical students at Kampala International University Western Campus. A standard Perceived Stress Scale (PSS) was used to categorize stress into low, moderate, and severe while the ability to cope with stress was categorized into below average, average, above average, and superior stresscoper (SS). Data on reaction time were acquired through VRT, ART, and TRT using the catch-a-ruler experiment, and this was analyzed using SPSS version 20. Results: This study shows that preclinical students are more stressed than clinical students (PSS prevalence for low stress = preclinical; clinical: 40, 60%). Moderate stress was 48.4 and 51.6% while high perceived stress was 75 and 25% among preclinical and clinical students. Among male and female students in preclinical years, higher TRT and VRT were found in clinical students showing that stress affects the tactile and visual cortical areas in the brain, although the VRT scores were only significantly (P = 0.0123) poor in male students than female students in biomedical sciences. Also, highly stressed individuals had higher TRT and ART and low VRT. SS had high VRT and ART and low TRT in preclinical students, demonstrating the importance of the visual cortex in stress plasticity. Multiple regression showed a close relationship between PSS, ability to cope with stress, age, and educational level (P < 0.05), demonstrating the importance of social and psychological support, especially in the biomedical sciences. Conclusion: Preclinical students suffer more from stress and are poorer SS than clinical students. This strongly impairs their cortical regions in the brain, thus affecting their academic productivity.

Highly active antiretroviral therapy-silver nanoparticle conjugate interacts with neuronal and glial cells and alleviates anxiety-like behaviour in streptozotocin-induced diabetic rats.

The inception of highly active antiretroviral therapy (HAART) has changed the management of human immunodeficiency virus (HIV) positive patients, with an improvement in life expectancy. However, neurological complications associated with high dosage and chronic administration of HAART have not been fully addressed. Therefore, this study evaluated the potential benefits of silver nanoparticles (AgNPs) conjugated-HAART (HAART-AgNPs) and its interaction with neuronal and glial cells in type-2 diabetic rats. Forty-two (n = 42) adult male Sprague-Dawley rats (250 ± 13 g) were divided into non-diabetic and diabetic groups. Each rat was administered with either distilled water, HAART, or HAART-AgNPs for eight weeks. After that, the prefrontal cortex (PFC) was excised for immunohistochemical, biochemical, and ultrastructural analysis. The formulated HAART-AgNPs were characterised by Ultraviolet-Visible, Transmission electron microscope, Energy Dispersive X-ray and Fourier transform infrared spectroscopy. Of the various concentrations of HAART-AgNPs, 1.5 M exhibited 20.3 nm in size and a spherical shape was used for this study. Administration of HAART-AgNPs to diabetic rats significantly decreased (p < 0.05) blood glucose level, number of faecal pellets, malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), Interleukin-1 beta (IL-1ß) compared with HAART-treated diabetic rats. Notably, there was a significant increase (p < 0.05) in antioxidant biomarkers (SOD and GSH), improvement in PFC-glial fibrillary acid protein (PFC-GFAP) positive cells and alleviation of anxiety-like behaviour in HAART-AgNPs treated diabetic rats. These results showed that HAART-AgNPs alleviates the anxiogenic effect and neuronal toxicity aggravated by HAART exposure via the reduction of oxidative and neuroinflammatory injury as well as preserving PFC GFAP-positive cells and neuronal cytoarchitecture.

Tenofovir-silver nanoparticles conjugate ameliorates neurocognitive disorders and protects ultrastructural and cytoarchitectonic properties of the prefrontal cortex in diabetic rats.

Tenofovir disoproxil fumarate (TDF) is the highly recommended antiretroviral drug in human immunodeficiency virus management. Although research has shown the neurological and metabolic disorders associated with TDF administration, the effect of TDF-silver nanoparticles conjugate (TDF-AgNPs) on the disorders has not been fully elucidated. Thus, this study evaluated the neuroprotective effects of TDF-AgNPs on ultrastructural and cytoarchitectonic properties of the prefrontal cortex (PFC) in diabetic rats. Forty-two adult male Sprague-Dawley rats (250 ± 13 g) were randomly divided into non-diabetic groups (1-3) and diabetic groups (4-6), each administered distilled water (0.5 ml/100g, p.o), TDF (26.8 mg/kg/bw, p.o) or TDF-AgNPs (6.7 mg/kg, i.p). After eight weeks of administration, cognitive function, oxidative injury and tissue inflammation were evaluated. Also, PFC ultrastructure was observed using transmission electron microscopy, Nissl staining and immunohistochemistry. Diabetic rats administered TDF exhibited cognitive deficits; and increases in blood glucose, malondialdehyde and interleukin-1 beta (IL-1ß) levels, which correlate with decreases in glutathione level, and superoxide dismutase (SOD) and catalase activities. Furthermore, loss of PFC astrocytes and neuronal organelles was observed. Conversely, TDF-AgNPs administration to diabetic rats improved cognitive deficits; and increased glutathione, SOD, and catalase, but reduced PFC malondialdehyde and IL-1ß concentrations. Notably, TDF-AgNPs prevented loss of PFC neurons and astrocytic cells, and morphology aberration of neuronal organelles. This study suggests that TDF-AgNPs attenuated cognitive deficits via silver nanoparticles' antioxidant and anti-inflammatory properties, preventing the loss of PFC astrocytes and neurons. The TDF-AgNPs may be utilized to ameliorate the neurological dysfunction caused by prolonged TDF administration.

Telfairia occidentalis stimulates hepatic glycolysis and pyruvate production via insulin-dependent and insulin-independent mechanisms.

BACKGROUND: Telfairia occidentalis (TO), a plant consumed for its nutritional and medicinal values, exhibits hypoglycaemic effect. However, the metabolic fate of the glucose following TO-induced insulin secretion and consequent hypoglycaemia is not clear. OBJECTIVE: This study determined the effect of ethyl acetate and n-hexane fractions of TO leaf extracts on some biochemical parameters in the glucose metabolic pathway to explain the possible fate of blood glucose following TO-induced hypoglycaemia. METHODS: Eighteen male Wistar rats (180-200 g) divided into control, n-hexane TO fraction- and ethyl acetate TO fraction-treated groups (n = 6/group) were used. The control animals received normal saline while the treated groups received TO at 100 mg/kg for seven days. After 24 h following the last dose, the animals were anaesthetised using ketamine; blood samples were collected and livers harvested to determine some biochemical parameters. RESULTS: Ethyl acetate TO fraction significantly increased plasma insulin, liver glucokinase activity and plasma pyruvate concentration, but significantly decreased plasma glucose and liver glycogen, without significant changes in plasma lactate, glucose-6-phosphate, liver glucose-6-phosphatase and lactate dehydrogenase activities when compared with control. N-hexane TO fraction significantly reduced liver glucose-6-phosphatase activity and glycogen but significantly increased plasma pyruvate, without significant changes in plasma glucose, insulin, glucose-6-phosphate and lactate concentrations; and liver glucokinase and lactate dehydrogenase activities. CONCLUSION: The present study showed that insulin-mediated TO-induced hypoglycaemia resulted in the stimulation of glycolysis and pyruvate production via insulin-dependent and insulin-independent mechanisms.

Possible mechanisms of the hypoglycaemic effect of artesunate: Gender implication.

BACKGROUND: We investigated the mechanism of artesunate's glucose-modulating effect especially with gender implication. METHODS: Twenty-five (25) male and 25 female rats were separately and blindly allocated into five identical groups (n = 5/group). Group I (control) received 0.2 ml/kg distilled water. Groups II and III both received 2.90 mg/kg artesunate on day one, but 1.45 mg/kg from day two till day five and day fifteen respectively. Groups IV and V both received 8.70 mg/kg artesunate on day one, but 4.35 mg/kg artesunate from day two till day five and day fifteen respectively. RESULTS: In male rats, glucose was reduced by both doses of artesunate at 5 days but increased by high dose at 15 days. Artesunate increased glycogen concentration at short duration which normalised at long duration in both genders. Artesunate increased G6P concentration only in male rats at 15 days but reduced G6Pase activity in male and female rats (except in those that received low and high doses of artesunate for 15 days). Artesunate increased insulin only in male rats treated with low dose artesunate for 5 days. Artesunate increased cortisol concentration in male but reduced it in female rats. Artesunate decreased glucagon concentration except in female rats treated with high dose for 5 days. Artesunate increased oestrogen concentration in male rats that received low dose artesunate for 5 days but reduced it in female rats that received high dose for 15 days. CONCLUSIONS: Artesunate reduces plasma glucose by reducing plasma glucagon concentrations and inhibiting liver glycogenolysis via inhibition of G6Pase activity in both sexes. Increase in insulin concentration contributed to the reduction in blood glucose caused by artesunate in male but not female rats; and artesunate-induced increase in G6P, a substrate for G6PD, could enhance NADPH generation and antioxidant enzyme activation in male rats.

Counter-regulatory responses to Telfairia occidentalis-induced hypoglycaemia.

BACKGROUND: Telfairia occidentalis (TO) has many biological activities including blood glucose regulation. Thus, it is being used in the treatment of diabetes mellitus. TO has been shown to cause insulin-mediated hypoglycaemia, which leads to post-hypoglycaemic hyperglycaemia. However, the mechanism involved in the post-hypoglycaemic hyperglycaemia is still poorly understood. OBJECTIVE: This research was designed to determine the response of glucoregulatory hormones and enzymes to TO treatment. METHODS: Thirty-five male Wistar rats were divided into seven oral treatment groups (n = 5/group), which received either of 100 mg/kg or 200 mg/kg TO for 7-, 10- or 14 days. RESULTS: The 7-day treatment with TO significantly increased the levels of insulin, glucagon, and glucose-6-phosphatase (G6Pase) activity but decreased the levels of glucose, adrenaline, and glucokinase (GCK) activity. The 10-day treatment with 100 mg/kg TO increased glucose and decreased GCK activity while 200 mg/kg for the same duration increased glucose, insulin, GCK and G6Pase activities but reduced glucagon. The 14-day treatment with 100 mg/kg TO decreased glucose and glucagon but increased cortisol, while 200 mg/kg TO for same duration increased insulin, but reduced glucagon and GCK activity. CONCLUSION: The TO's post-hypoglycaemic hyperglycaemia results from increased glucagon and G6Pase activity, and reduced GCK activity. Moreover, the glucagon response mainly depends on glucose rather than insulin.

Comparative effects of glibenclamide, metformin and insulin on fetal pancreatic histology and maternal blood glucose in pregnant streptozotocin-induced diabetic rats.

BACKGROUND: Oral hypoglycemic agents use during pregnancy was assumed to cause fetal macrosomia and skeletal deformities, and maternal complications due to significant transfer across placenta or ineffective control of blood glucose. OBJECTIVE: This study investigated effects of insulin, metformin and glibenclamide on maternal blood glucose; and fetal crown-rump length, gross malformation and pancreatic histology in pregnant streptozotocin-induced diabetic rats. METHODS: Twenty-five pregnant rats of groups 1 to 5 as normal and diabetic controls; and diabetic treated with insulin, metformin and glibenclamide were used. Experimental GDM was induced using 45 and 35mg/Kgbw of intraperitoneal streptozotocin. RESULTS: Metformin, Insulin and Glibenclamide significantly reduced maternal glucose by 140.6mg/dL, 103.2mg/dL and 98.54mg/dl; respectively and showed islets with regular interlobular ducts, islets with some irregular interlobular ducts, and islets with many irregular interlobular ducts in histological fetal pancreatic photomicrographs respectively. This depicts metformin having highest ameliorative effect. There were no significant differences in maternal and fetal body weights, maternal blood glucose between diabetic groups, and fetal gross examination. CONCLUSION: At the doses used in this research, metformin and glibenclamide showed no adverse effects on maternal and fetal features in the treatment of GDM. Thus, they can be used as safe and inexpensive alternatives to insulin.

A study on visual, audio and tactile reaction time among medical students at Kampala International University in Uganda.

BACKGROUND: Reaction time (RT) is an indicator of neural activity, however, its variation due to visual (VRT), audio (ART) and tactile (TRT) in African medical students has not been investigated. The aim of the study was to determine relationships between VRT, ART and TRT amongst medical students in Uganda. MATERIALS AND METHODS: This was a cross sectional study, the body mass index (BMI) and RT (i.e. VRT, ART and TRT) were determined using weighing scale with standiometer and the catch a ruler experiment respectively. A questionnaire was administered to collect information on participant's lifestyle patterns and analysis was done using SPSS Version 20. RESULTS: The mean (± SEM) VRT, ART and TRT in the study were found to be 0.148 ± 0.002s, 0.141 ± 0.002s and 0.139 ± 0.003s respectively. A strong correlation between TRT and ART was found to exist in the youthful Ugandan medical student's population. Furthermore, significant differences in ART and VRT were observed with sex, although these were absent amongst preclinical and clinical students, showing the importance of sex in RT. CONCLUSION: The low VRT and ART in Ugandan medical students is indicative of a healthy somatosensory connectivity, thus of academic importance.