Prediction of the 10-Year Risk of Cardiovascular Diseases Among Patients in Primary Health Care Centers in Eastern Province, Saudi Arabia.

Background Cardiovascular diseases (CVDs), primarily coronary artery disease (CAD) and stroke, stand as a leading cause of morbidity and mortality globally. Our objective was to predict the 10-year risk of CVD in the Eastern Province of Saudi Arabia. Methods This cross-sectional study was conducted in eight randomly selected primary healthcare centers using cluster sampling based on geographical location in Saudi Arabia's Eastern Province, specifically the Al-Ahsa region. The study aimed to assess the risk of developing CVD in the next 10 years among patients with at least one cardiovascular risk factor. Patients visiting the healthcare centers for checkups filled out the Framingham Cardiovascular Disease (10-year risk) score questionnaire. Results Of the 665 patients enrolled, 54.4% were female. The average age of the patients was 54.2 (SD 8.48) years. The overall average Framingham Risk Score (FRS) percentage was 19.2% (SD 15.4%). In terms of 10-year CVD risk, 34.6% of the patients were at high risk, 31.6% were at moderate risk, and 33.8% were considered low-risk individuals. Factors associated with a higher risk of CVD included older age, male gender, lower educational attainment, smoking, normal BMI, stage 2 hypertension, and diagnoses of hypertension, diabetes, and obesity. Conclusion Utilizing the FRS, it was determined that older men with lower educational levels had a higher 10-year risk of developing CVD. Furthermore, CVD risk factors such as diabetes, hypertension, obesity, and smoking were associated with individuals' CVD risk. Considering the ease of use and applicability of the FRS in daily clinical practice, as well as its potential to identify high-risk individuals, a more systematic implementation in general practice appears to be warranted.

Inhibition of hepatitis B virus activities by Rhazya stricta­derived acacetin and acetyl­ß­carboline.

Hepatitis B virus (HBV) causes acute and chronic liver diseases, leading to cirrhosis and hepatocellular carcinoma. Although direct-acting nucleoside analogs, such as lamivudine (LAM), adefovir and famciclovir, are available, emergence of drug-resistance due to mutations in HBV polymerase (POL) restricts their further use. Alternatively, numerous plant products and compounds isolated from plants have been reported to confer anti-HBV efficacies without any sign of resistance in vitro or in vivo. As, flavonoids and alkaloids are the most widely reported antivirals, the anti-HBV activities of the flavonoid acacetin (ACT) and the alkaloid acetyl-ß-carboline (ABC) from the aerial parts of Rhazya stricta were assessed in the present study. Both compounds were isolated from the ethyl acetate fraction of the total methanol extract using column and thin-layer chromatography, and their structures were determined by nuclear magnetic resonance spectroscopy (NMR). Both compounds (at 6.25-50 µg/ml) showed a lack of hepatocytotoxicity in cultured HepG2.2.15 cells. Anti-HBV ELISA [hepatitis B surface antigen (HBsAg) and hepatitis B pre-core-antigen (HBeAg)] on HepG.2.2.15 cells following treatment with selected concentrations (12.5, 25 and 50 µg/ml) of both compounds showed dose- and time-dependent anti-HBV activities. Compared with those in the untreated control at day 5, ACT and ABC (25 µg/ml, each) maximally inhibited HBsAg synthesis by 43.4 and 48.7%, respectively, whilst also maximally inhibiting HBeAg synthesis by 41.2 and 44.2%, respectively, in HepG2.2.15 cells. Comparatively, quercetin and LAM (standards; POL inhibitors) suppressed HBsAg (63.9 and 60.2%, respectively) and HBeAg synthesis (87.1 and 84.3%, respectively) by larger magnitudes. Molecular docking of ACT and ABC structures performed in AutoDock revealed their hydrogen bonding with the drug-sensitive [wild-type (wt)-POL] 'Tyr-Met-Asp-Asp' motif, in addition to the drug-resistant [mutant (mut)-POL] 'Tyr-Ile-Asp-Asp' motif residues of the polymerase binding-pocket, along with other electrostatic interactions. In the wt-POL complex, both compounds showed good interactions with Asp205. In the mut-POL complex, ACT and ABC interacted with Tyr203-Asp205 and Tyr203-Ile204, respectively. In conclusion, to the best of our knowledge, the present study demonstrates anti-HBV efficacies of ACT and ABC in vitro for the first time, endorsed by in silico data. However, further molecular and pharmacological studies are required to validate their pre-clinical therapeutic potential.

Impact of Ramadan Fasting on the Severity of Symptoms Among a Cohort of Patients With Gastroesophageal Reflux Disease (GERD).

INTRODUCTION:  Gastroesophageal reflux disease (GERD) is a condition caused by the reflux of stomach contents into the esophagus. Heartburn, chest discomfort, and regurgitation are the main symptoms. Medications, surgical procedures, and lifestyle modification are considered treatment options. Fasting is believed to be one of the lifestyle modifications that helps minimize GERD symptoms. Muslims abstain from eating, drinking, and smoking from dawn until dusk. The objectives of our study were to investigate the relationship between fasting and GERD symptoms and evaluate how fasting affects GERD symptoms in Saudi Arabia. METHODOLOGY: This was a longitudinal study that selected GERD patients for its consecutive sampling. The patients answered the questionnaires at two separate times: once during Ramadan and once after Ramadan. A validated gastroesophageal reflux disease health-related quality of life (GERD-HRQL) self-administered survey was used. RESULT: After Ramadan, heartburn symptoms significantly decreased, particularly when lying down. Overall, the 45-point heartburn score decreased from 17.9 during Ramadan to 14.3 thereafter. The regurgitation score decreased from 12.3 during Ramadan to 9.9 after fasting, with statistical significance (P = .049). Although satisfaction was much higher after Ramadan (17% vs. 15.1%), there was no statistical significance (P = .422), and 45.3% of the patients were satisfied with their health state during Ramadan compared to 34% after Ramadan. There was no relationship between the severity of GERD symptoms before or after fasting and the type of food, the timing of eating, or the amount of food consumed. CONCLUSION: The results suggested that Ramadan fasting may improve GERD symptoms. However, more studies are required to validate these results and comprehend the underlying mechanisms.

Upper gastrointestinal tract involvement in the management of bariatric patients in the Kingdom of Saudi Arabia.

BACKGROUND: Preoperative esophagogastroduodenoscopy (EGD) may affect the management of bariatric patients although this is not consistent universally. The present prospective study evaluated the effect of preoperative EGD findings in obese Saudi patients, including upper digestive symptoms (UDS) and comorbidities, on their planned surgery. METHODS: From January 2018 to May 2019, we conducted a 4-center retrospective observational study to evaluate the endoscopic findings among Saudi patients aged 18-65 years with a body mass index (BMI) >40 kg/m2. Preoperative data included UDS, comorbidities, Helicobacter pylori (H. pylori) infection assessed during a histopathological examination, and EGD findings. RESULTS: 717 patients underwent EGDs, and 432 underwent bariatric surgery. The mean BMI was 44.3±6.3 kg/m2, and the mean age was 27.8±11.8 years. The overall UDS prevalence was 49%, with the most frequent being gastroesophageal reflux disease 54% (387/717), followed by dyspepsia 44% (315/717). H. pylori infection was detected in 287/672 (42.4%) patients. The total percentage of patients with normal EGD was 36% (258/717). A delayed bariatric procedure was performed in 15% of the patients for the following reasons: 2.3% had large polyps of >1 cm (either hyperplastic or cystic polyps); 1.62% had esophagitis grade C and D based on the Los Angeles classification; 0.7% had Barrett's esophagus; and 5.7% had peptic ulcer disease. CONCLUSIONS: Our findings confirmed that obesity carries a profound health burden with a significant impact on health expenditures. Routine preoperative EGD in the obese Saudi population appears to be mandatory to identify factors that may change, delay, or postpone the bariatric procedure.

Oncoglabrinol C, a new flavan from Oncocalyx glabratus protects endothelial cells against oxidative stress and apoptosis, and modulates hepatic CYP3A4 activity.

Active herbal or natural compounds have high chemical diversity and specificity than synthetic drugs. Recently, we have validated the hypoglycemic salutation of Oncocalyx glabratus in rodent model, and demonstrated the activation of PPARα/γ by its newly ioslated flavan derivative Oncoglabrinol C (5,3'-Dihydroxyflavan 7-4'-O-digallate) in liver cells (HepG2). Here we evaluated the potential of Oncoglabrinol C against Dichlorofluorescin (DCFH) and Methylglyoxal (MGO) induced endothelial cells (HUVEC) oxidative and apoptotic damage, including activation of PXR-mediated hepatic CYP3A4. Our MTT assay showed protection of ~57% and ~63.5% HUVEC cells by 10 and 20 µg/ml doses of Oncoglabrinol C, respectively through attenuating DCFH triggered free-radicals. Also, the two doses effectively protected ~53% and ~65.5% cells, respectively by reversing MGO toxicity. In DCFH and MGO treated cells, Oncoglabrinol C (20 µg/ml) effectively downregulated caspase 3/7 activity by ~33% and ~43.5%, respectively. Moreover, in reporter gene (dual-luciferase) assay, Oncoglabrinol C (20 µg/ml) moderately activated hepatic CYP3A4. Molecular docking of Oncoglabrinol C indicated its strong interactions with cellular caspase 3/7, PPARα/γ and PXR proteins, which supported its anti-apoptotic (antagonistic) as well as pro-hypoglycemic and PXR/CYP activating (agonistic) activities. Taken together, our findings demonstrated the potential of Oncoglabrinol C in reversing the endothelial oxidative and apoptotic damage as well as in the activation of hepatic CYP3A4. This warrants further evaluations of Oncoglabrinol C and related compounds towards developing effective and safe drugs against diabetes associated cardiovascular disorders.

Functional implications of pH-induced conformational changes in the Sphingosine kinase 1.

Sphingosine kinase 1 (SphK1) catalyzes the conversion of sphingosine to sphingosine-1-phosphate that acts as a bioactive signalling molecule, and regulates various cellular processes including lymphocyte trafficking, angiogenesis and response to apoptotic stimuli. Abnormal expression of SphK1 has been observed in a wide range of cancers highlighting their role in tumour growth and metastasis. This enzyme also plays a critical role in metabolic and inflammatory diseases, including pulmonary fibrosis, diabetic neuropathy and Alzheimer's disease. In the present study, we have investigated the structural and conformational changes in SphK1 at varying pH using various spectroscopic techniques. Consistent results were observed with the function of SphK1 at corresponding pH values. SphK1 maintains its secondary and tertiary structure in the pH range of 7.5-10.0. However, protein aggregation was observed in the acidic pH range (4.0-6.5). At pH 2.0, the SphK1 exists in the molten-globule state. Kinase assay also shows that SphK1 activity was optimal in the pH range of 7.5-8.5. To complement in vitro results, we have performed 100 ns molecular dynamics simulation to examine the effect of pH on the structural stability of SphK1 at molecular level. SphK1 maintains its native conformation in the alkaline pH range with some residual fluctuations detected at acidic pH. A considerable correlation was noticed between spectroscopic, enzymatic activity and MD simulation studies. pH dependent structural changes can be further implicated to understand its association with disease condition, and cellular homeostasis with respect to protein function under variable pH conditions.

Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain.

Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through N-methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood-brain barrier (BBB) junction. GU, also modifies the characteristics of tight junction proteins (occludin and claudin) at the site of BBB by depolarizing the enzyme, protein tyrosine phosphatase that manifests its usefulness for passive delivery of nanocarriers to the brain. GU, thus, represents itself as an ideal ligand for the surface decoration of nanocarriers to successfully administer them across the brain via receptor-mediated drug delivery pathway. Hence, we have employed here, in-silico approaches to identify the potential GU-like molecules, as appropriate ligand(s) for surface engineering of nanoconstruct with the purpose of attaining targeted drug delivery to the brain. Structure-based virtual screening methods was used to filter PubChem database for the identification of bioactive compounds with >95% structure similarity with GU. We have further screened the compounds against NMDAR using molecular docking approach. Top hits were selected based on their high binding affinities and selectivity towards NMDAR, and their binding pattern was analysed in detail. Finally, all atom molecular dynamics simulation for 100 ns was carried out on free NMDAR and in-presence of the selected GU-like compound, gamma-l-glutamyl-l-cysteine to evaluate complex stability and structural dynamics. In conclusion, gamma-l-glutamyl-l-cysteine may act as potential binding partner of NMDAR which can further be evaluated in drug delivery system to brain across the BBB.Communicated by Ramaswamy H. Sarma.

The anti-hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera.

Although the approved hepatitis B virus (HBV)-polymerase inhibitors (e.g., lamivudine) often lead to drug-resistance, several natural products have shown promising efficacies. Though Aloe vera (AV) gel and its constituents are shown inhibitors of many viruses, their anti-HBV activity still remains elusive. We therefore, tested the anti-HBV potential of AV extract and its anthraquinones in hepatoma cells, including molecular docking, high-performance thin layer chromatography (HPTLC), and cytochrome P450 (CYP3A4) activation analyses. Our anti-HBV assays (HBsAg/HBeAg Elisa) showed maximal inhibition of viral antigens production by aloe-emodin (~83%) > chrysophanol (~62%) > aloin B (~61%) > AV extract (~37%) in HepG2.2.15 cells. Interestingly, the effect of aloe-emodin was comparable with lamivudine (~86%). Moreover, sequential treatment with lamivudine (pulse) followed by aloe-emodin (chase) enhanced the efficacy of monotherapy by ~12%. Docking (AutoDock Vina) of the anthraquinones indicated strong interactions with HBV-polymerase residues that formed stable complexes with high Gibbs's free energy. Further, identification of aloe-emodin and aloin B by validated HPTLC in AV extract strongly endorsed its anti-HBV potential. In addition, our luciferase-reporter gene assay of transfected HepG2 cells showed moderate induction of CYP3A4 by aloe-emodin. In conclusion, this is the first report on anti-HBV potential of AV-derived anthraquinones, possibly via HBV-polymerase inhibition. Of these, although aloin B exhibits novel antiviral effect, aloe-emodin appears as the most promising anti-HBV natural drug with CYP3A4 activating property towards its enhanced therapeutic efficacy.

Comparison of peri-implant clinical and radiographic status around short (6 mm in length) dental implants placed in cigarette-smokers and never-smokers: Six-year follow-up results.

BACKGROUND: It is hypothesized that peri-implant clinical and radiographic inflammatory parameters (probing depth [PD], bleeding on probing [BOP] and plaque index [PI]; and radiographic (crestal bone loss [CBL]) are worse among cigarette-smokers (CS) compared with never-smokers (NS) with short implants. PURPOSE: The present 6-year follow-up retrospective study compared the peri-implant clinical and radiographic parameters in CS and NS with short dental implants (6 mm in length). MATERIALS AND METHODS: Fifty-six male individuals were included. These individuals divided into 2 groups as follows: (a) Group-1: 29 self-reported systemically healthy CS with 48 short-implants; and (b) Group-2: 27 self-reported systemically healthy NS with 43 short implants. Peri-implant PD, PI, BOP, and CBL were measured. Group comparisons were done using the Kruskal-Wallis test and sample size was estimated. Level of significance was set at P values < .05. RESULTS: In groups 1 and 2, the follow-up durations were 6.2 ± 0.1 years and 6.1 ± 0.3 years, respectively. A cigarette smoking history of 8.9 ± 3.6 pack years was reported by individuals in Group-1. At follow-up, scores of peri-implant PD, BOP, PI, and mesial and distal CBL were comparable around short implants in both groups. CONCLUSION: Under strict oral hygiene maintenance protocols, short dental implants can remain functionally stable in CS in a manner similar to NS.

Chiral HPLC Separation and Modeling of Four Stereomers of DL-Leucine-DL-Tryptophan Dipeptide on Amylose Chiral Column.

Chiral high-performance liquid chromatography (HPLC) separation and modeling of four stereomers of DL-leucine-tryptophan DL-dipeptide on AmyCoat-RP column are described. The mobile phase applied was ammonium acetate (10 mM)-methanol-acetonitrile (50:5:45, v/v). The flow rate of the mobile phases was 0.8 mL/min with UV detection at 230 nm. The values of retention factors for LL-, DD-, DL-, and LD- stereomers were 2.25, 3.60, 5.00, and 6.50, respectively. The values of separation and resolution factors were 1.60, 1.39, and 1.30 and 7.76, 8.05, and 7.19. The limits of detection and quantitation were ranging from 1.0-2.3 and 5.6-14.0 µg/mL. The simulation studies established the elution orders and the mechanism of chiral recognition. It was seen that π-π connections and hydrogen bondings were the main forces for enantiomeric resolution. The reported chiral HPLC method may be applied for the enantiomeric separation of DL-leucine-DL-tryptophan in unknown matrices. Chirality 28:642-648, 2016. © 2016 Wiley Periodicals, Inc.