Vanillin attenuates thioacetamide-induced renal assault by direct and indirect mediation of the TGFß, ERK and Smad signalling pathways in rats.

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-ß1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule-1 (KIM-1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α-smooth muscle actin (α-SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α-SMA renal expression and TNFα, IL-6, TGF-ß1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM-1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF-ß type I receptors (ALK5) biding site.

A missense allele of PEX5 is responsible for the defective import of PTS2 cargo proteins into peroxisomes.

Peroxisomes, single-membrane intracellular organelles, play an important role in various metabolic pathways. The translocation of proteins from the cytosol to peroxisomes depends on peroxisome import receptor proteins and defects in peroxisome transport result in a wide spectrum of peroxisomal disorders. Here, we report a large consanguineous family with autosomal recessive congenital cataracts and developmental defects. Genome-wide linkage analysis localized the critical interval to chromosome 12p with a maximum two-point LOD score of 4.2 (θ = 0). Next-generation exome sequencing identified a novel homozygous missense variant (c.653 T > C; p.F218S) in peroxisomal biogenesis factor 5 (PEX5), a peroxisome import receptor protein. This missense mutation was confirmed by bidirectional Sanger sequencing. It segregated with the disease phenotype in the family and was absent in ethnically matched control chromosomes. The lens-specific knockout mice of Pex5 recapitulated the cataractous phenotype. In vitro import assays revealed a normal capacity of the mutant PEX5 to enter the peroxisomal Docking/Translocation Module (DTM) in the presence of peroxisome targeting signal 1 (PTS1) cargo protein, be monoubiquitinated and exported back into the cytosol. Importantly, the mutant PEX5 protein was unable to form a stable trimeric complex with peroxisomal biogenesis factor 7 (PEX7) and a peroxisome targeting signal 2 (PTS2) cargo protein and, therefore, failed to promote the import of PTS2 cargo proteins into peroxisomes. In conclusion, we report a novel missense mutation in PEX5 responsible for the defective import of PTS2 cargo proteins into peroxisomes resulting in congenital cataracts and developmental defects.

The prevalence of hypercholesterolemia and associated risk factors in Al-Kharj population, Saudi Arabia: a cross-sectional survey.

BACKGROUND: Hypercholesterolemia (HC) is an important precursor to many cardiovascular, cerebrovascular, and peripheral vascular diseases. A report conducted by the American Heart Association showed the prevalence of HC to be 11.9%, with around 28.5 million adults age ≥ 20 years having high cholesterol levels. This study aimed to evaluate the prevalence of HC and its associated risk factors among the general population of Al-Kharj, Saudi Arabia. METHOD: A cross-sectional study was conducted on the general population of Al-Kharj, Saudi Arabia in 2016. The representative sample consisted of 1019 individuals, who all participated on a voluntary basis. The statistical analysis was performed using SPSS version 25. RESULTS: The results of this study showed the prevalence of HC in the sample to be 12.5%. There was a significant moderate positive association between increasing age and the prevalence of HC (r = 0.240, P < 0.0001). Males had a significantly higher prevalence of HC (56.7%) compared to their female counterparts (43.3%) (X2 = 23.093, P ≤ 0.0001). BMI was positively and significantly associated with high cholesterol status. Participants in the overweight category had a significantly higher risk of HC (OR = 1.727; 95% CI = 1.58-1.914; P = 0.046). The non-obese (< 25 kg/m2) participants had an inverse significant association with the risk of hypercholesterolemia. (OR = 0.411; 95% CI = 0.216-0.783; P = 0.007). CONCLUSION: In this population-based study, the predominant risk factors of HC in Al-Kharj region were being of a Saudi nationality, male, having obesity, being unemployed, and being a civilian worker. There is a clear need for future screening studies of HC, as most previous studies have reported contradictory prevalence data (because they were conducted in different regions of KSA). Furthermore, well-designed prospective cohort studies are needed in the future to assess how the association between lifestyle behavioural factors such as dietary intake patterns and levels of physical activity may affect the relative risk of HC status.

Psychological predictors of chronic pain in Al Kharj region, Saudi Arabia.

BACKGROUND: Psychological distress is one of the major determinants for the experience progression, and recovery of chronic pain. However, it is unclear whether physical pain in specific body sites could be predictive of psychological illness. In this study, we aim to investigate the link between chronic pain in specific anatomical sites and psychological distress represented in the General Health Questionnaire-12 (GHQ-12 items). METHODS: A population-based cross-sectional study was conducted in Al Kharj region of Saudi Arabia. We included 1003 participants. Data were collected using the GHQ-12, and a subjective report on eight anatomical pain sites. Data analysis used statistical software SPSS version 26.0 for Windows statistical package. RESULTS: Chronic musculoskeletal pain in the neck and head regions was significantly associated with higher psychological distress. Other sites (back, lower limb, chest, abdominal and upper limb pain) were not associated with psychological distress. In multiple regression analysis, chronic 'general' pain was significantly associated with higher psychological distress (unstandardized Beta regression coefficient = 2.568; P < 0.0001). The patients with younger age were more likely to develop negative psychological disorders (unstandardized Beta = - 3.137; P = 0.038). Females were more likely to have higher psychological distress than males (unstandardized Beta = 2.464, P = 0.003). Single (not-married) people have a higher risk of psychological distress than married people (unstandardized Beta = 2.518, P = 0.025). Also, job type/status whether being unemployed (not working) or 'civilian' (civil servant/worker) was positively and significantly associated with an increased probability of psychological distress (unstandardized Beta = 1.436, P = 0.019). CONCLUSION: Chronic 'general' pain was significantly associated with negative psychological disorders. The government of Saudi Arabia needs to focus on patients with chronic 'general' pain, females, young and unmarried individuals as potentially 'high-risk' population subgroups for adverse psychological disorders, and subsequent long-term complications.

Knowledge and Practice of Burn First Aid Among Saudi Arabian Medical and Non-Medical University Students.

Burns are serious injuries, resulting in high morbidity and healthcare costs. Effective first aid improves outcomes. The aim of this study was to assess the knowledge and practice of first aid for burn injuries among medical and non-medical students in Saudi Arabia. A cross-sectional study (N = 408) was conducted, in which a questionnaire was administered assessing students' experience with burns, as well as their hypothetical responses to vignettes involving patients with burn injuries. Although most students reported having personal experience with burns, and had received some information regarding burn first aid, only about half were able to provide correct responses regarding first aid techniques, and medical students were no more accurate than non-medical students in their responses. Results suggest that members of the Saudi Arabian population may lack appropriate knowledge about burn first aid, and education and public information resources may help to remedy this problem.

Association of vitamin d with glycemic control in Saudi patients with type 2 diabetes: A retrospective chart review study in an emerging university hospital.

BACKGROUND: Vitamin D (mainly 25-hydroxyvitamin D, 25[OH]D) has stimulated increasing interest in Saudi Arabia over the current years due to its association with several different chronic diseases such as diabetes. This study aims to ascertain whether the vitamin D level has any influence on glycemic control in Saudi patients with type 2 diabetes (T2DM). METHOD: This retrospective study included 200 patients with T2DM who visited Prince Sattam Bin Abdulaziz University Hospital between January 2015 and December 2015. Venous blood was collected and examined for "serum/plasma levels of 25(OH)D" and related variables using kit methods. HbA1C levels <7% and ≥7% were taken as indicators of good and poor glycemic control, respectively. An association between vitamin D deficiency and poor glycemic control was determined using multinomial logistic regression analysis. RESULTS: Among the total of 200 patients with type 2 diabetes, 118 (59%) were female and 82 (41%) were males with the mean age 42.4 ± 14.8 years. Good glycemic control (HbA1c < 7) was observed in 127 (63.5%), and poor glycemic control (HbA1c > 7) was found in 73(36.5%). The mean serum 25(OH)vit D was 20.27 ± 8.66 ng/mL, with (52% vs 82%; P ≤ .001) of subjects identified to have vitamin D deficiency in good and poor glycemic control groups, respectively. CONCLUSION: Taken together, our results demonstrated an association of vitamin D level with poor glycemic control in patients with type 2 diabetes. However, additional studies with larger sample size from local population are warranted in future to confirm and extend the findings of the present study.

Leber congenital amaurosis: Current genetic basis, scope for genetic testing and personalized medicine.

Retinal dystrophies are one of the leading causes of pediatric congenital blindness. Leber's congenital amaurosis (LCA) encompasses one of the most severe forms of inherited retinal dystrophy responsible for early-onset childhood blindness in infancy. These are clinically characterized by nystagmus, amaurotic pupil response and markedly reduced or in most instances completely absent full-field electroretinogram. LCA exhibits immense genetic heterogeneity. With advances in next-generation genetic technologies, tremendous progress has been achieved over the last two decades in discovering genes and genetic defects leading to retinal dystrophies. Currently, 28 genes have been implicated in the pathogenesis of LCA and with initial reports of success in management with targeted gene therapy the disease has attracted a lot of research attention in the recent time. The review provides an update on genetic basis of LCA, scope for genetic testing and pharmacogenetic medicine in diagnosis and treatment of these diseases.

The prevalence of chronic pain and its associated factors among Saudi Al-Kharj population; a cross sectional study.

BACKGROUND: Chronic pain (CP) can be a symptom of many underlying health issues. The consequences of CP may vary from slight discomfort to disruption of quality of life and normal functioning. In this study, we aim to investigate the prevalence of CP and its associated factors in Al Kharj, Saudi Arabia. METHODS: This was a cross-sectional study conducted in Al Kharj, Saudi Arabia. We recruited 1031 participants for our study. Data was collected on socio-demographic, health predictors and anthropometric measurements (such as weight, height and waist circumference). The data analysis was performed on JMP®, Version 12. SAS Institute Inc., Cary, NC, 1989-2007. RESULTS: The prevalence of self-reported chronic pain in Al Kharj population was 19% with a mean age of 26.4 (SD = 8.6) years. The most common locations of pain included; back pain (30%), abdominal pain (26%), headache (13%), and any musculoskeletal pain (56%). Multiple logistic regression revealed that presence of a chronic disease (OR = 3.8; 95% CI = 2.3-6.2), psychological disease (OR = 2.3; 95% CI = 1.2-4.3), high General Health Questionnaire (GHQ)-12 score (OR = 1.06; 95% CI = 1.03-1.1), and pack-years of smoking (OR = 1.05; 95% CI = 1.01-1.08) were significantly related to chronic pain in Al Kharj population. CONCLUSIONS: Our study results found a high burden of chronic pain in this selected Saudi population. The most prevalent pain was low back pain. The presence of chronic and psychological diseases were strongly related to chronic pain. Future prospective studies are needed to establish the temporal relationship of chronic pain with these factors.

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-ß A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.

Carriers of mitochondrial DNA macrohaplogroup L3 basal lineages migrated back to Africa from Asia around 70,000 years ago.

BACKGROUND: The main unequivocal conclusion after three decades of phylogeographic mtDNA studies is the African origin of all extant modern humans. In addition, a southern coastal route has been argued for to explain the Eurasian colonization of these African pioneers. Based on the age of macrohaplogroup L3, from which all maternal Eurasian and the majority of African lineages originated, the out-of-Africa event has been dated around 60-70 kya. On the opposite side, we have proposed a northern route through Central Asia across the Levant for that expansion and, consistent with the fossil record, we have dated it around 125 kya. To help bridge differences between the molecular and fossil record ages, in this article we assess the possibility that mtDNA macrohaplogroup L3 matured in Eurasia and returned to Africa as basal L3 lineages around 70 kya. RESULTS: The coalescence ages of all Eurasian (M,N) and African (L3 ) lineages, both around 71 kya, are not significantly different. The oldest M and N Eurasian clades are found in southeastern Asia instead near of Africa as expected by the southern route hypothesis. The split of the Y-chromosome composite DE haplogroup is very similar to the age of mtDNA L3. An Eurasian origin and back migration to Africa has been proposed for the African Y-chromosome haplogroup E. Inside Africa, frequency distributions of maternal L3 and paternal E lineages are positively correlated. This correlation is not fully explained by geographic or ethnic affinities. This correlation rather seems to be the result of a joint and global replacement of the old autochthonous male and female African lineages by the new Eurasian incomers. CONCLUSIONS: These results are congruent with a model proposing an out-of-Africa migration into Asia, following a northern route, of early anatomically modern humans carrying pre-L3 mtDNA lineages around 125 kya, subsequent diversification of pre-L3 into the basal lineages of L3, a return to Africa of Eurasian fully modern humans around 70 kya carrying the basal L3 lineages and the subsequent diversification of Eurasian-remaining L3 lineages into the M and N lineages in the outside-of-Africa context, and a second Eurasian global expansion by 60 kya, most probably, out of southeast Asia. Climatic conditions and the presence of Neanderthals and other hominins might have played significant roles in these human movements. Moreover, recent studies based on ancient DNA and whole-genome sequencing are also compatible with this hypothesis.

Prevalence of overweight and obesity based on the body mass index; a cross-sectional study in Alkharj, Saudi Arabia.

BACKGROUND: Obesity and overweight are accompanied with several different chronic diseases. Overweight and obesity can be measured by using body mass index (BMI) and is also used widely as an index of relative adiposity among any population. The aim of the study is to evaluate the prevalence of overweight and obesity among general population in Al-Kharj, Saudi Arabia. METHODS: Cross-sectional analysis was undertaken from a representative sample (N = 1019) of the Al Kharj population. Anthropometric measurements including the waist circumference (in centimeters), height (in meters), and weight (in kilograms) of the subjects were undertaken by means of standard apparatus. SPSS 24.0 was utilized for statistical analysis of the data. RESULTS: Majority of respondents in this study were overweight and obese (54.3%) compared with 45.7% being non-obese. A linear positive association of increasing BMI with older age groups was present in males and females. Men had larger waist circumference, weight and height measures as compared with their female counterparts. Regression analysis showed increasing age, being married and high serum cholesterol to be the significant predictors of overweight and obesity while gender, education level, job status, and having diabetes were not. CONCLUSIONS: The obesity-overweight prevalence in the Saudi population is high mainly across both genders. However, the associated factors are potentially preventable and modifiable. The regional barriers to lifestyle modifications and interventions to encourage active lifestyles, especially among adolescents to limit the occurrence of obesity and ultimately promote health and wellbeing, are warranted. Furthermore, prospective studies are needed in future to confirm the aetiological nature of such associations.

Prevalence of hypertension and prehypertension and its associated cardioembolic risk factors; a population based cross-sectional study in Alkharj, Saudi Arabia.

BACKGROUND: Hypertension and prehypertension pose significant public-health and clinical challenges for both economically developed and developing nations. Prevalence of these conditions are frequently underreported because of its often-silent nature. Population-based studies that explore the occurrence and correlates of these conditions are scarce in Saudi Arabia. This study aimed at estimating the prevalence and associated factors of hypertension and prehypertension on a representative sample of males and females living in Al-Kharj town in Saudi Arabia. METHODS: Cross-sectional analysis was performed from January 2016 until June 2016 by recruiting a representative sample (n = 1019; aged 18 to 67 years) of the Al Kharj population. All participants completed a self-administered questionnaire, followed by a physical examination and blood test. Statistical analysis was carried out using SPSS version 24.0 for Windows. RESULTS: The prevalence of prehypertension was 66.1, 48.1 and 54.9% in male, female and all subjects, respectively. The prevalence of hypertension was 6.0, 4.2 and 4.9% in male, female and all subjects, respectively. Being overweight was associated with the highest risk of hypertension (OR = 4.98 [95% C.I. = 1.98-12.52], P = 0.001). People who were classified as class I obese had 3.5 times the risk of hypertension compared with the non-obese group (OR = 3.49 [95% C.I. = 1.42-8.63], P = 0.007). Risk of pre-hypertension was significantly lower in females (OR = 0.48 [95% C.I. = 0.32-0.71]) and tends to increase with obesity status. Gender-specific analyses found that males in the lowest education attainment level had a significantly increased risk of pre-hypertension (OR = 6.56 [95% C.I. = 1.27-33.85], P = 0.003). CONCLUSION: This population-based study in Saudi Arabia shows that hypertension and prehypertension are common conditions particularly among males. Overweight and obesity was associated with both conditions. In addition, lower education attainment was a significantly associated factor among males. Future prospective studies are needed to confirm the etiological nature of such associations.

The factor structure of the general health questionnaire (GHQ12) in Saudi Arabia.

BACKGROUND: The General Health Questionnaire-12 (GHQ-12) is one of the most unique and extensively used self-report instruments for evaluating psychological disorders and strains. However, the factor structure of GHQ-12 has not been fully explored. The current study aims to assess the factorial structure of GHQ-12 in a large cross-sectional data-set extracted from Al Kharj central region of Saudi Arabia. METHODS: Population based cross sectional data was extracted from January 2016 to June 2016 from Al Kharj population recruiting 1019 respondents aged 18 and above. Exploratory factor analysis (EFA) was applied together with multiple regression analysis to extract and retain factors. Mean GHQ-12 score for demographic and health-related traits were used for assessing this association. Statistical analysis was carried out using STATA version 12.1. RESULTS: Three factors, including social dysfunction, anxiety, and loss of confidence were extracted from the factor structure. 55% of the overall variance was obtained through these factors. Total score of GHQ-12 ranged from 0 to 32 with a mean score of 12. CONCLUSION: Investigation of the factor structure of GHQ-12 demonstrated that GHQ-12 is a good measure for evaluating the general health of Saudi population. Future studies based on a larger sample size of non-clinical respondents will be useful to evaluate the practical effectiveness of GHQ-12 factors.

Effects of using Antifungal Gel on Retentive Bond Strength of Two Forms of Denture Adhesives: An in vitro Study.

AIM: The purpose of this in vitro study is to compare the bond strength to denture acrylics efficacy of miconazole gel against two denture adhesives with improved retentive properties (zinc-free PoliGrip cream and Snug denture soft cushion). MATERIALS AND METHODS: Eight heat-cured acrylic samples were prepared measuring 0.7 cm × 1.4 cm flat tested surface. The two well-adapted tested surfaces were matched and fixed to Universal Testing Machine clamp. Vertical separating load was applied at a rate of 1 mm/min to yield the maximum load before denture adhesive failure occurs. These measurements were used to express the retention bond strength when improved denture adhesive material was applied alone in comparison with micon-azole nitrate gel. Results were analyzed using one-way analysis of variance (ANOVA) statistical analysis at p-value of < 0.05. RESULTS: There was a statistically significant reduction in the mean tensile strength when the antifungal gel was opposed by the zinc-free PoliGrip cream. However, such a significant difference was not evident when the Snug denture cushion was opposed by the miconazole gel. CONCLUSION: The addition of antifungal gel to denture adhesives reduces retentive bond strength of denture adhesives to denture acrylics. However, if an antifungal gel has to be used, then a denture adhesive cushion soft plastic liner may provide a better retentive option than denture adhesive cream. CLINICAL SIGNIFICANCE: The incorporation of an antifungal agent into denture adhesives is required in many denture patients to suppress fugal growth and eliminate the undesirable health effects associated with such infections.

Carriers of mitochondrial DNA macrohaplogroup R colonized Eurasia and Australasia from a southeast Asia core area.

BACKGROUND: The colonization of Eurasia and Australasia by African modern humans has been explained, nearly unanimously, as the result of a quick southern coastal dispersal route through the Arabian Peninsula, the Indian subcontinent, and the Indochinese Peninsula, to reach Australia around 50 kya. The phylogeny and phylogeography of the major mitochondrial DNA Eurasian haplogroups M and N have played the main role in giving molecular genetics support to that scenario. However, using the same molecular tools, a northern route across central Asia has been invoked as an alternative that is more conciliatory with the fossil record of East Asia. Here, we assess as the Eurasian macrohaplogroup R fits in the northern path. RESULTS: Haplogroup U, with a founder age around 50 kya, is one of the oldest clades of macrohaplogroup R in western Asia. The main branches of U expanded in successive waves across West, Central and South Asia before the Last Glacial Maximum. All these dispersions had rather overlapping ranges. Some of them, as those of U6 and U3, reached North Africa. At the other end of Asia, in Wallacea, another branch of macrohaplogroup R, haplogroup P, also independently expanded in the area around 52 kya, in this case as isolated bursts geographically well structured, with autochthonous branches in Australia, New Guinea, and the Philippines. CONCLUSIONS: Coeval independently dispersals around 50 kya of the West Asia haplogroup U and the Wallacea haplogroup P, points to a halfway core area in southeast Asia as the most probable centre of expansion of macrohaplogroup R, what fits in the phylogeographic pattern of its ancestor, macrohaplogroup N, for which a northern route and a southeast Asian origin has been already proposed.

A common variant near TGFBR3 is associated with primary open angle glaucoma.

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

Characteristics and outcome of surgically treated pituitary tumours in South Africa: a single-centre experience.

AIMS: To describe the clinical, biochemical, radiological and histological features and to determine the outcome of all patients with pituitary tumours treated surgically at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban over a 5-year period. RESEARCH DESIGN: Retrospective chart review from 2008 to 2012. Clinical, biochemical and radiological data were collected before and 1 year after surgery. Histopathology findings and perioperative complications were recorded. RESULTS: Seventy patients were included (age 44·8 ± 14·9 years, 55·7% female). Headache (84·1%) and visual disturbances (78·3%) were the predominant presenting symptoms (84·1% and 78·3%). Most tumours were macroadenomas (97·1%). Trans-sphenoidal surgery was employed in the majority (90%). A single procedure was required in 55·7% patients, two procedures in 30% and up to six in others. Complete resection was achieved in only nine patients (12·8%), residual tumour postsurgery was found in 48 (68·6%), and no change in tumour size was found in 13 (18·6%) patients. Additional medical therapy was used in 22 (31·4%) and radiotherapy in 13 (18·6%). On biopsy, the most common pathology was nonfunctional adenoma in 33 (47·1%); 29 (41·4%) were secretory tumours, and 8 (11·4%) were craniopharyngiomas. Overall mortality was 4·3%. The commonest surgical complication was cerebrospinal fluid (CSF) leak (10%; n = 7). New postsurgical pituitary hypofunction occurred in 50 (71·4%) patients. The outcome at 1 year was similar to that on discharge. CONCLUSIONS: Patients presenting to IALCH had large tumours, and complete resection was achieved in a minority. There was a low overall mortality but high rate of postsurgical pituitary hypofunction.

Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort.

BACKGROUND: To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG). METHOD: Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin. RESULTS: Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor "A" allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases. CONCLUSION: Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.

Lack of association between polymorphism rs540782 and primary open angle glaucoma in Saudi patients.

BACKGROUND: To investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG). METHOD: The study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay. RESULTS: The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor 'C' allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases. CONCLUSION: Polymorphism rs540782 is not a risk factor for POAG in the Saudi cohort.

Garlic extract increases non-clipped kidney tubular natriuresis and diuresis in the 2-kidney, 1-clip rat model: Significance in hypertension.

BACKGROUND: Angiotensin II (AngII) is a potent modulator of vascular tone and renal clearance function. Raw garlic aqueous extract (RGAE) inhibits angiotensin I converting enzyme (ACE) dipeptidase activity and therefore AngII generation in the 2-kidney, 1-clip rat model (2K-1Cr). OBJECTIVE: This study investigated the effect of RGAE on the non-clipped kidney clearance function and blood pressure (BP) in the 2 K-1Cr. METHOD: 2K-1Cr were anesthetized, cannulated and instrumentalized and the acute effect during the first hour post-administration of a single intravenous dose of RGAE (30mg/100gb.wt/0.3ml) was tested on: 1- The ACE dipeptidase activity estimated from a reduction in the vasopressor action of angiotensin I [(AngI, 200ng/0.2ml): the precursor of AngII] in one group (n=5); 2- The non-clipped (left) kidney (LK) clearance function in a second group (n=6). Similar protocols were carried out on two groups of normal rats (Nr: n=5+n=6). RESULTS: In the 2K-1Cr, RGAE partially, however significantly, decreased the vasopressor action of AngI. Furthermore, RGAE had no effect on systolic BP, mean BP, plasma osmolarity, LK cortical circulation or glomerular filtration rate. Alternatively, RGAE significantly increased LK urine volume, fractional excretion of water, sodium clearance and fractional excretion of sodium; while significantly decreasing heart rate and LK urine osmolarity. CONCLUSIONS: Our findings suggest that a single i.v. dose of RGAE causes ACE dipeptidase inhibition, thus reducing AngII generation and bioavailability in the 2K-1Cr. This action of RGAE enhances the non-clipped kidney clearance of sodium and water by modulating the tubular handling mechanisms.