A Multicenter Experience of Inducible Clindamycin Resistance in Staphylococcus aureus Infection among 800 Egyptian Patients with or without Diabetes Mellitus.

Staphylococcus aureus causes a wide range of illnesses, from skin infections and persistent bone infections to life-threatening septicemia and endocarditis. Methicillin-resistant S. aureus (MRSA) is one of the most common bacteria that cause nosocomial and community-acquired infections. Clindamycin is one of the most effective treatments for several bacterial infections. Despite this, these infections may develop inducible clindamycin resistance during treatment, leading to treatment failure. This study determined the incidence of inducible clindamycin resistance among S. aureus clinical isolates. A total of 800 S. aureus strains were identified from clinical samples collected from several university hospitals in Egypt. All isolates were examined for the presence of MRSA using cefoxitin (30 µg) and the Kirby Bauer disk diffusion technique. The induction phenotypes of all 800 S. aureus strains were evaluated using the disk approximation test (D test), as recommended by the Clinical and Laboratory Standard Institute. Of the 800 strains of S. aureus, 540 (67.5%) were identified as MRSA and 260 (32.5%) were classified as methicillin-sensitive S. aureus (MSSA). In MRSA infections, clindamycin constitutive and inducible resistance was more frequent than in MSSA infections (27.8% versus 11.5% and 38.9% versus 15.4%, respectively). Clindamycin-sensitive strains were more prevalent in MSSA (53.8%) than in MRSA (20.4%) infections. In conclusion, the frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use the D test in routine antimicrobial susceptibility testing to evaluate clindamycin susceptibility, as the inducible resistance phenotype can inhibit the action of clindamycin and thus affect treatment efficacy.

Metformin suppresses LRG1 and TGFß1/ALK1-induced angiogenesis and protects against ultrastructural changes in rat diabetic nephropathy.

Diabetic nephropathy (DN) has high prevalence and poor prognosis which make it a research priority for scientists. Since metformin, a hypoglycaemic drug, has been found to prolong the survival of mice with DN. This study aims at investigating the molecular mechanisms leading to DN in rats and to explore the role of leucine-rich α-2-glycoprotein-1 (LRG1), activin-like kinase1 (ALK1), and transforming growth factor-ß (TGFß1) in the pathologic alterations seen in DN. The aim was also extended to explore the protective action of metformin against DN in rats and its influence on LRG1and ALK1/TGFß1 induced renal angiogenesis. 24 male rats were used. Rats were assigned as, the vehicle group, the diabetic control group and diabetic + metformin (100 and 200 mg/kg) groups. Kidney samples were processed for histopathology, immunohistochemistry and biochemical analysis. Bioinformatic analysis of studied proteins was done to determine protein-protein interactions. Metformin reduced serum urea and creatinine significantly, decreased the inflammatory cytokine levels and reduced LRG1, TGFß1, ALK1 and vascular endothelial growth factor (VEGF) proteins in rat kidneys. Bioinformatic analysis revealed interactions between the studied proteins. Metformin alleviated the histopathological changes observed in the diabetic rats such as the glomerular surface area and increased Bowman's space diameter. Metformin groups showed decreased VEGF immunostaining compared to diabetic group. Metformin shows promising renoprotective effects in diabetic model that was at least partly mediated by downregulation of LRG1 and TGFß1/ALK1-induced renal angiogenesis. These results further explain the molecular mechanism of metformin in DN management.

Saponin-rich extract of Tribulus terrestris alleviates systemic inflammation and insulin resistance in dietary obese female rats: Impact on adipokine/hormonal disturbances.

Tribulus terrestris saponins (TTS) have been longley used as an overall tonic and recent studies showed they influence inflammatory conditions. We examined the ameliorative effect of a commercial formula of a saponin-rich extract of TT in a model of dietary obesity in female rats focusing on their ability to control the inflammatory burden, insulin resistance (IR), adipokine expression and the related reproductive system pathologies. Female rats were fed with high fat diet (HFD) for 14 weeks to launch diet-induced obesity; they were assigned as: the obese control female rats (OFR) which received no treatment and TTS (5 and 10 mg/kg/day) treated rats; they were compared to a normal rat group. We determined the IR index, serum/tissue inflammatory cytokines, and adipose tissue adipokine expression and examined the secondary ovarian pathologies. Body weight gain, serum triglycerides and IR (>5-fold) in the OFR group were greater than the normal group; TTS lessened these parameters compared with the OFR group. TTS, at 10 mg/kg dose, ameliorated mRNA expression of leptin and visfatin genes in addition to serum inflammatory cytokine levels. Moreover, TTS corrected the hyperprolactinemia and other hormonal disturbances and ameliorated the ovarian pathologies. This study highlighted that the anti-inflammatory properties of TTS helped in alleviation of IR and body weight gain in OFR. Upon correction of obesity manifestations, the gonadal hormone dysregulations and ovarian pathologies were subsequently ameliorated. We can consider TTS as a promising candidate that may alleviate the inflammatory burden, IR and adipokine expression in obesity and hence prevent the secondary gonadal complications in female subjects if appropriate clinical studies are available.

Variceal recurrence 4 years post endoscopic band ligation in hepatitis C patients who achieved sustained virological response with oral direct-acting antiviral therapy.

Oral Direct-acting antivirals (DAAs) are safe, highly effective altering disease burden and prognosis in hepatitis C patients. Sustained virologic response (SVR) is achieved nowadays in more than 90% of the treated patients and related to the improvements in functions of the liver, fibrosis plus survival. Furthermore, portal hypertension is thought to be improved with achievement of virological response, parallel to the improvements in hepatic inflammation and fibrosis. We aimed to assess the recurrence rate of oesophageal varices by long-term follow-up in patients treated with different DAAs regimens who had achieved SVR. We studied 176 Child A cirrhotic HCV patients who achieved SVR after DAAs treatment and had a history of endoscopic oesophageal varices obliteration and were on maximum tolerated propranolol dose. They were subjected to follow-up upper gastrointestinal endoscopy repeated every 6 months for 4 years. Fifty-two patients (29.5%) had recurrence of oesophageal varices observed during the 4-years follow-up upper GIT endoscopy. On multivariate analysis, platelet count was the only significant variable, P-value = .007*. HbA1C, HOMA IR, BMI 1 and BMI 2 showed non-significant differences between the studied groups. By ROC analysis, we identified baseline platelet count of 96 000/µL with 100% sensitivity (95% confidence interval [CI] [91%-100%]) and 74% specificity (95% CI [65%-81%]). Spearman correlation showed a positive correlation between AFP, age, AST, Bilirubin, creatinine, INR. Patients who achieved SVR post DAAs showed a significant decrease in oesophageal varices recurrence post endoscopic obliteration. Baseline platelet count was found to be a strong independent predictor for oesophageal varices recurrence.

Role of resistin, IL-6 and NH2-terminal portion proBNP in the pathogenesis of cardiac disease in type 2 diabetes mellitus.

INTRODUCTION: Epidemiological and genetic studies have recorded the association between proinflammatory cytokines and the development of insulin resistance, diabetes, and cardiovascular disease. The role of interleukin 6 (IL-6), NH2-terminal portion pro-brain natriuretic peptide (NT-proBNP) and resistin in the pathogenesis of heart disease in type 2 diabetes mellitus (T2DM) is still a matter of controversy. The current study aimed to evaluate the role of these biomarkers in the development of left ventricular systolic dysfunction and the ability to use them as non-invasive test in the prediction of left ventricular hypertrophy and systolic dysfunction in T2DM. RESEARCH DESIGN AND METHODS: 150 participants were included in this case-control study. Patients were divided into two subgroups according to echocardiographic findings: group 1a included 46 patients with type 2 diabetes mellitus and echocardiographic evidence of abnormal systolic function; group 1b included 54 patients with type 2 diabetes mellitus and with normal echocardiogenic study; and group 2 included 50 apparently healthy controls. Routine laboratory investigations such as complete blood count, liver and renal function tests, and lipid profile, serum IL-6, NT-proBNP, and resistin were measured in all participants. Conventional echocardiography was done with special concern on the assessment of left ventricular systolic function (ejection fraction). RESULTS: There was a significant increase in the level of resistin, NT-proBNP and IL-6 in group 1a patients compared with group 1b and in healthy controls. Echocardiographic parameters showed a significant increase in left ventricular mass index, left ventricle posterior wall thickness, interventricular septum thickness, and left ventricle mass in group 1a compared with group 1b and the control group. The increased left ventricular mass index was associated with higher levels of IL-6, NT-proBNP and resistin. CONCLUSIONS: Proinflammatory cytokines had a clear relation with left ventricular systolic dysfunction and hypertrophy and can be used as early non-invasive markers for detection of left ventricular remodeling and systolic dysfunction in patients with T2DM.

The Circulating Micro-RNAs (-122, -34a and -99a) as Predictive Biomarkers for Non-Alcoholic Fatty Liver Diseases.

BACKGROUND: It remains essential for patient safety to develop non-invasive diagnostic tools to diagnose non-alcoholic fatty liver rather than invasive techniques. AIM: Our case-control study was to address the value of circulating miRNAs as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases (NAFLD) and monitoring of disease progression. METHODS: Routine clinical assessment, laboratory tests, anthropometric study, and liver biopsy results reported for 210 patients with NAFLD (124 patients of simple steatosis (SS) and 86 of non-alcoholic steatohepatitis (NASH)). Apparently matched for age and gender, healthy participants (n= 90) were enrolled as a control group. Serum samples were tested for micro-RNAs (-122, -34a and -99a) by quantitative-PCR. RESULTS: By histopathology, 124 of the NAFLD group were of SS and 86 patients were of NASH. Compared with the control subjects, both mi-RNA-122 and -34a levels were increased in NAFLD (p< 001) and at a cut-off = 1.261, mi-RNA-122 had 92% sensitivity, 85% specificity to differentiate NAFLD from healthy controls, while mi-RNA-99a were significantly decreased in NAFLD patients with an observed decrease in disease severity, and at a cut-off = 0.46, miRNA-99a had 94% sensitivity and 96% specificity to discriminate SS from NASH. CONCLUSION: The integration of a circulating mi-RNA panel to diagnose NAFLD cases and to discriminate between SS and NASH. Large-scale study is still needed to verify the other mi-RNA profiles and their role in NAFLD pathogenesis and targeting therapy.