Vitamin K deficiency bleeding leading to the diagnosis of Crohn's disease.

We report the case of a 45 year old man who came to Emergency Room of Polyclinic for sudden onset of localized ecchymosis and widespread hematomas. He was subjected to blood count and first level investigations to assess coagulation. Based on the results, second level investigations were performed. Endoscopy of the gastrointestinal tract with histological examination revealed a diagnosis of Crohn's disease. Vitamin K deficiency causes the formation of vitamin K-dependent clotting factors that cannot perform their pro-coagulant action. Consequently, patients present with hemorrhagic manifestations. Clinical and laboratory features observed in this patient show that the deficiency of vitamin K-dependent coagulation factors may reveal a complex clinical condition such as an inflammatory bowel disease.

Effects of EPHX1 and CYP3A4 polymorphisms on carbamazepine metabolism in epileptic patients.

BACKGROUND: The aim of this study was to investigate the effect of two genetic polymorphisms in the coding regions (exon 3 and exon 4) of the EPHX1 gene, ie, 337T>C and 416A>G, respectively, on the metabolism of carbamazepine (CBZ) 10,11-epoxide (the active metabolite of CBZ) by evaluating the variation in serum CBZ 10,11-epoxide levels 4 hours after administration of the drug. Moreover, we reported the genotype frequencies of the CYP3A4*22 (rs 35599367, C>T) variant and its influence on the metabolism of CBZ. METHODS: The analysis was performed in 50 patients receiving CBZ as monotherapy. DNA was extracted from leukocytes using a commercially available kit. Serum CBZ 10,11-epoxide levels were measured by high-performance liquid chromatography. Allelic discrimination was performed using polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the difference in mean values for CBZ 10,11-epoxide levels according to genotype was performed using the Student's t-test with Statistical Package for the Social Sciences version 13 software. RESULTS: Fourteen percent of the study group were CC, 42% were CT, and 44% were TT for the EPHX1 337T>C variant. No GG homozygote was identified for the EPHX1 416A>G variant; 64% were AA and 36% were AG. When we compared serum CBZ 10,11-epoxide levels 4 hours after drug administration, we found no statistically significant difference between the 337 CC, CT, and TT genotypes. Similarly, no difference in serum CBZ 10,11-epoxide levels was found between 416A>G AA and AG. Genotype frequencies for the CYP3A4*22 (rs 35599367 C>T) allelic variant were 94% for CC and 6% for CT, with no statistically significant difference in serum CBZ 10,11-epoxide levels between these genotypes 4 hours after administration of the drug (2.6±1.3 µg/µL and 2.5±1.2 µg/µL, respectively). CONCLUSION: Although there is some evidence of involvement of these polymorphisms in enzyme activity in vitro, we found no interference with CBZ metabolism in vivo.

Prothrombotic gene variants as risk factors of acute myocardial infarction in young women.

BACKGROUND: Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age. METHODS: We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy). RESULTS: In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was significantly higher versus the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A; p<0.001). Among AMI patients we showed only in males that the allelic frequency of the MTHFR C677T variant was significantly higher as compared to the general population. Such difference was due to a significantly higher frequency in AMI males of the MTHFR C677T variant homozygous genotype (O.R. 3.05). DISCUSSION AND CONCLUSION: Our data confirm that young AMI in females is a peculiar phenotype with specific risk factors as the increased plasma procoagulant activity of FV and FII. On the contrary, the homozygous state for the 677T MTHFR variant may cause increased levels of homocysteine and/or an altered folate status and thus an increased risk for AMI, particularly in males. The knowledge of such risk factors (that may be easily identified by molecular analysis) may help to improve prevention strategies for acute coronary diseases in specific risk-group subjects.

Fetuin-A serum levels are not correlated to kidney function in long-lived subjects.

OBJECTIVES: Serum Fetuin A has been identified as an inhibitor of ectopic calcification. It is reduced in subjects with chronic kidney disease (CKD) and it has been proposed as a potential link between CKD and the higher prevalence of arterial calcification observed in these patients. During aging both the stiffening of arterial wall due to calcification and a decline in kidney function are frequent. The aim of the study is to investigate if Fetuin A serum levels are associated with aging and with AHSG T256S polymorphism. Moreover, we aim at investigate whether serum Fetuin A is correlated to kidney function in this setting of senescence. DESIGN AND METHODS: 256 health long-lived subjects (age 92 [81-100]) were recruited for the study. Serum Fetuin A was evaluated by ELISA, Cystatin C by immune-nephelometry. AHSG T256S was determinated by PCR-RFLP. RESULTS: Serum Fetuin A shows a significant correlation with age (r=0.20; P=0.0048). AHSG TS and SS genotypes are associated to lower levels of serum protein (0.27 [0.19-0.29] g/L vs 0.42 [0.32-0.49] g/L; P<0.027 and 0.34 [0.25-0.41] g/L vs 0.42 [0.32-0.49] g/L; P<0.001, respectively). No significant correlation between Fetuin A and Cystatin C was observed. CONCLUSIONS: Serum Fetuin A increases with age in elder individuals and subjects with the TS or SS AHSG polymorphism have lower levels of the circulating protein. No correlation with kidney function decline was observed. Other mechanisms should be investigated to explain the increase of Fetuin A with age.

Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity.

INTRODUCTION: It is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications. MATERIALS AND METHODS: We recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospitalized for every condition related to diabetic disease, but not for new vascular events. Adiponectin, Resistin and IL-6 serum levels were evaluated. RESULTS: Subjects of group A showed lower median plasma levels of adiponectin [7.7450 (4.47-12.17) µg/ml vs 8.480 (5.15-12.87) µg/ml], higher median plasma levels of IL-6 [3.21 (1.23-5.34) pg/ml vs 2.73 (1.24-3.97 pg/ml)] and of resistin [3.860 (2.96-6.29 ng/ml) vs 3.690 (2.,37-6.5 ng/ml)]. CONCLUSION: Our study demonstrated that diabetic subjects with diabetic foot showed in comparison with diabetics without diabetic foot higher IL-6 and resistin plasma levels, lower adiponectin plasma levels.