Management of arrhythmias in heart failure. What a practicing physician should know in the current times

Arrhythmias play a significant role in the mortality and morbidity as well as hospitalizations of patients who carry a diagnosis of congestive heart failure. With improving survival in a world of novel medications and devices, an understanding of the pathophysiology and management of these arrhythmias is crucial. Majority of the basic heart failure medications such as beta- -blockers, angiotensin converting enzyme inhibitors/aldosterone receptor blockers and aldosterone antagonists play a pivotal role in prevention of sudden cardiac deaths which can be a direct/indirect result of these arrhythmias. Anti-arrhythmic drugs and implantable cardioverter- -defibrillators were also beneficial in selected patients. Innovative electrophysiological techniques need to be considered in special situations

Fortilin Interacts with TGF-β1 and Prevents TGF-β Receptor Activation

Fortilin is a 172-amino acid multifunctional protein present in both intra- and extracellular spaces. Although fortilin binds and regulates various cellular proteins, the biological role of extracellular fortilin remains unknown. Here we report that fortilin specifically interacts with TGF-β1 and prevents it from activating the TGF-β1 signaling pathway. In a standard immunoprecipitation-western blot assay, fortilin co-immunoprecipitates TGF-β1 and its isoforms. The modified ELISA assay shows that TGF-β1 remains complexed with fortilin in human serum. Both bio-layer interferometry and surface plasmon resonance (SPR) reveal that fortilin directly bind TGF-β1. The SPR analysis also reveals that fortilin and the TGF-β receptor II (TGFβRII) compete for TGF-β1. Both luciferase and secreted alkaline phosphatase reporter assays show that fortilin prevents TGF-β1 from activating Smad3 binding to Smad-binding element. Fortilin inhibits the phosphorylation of Smad3 in both quantitative western blot assays and ELISA. Finally, fortilin inhibits TGFβ-1-induced differentiation of C3H10T1/2 mesenchymal progenitor cells to smooth muscle cells. A computer-assisted virtual docking reveals that fortilin occupies the pocket of TGF-β1 that is normally occupied by TGFβRII and that TGF-β1 can bind either fortilin or TGFβRII at any given time. These data support the role of extracellular fortilin as a negative regulator of the TGF-β1 signaling pathway

Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice

Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans

The Outcome of the Treatments of Chest Trauma Patients

Ninety-nine patients with chest trauma were clinically evaluated in terms of their prognoses. In accordance with advances in thoracic surgery, the survival rates were remarkably improved. However, six deaths were encountered in this series. The causes of deaths were attributable to associated injuries extend to two or three regions including the head and the abdomen so that precise detection and proper treatments should be made as quickly as possible. In conclusion, the prognoses of serious chest trauma patients are influenced by the presence and the degree of concomitant injuries as well as proper urgent managements

Esophageal Carcinomas with Synchronous and Metachronous Primary Malignant Carcinomas in Other Organs

Seventeen patients with 10 synchronous and 7 metachronous double cancers with carcinomas of the esophagus were surgically treated in the First Department of Surgery, Nagasaki University School of Medicine. All patients were men with an average of age 68.5. The incidence of double cancers with carcinoma of the esophagus accounted for 12.7% in a total of 134 of this series. The three triple cancers were included. Of the three, one was synchronous triple cancers in the esophagus, the stomach and the colon. The outcome was not necessarily satisfactory. Two had recurrence 3 and 5 months after surgery, but one is still alive for 33 months, free from carcinoma

การศึกษาการทำงานของ truncated WT1 และ WT1 ที่เกี่ยวข้องกับกระบวนการตายของเซลล์ในมะเร็งเต้านม (MCF-7) : รายงานวิจัยฉบับสมบูรณ์โครงการ

Office of the Higher Education CommissionThailand Research Fun

MicroRNAs in Inflammatory Bowel Disease and Its Complications

Inflammatory bowel disease (IBD), classified primarily between Crohn’s disease and ulcerative colitis, is a collection of chronic gastrointestinal inflammatory conditions that cause multiple complications because of systemic alterations in the immune response. One major player is microRNA (miRNA), which is found to be associated with multiple pathways in mediating inflammation, especially those of a chronic nature in IBD, as well as irritable bowel syndrome. Although there have been studies linking miRNA alterations in IBD, even differentiating Crohn’s disease and ulcerative colitis, this review focuses mainly on how miRNAs cause and mechanistically influence the pathologic complications of IBD. In addition to its role in the well-known progression towards colorectal cancer, we also emphasize how miRNA manifests the many extraintestinal complications in IBD such as cardiovascular diseases; neuropsychiatric conditions such as depression and anxiety disorders; and others, including various musculoskeletal, dermatologic, ocular, and hepatobiliary complications. We conclude through a description of its potential use in bettering diagnostics and the future treatment of IBD and its systemic symptoms

Symptomatic Patent Foramen Ovale with Hemidiaphragm Paralysis

Dyspnea accounts for more than one-fourth of the hospital admissions from Emergency Department. Chronic conditions such as Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and Asthma are being common etiologies. Less common etiologies include conditions such as valvular heart disease, pulmonary embolism, and right-to-left shunt (RLS) from patent foramen ovale (PFO). PFO is present in estimated 20–30% of the population, mostly a benign condition. RLS via PFO usually occurs when right atrium pressure exceeds left atrium pressure. RLS can also occur in absence of higher right atrium pressure. We report one such case that highlights the importance of high clinical suspicion, thorough evaluation, and percutaneous closure of the PFO leading to significant improvement in the symptoms

Ticagrelor induces paraoxonase-1 (PON1) and better protects hypercholesterolemic mice against atherosclerosis compared to clopidogrel.

Ticagrelor (TIC), a P2Y purinoceptor 12 (P2Y12)-receptor antagonist, has been widely used to treat patients with acute coronary syndrome. Although animal studies suggest that TIC protects against atherosclerosis, it remains unknown whether it does so through its potent platelet inhibition or through other pathways. Here, we placed hypercholesterolemic Ldlr-/-Apobec1-/- mice on a high-fat diet and treated them with either 25 mg/kg/day of clopidogrel (CLO) or 180 mg/kg/day of TIC for 16 weeks and evaluated the extent of atherosclerosis. Both treatments equally inhibited platelets as determined by ex vivo platelet aggregation assays. The extent of atherosclerosis, however, was significantly less in the TIC group than in the CLO group. Immunohistochemical staining and ELISA showed that TIC treatment was associated with less macrophage infiltration to the atherosclerotic intima and lower serum levels of CCL4, CXCL10, and TNFα, respectively, than CLO treatment. Treatment with TIC, but not CLO, was associated with higher serum activity and tissue level of paraoxonase-1 (PON1), an anti-atherosclerotic molecule, suggesting that TIC might exert greater anti-atherosclerotic activity, compared with CLO, through its unique ability to induce PON1. Although further studies are needed, TIC may prove to be a viable strategy in the prevention and treatment of chronic stable human atherosclerosis