Challenges to the treatment and new perspectives for the eradication of helicobacter pylori

Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.

A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis

Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis.

Fracture resistance of weakened bovine teeth after long-term use of calcium hydroxide

In some parts of the world, revascularization may not be the most feasible treatment option for necrotic immature teeth. Therefore, apexification remains the most widely utilized treatment option for these cases. This study aimed to evaluate the fracture resistance of weakened bovine tooth roots treated with various irrigant solutions as well as long-term application of calcium hydroxide intracanal medication (ICM). One hundred seventy bovine teeth were randomly divided into three experimental groups (n = 50) and two control groups (n = 10). Group SS was irrigated with physiologic solution; group CHX was treated with 2% chlorhexidine gel and group NaOCl was irrigated with 1% sodium hypochlorite. After instrumentation, root canals were dressed with calcium hydroxide and evaluated at different periods (15, 60, 90, 180, and 360 days). The specimens were loaded at a 45° angle to measure fracture resistance through the use of an EMIC test machine. A decrease in fracture resistance was observed during the time of ICM dressing. The highest values of fracture resistance were observed in group SS with 15 days of ICM, not differing from the control group. Irrigation with NaOCl associated with ICM for 15 days presented the lowest fracture resistance; however, a statistically significant difference was not observed when compared with SS and CHX in the same time period. In longer periods of exposure to ICM (180 and 360 days), root canals irrigated with NaOCl and CHX showed significantly lower fracture resistance than SS (P < 0.05). Apexification with periodic changes of calcium hydroxide medicament leads to weakness of the teeth independent of the irrigation solution used.

Dermatobia hominis: potencial risk of resistance to macrocyclic lactones

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Histopathological and cytological analysis of transmissible venereal tumor in dogs after two treatment protocols

The transmissible venereal tumor (TVT) is a contagious neoplasm of round cells that frequently affect dogs. The treatment consists of chemotherapy being more effective the vincristine alone, however the resistance emergence to this agent due multidrug resistance of the P-glycoprotein (P-gp), a transporter protein encoded by the MDR1 gene, has been taking the association with other drugs. Recent studies demonstrated the antitumoral effect of the avermectins when associated to the vincristine in the treatment of some neoplasms. Therefore, the objective of the present study was to compare the effectiveness of standard treatment of TVT with vincristine only as compared to combined treatment with vincristine and ivermectin, evaluated through number of applications of the two protocols, histopathological and cytological analysis from 50 dogs diagnosed with TVT during the period of 2007 to 2010. The combined protocol significant reduces the number of applications and cytological and histopathological findings collaborate with the hypothesis that the combination of vincristine and ivermectin promotes faster healing than the use of vincristine alone. Combination treatment with vincristine and ivermectin could be in the future an excellent therapeutic alternative for the treatment of TVT for probably reducing the resistance to vincristine, simultaneously reducing the cost of TVT treatment and a faster recovery of the dog.

Application of Mossbauer spectroscopy to the study of corrosion resistance in NaCl solution of plasma nitrided AISI 316L stainless steel

Corrosion research in steels is one of the areas in which Mossbauer spectroscopy has become a required analytical technique, since it is a powerful tool for both identifying and quantifying distinctive phases (which contain Fe) with accuracy. In this manuscript, this technique was used to the study of corrosion resistance of plasma nitrided AISI 316L samples in the presence of chloride anions. Plasma nitriding has been carried out using dc glow-discharge, nitriding treatments, in medium of 80 vol.% H-2 and 20 vol.% N-2, at 673 K, and at different time intervals: 2, 4, and 7 h. Treated samples were characterized by means of phase composition and morphological analysis, and electrochemical tests in NaCl aerated solution in order to investigate the influence of treatment time on the microstructure and the corrosion resistance, proved by conversion electron Mossbauer spectroscopy (CEMS), glancing angle X-ray diffraction (GAXRD), scanning electron microscopy (SEM) and potentiodynamic polarization. A modified layer of about 8 gin was observed for all the nitrided samples, independently of the nitriding time. A metastable phase, S phase or gamma(N), was produced. It seems to be correlated with gamma`-Fe-4 N phase. If the gamma(N) fraction decreases, the gamma` fraction increases. The gamma(N) magnetic nature was analyzed. When the nitriding time increases, the results indicate that there is a significant reduction in the relative fraction of the magnetic gamma(N) (in) phase. In contrast, the paramagnetic gamma(N) (p) phase increases. The GAXRD analysis confirms the Mossbauer results, and it also indicates CrN traces for the sample nitrided for 7 h. Corrosion results demonstrate that time in the plasma nitriding treatment plays an important role for the corrosion resistance. The sample treated for 4 h showed the best result of corrosion resistance. It seems that the epsilon/gamma` fraction ratio plays an important role in thin corrosion resistance since this sample shows the maximum value for this ratio. (c) 2008 Published by Elsevier B.V.

Low-Cost Ultra-Wide Genotyping Using Roche/454 Pyrosequencing for Surveillance of HIV Drug Resistance

Background: Great efforts have been made to increase accessibility of HIV antiretroviral therapy (ART) in low and middle-income countries. The threat of wide-scale emergence of drug resistance could severely hamper ART scale-up efforts. Population-based surveillance of transmitted HIV drug resistance ensures the use of appropriate first-line regimens to maximize efficacy of ART programs where drug options are limited. However, traditional HIV genotyping is extremely expensive, providing a cost barrier to wide-scale and frequent HIV drug resistance surveillance. Methods/Results: We have developed a low-cost laboratory-scale next-generation sequencing-based genotyping method to monitor drug resistance. We designed primers specifically to amplify protease and reverse transcriptase from Brazilian HIV subtypes and developed a multiplexing scheme using multiplex identifier tags to minimize cost while providing more robust data than traditional genotyping techniques. Using this approach, we characterized drug resistance from plasma in 81 HIV infected individuals collected in Sao Paulo, Brazil. We describe the complexities of analyzing next-generation sequencing data and present a simplified open-source workflow to analyze drug resistance data. From this data, we identified drug resistance mutations in 20% of treatment naive individuals in our cohort, which is similar to frequencies identified using traditional genotyping in Brazilian patient samples. Conclusion: The developed ultra-wide sequencing approach described here allows multiplexing of at least 48 patient samples per sequencing run, 4 times more than the current genotyping method. This method is also 4-fold more sensitive (5% minimal detection frequency vs. 20%) at a cost 3-5 x less than the traditional Sanger-based genotyping method. Lastly, by using a benchtop next-generation sequencer (Roche/454 GS Junior), this approach can be more easily implemented in low-resource settings. This data provides proof-of-concept that next-generation HIV drug resistance genotyping is a feasible and low-cost alternative to current genotyping methods and may be particularly beneficial for in-country surveillance of transmitted drug resistance.

EFFECT OF THERMAL TREATMENT ON THE CHEMICAL CHARACTERISTICS OF WOOD FROM Eucalyptus grandis W. Hill ex Maiden UNDER DIFFERENT ATMOSPHERIC CONDITIONS

Thermal treatment (thermal rectification) is a process in which technological properties of wood are modified using thermal energy, the result of Which is often value-added wood. Thermally treated wood takes on similar color shades to tropical woods and offers considerable resistance to destructive microorganisms and climate action, in addition to having high dimensional stability and low hygroscopicity. Wood samples of Eucalyptus grandis were subjected to various thermal treatments, as performed in presence (140 degrees C; 160 degrees C; 180 degrees C) or in absence of oxygen (160 degrees C; 180 degrees C; 200 degrees C) inside a thermal treatment chamber, and then studied as to their chemical characteristics. Increasing the maximum treatment temperatures led to a reduction in the holocellulose content of samples as a result of the degradation and volatilization of hemicelluloses, also leading to an increase in the relative lignin content. Except for glucose, all monosaccharide levels were found to decrease in samples after the thermal treatment at a maximum temperature of 200 degrees C. The thermal treatment above 160 degrees C led to increased levels of total extractives in the wood samples, probably ascribed to the emergence of low molecular weight substances as a result of thermal degradation. Overall, it was not possible to clearly determine the effect of presence or absence of oxygen in the air during thermal treatment on the chemical characteristics of the relevant wood samples.

GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

Background: Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model. Methods: Spontaneously hypertensive neonate rats (18/group) were treated with monosodium glutamate (MetS) during 9 days, and compared with Wistar-Kyoto (C) and saline-treated SHR (H). Blood pressure (BP) and lipid levels, C-reactive protein (CRP), interleukin 6 (IL-6), TNF-alpha and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo), 6 (6-mo) and 9 (9-mo) months of age. Results: MetS rats were more insulin resistant (p<0.001, all ages) and had higher BP (3-mo: p<0.001, 6-mo: p = 0.001, 9-mo: p = 0.015) as compared to C. At 6 months, CRP, IL-6 and TNF-alpha were higher (p<0.001, all comparisons) in MetS rats vs H, but adiponectin was lower in MetS at 9 months (MetS: 32 +/- 2, H: 42 +/- 2, C: 45 +/- 2 pg/mL; p<0.001). GLUT4 protein was reduced in MetS as compared to C rats at 3, 6 and 9-mo, respectively (Heart: 54%, 50% and 57%; Gastrocnemius: 37%, 56% and 50%; Adipose tissue: 69%, 61% and 69%). Conclusions: MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.

Antioxidant treatment protects against matrix metalloproteinase activation and cardiomyocyte injury during acute pulmonary thromboembolism

Increased reactive oxygen species (ROS) promote matrix metalloproteinase (MMP) activities and may underlie cardiomyocyte injury and the degradation of cardiac troponin I (cTI) during acute pulmonary thromboembolism (APT). We examined whether pretreatment or therapy with tempol (a ROS scavenger) prevents MMP activation and cardiomyocyte injury of APT. Anesthetized sheep received tempol infusion (1.0 mg kg(-1) min(-1), i.v.) or saline starting 30 min before or 30 min after APT (autologous blood clots). Control animals received saline. Hemodynamic measurements were performed. MMPs were studied in the right ventricle (RV) by gelatin zymography, fluorimetric activity assay, and in situ zymography. The ROS levels were determined in the RV and cTI were measured in serum samples. APT increased the pulmonary arterial pressure and pulmonary vascular resistance by 146 and 164 %, respectively. Pretreatment or therapy with tempol attenuated these increases. While APT increased RV + dP/dt (max), tempol infusions had no effects. APT increased RV MMP-9 (but not MMP-2) levels. In line with these findings, APT increased RV MMP activities, and this finding was confirmed by in situ zymography. APT increased the RV ROS levels and tempol infusion, before or after APT, and blunted APT-induced increases in MMP-9 levels, MMP activities, in situ MMP activities, and ROS levels in the RV. cTI concentrations increased after APT, and tempol attenuated these increases. RV oxidative stress after APT increases the RV MMP activities, leading to the degradation of sarcomeric proteins, including cTI. Antioxidant treatment may prevent MMP activation and protect against cardiomyocyte injury after APT.

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol.

Metabolic Disorders and Adipose Tissue Insulin Responsiveness in Neonatally STZ-Induced Diabetic Rats Are Improved by Long-Term Melatonin Treatment

Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell insufficiency. Rats with streptozotocin-induced diabetes during the neonatal period by the fifth day of age develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, polyuria, and polydipsia aggravated by insulin resistance in adulthood. In this study, we investigated whether the effect of long-term treatment with melatonin can improve insulin resistance and other metabolic disorders in these animals. At the fourth week of age, diabetic animals started an 8-wk treatment with melatonin (1 mg/kg body weight) in the drinking water at night. Animals were then killing, and the sc, epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed, and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Blood samples were collected for biochemical assays. Melatonin treatment reduced hyperglycemia, polydipsia, and polyphagia as well as improved insulin resistance as demonstrated by constant glucose disappearance rate and homeostasis model of assessment-insulin resistance. However, melatonin treatment was unable to recover body weight deficiency, fat mass, and adipocyte size of diabetic animals. Adiponectin and fructosamine levels were completely recovered by melatonin, whereas neither plasma insulin level nor insulin secretion capacity was improved in diabetic animals. Furthermore, melatonin caused a marked delay in the sexual development, leaving genital structures smaller than those of nontreated diabetic animals. Melatonin treatment improved the responsiveness of adipocytes to insulin in diabetic animals measured by tests of glucose uptake (sc, EP, and RP), glucose oxidation, and incorporation of glucose into lipids (EP and RP), an effect that seems partially related to an increased expression of insulin receptor substrate 1, acetyl-coenzyme A carboxylase and fatty acid synthase. In conclusion, melatonin treatment was capable of ameliorating the metabolic abnormalities in this particular diabetes model, including insulin resistance and promoting a better long-term glycemic control. (Endocrinology 153: 2178-2188, 2012)

Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (similar to 38%) and sympathetic effects (similar to 36%) were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice

Vinolo MA, Rodrigues HG, Festuccia WT, Crisma AR, Alves VS, Martins AR, Amaral CL, Fiamoncini J, Hirabara SM, Sato FT, Fock RA, Malheiros G, dos Santos MF, Curi R. Tributyrin attenuates obesity-associated inflammation and insulin resistance in high-fat-fed mice. Am J Physiol Endocrinol Metab 303: E272-E282, 2012. First published May 22, 2012; doi:10.1152/ajpendo.00053.2012.-The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against diet-induced obesity and associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice against obesity and obesity-associated insulin resistance and dyslipidemia without food consumption being affected. Tb attenuated the production of TNF alpha and IL-1 beta by peritoneal macrophages and their expression in adipose tissue. Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and infiltration by leukocytes and restored the production of adiponectin. These effects were associated with a partial reversion of hepatic steatosis, reduction in liver and skeletal muscle content of phosphorylated JNK, and an improvement in muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the beneficial effects of Tb are likely to be secondary to the reduction in body weight, we also found direct protective actions of butyrate reducing TNF alpha production after LPS injection and in vitro by LPS- or palmitic acid-stimulated macrophages and attenuating lipolysis in vitro and in vivo. The results, reported herein, suggest that Tb may be useful for the treatment and prevention of obesity-related metabolic disorders.

Wear and corrosion resistance of pack chromised carbon steel

Pack chromising treatment is an environmentally friendly alternative to hard chromium to form wear and corrosion resistant surface layers. In this work, samples of AISI 1060 steel were pack chromised for 6 and 9 h at 1000 and 1050 degrees C using different activator concentrations. Wear tests were performed in dry conditions and corrosion tests in natural sea water for the pack chromised samples and hard chromium. Pack chromising yielded the formation of layers with high chromium concentrations, high hardness and wear resistance. Increasing activator concentration causes no significant change on the morphology and thickness of the layers. The layers produced at 1050 degrees C yielded only a (Cr,Fe)(2)N1-x phase, and those obtained at 1000 degrees C are composed of a carbide mixture with (Cr,Fe)(2)N1-x. The sample treated at 1050 degrees C for 9 h resulted in an optimum condition by means of better wear resistance and corrosion properties, which were close to that exhibited by the hard chrome, indicating that pack chromising is a promising alternative.