A biochemical framework for SLC4A11, the plasma membrane protein defective in corneal dystrophies.

Mutations in the SLC4A11 protein, reported as a sodium-coup-led borate transporter of the human plasma membrane, are responsible for three corneal dystrophies (CD): congenital hereditary endothelial dystrophy type 2, Harboyan syndrome, and late-onset Fuch's CD. To develop a rational basis to understand these diseases, whose point mutations are found throughout the SLC4A11 sequence, we analyzed the protein biochemically. Hydropathy analysis and an existing topology model for SLC4A1 (AE1), a bicarbonate transporter with the lowest evolutionary sequence divergence from SLC4A11, formed the basis to propose an SLC4A11 topology model.

Occurrence of bisphenol A in indoor dust from two locations in the eastern United States and implications for human exposures.

Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins, which are used in many consumer products. Sources of human exposures to BPA include packaged and canned food products, indoor air, and dust ingestion. Information on the relative contributions of the pathways to BPA exposures is limited.

Novel role of specific Tudor domains in Tudor-Aubergine protein complex assembly and distribution during Drosophila oogenesis.

Germ cells give rise to the next generation and contain ribonucleoprotein particles, germ granules. In these granules, Piwi protein Aubergine has been shown to interact with Tudor protein in Drosophila. Tudor protein has 11 Tudor domains and it has been unclear to what extent all these domains are involved in the interaction with Aubergine.

Comparison of the remineralization potential of CPP-ACP and CPP-ACP with 900 ppm fluoride on eroded human enamel: An in situ study.

Objective: The aim of this in situ study was to compare the remineralization potential of pastes containing CPP-ACP and CPP-ACP with 900 ppm fluoride on human enamel softened by a cola drink.

Design: Forty-five enamel specimens obtained from human third molar teeth were eroded in a cola drink for 8 min and then attached to intra-oral devices worn by five volunteers. The specimens were subjected to three different in situ remineralization protocols using: (1) CPP-ACP (Group I), (2) CPP-ACP with 900 ppm fluoride (Group II), and (3) saliva (Group III, control).

Combined superoxide dismutase mimetic and peroxynitrite scavenger protects against neointima formation after endarterectomy in association with decreased proliferation and nitro-oxidative stress.

Objective: Reactive oxygen and nitrogen species (e.g., peroxynitrite) may trigger neointima formation leading to restenosis.

Off-pump versus on-pump coronary artery bypass procedures:postoperative renal complications in an Asian population.

Introduction: Diabetes and habitual smoking cause advanced coronary artery disease (CAD) in Asian patients at a younger age. No definite data exist as to whether off-pump (OPCAB) is better than conventional on-pump coronary artery bypass grafting (CCAB) in terms of postoperative renal complications. Thus, we aimed to compare the renal outcomes of on-pump and off-pump coronary artery bypass grafting (CABG) on our patients, which constituted a predominantly Asian population.

Effects of Custodiol-N, a novel organ preservation solution, on ischemia/reperfusion injury.

Objective: Custodiol (histidine-tryptophan-ketoglutarate solution) is a leading organ preservation solution. On the basis of this solution, the novel Custodiol-N was developed. The present study investigated the effects of Custodiol-N in a rat model of heart transplantation.

Deferoxamine, the newly developed iron chelator LK-614 and N-alpha-acetyl-histidine in myocardial protection.

During cold storage of donor hearts, reactive oxygen species produced by intracellular redox-active chelatable iron potentially alter myocardial function. To reduce this cold-induced injury we investigated the efficacy of two new modifications of the well established histidine-tryptophan-ketogluterate (HTK) solution (Custodiol) with the addition of N-alpha-acetyl-l-histidine and iron-chelators in a heterotopic rat heart transplantation model. The donor hearts were cardioplegically arrested with 20 ml cardioplegia and stored for 1 h.

Ethnic differences and functional analysis of MET mutations in lung cancer.

Purpose: African Americans have higher incidence and poorer response to lung cancer treatment compared with Caucasians. However, the underlying molecular mechanisms for the significant ethnic difference are not known. The present study examines the ethnic differences in the type and frequency of MET proto-oncogene (MET) mutation in lung cancer and correlated them with other frequently mutated genes such as epidermal growth factor receptor (EGFR), KRAS2, and TP53.

Myocardial protection with the use of L-arginine and N-alpha-acetyl-histidine.

Objective: Effective myocardial preservation is an important condition for cardiac surgery, especially in heart transplantation with long ischemia times. During ischemia and reperfusion, myocardial function is altered by cold-induced ischemic injury. Cold-induced ischemic injury is triggered by cold storage and the amino acid histidine, a main component of the storage solution histidine-tryptophan-ketoglutarate (HTK).

Pharmacological activation of soluble guanylate cyclase protects the heart against ischemic injury.

Background: The role of the nitric oxide/cGMP/cGMP-dependent protein kinase G pathway in myocardial protection and preconditioning has been the object of intensive investigations. The novel soluble guanylate cyclase activator cinaciguat has been reported to elevate intracellular [cGMP] and activate the nitric oxide/cGMP/cGMP-dependent protein kinase G pathway in vivo. We investigated the effects of cinaciguat on myocardial infarction induced by isoproterenol in rats.

Vardenafil protects against myocardial and endothelial injuries after cardiopulmonary bypass.

Objectives: Phosphodiesterase-5 inhibitors and elevated myocardial cyclic guanosine monophosphate levels can induce potent cardioprotection-like effects against ischaemia-reperfusion injury. We investigated the effects of vardenafil, a selective phosphodiesterase-5 inhibitor on myocardial and endothelial functions during reperfusion in a canine model of cardioplegic arrest and extracorporal circulation.

Methods: Vehicle-treated (control, n=8) and vardenafil-treated (30 microgkg(-1) intravenous (IV); n=8) anaesthetised dogs underwent hypothermic cardiopulmonary bypass with 60 min of hypothermic cardiac arrest.

Dose-dependent effects of a selective phosphodiesterase-5-inhibitor on endothelial dysfunction induced by peroxynitrite in rat aorta.

Reactive oxygen species, such as peroxynitrite, induce oxidative stress and DNA injury leading to endothelial dysfunction. It has been proposed, that elevated intracellular cyclic GMP (cGMP)-levels may contribute to an effective cytoprotection against nitro-oxidative stress. We investigated the dose-dependent effects of vardenafil, an inhibitor of phosphodiesterase-5, on endothelial dysfunction induced by peroxynitrite.

Selective phosphodiesterase-5 inhibition reduces neointimal hyperplasia in rat carotid arteries after surgical endarterectomy.

Objective: Long-term results of surgical vessel reconstruction are compromised by restenosis caused by neointimal hyperplasia. Recent studies suggest that reduced cyclic guanosine monophosphate signaling is associated with neointima formation. In a rat model of endarterectomy, we investigated the effect of pharmacologic inhibition of cyclic guanosine monophosphate degradation on neointima formation by using the selective phosphodiesterase-5 inhibitor vardenafil.

Use of electroconvulsive therapy for schizophrenia with comorbid Marfan syndrome.

The study of psychiatric disorders co-occurring with rare genetic syndromes has important therapeutic and pathophysiological implications. Electroconvulsive therapy (ECT) in schizophrenia with comorbid Marfan syndrome is challenging in view of multiorgan involvement. We report successful use of ECT in a patient who presented to us with catatonia and Marfan syndrome.

Comparative investigation of the left ventricular pressure-volume relationship in rat models of type 1 and type 2 diabetes mellitus.

Diabetes mellitus (DM) is associated with characteristic structural and functional changes of the myocardium, termed diabetic cardiomyopathy. As a distinct entity independent of coronary atherosclerosis, diabetic cardiomyopathy is an increasingly recognized cause of heart failure. A detailed understanding of diabetic cardiac dysfunction, using relevant animal models, is required for the effective prevention and treatment of cardiovascular complications in diabetic patients.

The phosphodiesterase-5 inhibitor vardenafil improves cardiovascular dysfunction in experimental diabetes mellitus.

Background And Purpose: Patients with diabetes mellitus exhibit generalized endothelial and cardiac dysfunction with decreased nitric oxide production. Elevated intracellular cyclic guanosine monophosphate (cGMP) levels contribute to an effective cardioprotection in different pathophysiological conditions. In this study, we investigated whether chronic treatment with the phosphodiesterase-5 inhibitor vardenafil could improve diabetic cardiovascular dysfunction by up-regulating the nitric oxide-cGMP pathway in the vessel wall and myocardium.

PAX5 is expressed in small-cell lung cancer and positively regulates c-Met transcription.

PAX5 is a nuclear transcription factor required for B cell development, and its expression was evaluated in upper aerodigestive malignancies and pancreatic cancer by immunoblotting. The PAX5 protein expression was relatively strong in small-cell lung cancer (SCLC, 11/12); however, its expression was not detected in non-SCLC (NSCLC, n=13), mesothelioma (n=7), pancreatic (n=6), esophageal (n=6) and head and neck cancer cell lines (n=12). In comparison, PAX8 and PAX3 expressions were absent or non-detectable in SCLC cell lines; however, PAX8 was expressed in most of the tested NSCLC cell lines (13/13) and also frequently in all the other cell lines.

Effects of selective phosphodiesterase-5-inhibition on myocardial contractility and reperfusion injury after heart transplantation.

Recently, the infarct reducing and cardioprotective effects of phosphodiesterase-5-inhibitors were described. In this study, we investigated these effects on ischemia/reperfusion injury in a rat model of heart transplantation. Three groups were assigned for our study: a vardenafil preconditioning group, an ischemic control, and a nonischemic control.

Improvement of aging-associated cardiovascular dysfunction by the orally administered copper(II)-aspirinate complex.

Background: Aging-associated nitro-oxidative stress causes tissue injury and activates proinflammatory pathways that play an important role in the pathogenesis of aging-associated cardiovascular dysfunction. It has been recently reported, that the copper(II)-aspirinate complex (CuAsp) exerts not only the well-known anti-inflammatory and platelet antiaggregating effects of aspirin, but, due to its superoxide dismutase mimetic activity, it acts as a potent antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated myocardial and endothelial dysfunction.