Caffeine protects against hippocampal alterations in type 2 diabetic rats via modulation of gliosis, inflammation and apoptosis.

Type 2 diabetes (T2D) is implicated in the injury of several organs, including the brain resulting in neuronal damage, which may lead to cognitive impairment and dementia. Additionally, it is linked to inflammation, cytokine release, apoptosis and various degenerative conditions. Astrocytes and microglia might have a role in mediating these processes. Caffeine, a psychoactive beverage, has been shown to reduce the risk of cognitive and memory impairment. This study proposes anti-inflammatory and anti-apoptotic role of caffeine, which can be mediated via microglia/astrocyte activation and overexpression of pro-inflammatory molecules. T2D was induced in rats by feeding with high fat high sugar diet and injecting a single low dose streptozotocin (STZ) intraperitoneally. Other diabetic rats were given caffeine orally (in two doses) for 5 weeks, starting 1 week before STZ injection. Measurement of plasma cytokines, TNFα and IL6, was performed using enzyme-linked immunosorbent assay (ELISA) technique. After sacrificing animals, brains were obtained and processed for histological evaluation. Immunohistochemistry was also performed using the following primary antibodies, anti-astrocyte marker GFAP, anti-microglia marker CD11b and apoptotic marker (anti-cleaved caspase-3). There was upregulation of IL6 and TNF-α in diabetic rats. Additionally, histological evaluation of the hippocampus of diabetic rats revealed cellular degeneration. There was increased immunostaining of GFAP, CD11b and cleaved caspase-3 in diabetic rats. Pretreatment with caffeine to diabetic rats, resulted in improvement of structural changes and decrease in cytokine levels and immuno-markers, expression, and this was in a dose-dependent manner. In conclusion, caffeine had an ameliorative role in enhancing hippocampal degenerative changes in T2D.

Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

Implementing Formative Assessment in Human Anatomy Practical Sessions: Medical Students' Perception and Effect on Final Exam Performance.

Background: Formative assessment with feedback is part of the assessment program in medical education to improve students' learning. Limited research has focused on its application and impact on practical anatomy education. Methods: This study aimed to examine medical students' perceptions of formative assessment in practical anatomy sessions of body systems-based educational units and explore its influence on final practical exam performance. A descriptive, cross-sectional study was conducted. Data was collected from 173 Year 2 medical students through a survey that addressed their perception of process and importance of formative assessment and feedback. The survey employed a 5-point Likert scale. Two open-ended questions were appended at the end of the survey. Students' performance in Unit 3 (where formative assessment was conducted) was compared to their performance in Unit 2 (where no formative assessment was conducted) and with the performance of the previous academic year's students in Unit 3 (where no formative assessment was conducted). Descriptive statistics were used. The level of statistical significance was set at p-value < 0.05. Responses to open-ended questions (qualitative data) were counted, categorized as themes, and presented as frequencies and percentages. Results: The survey showed high internal consistency, and its validity was established through exploratory factor analysis. Results showed that the mean mark for the unit with formative assessment and feedback was significantly higher than for the units without formative assessment and feedback. Students showed positive perception of formative assessment and feedback conducted after practical anatomy sessions. They reported useful insights regarding the benefits they gained from formative assessment and feedback as well as constructive suggestions for future improvements. Conclusion: The study indicates that students positively perceived formative assessment and feedback sessions after practical anatomy sessions. Findings also refer to a positive effect of formative assessment on students' performance in summative practical assessment in anatomy.

Frequency of palmaris longus absence and its association with other anatomical variations in the Egyptian population.

The palmaris longus (PL) is one of the most variable muscles in the human body. Racial differences in its variation have been documented. Several studies have attempted to correlate PL absence with other anatomical variations. This study was conducted to determine the prevalence of absence of PL, correlate it with gender and body side and to determine its association with other anatomical variations in the Egyptian population. The presence of PL was clinically determined in 386 Egyptians using the standard technique. All subjects were examined for the presence of the flexor digitorum superficialis (FDS) to the fifth finger. Allen's test was done to assess the completeness of the superficial palmar arch (SPA). The overall prevalence of absence of the PL in Egyptian subjects was 50.8%. There was no significant difference in PL absence with regard to the body side but a significant difference was seen as regards gender and when bilateral absence of PL was compared to its unilateral absence. Absence of FDS tendon to the fifth finger was seen in 1.3% subjects. There was no association between the absence of the FDS tendon to the fifth finger and either presence or absence of PL and also between the absence of PL and the incompleteness of SPA in both genders. In conclusion, the prevalence of absence of PL in the Egyptian population represents one of the highest rates of absence to be reported for this muscle, which is significantly different from that in other ethnic groups.

Pomegranate (Punica granatum) peel alleviates lithium-induced alterations in the thyroid gland of rats by modulating apoptosis and oxidative stress.

Lithium carbonate (LC) is known to alter thyroid gland function. Pomegranate (PG) is a fruit with multiple antioxidant and antiapoptotic properties. Here, we studied the effect of PG on LC-induced morphological and functional alterations in the thyroid glands of rats. Rats were divided into four groups: control, lithium, lithium-PG, and PG. After 8 weeks, the rats were sacrificed, the levels of thyroid hormones and oxidative stress markers were estimated, and thyroid tissues were subjected to histological, immunohistochemical, and ultrastructural evaluations. Compared to the control group, the lithium group showed significant changes in thyroid hormone levels, greater expression of the oxidant marker malondialdehyde, and lower expression of the antioxidant marker superoxide dismutase (SOD). Most of these changes improved upon PG treatment. Histological evaluation of the thyroid in the lithium group showed disorganization and follicle involution. Additionally, the periodic acid Schiff staining intensity and SOD immunoreactivity declined significantly, whereas the collagen fiber content and Bax immunoreactivity increased. The follicular ultrastructure showed marked distortion. These changes were mitigated upon PG treatment. In conclusion, PG alleviated the morphological and functional changes in the thyroid glands induced by LC by modulating apoptosis and oxidative stress.

Emerging mechanistic insights of selective autophagy in hepatic diseases.

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens via the lysosomal system. In addition, autophagy selectively recycles specific organelles such as damaged mitochondria (via mitophagy), and lipid droplets (LDs; via lipophagy) or eliminates specialized intracellular pathogenic microorganisms such as hepatitis B virus (HBV) and coronaviruses (via virophagy). Selective autophagy, particularly mitophagy, plays a key role in the preservation of healthy liver physiology, and its dysfunction is connected to the pathogenesis of a wide variety of liver diseases. For example, lipophagy has emerged as a defensive mechanism against chronic liver diseases. There is a prominent role for mitophagy and lipophagy in hepatic pathologies including non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), and drug-induced liver injury. Moreover, these selective autophagy pathways including virophagy are being investigated in the context of viral hepatitis and, more recently, the coronavirus disease 2019 (COVID-19)-associated hepatic pathologies. The interplay between diverse types of selective autophagy and its impact on liver diseases is briefly addressed. Thus, modulating selective autophagy (e.g., mitophagy) would seem to be effective in improving liver diseases. Considering the prominence of selective autophagy in liver physiology, this review summarizes the current understanding of the molecular mechanisms and functions of selective autophagy (mainly mitophagy and lipophagy) in liver physiology and pathophysiology. This may help in finding therapeutic interventions targeting hepatic diseases via manipulation of selective autophagy.

Impact Of Prenatal Administration Of Melamine On Foetal Growth In Rats.

BACKGROUND: Data on the potential effects of maternal exposure to melamine is scarce. We aimed to evaluate the impact of melamine administration on pregnancy outcome and foetal growth in rats. METHODS: Positively-mated female Sprague-Dawley rats (n=24) were treated from day 6 to day 20 of gestation with vehicle (control), melamine 300 mg/kg/day (group-1) or melamine 450 mg/kg/day (group 2). On day 21, the numbers of foetal resorptions and dead foetuses were recorded. Thereafter, pups were examined for external anomalies, and various growth parameters were measured. RESULTS: A remarkable increase in the number of resorptions was observed in group-2 compared to the other two groups. A significant increase in foetal weight and placental weight was seen in group-2 compared to control. Head length and placental diameter were low in group-1 compared to control. The ratio between crown-rump length and head length was significantly greater in group 2 compared to control indicating asymmetrical intrauterine growth restriction. The only influence observed in group 1 compared to control was a decrease in placental diameter. No gross foetal malformations or changes in umbilical cord length, crownrump length or biparietal diameter were observed in both melamine-treated groups. CONCLUSIONS: Maternal exposure to melamine during pregnancy increased the incidence of resorption and resulted in asymmetrical intrauterine growth restriction.

Genetic polymorphism of the glutathione S-transferase M1 and T1 genes in three distinct Arab populations.

Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals. GSTM1 deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence of GSTT1 null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution of GSTM1 and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution of GSTM1 gene (P=0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addresses GST gene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and drug effects in Arab populations.

Growth assessment of diabetic rat fetuses under the influence of insulin and melatonin: a morphologic study.

Hyperglycemia-induced oxidative stress makes an important contribution to the etiology of diabetic teratogenicity namely fetal growth and congenital dysmorphogenesis. The aim of this study is to evaluate the protective roles of melatonin and insulin against diabetic's embryolethality and teratogenicity. Diabetes was induced to virgin Sprague Dawley albino rats by a single peritoneal injection of alloxan. Thirty pregnant rats were divided equally into 5 groups: 1) Control 2) Diabetic 3) Diabetic insulin 4) Diabetic melatonin 5) Diabetic melatonin-insulin. Insulin and melatonin were administered daily throughout the whole gestational period. Fetuses were collected on day 20 of gestation and were examined for malformations and growth disorders. A significant increase in fetal growth parameters (Macrosomia) were noticed in the diabetic group compared to the control. Melatonin prevents the appearance of soft tissue anomalies, but it leads to fetal growth restriction of diabetic rats (Microsomia). No significant changes were noticed in fetal growth parameters in diabetic insulin or in diabetic melatonin-insulin groups compared to the control. Congenital anomalies were not seen in diabetic insulin and in diabetic melatonin-insulin groups while the rate of resorption was reduced in both groups when compared to the diabetic group. In conclusion, co-administration of melatonin with insulin leads to a slight non significant improvement of the protective role of insulin against diabetic embryolethality, teratogenicity and fetal growth changes.

Distribution of four HIV type 1-resistance polymorphisms (CCR5-Delta32, CCR5-m303, CCR2-64I, and SDF1-3'A) in the Bahraini population.

Allelic differences of chemokine (C-C motif ) receptor 5 (CCR5) and CCR2, as well as the ligand for the chemokine receptor CXCR4, stromal-derived factor (SDF-1), are known to suppress HIV-1 transmission and to be involved in delay in HIV-1 disease progression. The aim of our study was to investigate the frequencies of four mutations that confer resistance to HIV-1: CCR5-Delta32, CCR5-m303, CCR2-64I, and SDF1-3'A among Bahrainis. We have studied the DNA polymorphisms in 304 unrelated healthy Bahraini individuals without any known history of HIV-1 infection or AIDS symptoms. The CCR5-Delta32 mutation was detected by PCR analysis, while the CCR5-m303, CCR2-64I, and SDF1-3'A mutations were detected by PCR-restriction fragment length polymorphism (PCR-RFLP) tests. Allele frequencies and the fit to the Hardy-Weinberg equilibrium were evaluated using the Arlequin population genetics application. The frequencies of the CCR5-Delta32, CCR2-64I, and SDF1-3'A alleles were 2.8%, 8.9%, and 26.5%, respectively. No mutant alleles were detected for the CCR5-m303 mutation in 304 individuals. We estimated the risk of AIDS onset (relative hazard), computed from the three-locus genotype data. This is the first report of these four mutations conferring resistance to HIV-1 in the Bahraini population. The presence of the CCR5-Delta32 allele among Bahrainis may be attributed to the admixture with people of European descent. The CCR2-64I allele and especially the SDF1-3'A allele are predominant in the Bahraini population and may be associated with resistance to fast HIV-1 infection in Bahrainis, and thus their genotyping can be used for prognosis in HIV-infected individuals.

Growth assessment of children exposed to low frequency electromagnetic fields at the Abu Sultan area in Ismailia (Egypt).

UNLABELLED: A cross-sectional study was carried out to assess the growth of 780 children of both sexes, aged between 0-12 years, and living at two different areas in Ismailia, Egypt, with approximately similar socioeconomic standards. Based on a designed questionaire, the exposed group was formed of 390 children from the Abu Sultan area. They were chosen from families living within 50 meters nearby high voltage electric power lines. Another 390 children from the El-Sheikh Zayed area were chosen as the control group. Standard anthropometric measurements were carried out for each child. Plain X-ray was done on the hands of 200 randomly selected children from both groups (100 each) to assess their bone maturation. In the exposed group the weight was significantly decreased only at birth, while the circumferences of the head and chest as well as the height were significantly reduced at all studied ages. The radiological study revealed a significant delay in carpal bone ossification of the exposed children. IN CONCLUSION: Exposure to low frequency electromagnetic fields emerged from high voltage electric power lines increases the incidence of growth retardation of children. Isolating these power lines in a scientific way in order to shield both the magnetic and electric fields or removing them far away from the inhabitant areas is recommended.