Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization

Dentine dysplasia type II is an autosomal dominant disorder in which mineralization of the dentine of the primary teeth is abnormal. On the basis of the phenotypic overlap between, and shared chromosomal location with, dentinogenesis imperfecta type II, a second disorder of dentine mineralization, it has been proposed that the two conditions are allelic. As recent studies have shown that dentinogenesis imperfecta type II results from mutation of the bicistronic dentine sialophosphoprotein gene (DSPP ), we have tested this hypothesis by sequencing DSPP in a family with a history of dentine dysplasia type II. Our results have shown that a missense change, which causes the substitution of a tyrosine for an aspartic acid in the hydrophobic signal peptide domain of the protein, underlies the phenotype in this family. Biochemical analysis has further demonstrated that this mutation causes a failure of translocation of the encoded proteins into the endoplasmic reticulum, and is therefore likely to lead to a loss of function of both dentine sialoprotein and dentine phosphoprotein.     

Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis

The aim of this study was to examine the possible relationship between the plasma levels of leptin and tumor necrosis factor (TNF)- and the stage of hepatic fibrosis in a cohort of patients with chronic hepatitis C. Leptin and TNF levels were measured by RIA in 135 patients and in 75 age- and sex-matched controls. Liver disease was evaluated by the stage of fibrosis and the extent of inflammatory infiltrate in the liver biopsy. Leptin levels correlated with BMI values in healthy controls and in patients with chronic hepatitis C (men, r = 0.61, P = 0.0001; women, r = 0.68, P = 0.003). Leptin levels increased as hepatic fibrosis stage progressed both in male and in female patients (P < 0.001); also, TNF levels were higher in patients with an advanced stage of fibrosis (P = 0.006). In these patients, levels of leptin increased according to the progression of the stage of fibrosis; these data suggest that leptin may play a role in the regulation of hepatic fibrosis.     

A case of rhabdomyolysis and thromboembolic event secondary to fibrate monotherapy

Fibrates either alone or in combination with statins have been commonly used for the treatment of high non-HDL-cholesterol levels. In addition, this type of therapy is also associated with some adverse events like rhabdomyolysis. We present the first case in the literature describing the development of both rhabdomyolysis-induced acute renal failure and thromboembolic event under the treatment of fibrate monotherapy.     

Angiographic prevalence of myocardial bridging.

OBJECTIVE: Muscle fibers overlying the intramyocardial segment of an epicardial coronary artery are termed myocardial bridging. Variable prevalence has been described at autopsy and angiographic series with small and large sample sizes. The aim of the study was to investigate the angiographic prevalence of myocardial bridging in 25982 patients from Turkey. METHODS: We performed a retrospective study, evaluated the cases with myocardial bridging among patients undergone selective coronary angiography, and searched the angiographic prevalence of myocardial bridging in a very large sample size. We studied also the correlation between the severity of the bridging and risk factors for coronary artery disease. RESULTS: Among 25982 patients we found 316 cases of myocardial bridging in a retrospective manner. The total prevalence was 1.22%. Although, 96.52% of patients with myocardial bridging had the lesion in the left anterior descending coronary artery (LAD) as expected, distribution of bridges between mid- and distal segments were almost equal (52.79% and 47.21%, respectively). We subclassified patients in two groups, Group A (<50% of systolic compression) and Group B (>or=50% of systolic compression), according to the amount of systolic compression of LAD and studied relationship of risk factors for coronary artery disease between groups. Another subclassification was also made for patients having myocardial bridging without coronary or valvular heart disease and hypertrophic obstructive cardiomyopathy; Group 1 (<50% of systolic compression) and Group 2 (>or=50% of systolic compression). In these patients we studied correlation between the severity of the myocardial bridging and risk factors for coronary artery disease. The prevalence of bridges in circumflex and right coronary arteries individually and in all arteries as combination was also studied. CONCLUSION: In a very large group of patients from Turkey undergone selective coronary artery angiography, the angiographic prevalence of myocardial bridging was slightly higher than expected. Only diabetes mellitus as a risk factor for coronary artery disease was higher in groups representing <50% of systolic compression (Group A and 1) than in groups representing >or=50% of systolic compression (Group B and 2) but the importance of this result is not known.