Arginase inhibition alleviates hypertension in the metabolic syndrome

BACKGROUND AND PURPOSE: We have previously shown that arginase inhibition alleviates hypertension associated with in a diabetic animal model. Here, we investigated the protective effect of arginase inhibition on hypertension in metabolic syndrome. EXPERIMENTAL APPROACH: Metabolic syndrome was induced in rats by administration of fructose (10% in drinking water) for 12 weeks to induce vascular dysfunction. Three arginase inhibitors (citrulline, norvaline and ornithine) were administered daily in the last 6 weeks of study before and tail BP was recorded in conscious animals. Concentration response curves for phenylephrine (PE), KCl and ACh in addition to ACh-induced NO generation were obtained in thoracic aorta rings. Serum glucose, insulin, uric acid and lipid profile were determined as well as reactive oxygen species (ROS) and arginase activity. KEY RESULTS: Arginase activity was elevated in metabolic syndrome while significantly inhibited by citrulline, norvaline or ornithine treatment. Metabolic syndrome was associated with elevations in systolic and diastolic BP, while arginase inhibition significantly reduced elevations in diastolic and systolic BP. Metabolic syndrome increased vasoconstriction responses of aorta to PE and KCl and decreased vasorelaxation to ACh, while arginase inhibition completely prevented impaired responses to ACh. In addition, arginase inhibition prevented impaired NO generation and exaggerated ROS formation in metabolic syndrome. Furthermore, arginase inhibition significantly reduced hyperinsulinaemia and hypertriglyceridaemia without affecting hyperuricaemia or hypercholesterolaemia associated with metabolic syndrome. CONCLUSIONS AND IMPLICATIONS: Arginase inhibition alleviates hypertension in metabolic syndrome directly through endothelial-dependent relaxation/NO signalling protection and indirectly through inhibition of insulin resistance and hypertriglyceridaemia

Antibodies against gonadotropin-releasing hormone (GnRH) and destruction of enteric neurons in 3 patients suffering from gastrointestinal dysfunction

Background: Antibodies against gonadotropin-releasing hormone (GnRH) and gastrointestinal dysmotility have been found after treatment with GnRH analogues. The aim of this study was to examine the presence of such antibodies in patients with dysmotility not subjected to GnRH treatment and study the anti-GnRH antibody effect on enteric neurons viability in vitro. Methods: Plasma and sera from 3 patients suffering from either enteric dysmotility, irritable bowel syndrome (IBS) or gastroparesis were analysed for C-reactive protein (CRP), and for GnRH antibodies and soluble CD40 by ELISA methods. Primary cultures of small intestinal myenteric neurons were prepared from rats. Neuronal survival was determined after the addition of sera either from the patients with dysmotility, from healthy blood donors, antiserum raised against GnRH or the GnRH analogue buserelin. Only for case 1 a full-thickness bowel wall biopsy was available for immunohistochemical analysis. Results: All 3 patients expressed antibodies against GnRH. The antibody titer correlated to the levels of CD40 (r(s) = 1.000, p < 0.01), but not to CRP. Serum from case 3 with highest anti-GnRH antibody titer, and serum concentrations of sCD40 and CRP, when added to cultured rat myenteric neurons caused remarkable cell death. In contrast, serum from cases 1 and 2 having lower anti-GnRH antibody titer and lower sCD40 levels had no significant effect. Importantly, commercial antibodies against GnRH showed no effect on neuron viability whereas buserelin exerted a protective effect. The full-thickness biopsy from the bowel wall of case 1 showed ganglioneuritis and decrease of GnRH and GnRH receptor. Conclusion: Autoantibodies against GnRH can be detected independently on treatment of GnRH analogue. Whether the generation of the antibody is directly linked to neuron degeneration and chronic gastrointestinal symptoms in patients with intestinal dysmotility, remains to be answered

Risk factors and in-hospital outcomes in stroke and myocardial infarction patients

BACKGROUND: Acute stroke (AS) and acute myocardial infarction (AMI) share major risk factors such as age, gender, and high blood pressure. The main objective of this study was to compare vascular risk factor profiles with in-hospital outcomes in AS and AMI patients. METHODS: We evaluated 486 consecutive patients who were admitted to Bjelovar General Hospital with diagnoses of AS (ischaemic stroke or intracerebral haemorrhage; N = 380) or AMI (N = 106) during a one year period. The frequency of risk factors and in-patient mortality rates were assessed in both groups. For statistical analysis we used t-tests and χ(2 )tests. RESULTS: AS patients were significantly older than AMI patients: the mean age for AS patients was 68.9 ± 9.1 years, and for AMI patients was 62.8 ± 11.7 years (p < 0.001). AMI was significantly more common than AS in patients younger than 65 years; 51% of this group had AMI and 26% had AS (p < 0.001). Hypertension was a more common risk factor in AS patients (69% AS patients vs. 58% AMI patients; p = 0.042). Patients who died did not differ significantly in age between the groups. In-patient mortality rates were significantly higher in AS than AMI cases (31% vs. 12%, p < 0.001 for all patients; 37% vs.5%, p < 0.001 for men). Women hospitalized for AMI were more likely to die in hospital than men (28% vs. 5%; p = 0.002). CONCLUSIONS: We found that age at the time of presentation was a significant differentiating factor between patients with AS and AMI. The only exceptions were women, whose ages at the onset of AS and AMI were similar. In contrast, patients who died did not differ significantly in age. We observed significantly higher inpatient mortality for men (when adjusted for age) than for women with AS. The five-fold higher in-patient mortality rate in women than in men with AMI is most likely to have resulted from other factors related to treatment

Date (Phoenix dactylifera) Polyphenolics and Other Bioactive Compounds: A Traditional Islamic Remedy’s Potential in Prevention of Cell Damage, Cancer Therapeutics and Beyond

This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by conventional chemotherapy. Phoenix dactylifera exhibits potent anti-oxidative properties both in vitro and in vivo. This allows the fruit to prevent depletion of intrinsic protection from oxidative cell damage and assist these defense systems in reducing cell damage. Macroscopically, this mechanism may be relevant to the prevention of various adverse drug events common to chemotherapy including hepatotoxicity, nephrotoxicity, gastrotoxicity, and peripheral neuropathy. While such effects have only been studied in small animal systems, research suggests a potential application to more complex mammalian systems and perhaps a solution to some problems of chemotherapy in hepato-compromised and nephro-compromised patients

Information fusion for unsupervised image segmentation using stochastic watershed and Hessian matrix

International audienceThis study deals with information fusion for image segmentation. The evidence theory (or the Dempster–Shafertheory) allows the modellisation of uncertainty and imprecision in the information as well as the combination of different sources.Here, this approach is used in an unsupervised framework to combine the stochastic watershed segmentation which providesseveral segmentation results, with a Hessian operator in order to obtain a unique and efficient segmentation. The method istested on natural images from the Berkeley dataset and evaluated using several evaluation metrics. The fusion results surpassthose obtained with stochastic watershed alone

Information fusion for unsupervised image segmentation using stochastic watershed and Hessian matrix

International audienceThis study deals with information fusion for image segmentation. The evidence theory (or the Dempster–Shafertheory) allows the modellisation of uncertainty and imprecision in the information as well as the combination of different sources.Here, this approach is used in an unsupervised framework to combine the stochastic watershed segmentation which providesseveral segmentation results, with a Hessian operator in order to obtain a unique and efficient segmentation. The method istested on natural images from the Berkeley dataset and evaluated using several evaluation metrics. The fusion results surpassthose obtained with stochastic watershed alone

Epidemiology of nonfatal stroke and transient ischemic attack in Al-Kharga District, New Valley, Egypt

Wafaa MA Farghaly,1 Hamdy N El-Tallawy,1 Ghaydaa A Shehata,1 Tarek A Rageh,1 Nabil M Abdel-Hakeem,2 Mohamed A Abd Elhamed,1 Bastawy MA Al-Fawal,3 Reda Badry1 1Department of Neurology, Faculty of Medicine, Assiut University, Assiut, 2Department of Neurology, Faculty of Medicine, Al-Azhar University, Assiut Branch, Assiut, 3Aswan Health Insurance Hospital, Ministry of Health, Aswan, Egypt Background: Stroke is a medical emergency. Nonfatal stroke may cause permanent neurologic damage, complications, and disability. The aim of this study was to determine the epidemiology of nonfatal stroke in Al-Kharga District, New Valley, Egypt. Methods: The total population (62,583) was screened via a door-to-door study by three neurology specialists and 15 female social workers for demographic data collection. All subjects with probable stroke were subjected to a full clinical examination, neuroimaging (computed tomography and/or magnetic resonance imaging of the brain), and laboratory investigations including blood sugar, lipid profile, serum uric acid, a complete blood count, blood urea, and serum creatinine. Stroke severity and outcome were assessed using the Scandinavian Stroke Scale and Barthel Index. Carotid Doppler, echocardiography, and thyroid function tests were done in selected cases. Results: During the study period (June 1, 2005 to May 31, 2008), 351 subjects were diagnosed as having suffered a cerebrovascular stroke at some point during their lives, yielding a total lifetime prevalence of 5.6 per 1,000 population. Of these, 156 subjects were identified as having suffered a stroke during the year from January 1 to December 31, 2007, with an incidence rate of 2.5 per 1,000. Both prevalence and incidence rates were higher in urban (5.8 per 1,000 and 2.6 per 1,000, respectively) than rural communities (5.2 per 1,000 and 2.3 per 1,000), and were higher in males (6.1 per 1,000 and 2.7 per 1,000, respectively) than in females (5.1 per 1,000 and 2.3 per 1,000). Thrombotic stroke had the highest prevalence and incidence rates (4.2 per 1,000 and 1.7 per 1,000, respectively), whereas subarachnoid hemorrhage had the lowest prevalence and incidence rates (0.03 per 1,000 and 0.02 per 1,000). Conclusion: The prevalence of cerebrovascular accident in Al-Kharga lies in the lower range of that in developing countries, and is similar to that in industrialized countries. Keywords: prevalence, incidence, stroke, Egyp

Synthesis of Polyaluminum Chloride Coagulant from Waste Aluminum Foil and Utilization in Petroleum Wastewater Treatment

This work investigates the potential synthesis of cost-effective polyaluminum chloride (PACl) coagulant from waste household aluminum foil and utilization for treating petroleum wastewater (PWW), especially dissolved organic compounds (DOC, like octanol–water mixture) and nonsettleable suspended (NSS-kaolin) mineral particles. Based on the Standard Practice for Coagulation–Flocculation Jar Test, the efficiency of PACl for DOC and NSS removal was evaluated in relation to the effects of the operational parameters. The results demonstrated that the as-prepared PACl has an amorphous morphology with a Keggin-type e-Al13 molecular structure {Na[AlO4(OH)24(H2O)]·xH2O and good thermal stability up to 278 °C. PACl coagulant also exhibited a higher efficiency for NSS removal than DOC by around 1.5- to 1.9-fold under broad pH (5–7), while a higher acidic/alkaline pH disrupts the sweep floc formation. An increased PACl dosage (over 25 mg/L) also caused a decrease in the coagulation efficiency by 11.7% due to Al species’ transformation and pH depression (from 6.8 to 4.9) via increased PACl hydrolysis. With a fast rotating speed of 280 rpm for 2 min, the minimum dose of PACl (10–25 mg/L) can maximize the removal efficiency of NSS (~98%) and DOC (~69%) at pH 6.5 ± 0.5 and 35 °C after 30 min of settling time. Treating actual saline PWW samples (salinity up to 187.7 g/L) also verified the high efficacy of PACl coagulation performance in reducing the turbidity and dissolved hydrocarbons by more than 75.5% and 67.7%, respectively. These findings verify the techno-economic feasibility of the as-prepared PACl coagulant in treating PWW treatment at different salinity levels