Search

Valproic acid (VPA) is a powerful antiepileptic drug that was associated with several neurological and hepatic problems especially with increasing its dose and duration. These problems may be metabolic in origin and related to glucose homeostasis. So, the present study investigated the effect of different doses and durations of VPA on the expression of glucose transporters (Glut1 and Glut4), oxidative stress and inflammatory cytokine (IL-6) in the liver and specific brain regions. Seventy-two male Sprague-Dawley rats were randomly allocated into three equal groups: (1) saline group, (2) 200 mg VPA group and (3) 400 mg VPA group. By the end of experiments, the expressions of Glut1, Glut4 nuclear factor erythroid-like 2 related factor (Nrf2), IL-6 and oxidative stress markers [malondialdehyde (MDA) and glutathione (GSH)] in the liver, corpus striatum, prefrontal cortex (PFC) and cerebellum were assessed. We found that administration of VPA (200 mg and 400 mg) caused a significant decrease in the Glut1 and Glut4 expression in different tissues in a dose- and time-dependent manner (P < 0.01). Also, VPA (200 and 400 mg) caused a significant increase in MDA with a decrease in GSH in tissues at different times. Moreover, VPA (200 and 400 mg) caused significant upregulation in IL-6 expression and downregulation in Nrf2 expression (P < 0.01). The results suggest that increasing the dose and time of VPA therapy downregulates Glut1 and Glut4 in the liver and brain which may impair glucose uptake in these tissues. This effect was associated with enhanced oxidative stress, downregulation of nrf2 and upregulation of IL-6 in liver and brain tissues.

Cardiorenal syndrome (CRS) is a complex heart and kidney pathophysiologic disorder that leads to a bidirectional interrelationship between them. Abscisic acid (ABA) is a phytohormone that is present in plants, and is known to regulate fundamental physiological functions. This study aimed to explore the efficacy of ABA in surgically induced-CRS type 3 rats. Rats were randomly and equally divided into four groups. Rats in Group 1 received saline (Sham group), Group 2 included control induced-CRS rats, Group 3 rats (CRS+ABA) included CRS rats treated with ABA and Group 4 (CRS + ABA + Verapamil + propofol) were CRS rats treated with Verapamil, propofol and ABA. The rats were treated with the drugs daily for four weeks. At the end of the study, relative heart weight corrected QT interval (QTc), mean blood pressure (MBP), kidney functions, oxidative stress, NADPH oxidase 4 (NOX4), protein 53 (P53), and heat shock proteins-70 (HSP-70) expression was assessed and recorded. ABA led to a significant shortening of the ventricular action potential duration indicated by QTc. Furthermore, it significantly lowered heart weight, MBP, serum creatinine, NOX-4, and P-53 expression and augmented HSP-70 expression. In contrast, adding calcium channel blockers (CCBs) to ABA mitigated this effect. The results suggested that ABA has a potential protective role in CRS-induced cardiac hypertrophy and arrhythmia that could be mediated through inhibition of P-53, NOX-4, and an increase in HSP-70 expression.

There are many road defects appear in flexible pavement layers. Rutting, raveling and cracks are considered the main problems in Egypt. Using grouted macadam system as a surface asphaltic layer (or called Semi-Flexible Pavement (SFP)) has many advantages such as saving the natural asphalt and enhancing the performance against deteriorations. The main scope of this research is to evaluate and improve the performance of SFP using modified grout by additives as fine sand, Silica Fume (SF), Fly Ash (FA) and Super-Plasticizer (SP). Different mixing ratios for grout contents (cement: Fine sand: Additives: Water) were tried and tested using flow time (workability), flexural and compressive strength to achieve the optimal grout characteristics. Crushed siliceous-limestone was used in preparing open graded (porous) asphalt mixtures to obtain suitable permeability. After grouting the asphalt mixtures, Marshall and indirect tensile strength tests were performed. The results indicated that the use of equal amounts from cement and fine sand was preferred in grout. Silica fume was preferred as additive for improving the grout properties. The results obtained that the grouted macadam significantly improved the performance of pavement compared with traditional flexible pavement.

This study aims at characterization and design new special type of asphalt mixture havinglower asphalt content and higher rutting resistance to be used in paving surface layers atheavy loads areas. To achieve this objective, grouting technique of permeable open gradedasphalt mixtures was used. Such type of pavement is called as a semi-flexible pavement (SFP)or grouted macadam (GM). Different compaction efforts were used to achieve the requiredpercent of connected air voids between the bitumen coated aggregates. Crushed silicalimestone, crushed sand, and filler were used to prepare highly permeable asphalt mixtures.Asphalt contents of these mixes were determined theoretically and It was ostensibly examinedby the laboratory. Marshall molds representing open graded mixtures were prepared andgrouted using a grout composed of ordinary Portland cement (OPC) as well as a mixture ofsome concrete additives with different ratios. Choosing the suitable grout mixture dependedon the flow time, flexural and compressive strengths for lab-produced grout prisms.Measuring Marshall stability, Marshall flow, and indirect tensile strength test were conductedon grouted asphalt mixes to identify their properties. The same tests were conducted oncrushed silica limestone open graded mix of 2C gradation (Egyptian Standards for Roads) forcomparison purposes. Analyzing the study results, positive effect of grouting open gradedmixes was concluded using a mixture of OPC, fine sand, silica fume and superplasticizer. Therequired bitumen content for surface layers was decreased by percent between 27% to 37%compared with traditional dense asphalt mixtures. The resistance of rutting for grouted mixeswas increased through increasing stability and indirect tensile strength by about 3 times andmore compared with traditional open asphalt mixtures.

Background Systemic osteoporosis (OP) is evident among patients with early rheumatoid arthritis (ERA). This study aimed to investigate the OP risk factors in patients with ERA and who was treatment-naïve at inclusion. Subjects and Methods Systemic bone mineral density (BMD) of the lumbar spine (LS), femoral neck (FN) and total hip (TH) was measured in 135 treatment-naïve premenopausal females with early Rheumatoid Arthritis (ERA). For all patients, demographic data, vitamin D status, and the specific parameters of the disease, including disease activity, serum levels of rheumatoid factor and anti-citrullinated protein antibodies (ACPA) were evaluated. Results T score was Conclusion Presence of ACPA or RF is associated with increased risk for development of reduced systemic BMD from very early stage of rheumatoid arthritis. Furthermore, this risk increases more with higher levels of ACPA or RF. Measurement of BMD should be performed for ACPA- or RF-positive patients with early RA.

Background and aim of work Chronic inflammation is the basis of juvenile idiopathic arthritis (JIA). Hence, it is expected that JIA may produce harmful effects on the cardiovascular system. The aim of this study was to explore the presence of subclinical atherosclerosis and subclinical heart failure in JIA patients without manifest cardiovascular disease and to examine the risk factors that may be associated with the subclinical heart failure. Patients and methods Fifty JIA patients and 50 healthy matched controls were enrolled in this study. Inflammatory markers in the serum, together with intima-media thickness (IMT) and flow-mediated dilation (FMD) of brachial arteries as surrogate markers of subclinical atherosclerosis, were assessed and compared between patients and controls. Echocardiographic parameters of heart failure, including the Tei index and ejection fraction%, were also evaluated. Results JIA patients had significantly increased IMT and impaired endothelial dysfunction as measured by FMD% of the brachial artery in comparison with controls. JIA patients had significantly higher Tei index and significantly lower ejection fraction% in comparison with controls. In regression analysis only systemic JIA, FMD%, and IMT were significantly associated with the presence of subclinical heart failure among patients with JIA. Conclusion Our findings indicate the presence of subclinical heart failure in these patients. JIA patients with subclinical atherosclerosis, with systemic disease, and with active disease are at greatest risk of developing subclinical heart failure.

Background Non-alcoholic fatty liver disease (NAFLD) is associated with hyperlipidemia, obesity and type II diabetes. Due to increasing prevalence of these diseases globally, NAFLD is considered as a common form of chronic liver diseases. Vitamin D is a fat soluble vitamin with reported anti-inflammatory, anti-oxidant and immune modulating activity. Hypovitaminosis D often coexists with NAFLD and various studies reported beneficial role of vitamin D in modulating NAFLD. However, variable oral bioavailability, poor water solubility, and chemical degradation hinder the clinical application of vitamin D. Purpose We evaluated the potential protective effect of Vitamin D nanoemulsion (developed by sonication and pH-Shifting of pea protein isolate and canola oil) compared to conventional vitamin D against liver injury in rats fed with high fat diet (HFD). Methods We analyzed liver function enzymes, lipid profile, lipid metabolism, levels and histopathology of inflammation and fibrosis in rat liver tissues. Results HFD fed rats exhibited deterioration of liver function, poor lipid profile, decreased fatty acid oxidation and up-regulation of inflammatory cytokines and extracellular matrix deposition. Vitamin D administration reduced elevated liver enzymes, improved lipid profile, enhanced fatty acid oxidation and attenuated liver inflammation and fibrosis. Interestingly, vitamin D nanoemulsion was superior to conventional vitamin D with remarkable hepatoprotective effect against HFD-induced liver injury. Conclusion This study demonstrated vitamin D nanoemulsion as a more efficient formulation with more prominent hepatoprotective effect against HFD-induced liver injury compared to conventional oral vitamin D.

The androgen receptor (AR), a member of the nuclear receptor superfamily, playsimportant role in male reproductive functions. A functional androgen receptor isrequired for male embryonic sexual differentiation, pubertal development andregulation of spermatogenesis. The role of AR during spermatogenesis has been thesubject of intense interest for many years. Several reports have shown that ARfunction is required for the completion of meiosis and the transition of spermatocytesto haploid round spermatids. The aim of the present study was to determine theassociation between androgen receptor expression and fertilization ability of humansperm in different andrological diseases. Eighty semen samples obtained from menattending the Andrology Outpatient Clinic, Mansoura University Hospital wereincluded in the study .The samples were grouped into control (n=20), accessory sexgland inflammation (MAGI) ( n=18), varicocele ( n=25) and idiopathic infertility(n=17). The semen samples analyses were done according to the recommendation ofthe World Health Organization. Computer assisted semen analysis (Autosperm) wasperformed. The acrosome reaction of spermatozoa recovered from each sample wasassessed before and after stimulation with the calcium ionophore A23187 (Sigma, St.Louis, Missouri, USA) by the pisum sativum (Sigma, St. Louis, Missouri, USA)fluorescence method with simultaneous vitality stain (Hoechst 33258, Germany).RNA was extracted from sperm of all cases and controls. cDNA and amplification ofa gene region from 1648 to 2055 bp corresponding to the DNA binding domain plusthe hinge region of human androgen receptor was carried out by one step RT-PCR.The PCR product size of 400 bp was electrophoresed on agarose gel 2%electrophoresis. Androgen receptor expression was significantly decreased in MAGI,varicocele and idiopathic groups compared with the control (P

Colorectal anastomotic leakage is a serious complication leading to major postoperative morbidity and mortality. In the present study, we investigated the early detection of anastomotic leakage before its clinical presentation. Fifty-six patients with rectal cancer were included prospectively in this study. All patients underwent elective low anterior resection. Peritoneal samples were collected from the abdominal drains at the first, third, and fifth days postoperatively for bacteriological study (quantitative cultures for both aerobes and anaerobes) and cytokines (IL-6, IL-10, TNF) measurement. Patients were divided into two groups: those without symptomatic or clinical evidence of anastomotic leakage (AL; group 1) and those with clinical evidence of AL (group 2). Study variables included hospital stay, wound infection, operative time, blood loss, height of anastomosis, intraperitoneal cytokines, and microbiological study of peritoneal fluid. Clinically evident AL occurred in eight patients (14.3%) and diagnosed postoperatively on median day 6. Intraperitoneal bacterial colonization and cytokine levels were significantly higher in patients with clinical evidence of AL. Wound infection was significantly higher in anastomotic leakage group. The hospital stay for the patients with anastomotic leakage was significantly longer than those without AL (14 ± 1.41 vs. 5.43 ± 0.89 days). A significant difference among two groups was observed regarding operative time, blood loss, blood transfusion, and height of the anastomosis. The peritoneal cytokines levels and intraperitoneal bacterial colonization might be an additional diagnostic tool that can support the decision making of surgeons for early detection of anastomotic leak in colorectal surgery.

Objective To assess the efficacy of a combination of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa) as natural leukotriene inhibitor, antiinflammatory and antioxidant products respectively in controlling bronchial asthma. Subjects and methods The study comprised 63 patients with bronchial asthma that are further subdivided into two groups .Group 1 receiving oral capsule (combined herb) in a soft-gelatin capsule 3 times daily for 4 weeks and group 2 receiving placebo. Plasma leukotriene C4 (LTC4), nitric oxide (NO) and malondialdehyde (MDA) levels were measured and pulmonary function was also assessed in all patients enrolled in the study. Results There was a statistically significant decrease in the plasma levels of LTC4, (MDA), and NO in target therapy group when compared with placebo group. Conclusion The used extract contained Boswellia serrata, Curcuma longa and Glycyrrhiza has a pronounced effect in the management of bronchial asthma.

Background: Distinguishing which patient with early RA is to run a severe disease course with development of erosions and which is not at baseline evaluation is a major challenge in the management of RA. Objectives: To assess the changes of the blood flow signals in a total of 2 the studied joints from the start and after one year as well as to predict the future joint damage after one year by assessing the ability of synovial vascularity at baseline measured by power Doppler ultrasound (PDUS). Patients and Methods: This study was conducted on 34 consecutive early RA patients naive to DMARDs and glucocorticoids who underwent clinical, laboratory, radiologic and ultrasonography (US) assessment at baseline, and 1 year. The degree of US synovial proliferation (US-SP) was investigated in 28 joints using gray-scale ultrasonography. Synovial vascularity was investigated using PDUS and were scored on a 4-grade scale, and the total of the scores in the 28 joints was regarded as the total signal score (US-TSS). Results: The PD-TSS and US-SP correlated with DAS28-CRP, CRP and radiographic score and to a lesser extent with TJC, SJC and VAS-pain at baseline and one year. PD-TSS and US-SP significantly correlated with HAQ at baseline but not one year. In univariate analysis, the total radiographic score at 1 year and radiographic progression were significantly associated with baseline presence of anti-CCP, presence of RF, US-SP, PD-TSS, radiographic score and the count of joints that had been persistently swollen for the year follow up period. The baseline parameters identified by logistic regression as an independent predictive factor of radiographic score at 1 year and radiographic progression were PD-TSS and radiographic score. Conclusion: Radiographic score after 1 year and radiographic progression was predicted by baseline synovial vascularity and baseline radiographic score of joint damage. Degree of synovial vascularity and synovial proliferation as measured by ultrasonography are correlated with rheumatoid activity.

Aim: The aim of our study was to assess serum concentration of macrophage derived cytokine (MDC) and matrix metalloproteinase-9 (MMP-9) in patients with active and inactive SLE and in healthy volunteers. Subjects and Methods: The study included 40 patients with SLE and 40 healthy control. The serum level of MDC and MMP-9 were evaluated and compared between the patients and the controls. The association of the MDC and MMP-9 with disease activity, renal involvement, drug intake were also evaluated. Results: SLE patients had significantly lower MDC and lower MMP-9 than control (p

Androgen receptor, a member of the nuclear receptor superfamily, has important roles in male reproductive function. It is required for sexual differentiation, pubertal development, spermatogenesis regulation, meiosis completion and spermatocyte transition to haploid round spermatids. We assessed the association of androgen receptor expression and semen variables in infertile men with varicocele.A total of 299 men were grouped into healthy, fertile controls, infertile men without varicocele and men with infertility associated with varicocele. A history was obtained, clinical examination and semen analysis were done and reproductive hormones were estimated. Androgen receptor expression and the acrosome reaction were determined in recovered spermatozoa.Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile controls. Androgen receptor correlated positively with sperm count, motility, normal forms, velocity, linear velocity, acrosome reaction and α-glucosidase. It correlated negatively with serum follicle-stimulating hormone and estradiol. Multiple stepwise regression analysis of androgen receptor expression revealed that the sperm acrosome reaction and linearity index were the most affected independent variables.Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile men. Androgen receptor expression correlated positively with sperm count, motility, normal forms, velocity, linear velocity and acrosome reaction.