Novel insight into the dangerous connection between diabetes and heart failure

Heart failure (HF) affects approximately 1–2?% of the adult population. Diabetes mellitus (DM) is one of the most frequent comorbidities in HF, portending a worse prognosis. DM is associated with an increased risk of artery disease, and consequently of post-ischemic HF, but it may also alter directly the myocardial structure and function. Insights into the pathophysiological mechanisms of diabetic cardiomyopathy have been provided by both experimental and clinical investigations. In recent years, it has emerged that the fibrotic process is a result of the convergence of multiple neurohormonal alterations in diabetic cardiomyopathy at the basis of disease progression and phenotype determination: HF with reduced or preserved ejection fraction. Therapies for HF and DM should demonstrate an improved prognosis and have a neutral effect on glucose homeostasis and the risk of HF development.     

Absence of inferior vena cava as a rare cause of deep venous thrombosis complicated by liver and lung embolism

Congenital anomalies of the inferior vena cava such as absence or atresia are uncommon vascular defects and result from aberrant development during embryogenesis. We report a case of a young female patient affected by proximal deep venous thrombosis (DVT) complicated by liver and pulmonary embolism; subsequent extensive evaluation revealed the congenital absence of infrarenal inferior vena cava, with emboli probably occurring through collateral veins. Accordingly, in young patients with idiopathic DVT of the lower extremities and pelvic veins, the presence of inferior vena cava abnormalities should always be considered and investigated, together with classic coagulation factors, as a factor predisposing to thromboembolic complications.     

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS: Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohn's disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohn's disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p 相似文献   

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC,PAX6 and CYP1B1

Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods. We used whole-exome sequencing in 11 unrelated developmental eye disease patients, as it provides a strategy for assessment of multiple disease genes simultaneously. We identified five causative variants in four patients in four different disease genes, GJA8, CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients where clinical testing is frequently not undertaken due to lack of availability and cost. The results affected clinical management in all cases. These variants were detected in the cataract/microcornea and Peters anomaly patients. In two patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified with incomplete penetrance, highlighting the complex inheritance pattern associated with this phenotype. In the coloboma/microphthalmia patients, four other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene to be considered as a modifier in coloboma/microphthalmia.     

When oral anticoagulation therapy is needed in patients with cardiomyopathies: a review of literature

The question whether to anticoagulate patients with cardiomyopathy or not is over 50 years old. Multiple clinical trials have demonstrated the superior therapeutic effect of warfarin compared with placebo in the prevention of thromboembolic events amongst patients with nonvalvular atrial fibrillation. The purpose of our work is to review literature about the role of anticoagulation in the main cardiomyopathies.     

Biological Drugs: Classic Adverse Effects and New Clinical Evidences

The last 20 years was characterized by great improvements in the efficacy and tolerability of anticancer therapies. Most of these changes are related to the introduction of targeted drugs, which presents a better activity on the biology of cancer and less toxicity. Nevertheless, the initial enthusiasm was cooled by the emerging evidences of cardiac side effects. The aim of this review is to describe the actual knowledge about the possible cardiotoxicity of targeted drugs. The most important need is the detection of early cardiotoxicity and the evidence of subtle myocardial dysfunction that allows to begin a protective therapy. In our review we analyzed the non invasive imaging techniques to early predict myocardial dysfunction. Echocardiography seems to be the ideal method for her availability, safety and clinical usefulness, in particular the new echocardiographic techniques like speckle tracking.     

Characterization of putative regulatory isoforms of porcine tumor necrosis factor receptor 2 in endothelial cells

Tumor necrosis factor α (TNFα) and its receptors contribute to rejection of transplanted cells and organs. To elucidate how TNFα affects xenograft rejection, we previously cloned the cDNA of pig TNF-receptor 2 (pTNFR2) and found four isoforms: one comprising the full receptor with four cysteine-rich domains (CRD), a shorter variant (pTNFR2ΔE7-10) encoding for a soluble isoform, another lacking exon 4 (pTNFR2ΔE4) displaying only 3 CRD and poor ligand binding, and the smallest one generated by the two alternative splicings. All isoforms contained the pre-ligand assembly domain (PLAD) responsible for receptor trimerization. We now investigated their roles by structural, expression, and subcellular localization studies. Structural in silico analyses identified four amino acids potentially involved in TNFα binding and lacking in pTNFR2ΔE4. Quantitative RT-PCR determined regulated expression affecting the two pTNFR2 alternative splicings in cytokine-stimulated porcine aortic endothelial cells (PAEC). Particularly, human IL-1α and TNFα produced a strong mRNA upregulation of all isoforms, being the full receptor the predominant one. However, expression of pTNFR2 on PAEC did not correlate with mRNA and decreased after 24-hour exposure to IL-1α or TNFα. Notably, confocal microscopy confirmed the presence of pTNFR2 inside and on the plasma membrane, whereas pTNFR2ΔE4 located only intracellularly. Most interestingly, FRET analyses showed that membrane-bound isoforms pTNFR2 and pTNFR2ΔE4 colocalized intracellularly and associated through the PLAD. Our data show that pTNFR2ΔE4 bind and may retain the full receptor intracellularly. This mechanism has not been described in other species and represents a particularity that may affect the pathophysiology of pig xenografts.     

Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol

OBJECTIVE: We compared the hemodynamic effects of dobutamine and enoximone administration before and after long-term beta-blocker therapy with metoprolol or carvedilol in patients with chronic heart failure (HF). BACKGROUND: Patients with HF on beta-blocker therapy may need hemodynamic support with inotropic agents, and the hemodynamic response may be influenced by both the inotropic agent and the beta-blocker used. METHODS: The hemodynamic effects of dobutamine (5 to 20 microg/kg/min intravenously) and enoximone (0.5 to 2 mg/kg intravenously) were assessed by pulmonary artery catheterization in 29 patients with chronic HF before and after 9 to 12 months of treatment with metoprolol or carvedilol at standard target maintenance oral doses. Hemodynamic studies were performed after >/=12 h of wash-out from all cardiovascular medications, except the beta-blockers that were administered 3 h before the second study. RESULTS: Compared with before beta-blocker therapy, metoprolol treatment decreased the magnitude of mean pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP) decline during dobutamine infusion and increased the cardiac index (CI) and stroke volume index (SVI) response to enoximone administration, without any effect on other hemodynamic parameters. Carvedilol treatment abolished the increase in heart rate, SVI, and CI and caused a rise, rather than a decline, in PAP, PWP, systemic vascular resistance, and pulmonary vascular resistance during dobutamine infusion. The hemodynamic response to enoximone, however, was maintained or enhanced in the presence of carvedilol. CONCLUSIONS: In contrast with its effects on enoximone, carvedilol and, to a lesser extent, metoprolol treatment may significantly inhibit the favorable hemodynamic response to dobutamine. No such beta-blocker-related attenuation of hemodynamic effects occurs with enoximone.     

Electrolyte disturbances in chronic heart failure: Metabolic and clinical aspects

The pathophysiology of congestive heart failure (CHF) includes conditions (e.g., activation of the renin-angiotensin-aldosterone system) which, when combined with CHF therapies, make patients afflicted with this syndrome quite susceptible to electrolyte disturbances. The most commonly encountered are hyponatremia, hypokalemia, and hypomagnesemia. These derangements are of vast clinical importance; their development not only represents an immediate threat to the CHF patient (e.g., dysrhythmias secondary to hypokalemia), but are also indicative of underlying pathophysiologic events, an unfavorable clinical course, and occasionally an adverse therapeutic response. The optimal care of the CHF patient includes the recognition and management of these electrolyte disturbances.