Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity in rats.

UNLABELLED: Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. It is unknown whether renal tight junction (TJ) proteins expression and localization are modified in CP-induced nephrotoxicity. OBJECTIVE: To study if the expression of the TJ proteins occludin, claudin-2, claudin-5 and zonula occludens-1 (ZO-1) is modified in rats with CP-induced nephrotoxicity. MATERIALS AND METHODS: Male Wistar rats (n = 5/group) were injected with saline solution (V group), and the other group (CP group) was injected with a single dose of saline solution and CP (7.5 mg/kg i.p.). Rats were sacrificed 72 h after CP injection and blood, and 24-h urine samples were collected. Several plasma and urinary injury biomarkers as well as renal histopathology lesions, oxidative and nitrosative stress markers were evaluated, and protein levels of ocludin, claudin-2, claudin-5, ZO-1 were measured by Western blot. Statistically significant changes noted with different p < 0.05 versus V. RESULTS: Nephrotoxicity was evident by histological alterations, glycosuria, decrease in creatinine clearance, increase in fractional excretion of sodium, serum creatinine and kidney injury molecule-1. These changes were associated with oxidative/nitrosative stress (increased renal abundance of 3-nitrotyrosine and protein kinase Cß2 and decreased renal expression of nuclear factor-erythroid-2-related factor 2) and decreased activity of antioxidant enzymes. Finally, it was found that CP-induced renal damage was associated with decreased renal expression of occludin and claudin-2. DISCUSSION AND CONCLUSION: CP altered the TJ proteins expression and localization in the proximal tubule that was associated with oxidative/nitrosative stress.

Biosynthesis of Copper Nanoparticles with Medicinal Plants Extracts: From Extraction Methods to Applications.

Copper nanoparticles (CuNPs) can be synthesized by green methods using plant extracts. These methods are more environmentally friendly and offer improved properties of the synthesized NPs in terms of biocompatibility and functional capabilities. Traditional medicine has a rich history of utilization of herbs for millennia, offering a viable alternative or complementary option to conventional pharmacological medications. Plants of traditional herbal use or those with medicinal properties are candidates to be used to obtain NPs due to their high and complex content of biocompounds with different redox capacities that provide a dynamic reaction environment for NP synthesis. Other synthesis conditions, such as salt precursor concentration, temperature, time synthesis, and pH, have a significant effect on the characteristics of the NPs. This paper will review the properties of some compounds from medicinal plants, plant extract obtention methods alternatives, characteristics of plant extracts, and how they relate to the NP synthesis process. Additionally, the document includes diverse applications associated with CuNPs, starting from antibacterial properties to potential applications in metabolic disease treatment, vegetable tissue culture, therapy, and cardioprotective effect, among others.

Precipitation Stripping of V(V) as a Novel Approach for the Preparation of Two-Dimensional Transition Metal Vanadates.

Cobalt, nickel, manganese and zinc vanadates were synthesized by a hydrometallurgical two-phase method. The extraction of vanadium (V) ions from alkaline solution using Aliquat® 336 was followed by the production of metal vanadates through precipitation stripping. Precipitation stripping was carried out using solutions of the corresponding metal ions (Ni (II), Co (II), Mn (II) and Zn (II), 0.05 mol/L in 4 mol/L NaCl), and the addition time of the strip solution was varied (0, 1 and 2 h). The time-dependent experiments showed a notable influence on the composition, structure, morphology and crystallinity of the two-dimensional vanadate products. Inspired by these findings, we selected two metallic vanadate products and studied their properties as alternative cathode materials for nonaqueous sodium and lithium metal batteries.

Preparation of Volborthite by a Facile Synthetic Chemical Solvent Extraction Method.

In this work, the extraction of vanadium (V) ions from an alkaline solution using a commercial quaternary ammonium salt and the production of metal vanadates through precipitation stripping were carried out. The crystallization of copper vanadates from the extracts was performed using a solution containing a copper(II) source in concentrated chloride media as a stripping agent. In an attempt to control growth, a stabilizing polymer (polyvinylpyrrolidone, PVP) was added to the stripping solution. The structural characteristics of the crystallized products, mainly copper pyrovanadate (volborthite, Cu3V2O7(OH)2·(H2O)2) nanoflakes and nanoflowers and the experimental parameter influencing the efficiency of the stripping process were studied. From the results, the synthesis of nanostructured vanadates is a simple and versatile method for the fabrication of valuable three-dimensional structures providing abundant active zones for energy and catalytic applications.

The effect of cocoa, soy, oats and fish oil on metabolic syndrome in rats.

BACKGROUND: The effect of functional foods alone or in combination (cocoa + soy + oats + fish oil) on hepatic damage in rats affected with metabolic syndrome was investigated. RESULTS: Rats that were given cocoa showed a decrease in the levels of triglycerides (TGs) and glucose (63 and 32% respectively) as well as a decrease in blood pressure (15%). Animals fed with soy showed a reduction of 21% in total cholesterol, 15% in blood pressure and 44% in TGs, while feeding oats reduced the concentration of TGs by 53% (P < 0.5). Fish oil caused a reduction in TGs (56%) and glucose (26%). The effect on blood pressure was statistically significant for the groups supplemented with cocoa, soy, cocoa + oats and the total mix. The main finding was a reduction in liver steatosis in animals supplemented with cocoa + oats (from 30 to 4.7% steatosis). Cocoa or fish oil alone did not protect the liver from damage, while cocoa + fish oil did. CONCLUSION: The most relevant effects were that the cocoa + oats mix decreased steatosis by a very large percentage, as did the cocoa + fish oil mix and the mix of all four functional foods.

Bactericide Activity of Cellulose Acetate/Silver Nanoparticles Asymmetric Membranes: Surfaces and Porous Structures Role.

The antibacterial properties of cellulose acetate/silver nanoparticles (AgNP) ultrafiltration membranes were correlated with their integral asymmetric porous structures, emphasizing the distinct features of each side of the membranes, that is, the active and porous layers surfaces. Composite membranes were prepared from casting solutions incorporating polyvinylpyrrolidone-covered AgNP using the phase inversion technique. The variation of the ratio acetone/formamide and the AgNP content resulted in a wide range of asymmetric porous structures with different hydraulic permeabilities. Comprehensive studies assessing the antibacterial activity against Escherichia coli (cell death and growth inhibition of bacteria in water) were performed on both membrane surfaces and in E. coli suspensions. The results were correlated with the surface chemical composition assessed by XPS. The silver-free membranes presented a generalized growth of E. coli, which is in contrast with the inhibition patterns displayed by the membranes containing AgNP. For the surface bactericide test, the growth inhibition depends on the accessibility of E. coli to the silver present in the membrane; as the XPS results show, the more permeable membranes (CA30 and CA34 series) have higher silver signal detected by XPS, which is correlated with a higher growth inhibition. On the other hand, the inhibition action is independent of the membrane porous structure when the membrane is deeply immersed in an E. coli inoculated suspension, presenting almost complete growth inhibition.

Formation of large coronary arteries by cardiac progenitor cells.

Coronary artery disease is the most common cause of cardiac failure in the Western world, and to date there is no alternative to bypass surgery for severe coronary atherosclerosis. We report that c-kit-positive cardiac progenitor cells (CPCs) activated with insulin-like growth factor 1 and hepatocyte growth factor before their injection in proximity of the site of occlusion of the left coronary artery in rats, engrafted within the host myocardium forming temporary niches. Subsequently, CPCs divided and differentiated into endothelial cells and smooth muscle cells and, to a lesser extent, into cardiomyocytes. The acquisition of vascular lineages appeared to be mediated by the up-regulation of hypoxia-inducible factor 1alpha, which promoted the synthesis and secretion of stromal-derived factor 1 from hypoxic coronary vessels. Stromal-derived factor 1 was critical in the conversion of CPCs to the vascular fate. CPCs formed conductive and intermediate-sized coronary arteries together with resistance arterioles and capillaries. The new vessels were connected with the primary coronary circulation, and this increase in vascularization more than doubled myocardial blood flow in the infarcted myocardium. This beneficial effect, together with myocardial regeneration attenuated postinfarction dilated myopathy, reduced infarct size and improved function. In conclusion, locally delivered activated CPCs generate de novo coronary vasculature and may be implemented clinically for restoration of blood supply to the ischemic myocardium.

Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms.

Gulf War illness (GWI) afflicts military personnel who served during the Persian Gulf War and is notable for cognitive deficits, depression, muscle pain, weakness, intolerance to exercise, and fatigue. Suspect causal agents include the chemicals pyridostigmine (PB), permetrim (PM) and N,N-diethyl-m-toluamide (DEET) used as protectants against insects and nerve gases. No pre-clinical studies have explored the effects on skeletal muscle (SkM). Young male rats were provided PB, PM and DEET at equivalent human doses and physical restraint (to induce stress) for 3 weeks followed a 3-week recovery. GWI gastrocnemius weight was ~ 35% lower versus controls, which correlated with decreases in myofiber area, limb strength, and treadmill time/distance. In GWI rats, SkM fiber type relative abundance changed towards slow type I. Muscle wasting pathway proteins were upregulated while those that promote growth decreased as did mitochondrial endpoints and muscle ATP levels. Proteomic analysis of SkM also documented unique alterations in mitochondrial and metabolic pathways. Thus, exposure to GWI chemicals/stress adversely impacts key metabolic pathways leading to muscle atrophy and loss of function. These changes may account for GWI Veterans symptoms.

Cold and hot snare endoscopic techniques for removal of the Bravo pH monitoring capsule.

BACKGROUND: Currently, use of the Bravo capsule is a very common method for evaluating the gastroesophageal reflux because it has the advantage of being an intraesophageal catheter-free system. However, endoscopic removal of the capsule is necessary when technical problems or severe discomfort are present. Most frequently, endoscopists solve this problem by nudging the device with the tip of the endoscope to dislodge it; others have used a cold snare to produce traction on the capsule, and then tear the probe off. These techniques however are not free of complications. We report here the cold and hot snare techniques used in 4 of our patients, which resulted in the successful removal of the capsule without complications. METHODS: The polypectomy cold snare procedure is a typical polypectomy method. The cold snare loops the mucosal pedicle and tightly closes it until sectioning is achieved. In the hot snare technique, a monopolar coagulating current is added to the previous procedure, making the resection more feasible when the cold snare is not sufficient. Finally, in both situations, the probe is removed from the esophagus with the same snare. CONCLUSIONS: The cold and hot snare techniques are safe and simple endoscopic procedures when the removal of the Bravo capsule is required. We recommend the cold snare method as a first option and the hot snare method in case the former fails.

Synthesis and bactericide activity of nanofiltration composite membranes - Cellulose acetate/silver nanoparticles and cellulose acetate/silver ion exchanged zeolites.

The present work addresses the synthesis of nanofiltration composite membranes with bactericide properties. The cellulose acetate based membranes with polyvinylpyrrolidone coated silver nanoparticles, silver ion-exchanged ß-zeolite and ß-zeolite are casted by the phase inversion technique and subjected to an annealing post-treatment. They are characterized in terms of the nanofiltration permeation performance and antibacterial properties. The incorporation of silver nanoparticles produces a threefold increase in the membrane hydraulic permeability when compared to the silver-free membranes and the incorporation of silver ion loaded zeolite resulted in a 56.3% increase in hydraulic permeability. In contrast to the influence of silver presence, either in nanometric or in the ionic form, the presence of zeolite does not significantly influence the hydraulic permeability. The rejection coefficients to salts range from 83% to 93% for the silver ion-exchanged zeolite membrane and from 84% to 97% for the polyvinylpyrrolidone coated silver nanoparticles membrane. They are higher for sulfate salts than for chloride salts. The antibacterial properties of the membranes were evaluated against Escherichia coli. The results have shown that the silver ion-exchanged ß-zeolite membrane was effective in inactivating Escherichia coli after just 210 min of contact time. No bacterial activity was detected following 24 h of contact time with the membrane containing polyvinylpyrrolidone coated silver nanoparticles. A reduction of more than 6-log, in the number of Escherichia coli, was achieved for both membranes. The different patterns of bactericide activity are associated to the silver speciation in metallic or ionic form. The high flux nanofiltration composite membranes with bactericidal properties represent a strong asset in water treatment biofouling control.

(-)-Epicatechin induced reversal of endothelial cell aging and improved vascular function: underlying mechanisms.

The consumption of cocoa products rich in (-)-epicatechin is associated with reduced cardiovascular risk and improved vascular function. However, little is known about (-)-epicatechin's effects on aged endothelium. In order to characterize the health restoring effects of (-)-epicatechin on aged endothelium and identify the underlying mechanisms, we utilized high passage number (i.e. aged) bovine coronary artery endothelial cells and aortas of 3 and 18 month old rats. We evaluated cell senescence (ß-galactosidase), nitric oxide (NO) production through the endothelial nitric oxide synthase pathway, mitochondria related endpoints, citrate synthase activity and vascular relaxation. Cells were treated with water or (-)-epicatechin (1 µM) for 48 h and rats orally with either water or (-)-epicatechin (1 mg kg-1 day-1) for 15 days. Senescence associated ß-galactosidase levels doubled in aged cells while those treated with (-)-epicatechin only evidenced an ∼40% increase. NO levels in cells decreased by ∼33% with aging and (-)-epicatechin normalized them. Endothelial nitric oxide synthase phosphorylation levels paralleled these results. Aging increased total protein and synthase acetylation levels and (-)-epicatechin partially restored them to those of young cells by stimulating sirtuin-1 binding to the synthase. Phosphorylated sirtuin-1, mitofilin, oxidative phosphorylation complexes and transcriptional factor for mitochondria were reduced by ∼40% with aging and were restored by (-)-epicatechin. (-)-Epicatechin enhanced acetylcholine induced aged aorta vasodilation and stimulated NO levels while reducing blood pressure. In conclusion, (-)-epicatechin reverses endothelial cell aging and restores key control elements of vascular function. These actions may partly explain the epidemiological evidence for the beneficial effects of cocoa consumption on the incidence of cardiac and vascular diseases.

Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique.

UNLABELLED: This study aimed to determine the magnitude and distribution of tissue angiotensin-converting enzyme (ACE), mast-cell chymase, and angiotensin II, type 1, plasma membrane receptor (AT1R), in relation to collagen replacement in infarcted and noninfarcted left ventricular myocardial segments. A new radiotracer, 18F-fluorobenzoyl-lisinopril (FBL), was synthesized without compromising its affinity for tissue ACE. METHODS: Five- to 10-microm contiguous short-axis slices of explanted hearts from 3 patients with ischemic cardiomyopathy were incubated in vitro with FBL, with and without 10(-6) M lisinopril. Tissue radioactivity was recorded as a function of position in photostimulating luminescence units (PSL). Immunohistochemistry studies were performed with mouse monoclonal antibody against ACE, anti-mast cell chymase, and polyclonal antibody against the human AT1R. RESULTS: There was specific binding of FBL to ACE; mean FBL binding was 6.6 +/- 5.2 PSL/mm2, compared with 3.4 +/- 2.5 PSL/mm2 in segments incubated in solution containing cold, 10(-6) M lisinopril (P < 0.0001). Mean FBL binding was 6.3 +/- 4.5 PSL/mm2 in infarcted, 7.6 +/- 4.7 PSL/mm2 in periinfarcted, and 5.0 +/- 1.0 PSL/mm2 in remote, noninfarcted (P < 0.02 vs. periinfarcted) segments. The autoradiographic observations concerning FBL binding were confirmed by ACE and AT1R immunoreactivity. Distribution of mast cell chymase differed from ACE, as a higher number of mast cells was present in the remote, noninfarcted myocardium than in the periinfarcted myocardium (5.1 +/- 3.2 vs. 3.2 +/- 2.2 mast cells per field, P < 0.001). The number of mast cells in ischemic hearts exceeded that in normal hearts (4.2 +/- 2.7 vs. 1.5 +/- 1.2 mast cells per field, x200, P < 0.001). CONCLUSION: FBL binds specifically to ACE. The binding is nonuniform in infarcted, periinfarcted, and remote, noninfarcted segments, and there is apparently increased ACE activity in the juxtaposed areas of replacement fibrosis. On the other hand, the distribution of mast cell chymase appears nonuniform and disparate from ACE.

Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress.

Curcumin is a polyphenol and cisplatin is an antineoplastic agent that induces nephrotoxicity associated with oxidative stress, apoptosis, fibrosis and decrease in renal tight junction (TJ) proteins. The potential effect of curcumin against alterations in TJ structure and function has not been evaluated in cisplatin-induced nephrotoxicity. The present study explored whether curcumin is able to prevent the cisplatin-induced fibrosis and decreased expression of the TJ and adherens junction (AJ) proteins occludin, claudin-2 and E-cadherin in cisplatin-induced nephrotoxicity. Curcumin (200 mg kg(-1)) was administered in three doses, and rats were sacrificed 72 h after cisplatin administration. Curcumin was able to scavenge, in a concentration-dependent way, superoxide anion, hydroxyl radical, peroxyl radical, singlet oxygen, peroxynitrite anion, hypochlorous acid and hydrogen peroxide. Cisplatin-induced renal damage was associated with alterations in plasma creatinine, expression of neutrophil gelatinase-associated lipocalin and of kidney injury molecule-1, histological damage, increase in apoptosis, fibrosis (evaluated by transforming growth factor ß1, collagen I and IV and α-smooth muscle actin expressions), increase in oxidative/nitrosative stress (evaluated by Hsp70/72 expression, protein tyrosine nitration, superoxide anion production in isolated glomeruli and proximal tubules, and protein levels of NADPH oxidase subunits p47(phox) and gp91(phox), protein kinase C ß2, and Nrf2) as well as by decreased expression of occludin, claudin-2, ß-catenin and E-cadherin. Curcumin treatment prevented all the above-described alterations. The protective effect of curcumin against cisplatin-induced fibrosis and decreased proteins of the TJ and AJ was associated with the prevention of glomerular and proximal tubular superoxide anion production induced by NADPH oxidase activity.

Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease.

Chagas' disease is an important cause of cardiomyopathy. Endothelin-1, a vasoactive peptide has been implicated in the pathogenesis of chagasic cardiomyopathy. C57BL/6 x 129sv and CD1 mice were thus, infected with trypomastigotes of Trypanosoma cruzi (Brazil strain) and these infected mice were compared with infected mice treated with phosphoramidon. This compound inhibits endothelin-converting enzyme and neutral endopeptidases and does not affect the growth of the parasite in culture. Phosphoramidon was given in a dose of 10mg/kg for the initial 15 days post-infection None of the C57Bl/6 x 129sv mice died as a result of infection. However, there was marked myocardial inflammation and fibrosis in infected, untreated mice. The hearts of the infected, phosphoramidon-treated mice showed significantly less pathology. Cardiac magnetic resonance imaging of infected mice revealed right ventricular dilation that was less severe in those treated with phosphoramidon. Phosphoramidon-treated CD1 mice survived the acute infection. Transthoracic echocardiography demonstrated left ventricular dilation and reduced percent fractional shortening and relative wall thickness. These alterations were also attenuated as a result of phosphoramidon treatment. These data suggest that endothelin-1 contributes to the pathogenesis of chagasic cardiomyopathy and interventions that inhibit the synthesis of endothelin-1 and/or neutral endopeptidase might have a protective effect on myocardial structure and function in murine Chagas' disease.

Estudio Comparativo de Ansiedad y Disfunción Temporomandibular en Cirujanos Dentistas Residentes de dos Universidades Mexicanas / Comparative Study of Anxiety and Temporomandibular Dysfunctio in Resident Dental Surgeons of Two Mexican Universities

RESUMEN: La ansiedad puede ser un detonante de la disfunción temporomandibular (DTM). Se ha mencionado que el trastorno psicológico más frecuente en México es la "ansiedad" con 14,3 %. El objetivo es correlacionar y comparar los niveles de ansiedad y los grados de DTM en cirujanos dentistas residentes (CDR) de dos universidades mexicanas: la Facultad de Odontología de la Universidad de la Salle Bajío León, Guanajuato (FOULSB), y de la Facultad de Odontología de la Universidad Autónoma (FOUADY) de Yucatán México durante el periodo de septiembre 2017 a febrero 2018. El tipo de estudio fue correlacional, comparativo de cohorte transversal, siendo las variables: ansiedad (niveles según cuestionario de autoevaluación de ansiedad estado/rasgo STAI); signos y síntomas clínicos para el diagnóstico de DTM, (CDI/TTM Grupo I Desórdenes Musculares; Grupo II Desplazamientos discales; Grupo III Artralgia, osteoartritis). El tamaño de la muestra y criterios de inclusión en ambas universidades fueron: CDR en Odontología; que aceptaron participar en el estudio, mediante la firma del consentimiento informado y voluntario; hombres y mujeres; entre 25 a 34 años de edad. Criterios de exclusión: con tratamientos ortodónticos, quirúrgicos, enfermedades sistémicas o neurológicas y que sólo el día que se tomó la muestra presentaron otalgia o cefalea. El tipo de muestreo, por conveniencia. Se utilizó estadística descriptiva e inferencial. Los resultados: 40 CDR de la FOULSB, donde el 92,5 % (n=37) manifestaron tener niveles de ansiedad bajos, y el 7,5 % (n=3) moderado. El 65,8 % (n=26) presentó diagnóstico de DTM. De los 40 CDR de la FOUADY, 97,5 % (n=39) declararon tener niveles de ansiedad bajos, y el 2,5 % (n=1) obtuvo un nivel alto. El 67,5 % (n=27) presentaron signos y/o síntomas de DTM. La conclusión fue que no existieron diferencias estadísticamente significativas, ya que los CDR de ambas universidades presentaron porcentajes de DTM similares y también tuvieron niveles de ansiedad similares.

ABSTRACT: Anxiety can be a trigger for temporomandibular dysfunction (TMD). It has been mentioned that the most frequent psychological disorder in Mexico is "anxiety" with 14.3 %. The objective is to correlate and compare the levels of anxiety and the degrees of TMD in resident dentists (CDR) of two Mexican universities: the Faculty of Dentistry of the University of La Salle Bajío León, Guanajuato (FOULSB), and the Faculty of Dentistry. Dentistry of the Autonomous University (FOUADY) of Yucatan Mexico during the period from September 2017 to February 2018. The type of study was correlational, comparative crosssectional cohort, the variables being: anxiety (levels according to questionnaire self-assessment of anxiety state / trait STAI); clinical signs and symptoms for the diagnosis of TMD, (CDI / TTM Group I Muscle Disorders, Group II Displacement discs, Group III Arthralgia, osteoarthritis). The size of the sample and inclusion criteria in both universities were CDR in Dentistry; who agreed to participate in the study, by signing the informed and voluntary consent; men and women; between 25 to 34 years of age. Exclusion criteria: with orthodontic, surgical treatments, systemic or neurological diseases and that only the day the sample was taken showed otalgia or headache. The type of sampling, for convenience. Descriptive and inferential statistics were used. The results: 40 CDR of FOULSB, where 92.5 % (n = 37) reported having low anxiety levels, and 7.5 % (n = 3) moderate. Sixty-five point eight percent (n=26) presented diagnosis of TMD. Of the 40 CDRs of FOUADY, 97.5 % (n = 39) reported having low anxiety levels, and 2.5 % (n = 1) had a high level. Sixtyseven point five percent (n=27) presented signs and / or symptoms of TMD. The conclusion was that there were no statistically significant differences, since the CDRs of both universities presented similar DTM percentages and had similar levels of anxiety.

Determinación de la calidad de pulido de resinas de nanorrelleno empleando un microscopio de fuerza atómica / Determining the polishing quality of nanofilled resins using an atomic force microscope

Introducción: Los procedimientos de acabado y pulido de las restauraciones dentarias son fases determinantes en la práctica odontológica,ya que las superficies bien acabadas y pulidas aumentan la longevidadde la restauración, disminuyen la acumulación de placa y reducen las modificaciones del color marginal a la restauración y superficie. Objetivo: El propósito de este estudio fue evaluar tres diferentes sistemas de pulido: discos Sof-Lex, copas pulidoras Jiff y y sistema de un solopaso OptraPol, en función de la superficie obtenida en tres marcas deresinas estéticas nanohíbridas para zona anterior y posterior...

Introduction: The procedures for finishing and polishing dental restorations are crucial phases in dental practice, as well-fi nished andwell-polished surfaces increase the longevity of the restoration andreduce the buildup of plaque and marginal color changes in both therestoration and the surface. Objective: The purpose of this study wasto evaluate three diff erent polishing systems: Sof-Lex™, Jiff y® polishercups, and the OptraPol one-step system, based on the surface obtainedusing three brands of cosmetic nanohybrid resins in the anterior and posterior regions...

An adenosine derivative compound, IFC305, reverses fibrosis and alters gene expression in a pre-established CCl(4)-induced rat cirrhosis.

Cirrhosis is a complex process that involves a dynamic modification of liver cell phenotype associated to gene expression changes. This study investigates the reversing capacity of an adenosine derivative compound (IFC305) on a rat model of liver cirrhosis and gene expression changes associated with it. Rats were treated with IFC305 or saline for 5 or 10 weeks after cirrhosis induction (CCl(4) treatment for 10 weeks). Fibrosis score, collagenase activity and amount of hepatic stellate cells (HSC, activated and with a lipid-storing phenotype) were measured in livers. In addition, gene expression analysis was performed using 5K DNA microarrays and quantitative RT-PCR. Treatment of cirrhotic rats with IFC305 for 5 or 10 weeks compared to saline control, induced: (1) reduction of fibrosis (50-70%) and of collagen, of alpha-SMA and desmin proteins, as well as of activated HSCs in liver, (2) increased collagenase activity and cell number of lipid-storing HSC, (3) improved serum parameters of liver function, such as reduced activity of aminotransferases and bilirubin. Expression of 413 differential genes, deregulated in cirrhotic samples, tended to be normalized by IFC305 treatment. Some genes modulated at transcript level by IFC305 were Tgfb1, Fn1, Col1a1, C9, Apoa1, Ass1, Cps1, and Pparg. The present study shows that IFC305 reverses liver fibrosis through modulation of adipogenic and fibrosis-related genes and by ameliorating hepatic function. Thus, understanding of the anti-cirrhotic effect of IFC305 might have therapeutical potential in patients with cirrhosis.

Imaging the renin-angiotensin- aldosterone system in the heart.

The influence of the renin-angiotensin system (RAS) is recognized in cardiac and vascular injury. An extrinsic RAS has been known for decades, and an equally important intrinsic RAS has been discovered recently. The latter leads to pathologic tissue alterations in the absence of systemic stimuli and may be the main source of local tissue effects of RAS. A new radiotracer fluorobenzoyl-lisinopril was synthesized by radiolabeling benzoic acid active ester with 18F and reacting that with the epsilon-amino group of lisinopril. The presence of angiotensin-converting enzyme (ACE) activity and angiotensin II receptors was examined in relation to myocardial fibrosis. This tissue-specific radioligand represents the first study of ACE in the human heart. This article presents preliminary data on imaging the RAS in the human cardiac tissue and discusses the potential for clinical application of these imaging techniques to human patients.

Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease.

On the basis of previous observations, endothelin 1 (ET-1) has been suggested as contributing to the pathogenesis of Chagasic cardiomyopathy. Therefore, ET-1flox/flox;alpha-MHC-Cre(+) mice in which the ET-1 gene was deleted from cardiac myocytes and ET-1flox/flox;Tie 2 Cre(+) mice in which the ET-1 gene was deleted from endothelial cells were infected with Trypanosoma cruzi. Genetic controls for these cell-specific ET-1 knockout mice were used. Ninety percentage of all mice survived acute infection with the Brazil strain and were evaluated 130 days postinfection. Inflammation and fibrosis were observed in all infected mice; however, fibrosis was reduced in ET-1flox/flox;alpha-MHC-Cre(+) mice. Cardiac magnetic resonance imaging revealed that infection resulted in a significant increase in right ventricular internal diameter (RVID) in all mice except ET-1flox/flox;alpha-MHC-Cre(+) mice; i.e., RVID was not changed in infected ET-1flox/flox;alpha-MHC-Cre(+) mice. Echocardiography of the left ventricle demonstrated increased left ventricular end-diastolic diameter, reduced fractional shortening, and decreased relative wall thickness in infected mice. However, the magnitude of the changes was significantly less in ET-1flox/flox;alpha-MHC-Cre(+) mice compared to other groups. These data provide further evidence of a role for ET-1, particularly cardiac myocyte-derived ET-1, in the pathogenesis of chronic Chagasic cardiomyopathy.