The Discovery of Putative Small Molecules via Ligand-based Pharmacophore Modelling Targeting Human Tau Protein for an Effective Treatment of Parkinson’s Disease

@#Introduction: The human tau protein is a key protein involved in various neurodegenerative disease (NDs) including Parkinson’s disease (PD). The protein has high tendency to aggregate into oligomers, subsequently generating insoluble mass in the brain. Symptoms of PD include tremor, bradykinesia, rigidity, and postural instability. Currently drugs for PD treatment are only symptom-targeted while effective therapeutic treatment remains a challenge. The objective of this study is to identify novel promising anti-PD drugs using computational techniques. Method: ligand-based (LB) receptor modelling was conducted using LigandScout, validated and subjected to Glide XP docking, virtual screening, ADMET, and molecular dynamics predictions. Results: The adopted LB modelling generated pharmacophoric features of 5 hydrogen bond donors, 1 aromatic rings, and 7 hydrogen bond acceptors. The validation result indicated GH score of 0.73 and EF of 36.30 as validation protocols, probing it to be an ideal model. Using 3D query of the modelling a total of 192 compounds were retrieved from interbioscreen database containing 70,436 natural compounds. Interestingly, ligands 1, 2, 3, 4 and 5 orderly indicated higher binding affinities to the receptor with Glide XP docking of -7.451, -7.368, -7.101, -6.878, and -6.789 compared to a clinical drug Anle138b with -4.552 kcal/mol respectively. Furthermore, molecular dynamics and pkCSM pharmacokinetics demonstrated ligands 1, 2, & 4 having better stability and low toxicity profiles compared to the reference. Conclusion: In summary, the study pave way for discovery of small molecules that could be recommended as adjuvant /single candidate as ant-PD candidates upon further translational study.

Serum Hepcidin Level among Chronic Kidney Disease Subjects Accessing Healthcare in Braithwaite Memorial Specialist Hospital Port Harcourt

Hepcidin is the major controller of systemic iron homeostasis and the role of the kidney in regulating hepcidin level is vital in the whole process of iron and hepcidin relationship. This study was aimed at evaluating serum Hepcidin level among Chronic Kidney Disease subjects accessing Healthcare in BMSH Port Harcourt Metropolis. The study was conducted in Port Harcourt at Braithwaite Memorial Specialist Hospital among 55 CKD subjects and 33 normal individuals making up the control group. Subjects were selected randomly and 5mls of blood was collected in plain bottle using venipuncture technique for laboratory assessment of hepcidin. Hepcidin was assayed using competitive ELISA method. T-test was used to compare the mean difference oh hepcidin between both groups. Result showed that there was a significant difference in hepcidin level between CKD and control groups; 52.00±36.00ng/ml for CKD group and 16.00±13.00ng/ml for control group, p<0.05. This study has shown that CKD has a significant impact in hepcidin level blood and consequently on iron regulation

Phytochemical Screening and Antimicrobial Studies of Stem and Root Extracts of Crateva adansonii

Aim: This study was designed to explore the phytochemical and antimicrobial screening of the stem and root extracts of Crateva adansonii. Place and Duration of Study: Sample: Iyesi village, Ota, Ogun State, and analysis carried out at Department of Chemistry and Department of Biological Sciences, Covenant University, Ota, Ogun State and for duration of three months (November 2016 to February 2017). Methodology: Standard universal procedures were employed for both phytochemical and antimicrobial analysis. Results: The result obtained from the stem and root extracts of Crateva adansonii indicated the presence of flavonoids, terpenoids, alkaloids, and cardiac glycosides. Root extract was found to be richer in source of phytochemicals when compared to the stem extract. However, the highest antibacterial activity was observed against selected bacteria by both stem and root extracts. The potency of the root extract was observed to be higher than the stem extract against Bacillus cereus, Staphylococcus aureus, Aspergillus niger and Serratia spp. Conclusion: The preliminary studies on the stem and the root of Crateva adansonii extracts revealed their antimicrobial potential which could be further investigated for global utilization in pharmaceutical treatment, natural therapies, food preservation and cosmetic applications.

Effect of highly active antiretroviral therapy [HAART] on body mass index [BMI], pcv, cd4+t cell count and albumin of HIV seropositive women in Nigeria

To establish the effect of highly active antiretroviral therapy [HAART] on some parameters of HIV seropositive women in their reproductive ages in both follicular and luteal phases of their menstrual cycle Prospective and targeted for a particular group of HIV sero-positive women in a tertiary institution in Midwestern Nigeria. University of Benin Teaching Hospital, Edo State, Nigeria. A target population of 100 HIV seropositive women of reproductive age [range 18-40 years, mean = 29 years] and 50 seronegative women of same age group [mean = 32 years] as control were recruited before the commencement of HAART therapy. All subjects and controls were monitored at three-monthly intervals for a period of nine months. The parameters that were examined included body mass index [BMI], CD4[+] T cell count, packed cell volume [PCV] and albumin in both follicular and luteal phases of their menstrual cycles. HAART significantly [p < 0.05] raised BMI, CD4[+/] T cell count, PCV and albumin in both phases of the study. These parameters were initially significantly decreased by HIV infection. HAART has demonstrated great promise in the management of HIV seropositive women. More studies are encouraged to determine how HAART can maintain its current high level of efficiency in these women

Traumatic injuries in pregnant women: a case of motor vehicle accident for "ground round" discussion

The main objective for introducing this case study is to create a platform from which the importance of road traffic related injuries and traumas can be emphasized and discussed within and across various fields of investigation. The long term goal is to entice public campaign around unmet needs for higher road safety measures to reduce primary, secondary, and tertiary risks of injuries and traumas. a 28-year-old pregnant woman with a 16-week gestational age fetus was involved in a road car crash resulting in multiple traumas. Evaluation and treatment was initiated in the local Urgent Care Unit and continued in the emergency department and operation room. Patient underwent the following procedures: laparotomy, diverting colostomy, terminating pregnancy, right calcaneal traction and long leg splint, as well as multiple irrigation-debridements. Finally, the wound was left open and the patient was admitted to Intensive Care Unit. We hope that the introduction of this case for a "Ground Round" discussion will stir up a comprehensive discussion regarding the injury and trauma related preventive measures as well as treatment approaches in cases involving pregnant women in car accidents, and will bring about a holistic overview of this issue by the experts in various fields

The Prevalence and Antibiogram of Esherichia Coli from Clinical Specimens of Superficial Wounds; High Vagina and Antral Washouts in University of Benin Teaching Hospital; Benin City; Edo State

This study seeks to determine the prevalence of recovery of Escherichia coli from clinical specimens of superficial wounds; high vagina and antral washouts. This study which was prospective and cross-sectional involved six hundred and sixty eight (668) participants who were patients seen at the various facilities in the hospital. Males were two hundred and forty (35.9) Females were two hundred and twenty eight (34.3) while children were two hundred (29.9). Specimens of wounds; aspirates and high vagina were cultured on chocolate; blood and McConkey and Eosin methylene blue agars. Specimens on blood agar were incubated both aerobically and anaerobically for 24hrs. Isolates were identified by their colonial morphology and biochemical reactions and tested for sensitivity. Escherichia coli isolates demonstrated strong resistance to some of the antibiotics while they showed moderate sensitivity to ceftazidime; ofloxacin; clarithomycin and amoxicillin clavulanate. The increasing resistance of Escherichia coli to the commonly used antibiotics in the community is a cause of concern; and measures were suggested for effective resistance control

Relationship between placental alkaline phosphatase activity and cord blood glucose, albumin and neonatal birth weight at term

It has been observed that placental alkaline phosphatase (PAP) activity progressively rises as pregnancy advances, possibly, because of its increasing synthesis by placental tissue. The present investigation therefore, examines the relationship between placental alkaline phosphatase activity and the biochemical indices of foetal nutrition (cord blood glucose, albumin) and growth (neonatal birth weight). Placental and umbilical cord blood samples were collected from one hundred and five deliveries and prepared for both, placental alkaline phosphatase assay, and glucose and albumin estimations using standard procedures. The birth weights of the neonates at term were taken and recorded. Correlation analyses of the data obtained show significant positive relationships between PAP and cord blood glucose (r² = 0.86, p<0.05), albumin (r² = 0.71, p < 0.05) and birth weight (r² = 0.68, p<0.05), but no significant relationship with gestational age. PAP may be essential in nutrient mobilization to the foetus. However, further studies involving more subjects and an intrauterine growth retardation control group (IUGR) are required to fully document the present report.

Se ha observado que la actividad de la fosfatasa alcalina placentaria (PAP) aumenta progresivamente a medida que avanza el embarazo, posiblemente debido al incremento de su síntesis a través del tejido placentario. Por lo tanto, la presente investigación estudia la relación entre la actividad de la fosfatasa alcalina placentaria y los índices bioquímicos de la nutrición fetal (glucosa sanguínea de cordón umbilical, albúmina) y crecimiento (peso neonatal). Se recolectaron muestran placentarias y sanguíneas provenientes de 105 partos y preparadas tanto para el ensayo de fosfatasa alcalina placentaria como para estimaciones de glucosa y albúmina utilizando los procedimientos estándar. Se tomaron y registraron los pesos de los recién nacidos a término. El análisis y la correlación de los datos obtenidos muestran una relación significativamente positiva entre el PAP y la glucosa en sangre del cordón umbilical (r² = 0,86, P < 0,05), albúmina (r² = 0,71, P < 0,05) y peso al nacer (r² = 0,68, P < 0,05), pero no relación significativa con la edad gestacional. PAP puede ser esencial en la movilización de nutrientes para el feto. Sin embargo, se requieren estudios posteriores que incluyan más sujetos y un grupo control con retardo en el crecimiento intrauterino, para completar el presente reporte.