Beneficial role of simvastatin in experimental autoimmune myositis.

OBJECTIVE: Statins have immunomodulatory potential in autoimmune diseases but had not been studied as a disease-modifying agent in inflammatory myopathies. The objective of this study is to assess the effect of simvastatin in an experimental model of autoimmune myositis in mice on muscle strength and histopathology. METHODS: Four groups of mice (n = 5 per group) were selected for experimentally induced myositis. Mice were immunized with 1.5 mg myosin in complete Freund's adjuvant weekly for two times and injected with 500 ng pertussis toxin twice immediately after each immunization. From day 1 before immunization to 10 days after the last immunization, mice were treated with oral simvastatin (10 or 20 or 40 mg/kg) diluted in DMSO. The control group mice were injected with complete Freund's adjuvant weekly for two times and did not receive treatment. Non-immunized mice (n = 5 per group) were treated either with simvastatin (5 mg/kg or 20 mg/kg or 40 mg/kg of simvastatin diluted in DMSO) or with DMSO. RESULTS: Inflammation was observed in myositis groups with positive myositis-specific antibodies. Muscle strength dropped significantly after immunization. Immunized simvastatin 20 mg/kg treated group had significantly higher muscle strength versus non-treated myositis mice and versus other simvastatin doses. Besides, a trend toward higher serum Th17 percentage population was found in immunized non-treated mice, versus immunized simvastatin- treated mice, without significant difference. CONCLUSION: Simvastatin at 20 mg/kg decreases the severity of myositis in experimental autoimmune myositis and is a candidate of being a disease-modifying agent in inflammatory myopathies.

Epidemiological Study of Thyroid Pathology in a University Hospital.

OBJECTIVES: The incidence of papillary thyroid carcinoma increased in several countries. The purpose of this study was to quantify the changes in thyroid carcinomas in our University Hospital. STUDY DESIGN: Retrospective study. METHODS: All 1.927 thyroidectomy cases studied in the Pathology Department of Hotel-Dieu de France Hospital (Beirut, Lebanon), between 2003 and 2013, were included. RESULTS: The Female/Male Sex Ratio of the studied population was 3.7/1. The mean age of female patients was significantly lower than that of male patients. The most frequent diagnoses were multinodular goiter (78%) and papillary-carcinoma (26%). 337 cases had a single lesion on gross examination. 21 of them were diagnosed with follicular carcinoma and 59 with follicular adenoma. A statistically significant correlation was found between the unicity of the lesion on gross examination and the final diagnosis of a follicular neoplasm. Thyroid carcinoma was multifocal in 33% of the cases and bilateral in 24%. A statistically significant increase in thyroid carcinoma proportion (from 15% in 2003 to 44% in 2013) was found. Among all thyroid carcinomas, the proportion of papillary type increased from 65% in 2003 to 94% in 2013 ; this increase remained statistically significant after the exclusion of papillary micro-carcinomas, whose proportion was stable throughout the 11 years. CONCLUSIONS: In this study, we noted a statistically significant increase in the frequency of thyroid carcinoma, especially of the papillary type. The unicity of the lesion on gross examination is significantly associated with a follicular neoplasm.

Cardiorenal syndrome in hypertensive rats: microalbuminuria, inflammation and ventricular hypertrophy.

The aim of our study was to evaluate a possible association between microalbuminuria (MA), several low-grade inflammation factors and left ventricular hypertrophy (LVH) by using a pharmacological approach. This may provide new insights into the pathophysiologic mechanisms of the cardiorenal syndrome (CRS) linking early renal impairment with elevated cardiovascular risk. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (220-250 g). After the development of hypertension, rats were divided into four groups: 2K-1C (untreated), calcium channel blocker (amlodipine-treated), angiotensin receptor blocker (losartan-treated) and peripheral vasodilator (hydralazine-treated), which were treated for 10 weeks. Rats in the 2K-1C group had all developed hypertension, a significant increase in plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), brain natriuretic peptide (BNP) and C-reactive protein (CRP). Moreover MA and creatininaemia underwent a significant increase. Under treatment decreases were observed in systolic blood pressure (SBP), TNF-alpha, CRP, IL-6, BNP concentrations and creatininaemia. These results were related to the absence of MA which was significantly associated with reductions in cardiac mass and hypertrophy markers (BNP and beta-MHC gene expression) as well as renal interstitial inflammation. In conclusion, our results suggest that the reduction of MA is correlated with the decrease of the inflammatory components and seems to play an important role in protecting against cardiac hypertrophy and renal injury.

Serum proteomic profiling of obese patients: correlation with liver pathology and evolution after bariatric surgery.

OBJECTIVE: Chronic liver diseases, including cirrhosis, may develop in obese patients. Steatosis and non-alcoholic steatohepatitis (NASH) are risk factors for progression to fibrosis. To date, diagnosis of steatosis and NASH relies on liver biopsy. The aim of the study was to identify serum markers of steatosis and NASH in obese patients using SELDI-TOF ProteinChip. PATIENTS: Eighty obese non-alcoholic patient candidates for bariatric surgery and devoid of hepatitis B and C infection were selected. Serum samples were collected before surgery and at 6 months after surgery for 33 of these patients. Wedge liver biopsy was performed at the time of bariatric surgery. Twenty-four serum samples from healthy blood donors served as controls. The protein profiles of each serum were assessed using SELDI-TOF ProteinChip technology and were compared according to liver histological lesions. RESULTS: Twenty-four obese patients (30%) had non-significant liver lesions, 32 (40%) had significant steatosis and 24 (30%) had NASH. Comparison of serum protein profiles according to liver lesions identified three peaks (CM10-7558.4, CM10-7924.2 and Q10-7926.9) the intensity of which significantly increased according to the severity of the liver lesions (steatosis and NASH) and returned to normal after bariatric surgery. None was correlated with either liver function tests or metabolic parameters. Identification using immunoSELDI assay characterised these peaks as the double charged ions of alpha- and beta-haemoglobin subunits. CONCLUSION: The differential proteomic method demonstrated changes in serum protein profiles in obese patients according to severity of liver lesions. Free haemoglobin subunits may serve as a serum biomarker of the severity of liver damages.

[Progressive myoclonic epilepsy type Lafora]. / Epilepsie myoclonique progressive type Lafora.

Lafora's disease is a form of progressive myoclonic epilepsy characterized by seizures, myoclonus and dementia. We present the case of a 12-year-old girl who is complaining of epilepsy and myoclonic jerks starting a year ago, with deterioration of school performance, and abnormal EEG. The axillary skin biopsy showed PAS-positive inclusions in the cells of sweat glands, typical of Lafora's disease.

[Breast cancer: prognostic value of flow cytometry and hormone receptors. Apropos of a Lebanese series of patients]. / Cancer du sein: valeur pronostique de la cytometrie de flux et des recepteurs hormonaux. A propos d'une série libanaise.

OBJECTIVES: This study has three objectives. 1) First to establish the influence of flow cytometry and hormone receptors on overall survival and disease free survival of stage I to IIIA breast cancer patients. 2) Second to search for associations between the classical prognostic factors: age, menopausal status, histological and nuclear grading, tumor diameter, node metastases, stage, estrogen and progesterone receptors (ER, PR), as well as ploidy and S phase fraction. 3) And third to evaluate the effect of flow cytometry and hormone receptors on the response to neoadjuvant chemotherapy in stage IIIB and IV patients. MATERIAL AND METHODS: The series is composed of 150 patients with primary invasive breast cancer (149 females and one male), diagnosed at the St George Hospital Pathology Department and in whom an evaluation of the hormone receptors and a measuring, by flow cytometry, of ploidy and S phase fraction (SPF) were performed. Among them, 68 were followed for a mean period of 45 months. The disease free survival and the overall survival were recorded as well as the response to neoadjuvant chemotherapy. RESULTS: The authors did not find any statistically significant difference in survival between diploid and aneuploid tumors, tumors with SPF above and below 8%, those who are ER+ and ER- and those who are PR+ and PR-. But it seemed that diploid, low SPF and positive hormone receptors tumors had a tendency toward a better disease free survival. The multivariate analysis using the Cox proportional hazards identified the tumor diameter as being the only independent prognostic factor (p = 0.046). The nuclear grade reached a limit of significance (p = 0.08). Diploidy, low SPF and positivity of ER and PR were associated one to the other and to low histologic and nuclear grades. Finally, neither flow cytometry parameters nor hormone receptors were predictive of a susceptibility to neoadjuvant chemotherapy.