Neuroprotective effect of Crocus sativus against cerebral ischemia in rats

Metabolic Brain Disease - The present study aimed to investigate the role of vascular endothelial growth factor (VEGF) in the neuroprotective effect of Crocus sativus (saffron) against cerebral...     

Antibiotic resistance and prevalence of beta-lactamase in Haemophilus influenzae isolates-a surveillance study of patients with respiratory infection in Saudi Arabia

Haemophilus influenzae was isolated from patients with respiratory tract infections in five centers in Saudi Arabia. All of the 129 isolates tested by MIC agar dilution were fully susceptible to ceftazidime and ciprofloxacin but 13.2% were resistant to ampicillin, 7% to tetracycline, 5.4% to chloramphenicol, 3.9% to roxithromycin, and 1.6% to amoxicillin/clavulanic acid. Seventeen (13.2%) of all isolates produced TEM-1 type beta-lactamase, the majority (82%) characterized as biotype I or II with 4 (23.5%) encapsulated and belonging to serotype b. There was a clear distinction between the prevalence of beta-lactamase production in hospital patients (26.3% of 19 isolates) compared with community based patients (10.9% of 110 isolates). In addition, we report an increase in the prevalence of beta-lactamase negative, ampicillin intermediate strains (BLNAI) compared to previous studies in this defined geographical region. Changes in the frequency and nature of antimicrobial resistance in common respiratory pathogens confirms the need to maintain surveillance.     

Can melatonin be used as a marker for neonatal sepsis?

Background: Melatonin, an indolamine endogenously produced by pineal body, has important role as an anti-oxidant, anti-inflammatory and anti-apoptotic. Whether melatonin concentration changes in neonatal sepsis and whether it can be used as a marker of sepsis is unknown.

Objective: The objective of this study is to evaluate melatonin concentration in the serum as a marker for neonatal sepsis and compare it to standard markers.

Study design: We prospectively studied 40 neonates: 20 diagnosed with late neonatal sepsis and 20 healthy neonates as a control group. Markers of sepsis and melatonin concentration were compared between both groups.

Results: The sepsis groups had significantly increased immature to total neutrophils ratio (I/T ratio), and high sensitivity C-reactive protein (HsCRP), and decreased platelet count. Melatonin concentration was increased in sepsis group when compared to control group (27.2?±?3.3 versus 11.4?±?3.2?pg/ml, p?=?0.001), and positively correlated with HsCRP (r?=?0.952, p?=?0.001) and I/T ratio (r?=?0.326, p?=?0.015). Combining melatonin to HsCRP increased sensitivity and specificity to detect neonatal sepsis to 97.3 and 93.3%, respectively.

Conclusions: Endogenous melatonin concentration is increased in late neonatal sepsis and can potentially be used as a marker for sepsis especially when combined with CRP.     

Sarcocystis arieticanis (Apicomplexa: Sarcocystidae) infecting the heart muscles of the domestic sheep,Ovis aries (Artiodactyla: Bovidae), from K. S. A. on the basis of light and electron microscopic data

In the present study, the heteroxenous life cycle of Sarcocystis species from three strains of the slaughtered sheep at Al-Azizia and Al-Saada abattoirs in Riyadh city, K.S.A., was studied. Muscle samples of the oesophagus, diaphragm, tongue, skeletal and heart muscles were examined. Varied natural infection rates in the muscles of the examined sheep strains were recorded as 83 % in Niemy, 81.5 % in Najdy and 90 % in Sawakny sheep. Muscles of the diaphragm showed the highest infection level above all organs except Najdy sheep in which oesophagus has the highest rate. Also, the heart was the lowest infected organ (40 % Niemy, 44 % Najdy and 53 % Sawakny). Microscopic sarcocysts of Sarcocystis arieticanis are easily identified in sections through the heart muscles of the domestic sheep Ovis aries (Artiodactyla: Bovidae). Cysts measured 38.5–64.4 μm (averaged 42.66 μm) in width and 62.4–173.6 μm (averaged 82.14 μm) in length. The validity of this species was confirmed by means of ultrastructural characteristics of the primary cyst wall (0.1–0.27 μm thick) which revealed the presence of irregularly shaped crowded and hairy-like projections underlined by a thin layer of ground substance. This layer consisted mainly of fine, dense homogenous granules enclosing the developing metrocytes and merozoites that usually contain nearly all the structures of the apical complex and fill the interior cavity of the cyst. Several septa derived from the ground substance divided the cyst into compartments. The merozoites were banana-shaped and measured 12–16 μm in length with centrally or posteriorly located nuclei. Experimental infection of carnivores by feeding heavily infected sheep muscles revealed that the dog, Canis familiaris, is the only final host of the present Sarcocystis species. Gamogony, sporogonic stages and characteristics of sporulated oocysts were also investigated.     

Somatic FGF9 mutations in colorectal and endometrial carcinomas associated with membranous beta-catenin

We previously described striking molecular features including high frequency of membranous beta-catenin in subsets of familial colon cancers with as yet unknown predisposition. We hypothesized that such tumors might carry mutations in Wnt/beta-catenin target genes. Fibroblast growth factor 9 (FGF9) was an attractive target, as it maps to a common area of loss of heterozygosity (LOH) in colorectal carcinomas on 13q12.11. Here, we report, for the first time, the occurrence of FGF9 mutations in human cancers. We found a total of six distinct FGF9 mutations including one frameshift, four missense, and one nonsense, in 10 (six colorectal and four endometrial) out of 203 tumors and cell lines. The frameshift mutation was detected in five different tumors. Mapping of these mutations onto the crystal structure of FGF9 predicted that they should all lead to loss of function albeit through variable mechanisms. The p.R173K mutation should diminish ligand affinity for heparin/heparan sulfate, the p.V192M, p.D203G, and p.L188YfsX18 (FGF9(Delta205-208)) mutations should negatively impact ligand's interaction with receptor, while p.G84E and p.E142X (FGF9(Delta142-208)) mutations should interfere with ligand folding. Consistent with these structural predictions, the p.V192M, p.D203G, and p.L188YfsX18 (FGF9(Delta205-208)) mutations impaired the ability of ligand to activate mitogen-activated protein kinase (MAPK) cascade in cultured cells expressing FGF receptors. LOH was observed in seven out of nine FGF9 mutant tumors, supporting the predicted loss of function. Interestingly, eight out of 10 (80%) of the FGF9 mutant tumors showed normal membranous beta-catenin expression and the absence of mutation in the beta-catenin gene (CTNNB1). These data suggest that FGF9 plays a role in colorectal and endometrial carcinogenesis.     

Differentiation of acute osteoporotic from malignant vertebral compression fractures with conventional MRI and diffusion MR imaging

Aim

To evaluate the role of using a single shot spin echoplanar DW sequence (SSSEP-DWI) compared to conventional MRI and contrast enhanced T1WI in differentiation between vertebral osteoporotic fractures and malignant compression fractures. The sensitivity and specificity of (SSSEP-DWI) will also be calculated.

Tumor necrosis factor-α production from mononuclear cells in nephrotic syndrome

Tumor necrosis factor-alpha (TNF-alpha) levels in supernatant fluid from cultured peripheral blood mononuclear cells (PBMC) were measured by ELISA in 54 children with active non-inherited forms of primary nephrotic syndrome (PNS), 10 nephrotics in remission, and 10 healthy controls. Children with active PNS included 21 patients with steroid-sensitive (SS) minimal change nephrotic syndrome (MCNS), 5 patients with steroid-resistant (SR) MCNS, 11 with SR focal segmental glomerulosclerosis (FSGS), 6 patients with SS diffuse mesangial proliferation (DMP), 5 patients with SR DMP, and 6 patients with mesangiocapillary glomerulonephritis (MCGN). Patients with active PNS had elevated TNF-alpha production compared with controls. Remission was associated with normalization of TNF-alpha production. There was a positive correlation between TNF-alpha production and the degree of proteinuria ( r=0.34, P=0.013), mesangial hypercellularity ( r=0.42, P=0.028), and glomerulosclerosis ( r=0.46, P=0.001). By using ROC curve, TNF-alpha production greater or equal to a cut-off point of 50 pg/ml could be used to predict resistance to steroid therapy (predictability 93.2%). By discriminate analysis, TNF-alpha production could be used to discriminate between patients with SR MCNS, SR FSGS, and SR DMP (predictability 100%). In conclusion, TNF-alpha from cultured PBMC might be involved in the pathogenesis of proteinuria as well as the pathological changes that occur in non-inherited forms of PNS. TNF-alpha levels in PBMC culture could be used to predict the pathological type of PNS and the response of these patients to steroid therapy.     

Role of CD4+ and CD8+ T cells in murine skin and heart allograft rejection across different antigenic desparities

The factors that influence the relative contribution of the T cell subsets to allograft rejection remain unclear. We compared skin and heart rejection in CD4 Knockout (KO), and CD8 KO mice across full-, minor-, and class II histocompatibility antigen (HA) mismatches. Skin allografts were rejected by either CD4+ or CD8+ T cells alone at any degree of antigenic mismatch. However, either the absence of CD4+ cells or a lesser degree of HA mismatch resulted in prolongation of graft survival. In contrast, fully allogeneic heart grafts were accepted in CD4 KO recipients, and minor HA mismatched heart grafts were accepted by both CD4 KO and CD8 KO mice. Thus, the T cell subsets required for allograft rejection are determined by the immunogenicity of the tissue transplanted. In the absence of CD8+ T cells, perforin and Fas ligand (FasL) but not granzyme B mRNA were detected in rejecting grafts. Thus, granzyme B is a CD8+ cytotoxic T lymphocyte (CTL)-specific effector molecule.     

Role of endothelial adenosine receptor-mediated vasorelaxation in ethanol-induced hypotension in hypertensive rats

Our previous findings showed that chronic ethanol feeding lowers blood pressure in spontaneously hypertensive rats. The present study investigated the role of the adenosine receptor-endothelial nitric oxide (NO) pathway in the hypotensive response to ethanol. Changes in blood pressure were evaluated in radiotelemetered pair-fed rats receiving liquid diet with or without ethanol (2.5% or 5%, w/v) for 12 weeks. The vasorelaxant activity of the adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) in isolated aortic rings obtained from ethanol and control rats were evaluated. Ethanol (2.5% and 5%) lowered blood pressure in a dose-dependent manner. The hypotension started at week 1, reached its maximum at week 4 and remained so thereafter. In aortas with intact endothelium, NECA (10(-10) to 10(-4) M) produced a concentration-dependent relaxation of the phenylephrine-precontracted aortas. Compared with control rats, ethanol (2.5% and 5%) caused significant and concentration-related increases in NECA responses. This effect of ethanol was attenuated by the adenosine receptor antagonist 8-sulfophenyltheophylline and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Further, endothelium denudation abolished the ethanol-evoked enhancement of NECA responses. The vasorelaxant responses to acetylcholine or sodium nitroprusside in aortic rings were not influenced by ethanol. In conclusion, the present findings suggest that chronic ethanol enhances the NO-dependent vasorelaxant responses to adenosine receptor activation and this may explain, at least partly, the mechanism of the hypotensive effect of ethanol in spontaneously hypertensive rats.     

Repeated transurethral resection of recurrent superficial bladder tumors--does it affect the spread and stage of the tumor?

OBJECTIVES: This prospective study was done to demonstrate the effect of repeated resection of superficial bladder tumors (TURT) on deep malignant cell infiltration in bladder wall. MATERIAL AND METHODS: Thirty-six patients underwent radical cystectomy for invasive bladder cancer, 16 patients originally had superficial cancer that became invasive after repeated TURT (group I) and the other 20 patients (group II) presented with invasive bladder cancer from the start. Each cystectomy specimen was subjected to a thorough histopathological study. RESULTS: There was a statistically significant difference in pattern of local spread of malignant cells between the two groups. Isolated clusters of malignant cells in-between normal bladder muscle fibers, isolated subserosal malignant deposits as well as cells reaching the adjacent cervix uteri were found only in group I. Intravesical pressure was measured in another 10 patients during TURT and was found to be high reaching up to 80 cm H2O. CONCLUSIONS: We conclude that some malignant cells penetrate through the denuded urothelium during TURT by the effect of high intravesical pressure. This may be responsible, among other factors, for tumor recurrence with deeper stages.