Thymoquinone causes endothelium-dependent augmentation of contraction depending on activation of soluble guanylyl cyclase in isolated arteries

Poster - Vascular Responsiveness: no. 4/7INTRODUCTION: Experiments were designed to determine the effects of thymoquinone, an alkaloid with in vivo vasodilator properties, in isolated arteries. METHODS: Rings, with or without endothelium, of rat mesenteric arteries, rat aorta and porcine coronary arteries were suspended in conventional organ chambers for isometric tension recording. Certain rings were incubated with inhibitors of nitric oxide (NO) synthase inhibitor (L-N^G-nitroarginine methyl ester, L-NAME) or soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ). They were contracted with phenylephrine (rat arteries) or prostaglandin F_2alpha (porcine coronary arteries) and exposed to increasing ...postprin

Características físico-químicas de aceites de semillas extraídos de diferentes variedades de albaricoque (Prunus armeniaca L.) de Pakistán

The fruit seed oils from four varieties of apricot (Prunus armeniaca L.), namely, Halmas, Nari, Travet and Charmagzi were analyzed for different physico-chemical characteristics. The oil yield from the apricot seeds (kernels) ranged from 32.23-42.51%, while the protein, fiber and ash contents ranged from 13.21-20.90%, 5.13-9.81% and 2.11-3.89%, respectively. The extracted oils had an average iodine value (g of I/100 g of oil) of 96.4-106.3; density at 24 °C, 0.87-0.93 mg/mL; refractive index (40 °C), 1.4655-1.4790; saponification value, 189.1-199.4 mg of KOH/g oil; unsaponifiable matter, 0.59-0.88%; free fatty acid (mg of KOH/g oil), 0.41-1.28; and color (1-inch cell), 1.31-2.96R 1 14.8-29.8Y. With regard to the oxidation state, the tested oils showed values for specific extinction at 232 and 268 nm, 2.30-3.42 and 0.82-1.04, respectively, while the peroxide value was 1.0-2.32 meq O2/kg and, p-anisidine was 1.22-1.90. The major fatty acid found in the oils was oleic acid (62.34-80.97%) followed by linoleic (13.13-30.33%), palmitic (3.35-5.93%), linolenic (0.73-1.03%) and stearic (1.10-1.68%) acids. The contents of α-, γ-, and δ-, tocopherols in the oils ranged from 14.8-40.4, 330.8-520.8 and 28.5-60.2 mg/kg, respectively. The results of our present investigation revealed that apricot seed is a potential source of oil which can be used both for edible and oleochemical applications.Se han analizado las características físico-químicas de aceites de semillas de frutos de cuatro variedades diferentes de albaricoque, Halmas, Nari, Travet y Charmagzi (Prunus armeniaca L.). La producción de aceites de las semillas de albaricoque (hueso) osciló entre 32,23-42,51%, mientras que las proteínas, fibra y cenizas dieron valores de 13,21-20,90%, 5,13-9,81% y 2,11-3,89%, respectivamente. Los aceites extraídos presentaron valores promedio de índice de yodo, de 96,4-106,3 (g de I/100 g de aceite); densidades a 24 °C de 0,87-0,93 mg/mL, índices de refracción (40 °C) de 1,4655- 1,4790; índices de saponificación de 189.1-199,4 (mg KOH/g de aceite), materia insaponificable de 0,59-0,88%, valores de acidez libre de 0.41-1.28 (mg de KOH /g de aceite), y valores de color de 1,31-2.96R 14,8-29,8Y (celda de 1 pulgada). Con respecto al estado de oxidación de los aceites estudiados, estos mostraron valores de extinción específica a 232 y 268 nm de 2,30-3,42 y 0,82-1,04, respectivamente, mientras que dieron valores de índices de peróxidos de 1,0-2,32 meq O2/kg y de p-anisidina de 1,22-1,90. El principal ácido graso que se encuentra en los aceites fue el ácido oleico (62,34 -80,97%), seguido de linoleico (13,13-30,33%), palmítico (3,35-5,93%), linolénico (0,73 - 1,03%) y esteárico (1,10 a 1,68%). El contenido de α-, γ- y δ- tocoferoles en los aceites variaron desde 14,8 hasta 40,4, 330,8 a 520,8 y 28,5 hasta 60,2 mg/kg, respectivamente. Los resultados de nuestra investigación actual revela que la semilla de albaricoque es una fuente potencial de aceite que puede ser utilizado tanto para aplicaciones comestibles como oleoquímicas

The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia

BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22–0.89) was significantly associated with 30-day mortality. CONCLUSION: Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect

Mammalian NPC1 genes may undergo positive selection and human polymorphisms associate with type 2 diabetes

BACKGROUND: The NPC1 gene encodes a protein involved in intracellular lipid trafficking; its second endosomal loop (loop 2) is a receptor for filoviruses. A polymorphism (His215Arg) in NPC1 was associated with obesity in Europeans. Adaptations to diet and pathogens represented powerful selective forces; thus, we analyzed the evolutionary history of the gene and exploited this information for the identification of variants/residues of functional importance in human disease. METHODS: We performed phylogenetic analysis, population genetic tests, and genotype-phenotype analysis in a population from Saudi Arabia. RESULTS: Maximum-likelihood ratio tests indicated the action of positive selection on loop 2 and identified three residues as selection targets; these were confirmed by an independent random effects likelihood (REL) analysis. No selection signature was detected in present-day human populations, but analysis of nonsynonymous polymorphisms showed that a variant (Ile642Met, rs1788799) in the sterol sensing domain affects a highly conserved position. This variant and the previously described His215Arg polymorphism were tested for association with obesity and type 2 diabetes (T2D) in a cohort from Saudi Arabia. Whereas no association with obesity was detected, 642Met allele was found to predispose to T2D. A significant interaction was noted with sex (P = 0.041), and stratification on the basis of gender indicated that the association is driven by men (P = 0.0021, OR = 1.5). Notably, two NPC1 haplotypes were also associated with T2D in men (rs1805081-rs1788799, His-Met: P = 0.0012, OR = 1.54; His-Ile: P = 0.0004, OR = 0.63). CONCLUSIONS: Our data indicate a sex-specific effect of NPC1 variants on T2D risk and describe putative binding sites for filoviruses entry

Circulating leukocyte telomere length is highly heritable among families of Arab descent

Background Telomere length, an indicator of ageing and longevity, has been correlated with several biomarkers of cardiometabolic disease in both Arab children and adults. It is not known, however, whether or not telomere length is a highly conserved inheritable trait in this homogeneous cohort, where age-related diseases are highly prevalent. As such, the aim of this study was to address the inheritability of telomere length in Saudi families and the impact of cardiometabolic disease biomarkers on telomere length. Methods A total of 119 randomly selected Saudi families (123 adults and 131 children) were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for routine analyses of fasting glucose and lipid profile. Leukocyte telomere length was determined using quantitative real time PCR. Results Telomere length was highly heritable as assessed by a parent-offspring regression [h2 = 0.64 (p = 0.0006)]. Telomere length was modestly associated with BMI (R2 0.07; p-value 0.0087), total cholesterol (R2 0.08; p-value 0.0033), and LDL-cholesterol (R2 0.15; p-value 3 x 10-5) after adjustments for gender, age and age within generation. Conclusion The high heritability of telomere length in Arab families, and the associations of telomere length with various cardiometabolic parameters suggest heritable genetic fetal and/or epigenetic influences on the early predisposition of Arab children to age-related diseases and accelerated ageing

Tea and coffee consumption in relation to vitamin D and calcium levels in Saudi adolescents

Background Coffee and tea consumption was hypothesized to interact with variants of vitamin D-receptor polymorphisms, but limited evidence exists. Here we determine for the first time whether increased coffee and tea consumption affects circulating levels of 25-hydroxyvitamin D in a cohort of Saudi adolescents. Methods A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays. Results Improved lipid profiles were observed in both boys and girls, as demonstrated by increased levels of HDL-cholesterol, even after controlling for age and BMI, among those consuming 9–12 cups of coffee/week. Vitamin D levels were significantly highest among those consuming 9–12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure. Conclusion This study suggests a link between tea consumption and vitamin D levels in a cohort of Saudi adolescents, independent of age, BMI, gender, physical activity and sun exposure. These findings should be confirmed prospectively

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

Time-Course of Changes in Inflammatory Response after Whole-Body Cryotherapy Multi Exposures following Severe Exercise

The objectives of the present investigation was to analyze the effect of two different recovery modalities on classical markers of exercise-induced muscle damage (EIMD) and inflammation obtained after a simulated trail running race. Endurance trained males (n = 11) completed two experimental trials separated by 1 month in a randomized crossover design; one trial involved passive recovery (PAS), the other a specific whole body cryotherapy (WBC) for 96 h post-exercise (repeated each day). For each trial, subjects performed a 48 min running treadmill exercise followed by PAS or WBC. The Interleukin (IL) -1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha (TNF-α), protein C-reactive (CRP) and white blood cells count were measured at rest, immediately post-exercise, and at 24, 48, 72, 96 h in post-exercise recovery. A significant time effect was observed to characterize an inflammatory state (Pre vs. Post) following the exercise bout in all conditions (p<0.05). Indeed, IL-1β (Post 1 h) and CRP (Post 24 h) levels decreased and IL-1ra (Post 1 h) increased following WBC when compared to PAS. In WBC condition (p<0.05), TNF-α, IL-10 and IL-6 remain unchanged compared to PAS condition. Overall, the results indicated that the WBC was effective in reducing the inflammatory process. These results may be explained by vasoconstriction at muscular level, and both the decrease in cytokines activity pro-inflammatory, and increase in cytokines anti-inflammatory