Study on development and tissue permeation of different formulations of Fasudil.

OBJECTIVE: The study is intended to formulate Fasudil loaded vesicular system for application in the management of angina. MATERIALS AND METHODS: Fasudil was made into a complex with phospholipid, and other different formulations were made, including Fasudil solution, liposomal form, and Fasudil loaded into the gel. A drug characterization study was conducted and noted. Drug release was quantified and analyzed and, finally, inoculated in Sprague-Dawley rats. These rats underwent anginal induction, and each formulation's effect on angina was evaluated. RESULTS: Drug solution (F-Phos) and F-Phos-Lipo (liposomal dispersion form of the drug) have shown that more than half percent of them have been released within 1.5 hours, and the rapid release occurred from liposomal dispersion in the first hour. The study determined the viscosity of the different formulations, which was significantly (p<0.05) higher than the theoretical sum of the viscosity of each formulation. The study found that the F-Phos-Lipo+P-407HMS formulation is the most effective as its application has the minimum infarct area percentage compared to the other formulations and can also reduce creatine kinase levels significantly as compared to the different formulations (p<0.05). CONCLUSIONS: The study concluded that the typical gel formulation (liposomal Fasudil dispersed in hydroxypropyl methylcellulose solution, which is added to blank poloxamer 407) had been shown to have significantly anti-anginal properties, including easy administration, its application on the infarct area percentage and subsequently its pharmacological effect on the cardiac tissue.

Significance of Orlistat in management of dyslipidemia, systolic blood pressure and body mass index.

OBJECTIVE: The current study intends to find out the efficacy of Orlistat in the management of hyperlipidemia, Systolic Blood Pressure (SBP) and Body Mass Index (BMI). MATERIALS AND METHODS: This retrospective study has evaluated the lipid profiles of the patients, who have been using metformin therapy for Type 2 diabetes. The study has obtained data regarding the parameters like triglyceride, Total cholesterol (TC), LDL cholesterol, HDL cholesterol and LDL/HDL ratio, systolic blood pressure and Body Mass Index (BMI). Random distribution of patients was done into placebo and Orlistat groups. The placebo group received only metformin, and patients in the Orlistat group received Orlistat along with metformin. After 24 weeks, the follow-up study was done, and statistical analysis was conducted. RESULTS: The study found that the Orlistat group has significant improvement (p<0.05) more improvement in LDL cholesterol, HDL cholesterol, Total cholesterol, LDL/HDL Ratio and Triglycerides, while BMI and systolic blood pressure did not show a significant difference between placebo and Orlistat group. CONCLUSIONS: This study has concluded that Orlistat can be used for significant improvement in lipid profile. The study also found that Orlistat may not have a significant effect on reducing BMI and blood pressure without adequate lifestyle modification.

Prevalence of cardiovascular disease and osteoarthritis in obese population of Hail region, Saudi Arabia.

OBJECTIVE: The aim of the study was to analyze if there was a link between chronic diseases, like cardiovascular disease (CVD) and osteoarthritis (OA), and obesity in the population of Saudi Arabia's Hail region. MATERIALS AND METHODS: The study was conducted over 12 months using an observational cross-sectional survey on 172 patients from five clinics in Hail, Saudi Arabia. A total of 172 individuals with obesity (BMI ≥ 30) finally participated in this research. The study evaluated sociodemographic variables via an electronic questionnaire with voluntary participation. RESULTS: The study found a 76% prevalence of joint pain and 77.9% prevalence of cardiovascular abnormalities. Patients with CVD were older (58±23 vs. 56±12 years) than those with OA. CVD cases were found in 42 (31.3%) males and 92 (68.7%) females, whereas OA cases were recognized in 24 (18.5%) males and 106 (81.5%) females. The occurrence of various CVDs among our participants was 43 (32%) for high cholesterol, 64 (48%) for hypertension, and 27 for both high cholesterol and hypertension (20%). Definite osteophytes were found in 28 of 24 male knees (14 right and 14 left knees) and 175 of 106 female knees (88 right knees and 87 left knees). CONCLUSIONS: The prevalence of obesity in the Hail region has continued to be a risk factor for CVD and OA in 2019 and 2020. The Saudi population has shown a higher prevalence of radiographic evidence of OA of the knee and associated symptoms than western civilizations, and preventive interventions are desperately needed in order to minimize overweight and obesity.

Comparative analysis between mono approach and multi approaches in managing T2DM: a survey-based study.

OBJECTIVE: The aim of the study was to analytically compare the therapeutic effect of the addition of diet modification and regular exercise to oral agents. MATERIALS AND METHODS: This cross-sectional study surveyed 1248 participants via online and offline modes by employing a questionnaire about an individual's management of diabetes. Group 1 patients follow Single Approach Management for Type 2 Diabetes Mellitus (T2DM), while Group 2 and Group 3 patients follow Multi-Approach Management for T2DM. Based on the answers, the participants were classified into three groups. The diagnostic criteria of Diabetes Mellitus Type-2 in this study were done by determining morning Fasting Blood Sugar (FBS) and glycated Hemoglobin (HbA1c). RESULTS: The current study found 656 single oral agent users and 592 combination regimens users among all the study participants. The study also found that, among all participants, 511 patients were on mild to moderate diet modification while 325 patients were on moderate to severe diet modification. The study also noted that 232 males and 215 females took Complementary and Alternative Medicines (CAM). Of 447 patients, 12 showed menstrual abnormalities (2.6%), and 18 had mild diarrhoea (4%). The study also found that there is a vital significance of lowering FBS and HbA1c with the management strategies (p=0.000). The study showed a strong association between group 3 and improved FBS and HbA1c (p=0.000). CONCLUSIONS: This study reveals that diet modification and regular exercise improve FBS and HbA1c levels significantly. Hence, diet modification and exercise can be added as adjuvants and should be incorporated into the management guidelines of T2DM.

Stroke prevention: knowledge of the general population in Riyadh Region, Saudi Arabia.

OBJECTIVE: Stroke is a medical emergency that may lead to permanent neurological damage, complications, and disability. It is the second leading cause of death worldwide and one of the main causes of adult-acquired disabilities. Stroke can be prevented by controlling modifiable risk factors and the early detection of stroke warning signs. The current study aimed to assess the knowledge of the general population in the Riyadh region of Saudi Arabia about stroke. MATERIALS AND METHODS: A cross-sectional and community-based design was employed in this study. The sample was calculated as 432. A pre-tested structured questionnaire was used to collect data. The data was analyzed by SPSS software, version 23. Descriptive statistics were used. The Chi-square test was employed to test differences between qualitative variables, and a p-value less than 0.05 was considered significant. RESULTS: Results showed that 26.6 % of the population had good knowledge about stroke. Population with average and poor knowledge were 50.5% and 22.9%, respectively. The level of stroke knowledge is related to age; the older population aged 45 and more acquired the highest level of knowledge (50%) compared to the other groups. Age group 35-44 years received the least level of stroke knowledge (19.9%). The school teaching had the highest level (40.0%) of stroke knowledge than the other occupations. CONCLUSIONS: Stroke knowledge among the population of Saudi Arabia is inadequate. The stroke knowledge is related to age and occupation.

Convergent validity, ceiling, and floor effects of the English-ISYQOL against established quality of life questionnaires (SRS-22r and SAQ) and curve angles in adolescents with idiopathic scoliosis.

Scoliosis significantly impacts Quality of Life (QOL). Current quality of life questionnaires for adolescents with idiopathic scoliosis (AIS) have limitations. A new questionnaire for measuring QOL in AIS called the Italian Spine Youth Quality of Life (ISYQOL) has been developed to address these limitations but the English translation has not yet been validated. To determine the ceiling and floor effects, and the convergent validity of the ISYQOL questionnaire against established QOL questionnaires and Cobb angle in AIS. One hundred consecutive females with AIS, (10-18 years old), treated non-operatively. The English translation of the ISYQOL was compared to the following established questionnaires: Scoliosis Research Society-22r and the Spinal Appearance Questionnaire. The participants were 100 females (13.89+/-1.8 years) with 28.75+/-13.9° curve angles. The convergent validity of the ISYQOL score (60.3+/-12.44) was supported by significant correlation with the SRS-22r total score, function, pain, self-image, and mental health scores (r = 0.70, 0.54, 0.57, 0.52 and 0.50, respectively), and with the SAQ general, waist, and expectations domains (r = -0.6. -.52, and -0.56, respectively). Correlation with the Cobb angle was (r = -.37)(see Table 1). No ceiling effect was observed in the ISYQOL. Ceiling effects were observed for the SRS-22r and the SAQ. The ISYQOL demonstrated evidence of convergent validity. This study supports its suitability for QOL research in AIS. ISYQOL appears more likely to detect changes in evaluative studies than the SRS- 22r and the SAQ.

Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.

Projection length stimulated by oxytocin is modulated by the inhibition of calcium signaling in U-87MG cells.

Neuropeptide oxytocin contributes to the regulation of glial cell morphology. The precise mechanisms, however, are not yet fully understood. In the present study, we have investigated whether an oxytocin-induced increase of intracellular calcium is required for cell extension in astrocyte-like U-87MG cells. Oxytocin (1 µM) significantly increased the length of the cell projections measured by the green-fluorescent protein labeled microtubule-associated protein after 48 h. The knockdown of oxytocin receptors (OXTR) in U-87MG cells prevented the elongation of the projections. Incubation of U-87MG cells in the presence of oxytocin, resulted in a significant increase of intracellular calcium, specifically blocked by the OXTR antagonist L-371,257. Both quercetin, which is a phosphoinositide 3-kinase inhibitor, and the phospholipase C inhibitor U-73122 reduced oxytocin-induced elevation of intracellular calcium concentration. Conversely, neither diltiazem, an L-type voltage-gated calcium channel blocker nor tetracaine, which is a blocker of the ryanodine receptors, showed an effect on intracellular calcium levels. Treatment of cells with quercetin, U-73122 and the voltage-gated calcium channel blockers cilnidipine, ω-agatoxin and mibefradil prevented the elongation of projections stimulated by oxytocin. Oxytocin treatment resulted in a significant increase in gene and protein expression of the scaffolding protein SHANK3. Our results clearly show that activation of OXTRs contributes to the elongation of cell projections in astrocyte-like U-87MG cells and that this effect is mediated by an extracellular calcium influx accompanied by an increase in scaffolding proteins expression.

Downregulation of Oxytocin Receptor Decreases the Length of Projections Stimulated by Retinoic Acid in the U-87MG Cells.

Oxytocin is a neuropeptide widely expressed in the brain. Oxytocin plays a role in both proliferation and differentiation of various cells. Previous studies have suggested that oxytocin could affect the morphology of neuronal cells, therefore the objective of the present study was to test whether (1) oxytocin receptor stimulation/inhibition by specific ligands may change cell morphology and gene expression of selected cytoskeletal proteins (2) oxytocin receptor silencing/knockdown may decrease the length of cell projections (3) oxytocin receptor knockdown may affect human glioblastoma U-87MG cell survival. We confirmed the stimulatory effect of retinoic acid (10 µM) and oxytocin (1 µM) on projection growth. The combination of retinoic acid (10 µM) and oxytocin receptor antagonist (L-371,257, 1 µM) decreased projections length. Contrary to our assumptions, oxytocin receptor silencing did not prevent stimulation of length of projection by retinoic acid. Retinoic acid's and oxytocin's stimulation of projections length was significantly blunted in U-87MG cells with oxytocin receptor knockdown. Cell viability was significantly decreased in U-87MG cells with oxytocin receptor knockdown. Significantly higher levels of mRNA for cytoskeletal proteins drebrin and vimentin were observed in response to oxytocin incubation for 48 h. The data obtained in the present study clearly show that oxytocin induces formation and elongation of cell projections in astrocyte-like U-87MG cells. The effect is mediated by oxytocin receptors and it is accompanied by an increase in gene expression of drebrin and vimentin. Thus, oxytocin receptor signaling, particularly in the glial cells, may play an important role in native cell life, differentiation processes, and tumor progression, as well.

A systematic review of the prevalence and incidence of prescribing errors with high-risk medicines in hospitals.

WHAT IS KNOWN: Prescribing errors are the most common type of error in the medication use process. However, there is a paucity of literature regarding the prevalence or incidence of prescribing errors in high-risk medicines (HRMs). HRMs bear a heightened risk of causing significant patient harm when they are used in error. OBJECTIVE: The aim of this research was to systematically investigate the literature regarding the prevalence and incidence of prescribing errors in HRMs in inpatient settings. METHODS: A search strategy was developed based on four categories of keywords: prescribing errors, HRMs, hospital inpatients, and prevalence or incidence. All keywords were searched for in Medline, Embase, Cochrane and the International Pharmaceutical Abstracts. The search was limited to English quantitative studies that reported the incidence or prevalence of prescribing errors by medical prescribers, whether they were seniors or juniors, since 1985. RESULTS: Of the 3507 records identified, nine studies met the review criteria. The most frequent denominator in the included studies was medication orders, in eight studies, ranged from 0·24 to 89·6 errors per 100 orders of HRMs. Two studies reported 107 and 218 errors per 100 admissions prescribed HRMs, and one study reported 27·2 errors per 100 prescriptions with a HRM. The incidence of prescribing errors could not be calculated. WHAT IS NEW AND CONCLUSION: The prevalence of prescribing errors in HRMs in the inpatient setting has a very wide range that reflects the different data collection methods used within the included studies. Future studies in prescribing errors should use standardized approaches to enable comparison.

Long-term exposure of human gingival fibroblasts to cigarette smoke condensate reduces cell growth by modulating Bax, caspase-3 and p53 expression.

BACKGROUND AND OBJECTIVE: Smoking cigarettes increases the risk of oral tissue damage leading to periodontal disease. Gingival fibroblasts, the predominant cell type inhabiting gingival connective tissue, play a critical role in remodeling and maintaining gingival structure. The objective of this study was to investigate the effect of long-term exposure to cigarette smoke on human gingival fibroblast survival/apoptosis and the molecular pathways involved in these cell responses. MATERIAL AND METHODS: Human gingival fibroblasts were extracted from healthy non-smokers and cultured in the presence of cigarette smoke condensate (CSC). At the end of each time point, cell growth was evaluated by means of MTT assay. Apoptotic and necrotic gene's expression was investigated by polymerase chain reaction array and by annexin V/propidium iodide staining and cell cycle assays. Western blot was used to investigate Bax and p53 proteins. These tests were supported by caspase 3 activity analyses. RESULTS: High levels of CSC decreased cell growth and deregulated cell cycle progression by increasing the G(0)/G(1) and reducing the S and G(2)/M phases of the gingival fibroblasts. Polymerase chain reaction arrays revealed the activation of several apoptotic genes by CSC, including TNF receptors, caspases, Bax and p53. This was supported by increases in the Bax and p53 protein levels as well as by an elevated activity of caspase-3 in the CSC-exposed cells. Immunofluorescence staining demonstrated that both Bax and caspase-3 displayed a cytosolic and mitochondrial distribution in the CSC-exposed gingival fibroblasts, compared to controls. The damaging effect of CSC on gingival fibroblast growth was also supported by the decrease in interleukin 6 and 8 secretion by the gingival fibroblasts. CONCLUSION: These results suggest that CSC may contribute to deregulating fibroblast functions. This can compromise fibroblast-epithelial cell interactions, which ultimately increases the risk of gingival tissue damage and the onset of periodontitis.

Association between FTO, MC4R, SLC30A8, and KCNQ1 gene variants and type 2 diabetes in Saudi population.

Recent genome wide association studies identified many loci in several genes that have been consistently associated with type 2 diabetes mellitus in various ethnic populations. Among the genes that were most strongly associated with diabetes were fat mass- and obesity-associated, melanocortin 4 receptor, solute carrier family 30 member 8 (SLC30A8), and a member of the potassium voltage-gated channels. In the present study, we examined the association between variants in fat mass- and obesity-associated [rs9939609 (A/T)], melanocortin 4 receptor [rs17782313 (C/T), and rs12970134 (A/G)], SLC30A8 [rs13266634 (C/T)], and a member of the potassium voltage-gated channels [rs2237892(C/T)] genes in diabetes patients from Saudi Arabia. Genotypes were determined using the TaqMan single-nucleotide polymorphism genotype analysis technique. Minor allele frequency of the 4 variants tested was comparable between type 2 diabetes cases and controls. We observed an association between allele variants of SLC30A8 [rs13266634 (C/T)] and type 2-diabetes (P = 0.04). The other single-nucleotide polymorphisms examined in this study showed moderate or no correlation with diabetes in Saudis. Our data indicate that the SLC30A8 polymorphisms are associated with type 2 diabetes in the Saudi population. There is no evidence supporting an association between variants in the fat mass- and obesity-associated and melanocortin 4 receptor, and a member of the potassium voltage-gated channels genes and type 2 diabetes in the Saudi population.

Association of BRCA2 variants with cardiovascular disease in Saudi Arabia.

Abnormalities in the breast cancer tumor suppressor genes (BRCA1 and BRCA2) are associated with breast and ovarian cancer. Recently, two single nucleotide polymorphisms (SNPs; rs11571836 and rs1799943) were identified, both located in untranslated regions of chromosome 13, associated with cardiovascular disease (CVD) in a multi-ethnic population. We examined the association between these BRCA2 polymorphisms and traits of CVD patients from Saudi Arabia. We genotyped rs11571836 and rs1799943 in 159 unrelated CVD patients and 176 healthy controls. The genotype and allele distributions in the overall population revealed a statistically significant association between rs1799943 and CVD (P = 0.01-0.022), whereas no risk association was identified for rs11571836. Additionally, haplotype analysis using both SNPs demonstrated no association between the SNPs and CVD. The genotype distribution of the 2 SNPs in the normal Saudi population deviated significantly (P < 0.000001) from that of the 6 different HapMap populations (CEU, CHB-Han, JPT, YRI, GIH, and MKK), except for the JPT population for rs1799943. This is the first study to examine the association between these SNPs and CVD in a Saudi population. Our results suggest that the increased health risk associated with the rs11571836 genotype is specific to male patients suffering from CVD. Stratification of patients and controls based on gender revealed no association between rs1799943 and the risk of CVD in either gender. These SNPs should be evaluated in larger cohorts in different populations to determine their suitability as screening markers for predicting CVD risk earlier in life to implement necessary preventive measures.

Molecular cloning and cDNA characterization of Camelus dromedarius putative cytochrome P450s 1A, 2C, and 3A.

The domesticated one-humped Arabian camel, Camelus dromedarius, is one of the most important animals in the Arabian Peninsula. Most of its life, this animal is exposed to both intrinsic and extrinsic genotoxic factors that are known to cause gross metabolic alterations in many organisms. This study determined the full length coding sequence of 3 cytochrome P450s cDNAs; namely, CYP450 1A1, CYP450 2C and CYP450 3A using reverse transcription polymerase chain reaction. The C. dromedarius CYP450s 1A1, 2C, and 3A have open reading frames of 1563, 1473, and 1566 bp and cDNAs that encode proteins of 520, 490, and 521 amino acid residues, respectively. The molecular weights calculated for CYP1A1, 2C, and 3A were found to be 58.651, 56.03, and 58.594 kDa, while the predicted calculated isoelectric points using a computer algorithm were 7.315, 6.579, and 9.46. The deduced amino acid sequences of these CYPs showed the membrane anchored signal peptide, the conserved proline-rich amino terminus and the characteristic heme-binding signature localized near the carboxy terminus of the protein.

Characterization and cross-species amplification of microsatellite markers in African Silverbill (Lonchura cantans).

We tested the cross-amplification of eight microsatellites developed for Bengalese finch in African Silverbill (Lonchura cantans). In order to develop resources for conservation genetic studies in the species L. cantans, we tested the amplification success and polymorphism in eight previously developed microsatellite loci, in L. cantans. All eight microsatellite markers were successfully amplified, of which all were polymorphic, with 3 to 9 alleles and an expected heterozygosity (HE) ranging from 0.606 to 0.718. On average, there were 5.25 alleles/locus and a mean HE of 0.6456. These eight polymorphic markers could be of potential use in studies of genetic variability, population structure, and reproductive strategy of African Silverbills. The markers tested should be useful for population and conservation genetic studies in this genus, and, in particular, for species closely related to the source species, L. cantans.

Premature aging and cancer in nucleotide excision repair-disorders.

During the past decades, the major impact of DNA damage on cancer as 'disease of the genes' has become abundantly apparent. In addition to cancer, recent years have also uncovered a very strong association of DNA damage with many features of (premature) aging. The notion that DNA repair systems protect not only against cancer but also equally against to fast aging has become evident from a systematic, integral analysis of a variety of mouse mutants carrying defects in e.g. transcription-coupled repair with or without an additional impairment of global genome nucleotide excision repair and the corresponding segmental premature aging syndromes in human. A striking correlation between the degree of the DNA repair deficiency and the acceleration of specific progeroid symptoms has been discovered for those repair systems that primarily protect from the cytotoxic and cytostatic effects of DNA damage. These observations are explained from the perspective of nucleotide excision repair mouse mutant and human syndromes. However, similar principles likely apply to other DNA repair pathways including interstrand crosslink repair and double strand break repair and genome maintenance systems in general, supporting the notion that DNA damage constitutes an important intermediate in the process of aging.

Interleukin 17A and F and asthma in Saudi Arabia: gene polymorphisms and protein levels.

BACKGROUND: Asthma is a multifactorial disorder, and both genetic and environmental factors contribute to its development. We investigated the possible association between asthma and 5 single-nucleotide polymorphisms (SNPs) in the interleukin 17 (IL17) gene--rs17880588 (G/A) and rs17878530 (C/T) in IL17A and rs763780 (T/C), rs11465553 (T/C), and rs2397084 (G/A) in IL17F--and compared levels of the proteins IL17A and IL17F in asthma patients with those of controls. PATIENTS AND METHODS: The study group included 100 asthma patients and 102 ethnically matched controls. Genotyping was performed on purified DNA using reverse transcriptase-polymerase chain reaction with specific primers and probes. Levels of IL17A and IL17F were measured in plasma using enzyme-linked immunosorbent assay. RESULTS: Genotyping showed that AG heterozygotes of rs17880588 in IL17A were significantly more common in the control group than among the asthma patients (P < .05); no significant associations were observed for any of the other SNPs examined. Levels of IL17A and IL17F were both higher in asthma patients (IL17A, 2.242 [0.099] vs 2.752 [0.287] pg/mL; IL17F, 236.01 [38.28] vs 700 [201.078] pg/mL). The difference was statistically significant for IL17F (P = .025, t test). Levels of IL17A and IL17F were positively and significantly correlated in the asthma patients CONCLUSION: Of all the SNPs analyzed, only rs17880588 showed a significant association with asthma in the Saudi population we studied. Levels of IL17A and IL17F were significantly upregulated in the asthma patients. The morphology of IL17F appeared to affect expression levels.