Slc39a13/Zip13: A Crucial Zinc Transporter Involved in Tooth Development and Inherited Disorders

Zinc (Zn) is an essential trace element and it plays indispensable roles in cellular processes for embryonic and postnatal development in mammals. Zn deficiency causes growth retardation, reduced bone volume, dental decay, skin diseases, and other conditions. Zn homeostasis is tightly controlled by the action of Zn transporters and metallothioneins, which together intricately regulate the Zn concentration and distribution in cells. We recently investigated the role of the Zn transporter Slc39a13/Zip13 in mice and humans. Mice deficient in Zip13 show changes in the tooth, bone, and connective tissues, and impairments in BMP and TGF-β signaling. A unique variant of Ehlers-Danlos syndrome (EDS) with hypodontia was found, in which Zip13 possesses a loss-of-function mutation, indicating that Zip13-mediated Zn homeostasis is crucial for tooth, bone and connective tissue development in mice and humans. In this review, we describe how Zn affects biological events especially in tooth development, with recent progress uncovering the roles of the Zn transporter Zip13 in mammalian health and diseases.     

Correlation of mandibular bone quality with neurosensory disturbance after sagittal split ramus osteotomy

Our aim was to find out whether the quality of bone around the inferior alveolar nerve is correlated with neurosensory disturbance to the nerve after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Computed tomograms (CT) were taken of 35 patients with mandibular prognathism and 35 without. To assess the density of bone around the inferior alveolar nerve, the width of the buccal cortical bone in the mandibular second molar regions was measured on CT. The Hounsfield units (HU) in the same regions were also measured. The number of HU in the mandible around the second molar regions was significantly higher (p < 0.01) in those with neurosensory disturbance (p < 0.01). The quality of bone measured by HU is associated with an increased risk of neurosensory disturbance, but the width of buccal bone is not.     

Stroke volume variation obtained with Vigileo/FloTrac? system during bleeding and fluid overload in dogs

Purpose  

Stroke volume variation (SVV) is a parameter for estimating fluid responsiveness. Recently, the Vigileo™ and the Flo-Trac™ sensor (Edwards Lifesciences, Irvine, CA, USA) were made available for clinical use to estimate SVV. The aim of this study was to investigate the relationship between the circulating blood volume and SVV, measured by the Vigileo-FloTrac™ system (SVV-FloTrac) or by central venous pressure (CVP), during a dynamic change in circulating blood transfusion volume, using a continuous constant bleeding and fluid-overload model in dogs.     

Mechanisms of Disease: ryanodine receptor defects in heart failure and fatal arrhythmia

Abnormal regulation of intracellular Ca(2+) by sarcoplasmic reticulum plays a part in the mechanism underlying contractile and relaxation dysfunction in heart failure (HF). The protein-kinase-A-mediated hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum has been shown to cause the dissociation of FKBP12.6 (also known as calstabin-2) from ryanodine receptors in HF. In addition, several disease-linked mutations in the ryanodine receptors have been reported in patients with catecholaminergic polymorphic ventricular tachycardia or arrhythmogenic right ventricular cardiomyopathy type 2. The unique distribution of these mutation sites has led to the concept that the interaction among the putative regulatory domains within the ryanodine receptors has a key role in regulating channel opening. The knowledge gained from various studies of ryanodine receptors under pathologic conditions might lead to the development of new pharmacological or genetic strategies for the treatment of HF or cardiac arrhythmia. In this review, we focus on the role of the Ca(2+)-release channel, the ryanodine receptor, in the pathogenesis of HF and fatal arrhythmia, and the possibility of developing new therapeutic strategies for targeting this receptor.     

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction： A hint for early diagnosis of gallbladder carcinoma

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19900 IU/L and that of the gallbladder was 127000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient's poor prognosis.     

Underappreciated predictors for postdischarge mortality in acute hospitalized oldest-old patients

BACKGROUND: Although oldest-old, those aged 85 years and older, patients are the fastest growing segment, clinical evidences regarding the acute care of oldest-old patients are still lacking. Because acute medical conditions requiring emergent hospitalization is frequently followed by high rate of progressive physical decline and increased mortality after discharge in oldest-old patients, prognostic information collected during hospitalization can provide the basis for discussion about the goals of care and therapy. The aim of our study was to identify predictive factors for postdischarge mortality in oldest-old patients. METHODS: The study included 403 oldest-old patients discharged from the acute care setting of a general hospital, who were followed-up for 1 year. Predictive values of the patients' characteristics collected during their hospitalization for 1-year mortality were identified utilizing Cox proportional hazard regression analysis. RESULTS: During 1-year follow-up, 104 patients (25.8%) died. The variables independently associated with 1-year mortality in multivariate analysis were the Charlson Comorbidity Index equal or greater than 2 [HR (hazard ratio) 4.71, 95%CI (confidence interval) 1.09-20.42], six or more prescribed medications at discharge (HR 3.12, 95% CI 1.39-6.99), benzodiazepines use (HR 1.64, 95% CI 1.04-2.60), nonsteroidal anti-inflammatory drugs use (HR 1.70, 95% CI 1.10-2.63), albumin less than or equaling 3.4 g/dl (HR 2.16, 95% CI 1.13-4.14), hemoglobin 10-12 g/dl (HR 2.32, 95% CI 1.22-3.56), hemoglobin less than 10 g/dl (HR 2.67, 95% CI 1.43-4.95), the presence of pressure sores (HR 1.84, 95% CI 1.14-2.97), and a history of delirium (HR 2.24, 95% CI 1.32-3.79). Functional impairment assessed by the Katz Index was only weakly associated with mortality (HR 1.24, 95% CI 0.53-2.91). CONCLUSION: Although often underappreciated, polypharmacy, particular medication use, anemia, the presence of pressure sores, and a history of delirium were important predictors for postdischarge mortality in oldest-old patients.     

Role of endothelial damage in the pathogenesis of interstitial pneumonitis in patients with polymyositis and dermatomyositis

OBJECTIVE: Polymyositis and dermatomyositis (PM/DM) are often complicated by interstitial pneumonitis (IP), which is an important cause of death. It has been reported that blood concentration of transforming growth factor-beta (TGF-beta), which is produced by a wide range of cells including endothelial cells and enhances the fibrotic changes in various tissues, is increased in PM/DM with IP. Endothelial damage is likely to exist in PM/DM. We studied the relationship between endothelial damage and IP in PM/DM. METHODS: Blood levels of sialylated carbohydrate antigen KL-6, TGF-beta, endothelin-1 (ET-1), thrombomodulin (TM), and plasminogen activator inhibitor-1 (PAI-1) were determined in 43 patients with PM or DM with or without IP, and the relationship between these measures was analyzed. RESULTS: Blood levels of KL-6 and TGF-beta were higher in the patients with IP than those without, and these measures were well correlated with each other. Levels of ET-1, TM, and PAI-1, all known to reflect the extent of endothelial damage, were also increased in patients with IP, and these measures correlated well with TGF-beta. CONCLUSION: Our data suggest that endothelial damage might play an important role through the production of fibrosis-enhancing factors such as TGF-beta or ET-1 in PM/DM.