The potential antiepileptic activity of astaxanthin in epileptic rats treated with valproic acid.

OBJECTIVES: Epilepsy is a neurological disease characterized by sudden, abnormal, and hyper- discharges in the central nervous system (CNS). Valproic acid (VPA) is commonly used as a broad-spectrum antiepileptic therapeutic. However, in many cases, patients develop resistance to VPA treatment due to overwhelming oxidative stress, which in turn might be a major catalyst for disease progression. Therefore, antioxidants can potentially become therapeutic agents by counteracting reactive oxygen species (ROS)-mediated damage. The present study is aimed to evaluate the potential antiepileptic effect of astaxanthin (ASTA) in pentylenetetrazol (PTZ) induced epileptic model rats that are chronically treated with VPA for 8 weeks. METHOD: Fifty-male Wistar rats were randomly divided into five groups: Non-PTZ group, PTZ, PTZ/VPA, PTZ/ASTA, and PTZ/VPA/ASTA treated groups. RESULTS: PTZ/VPA treated group showed a neuroprotective effect with improvement in antioxidant levels, behavioral test, and histopathological changes induced by PTZ. VPA also exhibited an anti-inflammatory effect as its treatment resulted in the reduction of tumor necrosis factor-α (TNF-α). ASTA exhibited an anticonvulsant effect and enhanced anti-inflammatory effect as compared to VPA. During the combined therapy, ASTA potentiated the antiepileptic effect of the VPA by reducing the oxidative stress and TNF-α as well as increased the glutathione (GSH) levels. Also, there were substantial improvements in the behavioral and histopathological changes in the VPA/ASTA treated group as compared to the VPA treated group. CONCLUSION: ASTA could have an antiepileptic and anti-inflammatory effect by reducing ROS generation. Therefore, co-administration of both the therapeutics (VPA/ASTA) has a synergistic effect in treating epilepsy and could potentially minimize recurrence and/or exacerbation of seizures.

Anti-Fibrotic Efficacy of Apigenin in a Mice Model of Carbon Tetrachloride-Induced Hepatic Fibrosis by Modulation of Oxidative Stress, Inflammation, and Fibrogenesis: A Preclinical Study.

BACKGROUND: Hepatic fibrosis is a major health problem all over the world, and there is no effective treatment to cure it. Hence, the current study sought to assess the anti-fibrotic efficacy of apigenin against CCl4-induced hepatic fibrosis in mice. METHODS: Forty-eight mice were put into six groups. G1: Normal Control, G2: CCl4 Control, G3: Silymarin (100 mg/kg), G4 and G5: Apigenin (2 &20 mg/Kg), G6: Apigenin alone (20 mg/Kg). Groups 2, 3, 4, and 5 were given CCl4 (0.5 mL/kg. i.p.) twice/week for six weeks. The level of AST, ALT, TC, TG, and TB in serum and IL-1ß, IL-6, and TNF-α in tissue homogenates were assessed. Histological studies by H&E staining and Immunostaining of liver tissues were also performed. RESULTS: The CCl4-challenged group showed increased serum AST (4-fold), ALT (6-fold), and TB (5-fold). Both silymarin and apigenin treatments significantly improved these hepatic biomarkers. The CCl4-challenged group showed reduced levels of CAT (89%), GSH (53%), and increased MDA (3-fold). Both silymarin and apigenin treatments significantly altered these oxidative markers in tissue homogenates. The CCl4-treated group showed a two-fold increase in IL-1ß, IL-6, and TNF-α levels. Silymarin and apigenin treatment considerably decreased the IL-1ß, IL-6, and TNF-α levels. Apigenin treatment inhibited angiogenic activity, as evidenced by a decrease in VEGF (vascular endothelial growth factor) expression in liver tissues, and a decline in vascular endothelial cell antigen expression (CD34). CONCLUSIONS: Finally, these data collectively imply that apigenin may have antifibrotic properties, which may be explained by its anti-inflammatory, antioxidant, and antiangiogenic activities.

Toxic trespassers: Uncovering phthalates and organophosphate flame retardants in children's rooms and their health implications.

Organophosphate flame retardants (OPEs) and phthalates have garnered significant attention due to their widespread presence in indoor environments. Many recent investigations have reported extensive contamination of indoor dust, air, children's toys, and other environmental compartments with these chemicals. This research aimed to analyze OPEs and phthalates in air (PM10) and dust samples collected from the bedrooms of children (N = 30) residing in various households in Jeddah, Saudi Arabia. High mean levels (ng/g) of phthalates namely DEHP (1438600) and DnBP (159200) were found in indoor dust while TPhP (5620) was the major OPEs in indoor dust. Similarly, DEHP and DnBP were the predominant phthalates in PM10 samples, exhibiting mean levels of 560 and 680 ng/m3, respectively. However, TCPP was the main OPEs with average levels of 72 ng/m3 in PM10 samples. The majority of individual phthalates and OPEs were detected in 90-100 % of the dust samples, whereas in PM10 samples, their presence ranged from 25 % to 100 %. The concentrations of OPEs were notably greater than those of PBDEs and other BFRs previously reported in these samples, suggesting their broader use than alternative BFRs. The estimated long-term non-carcinogenic risk, hazardous index (HI) and daily exposure via dust for children was above threshold levels for DEHP. On the other hand, the cumulative risk of cancer was below the concerning levels. Further research is required to explore diverse groups of chemicals in indoor microenvironments particularly significant for children, such as kindergartens, primary schools, and their rooms at home.

Molecularly tracing of children exposure pathways to environmental organic pollutants and the Autism Spectrum Disorder Risk.

Organic pollutants (OPs) including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) have showed neuro-damaging effects, but studies concerning the autism spectrum disorder (ASD) risk are limited. A case-control study with ASD (n = 125) and healthy control (n = 125) children was conducted on the different land use settings across Punjab, Pakistan. Serum concentrations of 26 OCPs, 29 PCB congeners, 11 PBDEs and 32 PAHs were measured. Serum PCB77 (AOR = 2.00; 95% CI: 1.43, 2.18), PCB118 (AOR = 1.49; 95% CI: 1.00, 2.00), PCB128 (AOR = 1.65; 95% CI: 1.01, 1.91), PCB153 (AOR = 1.80; 95% CI: 1.55, 1.93) were significantly higher, but PCB187 (AOR = 0.37; 95% CI: 0.24, 0.49) was significantly lower in the ASD cases when compared to the controls. Serum BDE99 (AOR = 0.48; 95% CI: 0.26, 0.89) was significantly higher in the healthy controls than in the ASD cases. Among the analyzed OCPs, p,p'-DDE (AOR = 1.50; 95% CI: 1.00, 1.85) was significantly elevated in the ASD cases with comparison in the controls. For PAHs, serum dibenzothiophene (AOR = 7.30; 95% CI: 1.49, 35.85) was significantly higher in the ASD, while perylene (AOR = 0.25; 95% CI: 0.06, 1.10) and fluorene (AOR = 0.21; 95% CI: 0.06, 0.72) were significantly higher in the controls. In addition, many of the serum pollutants were significantly associated with GSTT1, GSTM1 (null/present polymorphism) and presented the genotypic variation to respond xenobiotics in children. The children living in proximity to urban and industrial areas had a greater exposure to most of the studied pollutants when compared to the rural children, however children residing in rural areas showed higher exposure to OCPs. This comprehensive study documents an association between environmental exposure risk of several organic pollutants (OPs) from some contaminated environmental settings with ASD risk in children from Pakistan.

Polycyclic Aromatic Hydrocarbons in Indoor Dust Collected during the COVID-19 Pandemic Lockdown in Saudi Arabia: Status, Sources and Human Health Risks.

To control the spread of coronavirus disease (COVID-19), Saudi Arabia's government imposed a strict lockdown during March-July 2020. As a result, the public was confined to indoors, and most of their daily activities were happening in their indoor places, which might have resulted in lower indoor environment quality. Polycyclic aromatic hydrocarbons (PAHs) were analyzed in household dust (n = 40) collected from different residential districts of Jeddah, Saudi Arabia, during the lockdown period. PAHs' levels were two folds higher than the previously reported PAHs in indoor dust from this region. We detected low molecular weight (LMW) with two to four aromatic ring PAHs in all the samples with a significant contribution from Phenanthrene (Phe), present at an average concentration of 1590 ng/g of dust. Although high molecular weight (HMW) (5-6 aromatic ring) PAHs were detected at lower concentrations than LMW PAHs, however, they contributed >90% in the carcinogenic index of PAHs. The estimated daily intake (EDI) of specific PAHs was above the reference dose (RfD) for young children in high-end exposure and the calculated Incremental Lifetime Cancer Risk (ILCR) was >1.00 × 10-4 for both Saudi adults and young children. The study highlighted that indoor pollution has increased significantly during lockdown due to the increased indoor activities and inversely affect human health. This study also warrants to conduct more studies involving different chemicals to understand the indoor environment quality during strict lockdown conditions.

Brominated Flame Retardants in Children's Room: Concentration, Composition, and Health Risk Assessment.

Children spend most of their daily time indoors. Many of the items used indoors, such as furniture, electronics, textile, and children toys, are treated with chemicals to provide longevity and fulfil the safety standards. However, many chemicals added to these products are released into the environment during leaching out from the treated products. Many studies have reported brominated flame retardants (BFRs) in indoor environments; however, few have focused on environments specified for young children. In this study, paired air (PM10) and dust samples were collected from the rooms (n = 30) of Saudi children. These samples were analyzed for different congeners of polybrominated diphenyl ethers (PBDEs) and three important alternative flame retardants using gas chromatography-mass spectrometry. Decabromodiphenyl ether (BDE 209) was the most important analyzed BFR in dust and PM10 samples with a median value of 3150 ng/g of dust and 75 pg/m3. This indicates the wider application of BDE 209 has implications for its occurrence, although its use has been regulated for specified uses since 2014. Among alternative BFRs, 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), Bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), and 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE) were found with a median levels of 10, 15 and 8 ng/g of dust, respectively. However, alternative BFRs were present in <50% of the PM10 samples. The calculated long term and daily exposures via indoor dust and PM10 of Saudi children from their rooms were well below the respective reference dose (RfD) values. Nonetheless, the study highlights BDE 209 at higher levels than previously reported from household dust in Saudi Arabia. The study warrants further extensive research to estimate the different classes of chemical exposure to children from their rooms.

Contextual Analysis of Stakeholder Opinion on Management and Leadership Competencies for Undergraduate Medical Education: Informing Course Design.

BACKGROUND: The study aimed to conduct a contextual analysis of interviews intended to assist with the future design of a feasible and relevant leadership and management course for undergraduate medical students at King Abdulaziz University (KAU), Saudi Arabia. METHODS: This was a cross-sectional study conducted at King Abdulaziz University (KAU), Saudi Arabia, during 2019. An exploratory qualitative approach, utilizing systematic content analysis, was used. Data were collected using semi-structured interviews that were conducted with 10 leaders who were stakeholders at KAU, health service providers at KAU hospital, and stakeholders in the Ministry of Health. RESULTS: This study revealed critical findings that highlighted the areas in which KAU could instill better and adequate leadership and management skills in their undergraduate medical students. Multiple core categories for a leadership and management curriculum emerged with many interrelated themes. Most participants mentioned that leadership can be taught and that early exposure is beneficial for developing skills. Additionally, they stated that leaders should have a vision and the ability to articulate that vision. CONCLUSIONS: Different implementation challenges were described in relation to the availability of human resources, the current short supply of suitable teachers, and program design. Teaching methods recommended included simulations, lectures, and a project-based approach. Assessment methods that were recommended included objective structured clinical examination (OSCE), formative and summative assessments, self-assessments, and portfolios.

Relationship between CNS and Immunology: Correlation with Psychology.

BACKGROUND: Higher animals, especially the human beings have the privilege of employing advanced central nervous system (CNS) as well as the evolved immune system to ward off various onslaughts throughout their life. Alterations in inflammatory and neural regulatory pathways lead to several disorders that are now becoming the cause of concern across the world. Deregulation in bidirectional network, particularly in aging population, leads to several neurodegenerative diseases such as dementia as a one of the major characteristics. OBJECTIVE: Interestingly, research updates have signified the role of abrupt immune regulation in several brain diseases, establishing a link between altered immune system and CNS related diseases. In the later period of life, the altered immune response in the pathogenesis of major psychiatric disorders, has become more visible. In the present manuscript, we present a synopsis on the linkage of CNS and immune system with respect to psychology, with the aim to further understand the biological machinery of psychoneuroimmunological disorders. The immune system of human being plays an important role in keeping pathogen onslaughts on bay. CONCLUSION: Our manuscript concludes a close relationship between emotion and psychology to diseases and immunology, proclaiming the need of providing enhanced attention on mechanistic aspect of psychoneuroimmunological disorders.

Molecular docking and in vitro studies of soap nut trypsin inhibitor (SNTI) against phospholipase A2 isoforms in therapeutic intervention of inflammatory diseases.

Therapeutic value of allelochemicals in inflammatory disorders and the potential drug targets need to be elucidated to alleviate tissue and vascular injury. Natural anti-inflammatory agents are known to cause minimal adverse effects. Presence of different secondary metabolites (allelochemicals), protease inhibitors like soap nut trypsin inhibitor (SNTI) from Sapindus trifoliatus and allied compounds from natural sources cannot be blithely ignored as natural therapeutics. In the present study, SNTI, a prospective protease inhibitor isolated from the seeds of Sapindus trifoliatus were subjected to docking against three isoforms of Phospholipase A2 (PLA2) molecules of the inflammatory pathways which are localized in the membrane, cytosol and pancreas. Eleven ligand molecules were selected from Sapindus trifoliatus and docked against membrane, cytosolic and pancreatic PLA2. Cytosolic PLA2 showed a strong inhibition by Kampferol, a secondary metabolite from seed endosperm of Sapindus trifoliatus. SNTI showed best interaction with membrane PLA2 in both in silico as well as in in vitro studies. SNTI showed IC50 value of 29.02 µM in in vitro assay. Docking interaction profiles and in vitro studies validate selected molecules from Sapindus trifoliatus as immunomodulators and can mollify inflammatory responses.

Identification of Electrophysiological Changes in Alzheimer's Disease: A Microarray Based Transcriptomics and Molecular Pathway Analysis Study.

BACKGROUND & OBJECTIVE: Involvement of amyloid beta and tau proteins in pathogenesis of Alzheimer's disease (AD) has been studied extensively. However, electrophysiological activity, and cellular processes like membrane transport are mostly unstudied. Electrophysiological processes provide a bridge between brain activity and cognition, and show promise as translatable biomarkers in preclinical and clinical applications. Biochemical imbalance leads to change in glutamate-based neurotransmission, antioxidant capacity, and in membrane polarization-repolarization events, eventually, resulting in AD. We hypothesize that in AD, these processes are unified at a single metabolic hub and we carried out a holistic system-biology approach. METHOD: In the present study, we integrated and analyzed multiple AD expression datasets from the GEO database to identify significant genes associated with electrophysiological pathways and attempted determination of interconnected canonical molecular pathways. Partek Genomic suite based expression analysis identified 200 significantly expressed genes using cut-off value of ≤ 0.05 and 2 fold change. Transducer of ERBB2, 2 (TOB2); lactotransferrin (LFT) and RAS-like, family 12 (RASL12) were most up-regulated genes, while neurofilament light polypeptide (NEFL); collagen, type V, alpha 2 (COL5A2); visinin-like 1 (VSNL1); cannabinoid receptor 1 (brain) (CNR1); neurofilament, medium polypeptide (NEFM); regulator of G-protein signaling 4 (RGS4), and synaptosomalassociated protein, 25kDa (SNAP25) were most down-regulated ones. CONCLUSION: Interestingly, we found majority of transporter genes identified in dataset as downregulated. Ingenuity pathways analysis revealed glutamate receptor signaling, CREB signaling, dopamine- DARPP32 feedback in cAMP signaling, fMLP signaling in neutrophils, and synaptic long term potentiation pathway playing critical role in AD pathophysiology and having correlation with electrophysiological dysfunction.

Effect of the combined administration of vitamin-E and 5-aminosalicylic acid on acrylamide-induced testicular toxicity.

OBJECTIVES: This study aimed to evaluate the comparative protective antioxidant effect of 5-aminosalicylic acid (5-ASA) and vitamin-E against acrylamide (ACR)-induced testicular toxicity in rats. METHODS: This study was performed at King Fahad Medical Research Centre, Jeddah, KSA. A total of 49 adult Wistar rats (250 ± 20 gm) that were 60 days old were divided into seven groups (control, ACR alone, ACR + 5-ASA, ACR + Vitamin-E, ACR + 5-ASA + Vitamin-E, Vitamin-E alone, 5-ASA alone). Acrylamide [45 mg/kg (bw)/day] and vitamin-E [200 mg/kg (bw)/day] were gavaged orally, and 5-ASA [25 mg/kg (bw)/day] were injected intra-peritoneally for five consecutive days after one day of observation. Rats were sacrificed by cervical dislocation. Histopathology of the testis, enzyme linked immunosorbent assay (ELISA) of testosterone, the lactate dehydrogenase (LDH) assay and a caudal sperm count were performed. RESULTS: Rats treated with ACR showed signs of aggression and rough coats, with reduced food and water intake. ACR treated rats showed histopathological changes in the form of a sloughed seminiferous epithelium in the tubular lumen with no multinucleated giant cells. Shrinkage of seminiferous tubules with widening of the interstitial space was also observed with atrophy and the shedding of normal mucosa. Our results indicated that maximum protection was conveyed by the combined antioxidant effect of vitamin-E and 5-ASA on testicular histopathology. CONCLUSION: We conclude that acrylamide-induced degeneration of seminiferous tubules can be partially reversed by the administration of 5-ASA and vitamin-E and suggests restricting exposure to ACR.

Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats.

OBJECTIVES: To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out.  Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats.  Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E.

Cadaver dissection: A positive experience among Saudi female medical students.

OBJECTIVES: The objectives of this study were to evaluate first-year undergraduate female preclinical medical students' behaviours, experiences, and emotions regarding cadaver dissection. The evaluation was performed during the 2013-2014 academic year, six months after starting the dissection course. METHODS: A 14-statement questionnaire was administered to a group of 200 first-year undergraduate female preclinical medical students at the College of Medicine, King Abdulaziz University (KAU), KSA. For each question, the students responded by selecting either "Yes," "No," or "Undecided." Statistical analysis was performed after collection of the questionnaire responses. RESULTS: The results showed that 90% of the students agreed that cadaver dissection provided the best and shortest way to study anatomy. Also, 89% were excited during their first visit to the dissection room, and 79% were satisfied that dissection of a cadaver was ethically acceptable. The majority of the students (over 90%) declared that dissection of a cadaver was one of the best teaching strategies for facilitating the acquisition of knowledge of human anatomy. CONCLUSIONS: Saudi female first-year undergraduate medical students at KAU showed positive attitudes toward cadaver dissection during their human anatomy course. This study prompts the need for exploration of gender differences in perception regarding cadaver dissection.

Organohalogenated contaminants in type 2 diabetic serum from Jeddah, Saudi Arabia.

Most of the organohalogenated contaminants (OHCs) have high environmental stability and are lipophilic in nature, thus bioaccumulate through the various routes e.g., inhalation, dermal contact and food intake. Human exposure to these OHCs can induce adverse health effects. Studies on the occurrence of OHCs in human samples from Saudi Arabia are scarce. Therefore, this study aimed at providing preliminary insight on the occurrence of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated biphenyl ethers (PBDEs) in diabetic and non-diabetic donors from KSA. Serum samples were collected from type 2 diabetic patients (n = 40) and control donors (n = 20) to study the impact of OHCs on their health. For the first time we studied the difference of Æ©OHCs in type 2 diabetic and control participants. The order of obtained results was Æ©OCPs (35-650 ng/g lw)> Æ©PCBs (15-90 ng/g lw)> Æ©PBDEs (1.5-68 ng/g lw). The major contributors were p,p'-DDE (median 44 ng/g lw), PCB 153 (2.3 ng/g lw), PCB 138 (2.1 ng/g lw), BDE 153 (1.2 ng/g lw) and BDE 47 (0.85 ng/g lw). Exposure to different OHCs between male and female donors was not significantly different (p > 0.05). However, Æ©PCBs and Æ©OHCs were significantly higher (p < 0.05) in diabetic donors than those of control group. We computed significantly positive correlations (p < 0.05) among different OHCs and between OHCs and age factor. The current study highlights the presence of different OHCs in humans from Jeddah, KSA. This is a preliminary study based on small sample size but our results suggested that detailed studies are required to understand the sources of these pollutants and their impact on human health.