Search

Secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD), and its development and progression are affected by various factors. The aim of the present study was to identify the risk factors for SHPT in patients with CKD. A retrospective study was performed in 498 patients (305 males and 193 females) with CKD, observed in the The First Hospital of Jilin University between January 2008 and December 2012. The demographic, clinical and laboratory data were collected. Patients were divided into the SHPT group (n=424) with elevated serum parathyroid hormone (PTH) expression levels and the control group (n=74) with normal serum PTH expression levels. Univariate and multivariate regression analyses were employed to explore the risk factors for SHPT. Serum PTH expression levels in women with CKD were significantly higher than in men (P=0.047). Serum PTH expression levels were positively correlated with the expression levels of serum creatinine (P<0.01), phosphorus (P<0.01), C-reactive protein (P<0.05), triglyceride (P<0.05), cholesterol (P<0.05) and low-density lipoprotein cholesterol (P<0.05), but were negatively correlated with the expression levels of hemoglobin (P<0.05), calcium (P<0.01) and CO2 combining power (P<0.01) in patients with CKD. Multivariate analysis showed that the serum expression levels of creatinine [µmol/l; odds radio (OR), 1.003; 95% confidence interval (CI), 1.002-1.004; P=0.001] and phosphorus (mmol/l; OR, 2.19; 95% CI, 1.254-3.826; P=0.006) in patients with CKD significantly influenced serum PTH expression levels. The SHPT risk factors include female gender, low calcium, high phosphorus, acidosis, anemia, hypertension, hyperlipidemia and micro-inflammation, with blood phosphorus and creatinine being independent risk factors. [ABSTRACT FROM AUTHOR]

We examined the distribution of silver in pregnant mice and embryos/fetuses following intravenous injections of 10 nm silver nanoparticles (AgNPs) or soluble silver nitrate (AgNO3) at dose levels of 0 (citrate buffer control) or 66 µg Ag/mouse to pregnant mice on gestation days (GDs) 7, 8 and 9. Selected maternal tissues and all embryos/fetuses from control, AgNP- and AgNO3-treated groups on GD10 and control and AgNP-treated groups on GD16 were processed for the measurement of silver concentrations, intracellular AgNP localization, histopathology and gross examination of tissue morphology. Inductively-coupled plasma mass spectrometry revealed silver in all examined tissues following either AgNP or AgNO3treatment, with highest concentrations of silver in maternal liver, spleen and visceral yolk sac (VYS), and lowest concentrations in embryos/fetuses. For VYS, mean silver concentration following AgNO3treatment (4.87 ng Ag/mg tissue) was approximately two-fold that following AgNP treatment (2.31 ng Ag/mg tissue); for all other tissues examined, mean silver concentrations following either AgNP or AgNO3treatment were not significantly different from each other (e.g. 2.57 or 2.84 ng Ag/mg tissue in maternal liver and 1.61 or 2.50 ng Ag/mg tissue in maternal spleen following AgNP or AgNO3treatment, respectively). Hyperspectral imaging revealed AgNP aggregates in maternal liver, kidney, spleen and VYS from AgNP-treated mice, but not AgNO3-treated mice. Additionally, one or more embryos collected on GD10 from eight of ten AgNP-treated mice appeared small for their age (i.e. Theiler stage 13 [GD8.5] or younger). In the control group (N = 11), this effect was seen in embryos from only one mouse. In conclusion, intravenous injection of 10 nm AgNPs to pregnant mice resulted in notable silver accumulation in maternal liver, spleen and VYS, and may have affected embryonic growth. Silver accumulation in embryos/fetuses was negligible. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the effect of denture base resin containing silver nanoparticles (nano-silver) on Candida albicans adhesion and biofilm formation.Background: Epidemiological studies report that approximately 70% of removable denture wearers suffer from denture stomatitis. Candida albicans adhesion and biofilm formation are regarded as essential prerequisites for denture stomatitis.Materials and Methods: The bioactivity and biomass of C. albicans biofilm, which was incubated in a series of twofold dilutions of nano-silver suspension at 37°C for 24 h, were determined using XTT reduction and crystal violet assays, respectively. The denture base resin specimens containing nano-silver were then used in C. albicans adhesion (37°C; 90 min; n = 9) and biofilm formation assays (37°C; 72 h; n = 9). Confocal laser scanning microscopy was used to evaluate the architectural properties of average thickness and live/dead cell ratio in the different biofilm stages that developed on the specimens.Results: The bioactivity and biomass of C. albicans biofilm successively decreased with increasing nano-silver solution concentration. Denture base resin containing nano-silver had no effect on adhesion at low concentrations, but it exhibited anti-adhesion activity at a high concentration (5%). For 72 h biofilm formed on the resin specimens, the thickness and live/dead cell ratio were successively reduced with increasing nano-silver concentrations.Conclusion: Nano-silver had antifungal activity and inhibited C. albicans biofilm formation. Antifungal activity and an inhibitory effect on adhesion and biofilm formation by denture base resin containing nano-silver were discovered, especially at a higher concentration. [ABSTRACT FROM AUTHOR]

The rodent hindlimb unloading (HU) model was developed in the 1980s to make it possible to study mechanisms, responses, and treatments for the adverse consequences of spaceflight. Decades before development of the HU model, weightlessness was predicted to yield deficits in the principal tissues responsible for structure and movement on Earth, primarily muscle and bone. Indeed, results from early spaceflight and HU experiments confirmed the expected sensitivity of the musculoskeletal system to gravity loading. Results from human and animal spaceflight and HU experiments show that nearly all organ systems and tissues studied display some measurable changes, albeit sometimes minor and of uncertain relevance to astronaut health. The focus of this review is to examine key HU results for various organ systems including those related to stress; the immune, cardiovascular, and nervous systems; vision changes; and wound healing. Analysis of the validity of the HU model is important given its potential value for both hypothesis testing and countermeasure development. [ABSTRACT FROM AUTHOR]

The transient receptor potential (TRP) family of ion channels is widely expressed in many cell types and plays various physiological roles. Growing evidence suggests that certain TRP channels are functionally expressed in the immune system. Indeed, an increasing number of reports have demonstrated the functional expression of several TRP channels in innate and adaptive immune cells and have highlighted their critical role in the activation and function of these cells. However, very few reviews have been entirely dedicated to this subject. Here, we will summarize the recent findings with regards to TRP channel expression in T cells and discuss their emerging role as regulators of T cell activation and functions. Moreover, these studies suggest that beyond their pharmaceutical interest in pain management, certain TRP channels may represent potential novel therapeutic targets for various immune-related diseases. [ABSTRACT FROM AUTHOR]

Background: It was the aim of this study to evaluate the antibacterial impact of two silver(I) carbohydrate complexes with tripodal thioglycosides, namely tris[2-(β-D-thio-glucopyranosyl) ethyl]-amine-silver(I)-nitrate (3) and tris[2-(α-D-thio-manno-pyranosyl) ethyl]-amine-silver(I)-nitrate (4), on five oral pathogenic bacterial strains. Furthermore, cytocompatibility was tested using human gingival fibroblasts (HGF). Methods: Minimum inhibitory concentrations (MIC) were determined on five oral pathogenic bacterial strains by using the broth microdilution method: Fusobacterium nucleatum (ATCC 10953), Aggregatibacter actinomycetemcomitans (ATCC 33384), Porphyromonas gingivalis (ATCC 33277), Streptococcus mutans (ATCC 25175) and Enterococcus faecalis (DSMZ 20376). Furthermore, antimicrobial efficiency was tested using agar diffusion assays. To evaluate cytocompatibility, human gingival fibroblasts (HGFs) were exposed to AgNO3 and complex 3 followed by a live/dead staining. Results: MIC of the silver(I) complexes ranged between 0.625 and 5.0 mmol/L. The silver complexes 3 and 4 showed higher antibacterial efficiency against all tested species than AgNO3. Antibacterial efficiency of complexes 3 and 4 on F. nucleatum (≥18 mm) and A. actinomycetemcomitans (≥23 mm) was more pronounced than against P. gingivalis (≥15 mm). Complex 3 (20 mM) induced the largest inhibition zones (30 to 31 mm) on Gram-negative strains. For Gram-positive strains, the largest inhibition zones were achieved by complex 3 (20 mM/S. mutans: 28 mm, E. faecalis: 18mm). Complex 3 had a lower cytotoxic impact on HGFs compared to AgNO3 by the power of ten. Conclusions: The findings suggest that silver(I) carbohydrate complexes 3 and 4 might function as novel antimicrobial agents for the treatment of periodontal, carious or endodontic diseases. [ABSTRACT FROM AUTHOR]

Sitosterolemia is an autosomal recessive disorder characterized by increased plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, severe hypercholesterolemia have been reported in patients with sitosterolemia, especially in children. Sitosterolemia is caused by increased intestinal absorption and decreased biliary excretion of sterols resulting from biallelic mutations in either ABCG5 or ABCG8, which encode the sterol efflux transporter ABCG5 and ABCG8. Patients with sitosterolemia show extreme phenotypic heterogeneity, ranging from almost asymptomatic individuals to those with severe hypercholesterolemia leading to accelerated atherosclerosis and premature cardiac death. Hematologic manifestations include hemolytic anemia with stomatocytosis, macrothrombocytopenia, splenomegaly, and abnormal bleeding. The mainstay of therapy includes dietary restriction of both cholesterol and plant sterols and the sterol absorption inhibitor, ezetimibe. Foods rich in plant sterols include vegetable oils, wheat germs, nuts, seeds, avocado, shortening, margarine and chocolate. Hypercholesterolemia in patients with sitosterolemia is dramatically responsive to low cholesterol diet and bile acid sequestrants. Plant sterol assay should be performed in patients with normocholesterolemic xanthomas, hypercholesterolemia with unexpectedly good response to dietary modifications or to cholesterol absorption inhibitors, or hypercholesterolemia with poor response to statins, or those with unexplained hemolytic anemia and macrothrombocytopenia. Because prognosis can be improved by proper management, it is important to find these patients out and diagnose correctly. This review article aimed to summarize recent publications on sitosterolemia, and to suggest clinical indications for plant sterol assay. [ABSTRACT FROM AUTHOR]

The use and functionality of electronic health records (EHRs) have increased rapidly in the past decade. Although the primary purpose of EHRs is clinical, researchers have used them to conduct epidemiologic investigations, ranging from cross-sectional studies within a given hospital to longitudinal studies on geographically distributed patients. Herein, we describe EHRs, examine their use in population health research, and compare them with traditional epidemiologic methods. We describe diverse research applications that benefit from the large sample sizes and generalizable patient populations afforded by EHRs. These have included reevaluation of prior findings, a range of diseases and subgroups, environmental and social epidemiology, stigmatized conditions, predictive modeling, and evaluation of natural experiments. Although studies using primary data collection methods may have more reliable data and better population retention, EHR-based studies are less expensive and require less time to complete. Future EHR epidemiology with enhanced collection of social/behavior measures, linkage with vital records, and integration of emerging technologies such as personal sensing could improve clinical care and population health. [ABSTRACT FROM AUTHOR]

In acute respiratory distress syndrome, both reactive oxygen species (ROS) and increased intracellular calcium ([Ca2+]i) are thought to play important roles in promoting endothelial paracellular permeability, but the mechanisms linking ROS and ([Ca2+]i) in microvascular endothelial cells are not known. In this study, we assessed the effect of hydrogen peroxide (H2O2) on [[Ca2+]i]) in mouse and human lung microvascular endothelial cells (MLMVEC and HLMVEC, respectively). We found that in both MLMVECs and HLMVECs, exogenously applied H2O2 increased ([Ca2+]i) through Ca influx and that pharmacologic inhibition of the calcium channel transient receptor potential vanilloid 4 (TRPV4) attenuated the H2O2-induced Ca2+ influx. Additionally, knockdown of TRPV4 in HLMVEC also attenuated calcium influx following H2O2 challenge. Administration of H2O2 or TRPV4 agonists decreased transmembrane electrical resistance (TER), suggesting increased barrier permeability. To explore the regulatory mechanisms underlying TRPV4 activation by ROS, we examined H2O2-induced Ca influx in MLMVECs and HLMVECs with either genetic deletion, silencing, or pharmacologic inhibition of Fyn, a Src family kinase. In both MLMVECs derived from mice defficient for Fyn and HLMVECs treated with either siRNA targeted to Fyn or the Src family kinase inhibitor SU-6656 for 24 or 48 h, the H2O2-induced Ca influx was attenuated. Treatment with SU-decreased the levels of phosphorylated, but not total, TRPV4 protein and had no effect on TRPV4 response to the external agonist, GSK1016790A. In conclusion, our data suggest that application of exogenous H2O2 increases ([Ca2+]i) and decreases TER in microvascular endothelial cells via activation of TRPV4 through a mechanism that requires the Src kinase Fyn. [ABSTRACT FROM AUTHOR]

Intracellular pathogenic bacteria can lead to some of the most life-threatening infections. By evolving a number of ingenious mechanisms, these bacteria have the ability to invade, colonize and survive in the host cells in active or latent forms over prolonged period of time. A variety of nanoparticulate systems have been developed to optimize the delivery of antibiotics. Main advantages of nanoparticulate systems as compared with free drugs are an efficient drug encapsulation, protection from inactivation, targeting infection sites and the possibility to deliver drugs by overcoming cellular barriers. Nevertheless, despite the great progresses in treating intracellular infections using nanoparticulate carriers, some challenges still remain, such as targeting cellular subcompartments with bacteria and delivering synergistic drug combinations. Engineered nanoparticles should allow controlling drug release both inside cells and within the extracellular space before reaching the target cells. [ABSTRACT FROM AUTHOR]

Despite development of new approaches for the treatment of cancer disease, it is the second cause of mortality in world. Annually, 30000 persons die in Iran due to cancer diseases. Eighty percent of cancer patients are children which about 50% children lead to death. Given the high rate of cancer-related death, the new approaches for prevention, control, early diagnosis, and treatment of this disease seem necessary. Investigation of new strategies is the major challenge for scientists at recent century. Nanotechnology as a new scientific field with novel and small compounds utilized different fields over the past ten years especially in medicine. This science has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic schedules. Therefore, it has the potential applications for cancer detection and therapy. This review will discuss the therapeutic applications of different nanomaterials in diagnosis, imaging, and delivery of therapeutic agents for the treatment of cancer with a major focus on their applications for the treatment of cancer and cancer-related diseases in children. The advancements in established nanoparticle technologies such as liposomes, polymer micelles, and functionalization regarding tumor targeting and controlled release strategies as well as drug delivery were discussed. It will also review the blood toxicity of used nanostructures. [ABSTRACT FROM AUTHOR]

Three different sizes (15.9 ± 2.1 nm, 26.4 ± 3.2 nm and 39.8 ± 4.0 nm, respectively) of citrate-coated silver nanoparticles (SNPs) have been synthesized and characterized. The interactions of the synthesized SNPs with human serum albumin (HSA) at physiological pH have been systematically studied by UV-vis absorption spectroscopy, fluorescence spectroscopy, synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The results indicate that the SNPs can bind to HSA with high affinity and quench the intrinsic fluorescence of HSA. The binding constants and quenching rate constants were calculated. The apparent association constants ( Kapp) values are 2.14 × 104 M-1 for 15.9 nm SNP, 1.65 × 104 M-1 for 26.4 nm SNP and 1.37 × 104 M-1 for 39.8 nm SNP, respectively. The values of binding constant obtained from the fluorescence quenching data match well with that determined from the absorption spectral changes. These results suggest that the smaller SNPs have stronger interactions to HSA than the larger ones at the same concentrations. Synchronous fluorescence, three-dimensional fluorescence and CD spectroscopy studies show that the synthesized SNPs can induce slight conformational changes in HSA. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Conditions during spaceflight, such as the loss of the head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose of the present study was to determine the effects of long-term spaceflight on the functional, mechanical, and structural properties of cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from spaceflight (SF) (n = 6), habitat control (HC) (n = 6), and vivarium control (VC) (n = 16) mice were used for in vitro functional and mechanical testing and histological structural analysis. The results demonstrate that vasoconstriction elicited through a voltage-gated Ca2+ mechanism (30-80 mM KCl) and thromboxane A2 receptors (10-8 - 3 x 10-5 M U46619) are lower in cerebral arteries from SF mice. Inhibition of Rho-kinase activity (1 µM Y27632) abolished group differences in U46619-evoked contractions. Endothelium-dependent vasodilation elicited by acetylcholine (10 µM, 2 µM U46619 preconstriction) was virtually absent in cerebral arteries from SF mice. The pressure-diameter relation was lower in arteries from SF mice relative to that in HC mice, which was not related to differences in the extracellular matrix protein elastin or collagen content or the elastin/collagen ratio in the basilar arteries. Diameter, medial wall thickness, and medial cross-sectional area of unpressurized basilar arteries were not different among groups. These results suggest that the microgravity-induced attenuation of both vasoconstrictor and vasodilator properties may limit the range of vascular control of cerebral perfusion or impair the distribution of brain blood flow during periods of stress. [ABSTRACT FROM AUTHOR]

The mechanisms linking cell volume sensing to volume regulation in mammalian cells remain incompletely understood. Here, we test the hypothesis that activation of nonreceptor tyrosine kinases Src, focal adhesion kinase (FAK), and Janus kinase-2 (Jak2) occurs after osmotic shrinkage of NIH3T3 fibroblasts and contributes to volume regulation by activation of NKCC1. FAK phosphorylation at Tyr397, Tyr576/577, and Tyr861 was increased rapidly after exposure to hypertonic (575 mOsm) saline, peaking after 10 (Tyr397, Tyr576/577) and 10-30 min (Tyr861). Shrinkage-induced Src family kinase autophosphorylation (pTyr416-Src) was induced after 2-10 min, and immunoprecipitation indicated that this reflected phosphorylation of Src itself, rather than Fyn and Yes. Phosphorylated Src and FAK partly colocalized with vinculin, a focal adhesion marker, after hypertonic shrinkage. The Src inhibitor pyrazolopyrimidine-2 (PP2, 10 µM) essentially abolished shrinkage-induced FAK phosphorylation at Tyr576/577 and Tyr861, yet not at Tyr397, and inhibited shrinkage-induced NKCC1 activity by ~50%. The FAK inhibitor PF-573,228 augmented shrinkage- induced Src phosphorylation, and inhibited shrinkage-induced NKCC1 activity by ~15%. The apparent role of Src in NKCC1 activation did not reflect phosphorylation of myosin light chain kinase (MLC), which was unaffected by shrinkage and by PP2, but may involve Jak2, a known target of Src, which was rapidly activated by osmotic shrinkage and inhibited by PP2. Collectively, our findings suggest a major role for Src and possibly the Jak2 axis in shrinkage-activation of NKCC1 in NIH3T3 cells, whereas no evidence was found for major roles for FAK and MLC in this process. [ABSTRACT FROM AUTHOR]

Silver nanoparticles were successfully synthesized with chitosan hydrolysate as stabilizing agent at room temperature. Silver nitrate, glucose and sodium hydroxide were used as silver precursor, reducing agent and accelerator respectively. Chitosan hydrolysate was produced by enzymatic process with papain enzyme. Molecular weight of chitosan hydrolysate determined by viscosimetry method based on Mark-Howink equation. The effect of molecular weight of chitosan hydrolysate as stabilizing agent and AgNO3 concentration toward surface plasmon resonance (SPR) of silver nanoparticle was investigated. It is also reported the antibacterial activity of silver-chitosan nanocomposites against Staphylococcus aureus and Escherichia coli. The products of silver nanoparticles were characterized by UV-Vis spectroscopy and transmission electron microscopy (TEM). The result showed that the formation of silver nanoparticles was shown by the appearance of surface plasmon resonance (SPR) at 403-421nm from the corresponding UV-Vis spectra. The molecular weight of chitosan hydrolysate affects the absorbance intensity and the wavelength of SPR. Silver nanoparticles were spherical in shape as identified by TEM images with size in range of 4-26nm. The silver nanoparticles have showed high antibacterial activity against Escherichia coli and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca2+ current, K+ currents, action potential ( AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the ICa,L was reduced by 50.7% (n = 5) after perfusion with 300 μM geraniol. Moreover, geraniol prolonged the AP duration ( APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K+ current (Ito) (59.7%, n = 4), the non-inactivation K+ current (Iss) (39.2%, n = 4) and the inward rectifier K+ current ( IK1) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca2+ and voltage-gated K+ currents, ultimately acting against ouabain-induced arrhythmias. [ABSTRACT FROM AUTHOR]

Objectives The majority of research performed on cellular stress and apoptosis focuses on mitochondrial dysfunction; however, the importance of the endoplasmic reticulum dysfunction and the link to metabolic diseases has gained a substantial interest. This review focuses on the potential of terpenoids to influence endoplasmic reticulum stress and the possible role terpenoids play as the treatment of metabolic diseases. Key findings Metabolic diseases develop as a result of a cascade of cellular pathways. In most cases, cells are able to compensate for the disruption of the cellular homeostasis although the initiation of response pathways; however, chronic stress initiates apoptotic pathways. This reviewed (1) showed the importance of phytoterpenoids to influence endoplasmic reticulum ( ER) stress and homeostasis, (2) showed how regulating ER stress affect the cell survival and death, and (3) highlighted some examples of how the progression of metabolic diseases can be influenced by ER. Summary Due to the substantial number of terpenoids that have been identified in literature, this review gave examples of 21 terpenoids that have been documented to have an effect on the different proteins associated with ER stress, how these plant terpenoids influence ER dysfunction and metabolic diseases such as diabetes, cancer, liver, and neurological diseases and parasitic infections. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid family type 4 (TRPV4) channels are expressed in central neuroendocrine neurons and have been shown to be polymodal in other systems. We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 μM) and by a Src kinase inhibitor PP2 (10 μM). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 ± 2.8% n = 5 and ANG II 80.5 ± 2.4% n = 5). This ANG II-induced increase in calcium influx was also blocked by 1 μM losartan and 10 μM PP2 (losartan 26.4 ± 3.8% n = 5 and PP2 19.7 ± 3.9% n = 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway. [ABSTRACT FROM AUTHOR]

Candida albicans is the most common fungal pathogen in humans, and recently some studies have reported the antifungal activity of silver nanoparticles (AgNPs) against some Candida species. However, ultrastructural analyses on the interaction of AgNPs with these microorganisms have not been reported. In this work we evaluated the effect of AgNPs on C. albicans, and the minimum inhibitory concentration (MIC) was found to have a fungicidal effect. The IC50 was also determined, and the use of AgNPs with fluconazole (FLC), a fungistatic drug, reduced cell proliferation. In order to understand how AgNPs interact with living cells, the ultrastructural distribution of AgNPs in this fungus was determined. Transmission electron microscopy (TEM) analysis revealed a high accumulation of AgNPs outside the cells but also smaller nanoparticles (NPs) localized throughout the cytoplasm. Energy dispersive spectroscopy (EDS) analysis confirmed the presence of intracellular silver. From our results it is assumed that AgNPs used in this study do not penetrate the cell, but instead release silver ions that infiltrate into the cell leading to the formation of NPs through reduction by organic compounds present in the cell wall and cytoplasm. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls. Methods: Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays. Results: Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma - apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL - apoB, apoC3, and apoE were increased; (3) LDL - apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001). Conclusions: Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined. [ABSTRACT FROM AUTHOR]

As the number of total joint arthroplasty and internal fixation procedures continues to rise, the threat of infection following surgery has significant clinical implications. These infections may have highly morbid consequences to patients, who often endure additional surgeries and lengthy exposures to systemic antibiotics, neither of which are guaranteed to resolve the infection. Of particular concern is the threat of bacterial biofilm development, since biofilm-mediated infections are difficult to diagnose and effective treatments are lacking. Developing therapeutic strategies have targeted mechanisms of biofilm formation and the means by which these bacteria communicate with each other to take on specialized roles such as persister cells within the biofilm. In addition, prevention of infection through novel coatings for prostheses and the local delivery of high concentrations of antibiotics by absorbable carriers has shown promise in laboratory and animal studies. Biofilm development, especially in an arthoplasty environment, and future diagnostic and treatment options are discussed. [ABSTRACT FROM AUTHOR]

Foley's catheters were coated with Silver (Ag), plasma polymerized aniline (PPAni) and Ag−PPAni composite by plasma based deposition processes which were characterized by XRD, EDX, SEM, and FT-IR spectroscopy and bioassays were performed to validate their efficacies to kill planktonic cells as well as to remove biofilm. The analyses confirmed the formation of Ag nanoparticles (AgNPs), PPAni and Ag−PPAni composite and also corroborated their successful deposition over the catheters. Antibacterial assays showed that coated catheters were capable of killing planktonic cells of most commonly encountered uropathogens and equally capable of eradicating biofilm formation by the uropathogens as evident from the reduced cfu/ml. UV-vis spectroscopy results showed that the nanoparticle coated catheters were capable of gradual release of AgNPs, killing all planktonic cells in solution over the time. Foley's catheters coated with AgNPs and their composites by one step plasma process were non-toxic devices capable of killing planktonic cells and proficient in eradicating biofilm formation which could be used to cutback the likelihood of the catheter related complications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1223-1235, 2014. [ABSTRACT FROM AUTHOR]

Hypertension is a common side effect of calcineurin inhibitors (CNIs), which are drugs used to prevent rejection after transplantation. Hypertension after kidney transplantation has been associated with earlier graft failure and higher cardiovascular mortality in the recipient. Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension. These insights raise the question whether polymorphisms in the genes encoding these proteins increase the risk of CNI-induced hypertension. Predicting who is at risk for CNI-induced hypertension may be useful for when selecting specific interventions, including dietary salt restriction, thiazide diuretics or a CNI-free immunosuppressive regimen. This review aims to explore the pharmacogenetics of CNI-induced hypertension, highlighting the knowns and unknowns. [ABSTRACT FROM AUTHOR]

Biofilm formation on implanted medical devices is becoming more recognized as both a common finding and a potential problem. Although seen frequently in nature, these sequestered bacterial communities are proving to be an assiduous enemy as medical device technologies advance. The penile prosthesis has gone through many improvements, now with a more reliable mechanical function and a reduced infection rate. However, there remains a notable increase in infectious risk in revisions compared to novel cases, with many implants found to harbor a subclinical bacterial presence isolated in biofilms. This article focuses on recent updates in implant technology and surgical technique to combat infection, and reviews current research on biofilm prevention and treatment. [ABSTRACT FROM AUTHOR]

Over the past 25 years a growing number of distinct syndromes/mutations associated with compromised mitochondrial function have been identified that share a common feature: urinary excretion of 3-methylglutaconic acid (3MGA). In the leucine degradation pathway, carboxylation of 3-methylcrotonyl CoA leads to formation of 3-methylglutaconyl CoA while 3-methylglutaconyl CoA hydratase converts this metabolite to 3-hydroxy-3-methylglutaryl CoA (HMG CoA). In 'primary' 3MGA-uria, mutations in the hydratase are directly responsible for the accumulation of 3MGA. On the other hand, in all 'secondary' 3MGA-urias, no defect in leucine catabolism exists and the metabolic origin of 3MGA is unknown. Herein, a path to 3MGA from mitochondrial acetyl CoA is proposed. The pathway is initiated when syndrome-associated mutations/DNA deletions result in decreased Krebs cycle flux. When this occurs, acetoacetyl CoA thiolase condenses two acetyl CoA into acetoacetyl CoA plus CoASH. Subsequently, HMG CoA synthase 2 converts acetoacetyl CoA and acetyl CoA to HMG CoA. Under syndrome-specific metabolic conditions, 3-methylglutaconyl CoA hydratase converts HMG CoA into 3-methylglutaconyl CoA in a reverse reaction of the leucine degradation pathway. This metabolite fails to proceed further up the leucine degradation pathway owing to the kinetic properties of 3-methylcrotonyl CoA carboxylase. Instead, hydrolysis of the CoA moiety of 3-methylglutaconyl CoA generates 3MGA, which appears in urine. If experimentally confirmed, this pathway provides an explanation for the occurrence of 3MGA in multiple disorders associated with compromised mitochondrial function. [ABSTRACT FROM AUTHOR]

Surgeons are constantly looking for minimally invasive ways to treat their patients, as recovery is faster when a lesser trauma is inflicted upon a patient, scarring is lessened and there are usually fewer complications in the aftermath of the operation. Through nanotechnology, tiny biosensors could be constructed which could take these factors into account, thus shortening a patients recovery period and saving hospitals money, reducing infection rates within the hospital, reducing the waiting lists for operation and allowing doctors to treat more patients in the same period of time. One of the greatest achievements of nanotechnology in surgery will be what we call the 'ideal graft'; that is, biocompatible and durable 'repairs' of parts of the body like arteries, joints or even organs. At first, these repairs will be used for healing, but soon afterwards, they will be used for transcendence: to enhance current human abilities. [ABSTRACT FROM AUTHOR]

Evidence from recent ground and spaceflight studies with animals and humans supports the notion that microgravity-induced vascular remodeling contributes to postflight orthostatic intolerance. In the vascular beds of lower body, such as in splanchnic and lower limb circulation, resistance vessels would undergo hypotrophy and decrement in myogenic tone and vasoreactivity. Thus, despite the concurrent sympathetic activation, the increase in peripheral vascular resistance would still be compromised while astronauts were re-exposed to Earth’s 1-G gravity, since ~75 % of the total vascular conductance lies below the heart. On the contrary, cerebral arteries would undergo hypertrophy and vasoreactivity enhancement due to adaptation to cerebral hypertension, which protects the down-stream microcirculation in the brain during spaceflight. However, the enhanced vasoreactivity of cerebral vessels might also aggravate postflight orthostatic intolerance, particularly after long-duration spaceflight. Animal studies have indicated that the underlying mechanisms may involve ion-channel remodeling in vascular smooth muscle cells and vascular NO-NOS and local renin–angiotensin system (L-RAS). Furthermore, vascular remodeling and associated ion-channel and L-RAS changes can be prevented by a countermeasure of daily short-duration restoring to normal standing posture. These findings substantiate in general the hypothesis that redistribution of transmural pressure along the arterial vasculature due to the removal of gravity might be the primary factor that initiates vascular remodeling in microgravity, and daily short-duration restoring its normal distribution by intermittent artificial gravity (IAG) can effectively prevent the vascular adaptation and hence postflight cardiovascular deconditioning. IAG might also be beneficial in maintaining vascular health during future long-duration space flight. [ABSTRACT FROM AUTHOR]

Silver has been used for centuries. Today, silver and silver nanoparticles (AgNPs) are used in a wide range of healthcare, food industry, domiciliary applications, and are commonly found in hard surface materials and textiles. Such an extensive use raises questions about its safety, environmental toxicity and the risks associated with microbial resistance and cross-resistance. If the mechanisms of antimicrobial action of ionic silver (Ag+) have been studied, there is little understanding of AgNPs interactions with microorganisms. There have been excellent reviews on the bacterial resistance mechanisms to silver, but there is a paucity of information on resistance to AgNPs. Silver toxicity and accumulation in the environment has been studied and there is a better understanding of silver concentration and species in different environmental compartments. However, owing to the increased applications of silver and AgNPs, questions remain about the presence and consequences of AgNPs in the environment. This review provides an historical perspective of silver usage, an overview of applications, and combined information of microbial resistance and toxicity. Owing the evidence provided in this review, a call for a better understanding and control of silver usage, and for tighter regulations of silver and AgNPs usage is proposed. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive channel in pulmonary arterial smooth muscle cells (PASMCs). Its upregulation by chronic hypoxia is associated with enhanced myogenic tone, and genetic deletion of trpv4 suppresses the development of chronic hypoxic pulmonary hypertension (CHPH). Here we further examine the roles of TRPV4 in agonist-induced pulmonary vasoconstriction and in the enhanced vasoreactivity in CHPH. Initial evaluation of TRPV4-selective antagonists HC-067047 and RN-1734 in KCl-contracted pulmonary arteries (PAs) of trpv4-/- mice found that submicromolar HC-067047 was devoid of off-target effect on pulmonary vasoconstriction. Inhibition of TRPV4 with 0.5 μM HC-067047 significantly reduced the sensitivity of serotonin (5-HT)-induced contraction in wild-type (WT) PAs but had no effect on endothelin-1 or phenylephrine-activated response. Similar shift in the concentrationresponse curve of 5-HT was observed in trpv4-/- PAs, confirming specific TRPV4 contribution to 5-HT-induced vasoconstriction. 5-HT-induced Ca2+ response was attenuated by HC-067047 in WT PASMCs but not in trpv4-/- PASMCs, suggesting TRPV4 is a major Ca2+ pathway for 5-HT-induced Ca2+ mobilization. Nifedipine also attenuated 5-HT-induced Ca2+ response in WT PASMCs but did not cause further reduction in the presence of HC-067047, suggesting interdependence of TRPV4 and voltage-gated Ca2+ channels in the 5-HT response. Chronic exposure (3-4 wk) of WT mice to 10% O2 caused significant increase in 5-HT-induced maximal contraction, which was partially reversed by HC-067047. In concordance, the enhancement of 5-HT-induced contraction was significantly reduced in PAs of CH trpv4-/- mice and HC-067047 had no further effect on the 5-HT induced response. These results suggest unequivocally that TRPV4 contributes to 5-HT-dependent pharmaco-mechanical coupling and plays a major role in the enhanced pulmonary vasoreactivity to 5-HT in CHPH. [ABSTRACT FROM AUTHOR]

Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Introduction: Most current root-end filling materials do not provide a perfect seal. Thus, a microscopic space is likely to exist in the interface between walls of the root-end cavity and filling material, which allows microorganisms and their products to penetrate. In addition to good sealing ability and biocompatibility, root-end filling materials should ideally have some antimicrobial activity. Therefore, this in vitro study aimed to evaluate the antimicrobial properties of Angelus white mineral trioxide aggregate (MTA) and the mixture of MTA with silver nanoparticles (1% weight; MTA/SN). Materials and Methods: Antimicrobial properties of MTA and MTA/SN were tested by agar diffusion technique against Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. The microbial inhibition zones around the materials were measured by a caliper with 0.1-mm accuracy. Student's t-test was used for comparison between the two groups in normal data distribution and Man-Whitney U test for non-normal distribution. Results: Student's t-test revealed that for E. faecalis, C. albicans, and P. aeruginosa, microbial inhibition zone of MTA/SN was significantly greater than that of MTA (P=0.000). Mann-Whitney U test indicated no significant difference between the effect of MTA and MTA/SN on S. aureus (P>0.05). Conclusion: Based on the results of this study, adding silver nanoparticles to MTA improved its antimicrobial efficacy. [ABSTRACT FROM AUTHOR]

Perinatal survival rates after intrauterine transfusions (IUT) for red cell alloimmunisation now exceed 90%, which demonstrates the safety and efficacy of one of the most successful procedures in fetal therapy. However, improved perinatal survival could lead to an increased number of children with long-term disabilities. The importance of long-term follow-up studies in fetal therapy lies in both the necessity of evaluation of antenatal management as well as in evidence-based preconceptional and prenatal counselling. This review describes the possible long-term cardiovascular and neurodevelopmental sequelae after IUT treatment for different indications including red cell alloimmunisation, parvovirus B19 infection, fetomaternal haemorrhage and twin anaemia-polycythaemia sequence. © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and objectives: Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery. Methods: This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012. Results: Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group. Conclusions: Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients. [ABSTRACT FROM AUTHOR]