Propofol EDTA and reduced incidence of infection

Propofol formulated in a lipid vehicle supports the growth of microorganisms. There have been worldwide reports of extrinsic microbial contamination of propofol leading to outbreaks of serious postoperative nosocomial infections. Therefore it is essential that medical professionals follow strict aseptic precautions when handling propofol, as recommended by manufacturers of propofol and the Centers for Disease Control and Prevention. Non-adherence to these recommendations increases the risk of nosocomial postoperative infections, which impose a heavy burden of morbidity and mortality and have serious economic consequences. It has also been recommended that the use of EDTA-containing formulations of propofol be considered. In vitro studies have confirmed that EDTA added to propofol retards microbial growth. Data on the incidence of nosocomial infections before and after the introduction of propofol with EDTA indicates that there have been no further cluster outbreaks and individual nosocomial infections appear to have been reduced. The addition of EDTA is an additional safety precaution to good aseptic practice.     

Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors

PURPOSE: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. METHODS AND MATERIALS: A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. RESULTS: There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. CONCLUSIONS: One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function.     

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.     

Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP

Ptprz is a receptor-type protein tyrosine phosphatase predominantly expressed in the brain as a chondroitin sulfate proteoglycan. Ptprz-deficient mice exhibit an age (maturation)-dependent impairment of spatial learning in the Morris water maze test and enhancement of long-term potentiation (LTP) in the CA1 region in hippocampal slices. The enhanced LTP is canceled out by pharmacological inhibition of Rho-associated kinase (ROCK), suggesting that the lack of Ptprz causes learning impairment due to aberrant activation of ROCK. Here, we report that Ptprz-deficient mice exhibit impairments in hippocampus-dependent contextual fear memory because of abnormal tyrosine phosphorylation of p190 RhoGAP, a GTPase-activating protein (GAP) for Rho GTPase. We found that phosphorylation at Y1105, a major tyrosine phosphorylation site on p190 RhoGAP, is decreased 1h after the conditioning in the hippocampus of wild-type mice, but not of Ptprz-deficient mice. Pleiotrophin, a ligand for Ptprz, increased tyrosine phosphorylation of p190 RhoGAP in B103 neuroblastoma cells. Furthermore, Ptprz selectively dephosphorylated pY1105 of p190 RhoGAP in vitro, and the tyrosine phosphorylation at Y1105 controls p190 RhoGAP activity in vivo. These results suggest that Ptprz plays a critical role in memory formation by modulating Rho GTPase activity through dephosphorylation at Y1105 on p190 RhoGAP.