Olmesartan modulates proliferating cell nuclear antigen expression and improves dextran sulfate - induced ulcerative colitis in rats

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by sudden attacks of remissions and exacerbations with increased incidence of cancer colon. The present study aims to determine the possible ameliorative mechanisms of Olmesartan in UC induced experimentally in rat.Methods: Adult albino rats were randomly grouped into control, UC model non treated group: Rats received dextran sodium (DSS) orally for 21 days with intra-colic administration of acetic acid (AA) for 3 consecutive days for induction of UC model, Olmesartan (1, 5, 10mg/kg/orally) and UC + Olmesartan in different doses (1 mg, 5 mg and 10 mg/kg/day orally).Results: DSS orally and AA intra-rectal produced sever colitis manifested by significant weight loss, watery and bloody diarrhea. Significant increase in serum and colonic tissue levels of tumor necrosis factor alpha and interleukine-1β. Pro-apoptotic Bax protein, myeloperoxidase (MPO) and expression of PCNA significantly increased in colonic tissue. Lipid peroxidation (MDA) significantly elevated while reduced glutathione (GSH) was depleted in UC non-treated group compared with normal control group. Treatment with Olmesartan (5 mg, 10 mg/kg/day, orally) ameliorated mucosal ulceration and improved inflammatory signs as confirmed by immunohistochemical and histopathological examination. Also, Olmesartan significantly attenuates overexpression of PCNA in colonic mucosa.Conclusions: Our results point out that Olmesartan had ameliorative effects on UC by its anti-inflammatory, antioxidant and anti-apoptotic effects and attenuates PCNA expression which is the main cause of dysplasia and colorectal cancer. Olmesartan may be a promising therapeutic drug for treating UC and protection of colorectal carcinoma. 

Processing of LtaS restricts LTA assembly and YSIRK preprotein trafficking into <i>Staphylococcus aureus</i> cross-walls

Septal membranes of Staphylococcus aureus serve as the site of secretion for precursors endowed with the YSIRK motif. Depletion of ltaS, a gene required for lipoteichoic acid (LTA) synthesis, results in the loss of restricted trafficking of YSIRK precursors to septal membranes. Here, we seek to understand the mechanism that ties LTA assembly and trafficking of YSIRK precursors. We confirm that catalytically inactive lipoteichoic acid synthase (LtaS)T300A does not support YSIRK precursor trafficking to septa. We hypothesize that the enzyme’s reactants [gentiobiosyldiacylglycerol (Glc2-DAG) and phosphatidylglycerol (PG)] or products [LTA and diacylglycerol (DAG)], not LtaS, must drive this process. Indeed, we observe that septal secretion of the staphylococcal protein A YSIRK precursor is lost in ypfP and ltaA mutants that produce glycerophosphate polymers [poly(Gro-P)] without the Glc2-DAG lipid anchor. These mutants display longer poly(Gro-P) chains, implying enhanced PG consumption and DAG production. Our experiments also reveal that in the absence of Glc2-DAG, the processing of LtaS to the extracellular catalytic domain, eLtaS, is impaired. Conversely, LTA polymerization is delayed in a strain producing LtaSS218P, a variant processed more slowly than LtaS. We conclude that Glc2-DAG binding to the enzyme couples catalysis by LtaS and the physical release of eLtaS. We propose a model for the temporal and localized assembly of LTA into cross-walls. When LtaS is not processed in a timely manner, eLtaS no longer diffuses upon daughter cell splitting, LTA assembly continues, and the unique septal-lipid pool, PG over DAG ratio, is not established. This results in profound physiological changes in S. aureus cells, including the inability to restrict the secretion of YSIRK precursors at septal membranes

Association of ghrelin and leptin with reproductive hormones in constitutional delay of growth and puberty

<p>Abstract</p> <p>Background</p> <p>Constitutional delay of growth and puberty (CDGP) is a variation of the onset and timing of pubertal development without a defined endocrine abnormality. Recently published studies indicate that leptin and ghrelin play a role in puberty initiation and progress. They have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that elevated ghrelin and reduced leptin concentrations could be implicated in altering the tempo of puberty in adolescents with CDGP. So in the current study we evaluate variations in leptin and ghrelin levels in adolescent boys with CDGP, the relationships between both hormones and reproductive hormones including LH, FSH and testosterone were also evaluated.</p> <p>Methods</p> <p>The study enrolled 23 adolescent boys with CDGP and 20 healthy controls matched for age and sex. Weight, height, BMI, testicular volume, bone age, bone age delay, serum FSH, LH, testosterone, leptin and ghrelin were assessed.</p> <p>Results</p> <p>Adolescent boys with CDGP had significantly lower leptin and higher ghrelin than normal controls. Leptin was positively correlated with BMI, bone age, testicular volume, FSH, LH and testosterone and negatively correlated with delayed bone age and ghrelin. Ghrelin was negatively correlated with BMI, bone age, testicular volume, FSH, LH and testosterone. With multiple regression analysis BMI, FSH, LH, testosterone and ghrelin remained independently correlated with leptin while BMI, LH and testosterone remained independently correlated with ghrelin.</p> <p>Conclusion</p> <p>Elevated serum ghrelin and decreased leptin concentrations and their associations with reproductive hormones may explain the sexual immaturity in adolescent boys with CDGP.</p

Comparison of the accuracy of two scoring systems in predicting the outcome of organophosphate intoxicated patients admitted to intensive care unit (ICU)

AbstractIntroductionOrganophosphates(OP) are one of the most common causes of poisoning, especially in developing countries, with high morbidity and mortality. As mortality rate of OP poisoning is still high, early diagnosis and appropriate treatment is often life saving. OP is the main cause of poisoning and death in the poison control centre (PCC), Ain Shams University (ASU) in Egypt.ObjectiveTo compare the accuracy of acute physiology and chronic health evaluation score (APACHE IV) and simplified acute physiology score (SAPS II) in the prediction of mortality of patients with organophosphate poisoning (OPP) who required admission to the Intensive Care Unit (ICU) of PCC of ASU between January 1st, 2009 and December 31st, 2009.MethodsA prospective study conducted by collecting data on consecutive patients with acute OPP admitted to the intensive care unit over 12months. Data required to calculate the patients’ predicted mortality by (APACHE) IV and (SAPS) II scoring systems were collected.ResultsNinety patients were recruited in the study with acute OP toxicity. The observed mortality following acute OP toxicity was 13.3% (12 patients). The area under the receiver operator characteristic (ROC) curves of APACHE IV score was better than SAPS II score (0.921±0.054 SE, 0.807±0.078 SE, respectively). APACHE IV and SAPS II scores were significantly higher in the non-survival than in the survival group (P<0.05).ConclusionAPACHE IV and SAPS II scores calculated within the first 24h are good prognostic indicators among patients with acute OP toxicity that required ICU admission with preference to APACHE IV score. APACHE IV and SAPS II scores above 89, 44, respectively within the first 24h are a predictor of poor outcome in patients with acute OP toxicity.RecommendationApplication of APACHE IV and SAPS II scores is a good predictor of high mortality in OP intoxicated patients which helps in proper allocation of resources

Can deficit irrigations be an optimum solution for increasing water productivity under arid conditions? A case study on wheat plants

Water scarcity is of growing concern in many countries around the world, especially within the arid and semi-arid zones. Accordingly, rationalizing irrigation water has become an obligation to achieve the sustainable developmental goals of these countries. This may take place via using deficit irrigation which is long thought to be an effective strategy to save and improve water productivity. The current study is a trial to evaluate the pros and cons of using 50 and 75 % of the irrigation requirements (IR) of wheat (deficit irrigations) versus 100 %IR, while precisely charting changes in wheat growth parameters, antioxidant enzymes in plant shoots and the overall nutritional status of plants (NPK contents). Accordingly, a field experiment was conducted for two successive seasons, followed a split-plot design in which deficit irrigations (two irrigations to achieve 50 % of the irrigations requirements (IR), three irrigations to attain 75 % IR, and four irrigations to fulfill 100 % IR) were placed in main plots while four different studied wheat cultivars were in subplots. Results obtained herein indicate that deficit irrigations led to significant reductions in growth parameters and productivity of all wheat cultivars, especially when using 50 % IR. It also decreased NPK contents within plant shoots while elevated their contents of proline, peroxidase, and catalase enzymes. On the other hand, this type of irrigation decreased virtual water content (VWC, the amount of water used in production on ton of wheat grains). Stress tolerance index (STI), and financial revenues per unit area were also assessed. The obtained values of grain productivity, STI, VWC and financial revenues were weighted via PCA analyses, and then introduced in a novel model to estimate the efficiency of deficit irrigations (ODEI) whose results specified that the overall efficiency decreased as follows: 50 %IR &lt; 75 %IR &lt; 100 %IR. In conclusion, deficit irrigation is not deemed appropriate for rationalizing irrigation water while growing wheat on arid soils

Open-array analysis of genetic variants in Egyptian patients with type 2 diabetes and obesity

Background: Diabetes mellitus is considered a major public health problem worldwide. Susceptibility to diabetes is influenced by both genetic and environmental determinants.Aims/hypothesis: The aim of the present study was to test for 16 independent single nucleotide polymorphisms (SNPs) in established Type 2 diabetes (T2D) and obesity susceptibility loci by GWAS in a sample of Egyptian patients to find out if there is shared genetic background underlying both disease entities.Methods: Genotyping was performed using OpenArray protocol on the QuantStudioTM 12K Flex Real- Time PCR System. In the present case control study a custom array was designed to facilitate costeffective analysis of selected SNPs related to glycolysis, gluconeogenesis, inflammation, insulin signalling, and immune function.Results: Seven gene variants showed significant association with the risk of T2D patients including FCGRA2, STAT4, CELSR2, PPARG, EXT2 rs3740878, GCKR, PTGS1. Factors that significantly affect T2D were obesity (p &lt; 0.001) and GCKR (p = 0.001) and PTGS1 (p = 0.001) gene variants. Gene variants that showed significant or borderline effect on obesity were MTHFD1, EXT2 rs3740878, GCKR and PTGS1 (p = 0.03, 0.017, 0.059, 0.006) respectively.Conclusions/interpretation: Overlapping genetic aspects should be considered and the presence of risk alleles of different genes together could contribute to the risk of T2D or obesity or both. The MTHFD1 and EXT2rs3740878 gene variants significantly affect obesity and not shared with T2D. Gene variants that showed combined effect on both disease entities were GCKR and PTGS1. These findings provide a basis for future studies on a larger scale. More stress on the risk gene variants that have a combined impact on both diabetes and obesity is recommended to improve risk prediction and preventive strategies

Detection and Molecular Characterization of Some Virulence Genes of Escherichia Coli Isolated from Milk in Dairy Cow Farms

Coliform pathogens, primarily E. coli, were discovered throughout the farm, causing environmental mastitis and can be shed from the udder into the milk; they are concerned about severe gastrointestinal disruption and potential enteropathogenic and/or toxic strains, posing a risk to public health. The objectives of this study were to identify the incidence and harmful serotypes of pathogenic Escherichiacoliand some of their virulent genes, which were isolated from the collected milk of some dairy farms in the Delta region and Cairo-Alexandria desert road farms, in Egypt during one year using the polymerase chain reaction (PCR) technique after bacteriological and serological identification as well as determine the antimicrobial susceptibility of the isolated strains. 150 milk samples in total were gathered (100 milk samples from bulk milk tanks and the other 50 samples from clinically mastitic dairy cows). According to our finding, the mean values of somatic cell count (SCC), standard plate count (SPC), and coliform count (CC) in the hundred bulk tank milk samples were 3.67  1.08×104/ml, 7.08×104± 6.25×104 cfu/ml and 3.04×102±1.43×102/ml, respectively. The bacteriological investigation exhibited that, the Escherichiacoli incidences from bulk tank milk (BTM) and mastitic milk samples (MMS) were 12% and 18%, respectively. The detected   E.coli serotypes including, O26, O44, O55:K99, O111, O119 and O157:H7 from MMS, while O1, O55, O78, O86, O124 and O158:H10 from BTM. Molecular virulence characterization of E.coli strains showed that, Shiga toxins 2 (stx2) gene is present in O157:H7, while the stx1 gene present in O26.  The Intimin gene (eaeA) is involved in four strains, O44, O111, O119, and O157:H7. Positive amplification of a biofilm gene (adrA) appeared in all E.coli strains. The outcome of the antimicrobial susceptibility revealed high resistance to amoxicillin (85.71%), streptomycin (80.95%), ampicillin (71.43%), and flucloxacillin (61.90%). Meanwhile, the highest susceptibility was to ciprofloxacin (95.24%) followed by enrofloxacin (90.48%), neomycin (80.95%), and gentamycin (76.19%). Effective hygienic measurements are required to avoid toxigenic and pathogenic E.coli and more future studies should be performed to increase awareness in dairy farms

Clinical characteristics and precipitating factor(s) associated with diabetic ketoacidosis presentation in children with newly diagnosed diabetes

Background. To compare the demographic and clinical characteristics of children with newly clinically diagnosed type 1 diabetes (T1DM) who presented with diabetic ketoacidosis (DKA) versus non DKA presentation and to identify the precipitating factor(s) related to progression to DKA. Methods. Over a 3 month period, 99 patients newly diagnosed with T1DM were recruited from Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU), Cairo University, with 53 patients presented with DKA and 46 were non DKA. Results. Polyuria, polydipsia, weight loss, polyphagia and nocturia were the most common symptoms preceding the diagnosis among the whole study group (93.8%, 92% and 80.8%, 76.8%, 46.5 % respectively) with no difference between DKA and non DKA groups. Delayed diagnosis occurred in 98.1% and 58.7% of DKA and non DKA groups respectively. In the DKA group the diagnosis of diabetes was missed in 69.8% and in 28.3% the initiation of insulin therapy was delayed despite diagnosis. Multivariate analysis performed to identify the most significant precipitating factor(s) associated with the development of DKA at diabetes diagnosis showed that delayed start of insulin therapy was the most significant factor (OR = 1.267, P value = 0.023). Conclusion. The prevalence of DKA is high among Egyptianchildren at diagnosis of type 1 diabetes. It is not only caused by misdiagnosis and mismanagement of diabetes, but also delayed initiation of insulin therapy in those diagnosed. This highlights the importance of increasing awareness concerning clinical features of diabetes in children and the urgency of insulin therapy among primary health care professionals and the community

Pigment epithelium-derived factor inhibits retinal microvascular dysfunction induced by 12/15-lipoxygenase-derived eicosanoids

We recently demonstrated that 12/15-lipoxygenase (LOX) derived metabolites, hydroxyeicosatetraenoic acids (HETEs), contribute to diabetic retinopathy (DR) via NADPH oxidase (NOX) and disruption of the balance in retinal levels of the vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). Here, we test whether PEDF ameliorates retinal vascular injury induced by HETEs and the underlying mechanisms. Furthermore, we pursue the causal relationship between LOX–NOX system and regulation of PEDF expression during DR. For these purposes, we used an experimental eye model in which normal mice were injected intravitreally with 12-HETE with/without PEDF. Thereafter, fluorescein angiography (FA) was used to evaluate the vascular leakage, followed by optical coherence tomography (OCT) to assess the presence of angiogenesis. FA and OCT reported an increased vascular leakage and pre-retinal neovascularization, respectively, in response to 12-HETE that were not observed in the PEDF-treated group. Moreover, PEDF significantly attenuated the increased levels of vascular cell and intercellular adhesion molecules, VCAM-1 and ICAM-1, elicited by 12-HETE injection. Accordingly, the direct relationship between HETEs and PEDF has been explored through in-vitro studies using Müller cells (rMCs) and human retinal endothelial cells (HRECs). The results showed that 12- and 15-HETEs triggered the secretion of TNF-α and IL-6, as well as activation of NFκB in rMCs and significantly increased permeability and reduced zonula occludens protein-1 (ZO-1) immunoreactivity in HRECs. All these effects were prevented in PEDF-treated cells. Furthermore, interest in PEDF regulation during DR has been expanded to include NOX system. Retinal PEDF was significantly restored in diabetic mice treated with NOX inhibitor, apocynin, or lacking NOX2 up to 80% of the control level. Collectively, our findings suggest that interfering with LOX–NOX signaling opens up a new direction for treating DR by restoring endogenous PEDF that carries out multilevel vascular protective functions.National Eye Institute 5R01EY023315-02, Qatar National Research Fund NPRP 4-1046-3-284, and Vision Discovery Institute (MA), Mr. and Mrs. Richards travel award (ASI)

Effect of Laser Therapy on the Osseointegration of Immediately Loaded Dental Implants in Patients under Vitamin C, Omega-3 and Calcium Therapy

BACKGROUND: The use of laser therapy in the biostimulation of bone repair has been growing steadily.AIM: This study aimed to evaluate the radio-densitometric effect of low-intensity laser therapy on the osseointegration of immediately loaded dental implants in patients under vitamin C, omega-3 and calcium therapy.PATIENTS AND METHODS:  A single implant was placed in the mandibular first molar region of twenty patients which were equally divided into two groups. In the non-laser group, the healing phase was left to progress spontaneously without any intervention, while in the laser group it was augmented with low-level laser therapy of wavelength 904 nm in contact mode, continuous wave, 20 mW output power and exposure time 30 sec with a dose 4.7 J/cm2. Patients in both groups were given vitamin C, calcium and omega-3 starting one month preoperatively. Postoperative digital panoramas were taken immediately after surgery, 1.5 months and 6 months postoperatively. Changes in bone density along the bone-implant interface at the mesial, distal and apical sides were assessed using the Digora software.RESULTS: Independent student t-test was used to compare means of variables between the laser and the non-laser group while repeated measures ANOVA was used to compare bone densities at different times for the same group. Significant increased differences were observed at the mesial, distal and apical sides surrounding the implants of both groups per time. However, the rate of increase was significantly higher in the laser group.  The mean difference at the mesial side after 6 months was 21.99 ± 5.48 in the laser group and 14.21 ± 4.95 in the non-laser group, while it read 21.74 ± 3.56 in the laser group and 10.78 ± 3.90 in non-laser group at the distal side and was 18.90 ± 5.91 in the laser group and 10.39 ± 3.49 in non-laser group at the apical side. Significance was recorded at P = 0.004, P = 0.0001, and 0.001 at the mesial, distal and apical sides respectively.CONCLUSION: The low-intensity laser irradiation significantly promoted bone healing and speeded up the osseointegration process emphasising the laser’s biostimulatory effect