Regular and moderate aerobic training before allergic asthma induction reduces lung inflammation and remodeling.

Experimental studies have reported that aerobic exercise after asthma induction reduces lung inflammation and remodeling. Nevertheless, no experimental study has analyzed whether regular/moderate aerobic training before the induction of allergic asthma may prevent these inflammatory and remodeling processes. For this purpose, BALB/c mice (n = 96) were assigned into non-trained and trained groups. Trained animals ran on a motorized treadmill at moderate intensity, 30 min/day, 3 times/week, for 8 weeks, and were further randomized into subgroups to undergo ovalbumin sensitization and challenge or receive saline using the same protocol. Aerobic training continued until the last challenge. Twenty-four hours after challenge, compared to non-trained animals, trained mice exhibited: (a) increased systolic output and left ventricular mass on echocardiography; (b) improved lung mechanics; (c) decreased smooth muscle actin expression and collagen fiber content in airways and lung parenchyma; (d) decreased transforming growth factor (TGF)-ß levels in bronchoalveolar lavage fluid (BALF) and blood; (e) increased interferon (IFN)-γ in BALF and interleukin (IL)-10 in blood; and (f) decreased IL-4 and IL-13 in BALF. In conclusion, regular/moderate aerobic training prior to allergic asthma induction reduced inflammation and remodeling, perhaps through increased IL-10 and IFN-γ in tandem with decreased Th2 cytokines.

Silver-gelatine bionanocomposites for qualitative detection of a pesticide by SERS.

The controlled release of pesticides using hydrogel vehicles is an important procedure to limit the amount of these compounds in the environment, providing an effective way for crop protection. A key-step in the formulation of new materials for these purposes encompasses the monitoring of available pesticides in the gel matrix under variable working conditions. In this work, we report a series of bionanocomposites made of Ag nanoparticles (NPs) and gelatine A for the surface enhanced Raman scattering (SERS) detection of sodium diethyldithiocarbamate (EtDTC) as a pesticide model. These studies demonstrate the effectiveness of these substrates for the detection of EtDTC in aqueous solutions in a concentration as low as 10(-5) M. We have monitored the Raman signal enhancement of this analyte in bionanocomposites having an increasing amount of gelatine due to their relevance in formulating hydrogels of variable gel strengths. Under these conditions, the bionanocomposites have shown an effective SERS activity using EtDTC, demonstrating their effectiveness in the qualitative detection of this analyte. Finally, experiments involving the release of EtDTC from Ag/gelatine samples have been monitored by SERS, which attest the potential of this spectroscopic method in the laboratorial monitoring of hydrogels for pesticide release.

Color flow Doppler sonography for the etiologic diagnosis of thyrotoxicosis.

The objective of this prospective study was to compare the results of color flow Doppler sonography (CFDS) and radioiodine scintigraphy in patients with thyrotoxicosis. A total of 176 patients, 102 with clinical thyrotoxicosis and 74 with subclinical dysfunction, were included. Pregnant and breast-feeding women, patients using amiodarone or recently exposed to iodinated contrast, and patients treated with antithyroid drugs were excluded. Total T3, free T4, TSH, and anti-TSH receptor antibodies were measured before scintigraphy and CFDS. Excluding one patient whose etiology of thyrotoxicosis remained undefined, CFDS showed 100% specificity. In fact, in all 10 cases in which scintigraphy and CFDS provided discordant results, the diagnosis suggested by the latter was correct. In patients with clinical thyrotoxicosis, the sensitivity of CFDS was 96% for diffuse toxic goiter, 95% for the absence of hyperfunction, and 100% for toxic nodular disease. In patients with subclinical dysfunction, the sensitivity of CFDS was 72.7% for diffuse toxic goiter, 90% for toxic adenoma, and 86.6% for toxic multinodular disease. CFDS was inconclusive in patients with parenchymal blood flow with patchy uneven distribution or with macronodules in which nodule vascularity compared to the remaining parenchyma did not permit to establish the diagnosis with certainty. CFDS can be used instead of scintigraphy not only in situations in which the latter is contraindicated or of limited value to define the etiology of thyrotoxicosis.

Parkin is a critical player in the effects of caffeine over mitochondrial quality control pathways during skeletal muscle regeneration in mice.

AIM: This study aimed to investigate the effects of caffeine on pathways associated with mitochondrial quality control and mitochondrial capacity during skeletal muscle regeneration, focusing on the role of Parkin, a key protein involved in mitophagy. METHODS: We used in vitro C2C12 myoblast during differentiation with and without caffeine in the medium, and we evaluated several markers of mitochondrial quality control pathways and myotube growth. In vivo experiments, we used C57BL/6J (WT) and Parkintm 1Shn lineage (Parkin-/- ) mice and injured tibial anterior muscle. The mice regenerated TA muscle for 3, 10, and 21 days with or without caffeine ingestion. TA muscle was used to analyze the protein content of several markers of mitochondrial quality pathways, muscle satellite cell differentiation, and protein synthesis. Furthermore, it analyzed mtDNA, mitochondrial respiration, and myofiber growth. RESULTS: C2C12 differentiation experiments showed that caffeine decreased Parkin content, potentially leading to increased DRP1 and PGC-1α content and altered mitochondrial population, thereby enhancing growth capacity. Using Parkin-/- mice, we found that caffeine intake during the regenerative process induces an increase in AMPKα phosphorylation and PGC-1α and TFAM content, changes that were partly Parkin-dependent. In addition, the absence of Parkin potentiates the ergogenic effect of caffeine by increasing mitochondrial capacity and myotube growth. Those effects are related to increased ATF4 content and activation of protein synthesis pathways, such as increased 4E-BP1 phosphorylation. CONCLUSION: These findings demonstrate that caffeine ingestion changes mitochondrial quality control during skeletal muscle regeneration, and Parkin is a central player in those mechanisms.

Inhibition of initial adhesion of oral bacteria through a lectin from Bauhinia variegata L. var. variegata expressed in Escherichia coli.

AIMS: The aim of the present work was to study the in vitro effect of native and recombinant Bauhinia variegata var. variegata lectins in inhibiting early adhesion of Streptococcus mutans, Streptococcus sanguis and Streptococcus sobrinus to experimentally acquired pellicle. METHODS AND RESULTS: Native lectin from B. variegata (BVL) was purified by affinity chromatography of extract of seeds. The recombinant lectin (rBVL-I) was expressed in E. coli strain BL21 (DE3) from a genomic clone encoding the mature B. variegata lectin gene using the vector pAE-bvlI. Recombinant protein deposited in inclusion bodies was solubilized and subsequently purified by affinity chromatography. The rBVL-I was compared to BVL for agglutination of erythrocytes and initial adherence of oral bacteria on a saliva-coated surface. The results revealed that rBVL-I acts similarly to BVL for agglutination of erythrocytes. Both lectins showed adhesion inhibition effect on Step. sanguis, Step. mutans and Step. sobrinus. CONCLUSION: We report, for the first time, the inhibition of early adhesion of oral bacteria by a recombinant lectin. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results support the proposed biotechnological application of lectins in a strategy to reduce development of dental caries by inhibiting the initial adhesion and biofilm formation.

Antral follicle responsiveness to follicle-stimulating hormone administration assessed by the Follicular Output RaTe (FORT) may predict in vitro fertilization-embryo transfer outcome.

BACKGROUND: Looking for a qualitative marker of ovarian function, we aimed to verify whether responsiveness of antral follicles to FSH administration, as reflected by the Follicular Output RaTe (FORT), is related to their reproductive competence. METHODS: We studied 322 IVF-ET candidates aged 25-43 years who underwent controlled ovarian hyperstimulation with similar initial FSH doses. Antral follicle (3-8 mm) count (AFC) and pre-ovulatory follicle (16-22 mm) count (PFC) were performed, respectively, at the achievement of pituitary suppression (before FSH treatment) and on the day of hCG administration. The FORT was calculated by PFC × 100/AFC. FORT groups were set according to tercile values: low (<42%; n= 102), average (42-58%; n= 123) and high (>58%; n= 97). RESULTS: The average FORT was 50.6% (range, 16.7-100.0%). Clinical pregnancy rates per oocyte retrieval increased progressively from the low to the high FORT groups (33.3, 51.2 and 55.7%, respectively, P< 0.003) and such a relationship assessed by logistic regression was independent of the confounding covariates, women's ages, AFC and PFC. CONCLUSIONS: The observed relationship between IVF-ET outcome and the percentage of antral follicles that effectively respond to FSH administration reaching pre-ovulatory maturation suggests that FORT may be a qualitative reflector of ovarian follicular competence. Further studies with broader inclusion criteria and more personalized protocols are needed to validate these results.

Intake, performance, and feeding behavior of Holstein and Holstein × Gyr heifers grazing intensively managed tropical grasses during the rainy season.

Holstein × Gyr and Holstein are the primary dairy breeds used in tropical systems, but when rearing under pasture, feed intake, behavior, and performance might differ between them. This study aimed to evaluate the voluntary intake, nutrient digestibility, performance, and ingestive behavior of Holstein and Holstein × Gyr (½ Holstein × ½ Gyr) heifers managed in a rotational system of Guinea grass (Panicum maximum Jacq. cv. Mombaça). The experiment was conducted during the summer season throughout four periods of 21 d. Two 8-heifers (four Holstein and four Holstein × Gyr) groups, averaging 258.6 ±â€¯24.79 kg and 157.1 ±â€¯24.99 kg BW, were used. Each group grazed a separate set of 16 paddocks, and all heifers received a concentrate supplement daily. Heifers were weighed at the beginning and end of the experiment. Fecal, forage and concentrate samples were evaluated for their DM, CP, crude fat, ash, NDF, and indigestible NDF. Feeding behavior was evaluated through 24 h of live observation for 48 h of each experimental period. Grazing, ruminating, resting, and intake of concentrate times were recorded, and rumination criteria, bout criteria, mealtime, meal frequency, and meal duration were calculated. There was no difference in total dry matter intake (DMI), but forage DMI of Holstein × Gyr was 11.70 % greater than the Holstein heifers. The Holstein × Gyr heifers had greater NDF intake and feed efficiency tended to show greater CP and NDF digestibilities, consequently, they had greater average daily gain (ADG). Holstein grazed less than Holstein × Gyr heifers in the afternoon. Ruminating time was 18.43 % lower for Holstein than Holstein × Gyr heifers, and rumination criteria (i.e. longest non-feeding interval within a rumination event) were greater for Holstein heifers. Holstein heifers presented more prolonged rumination bouts and resting time than Holstein × Gyr heifers. Holstein × Gyr can ingest and ruminate greater amounts of fibrous material, and Holstein heifers needed to spend more time ruminating the cud. Overall, even though the behavior was not markedly different between breeds, rearing young Holstein heifers in tropical pasture conditions is less suitable than Holstein-Gyr because of their lower ADG. Therefore, this management condition seems appropriate for Holstein × Gyr but inappropriate for Holstein dairy heifers.

Nanostructured functionalized magnetic platforms for the sustained delivery of cisplatin: Synthesis, characterization and in vitro cytotoxicity evaluation.

Cisplatin has demonstrated extraordinary anticancer activity against a variety of solid tumors. However, its clinical efficacy is contrasted by its toxicity profile. Having in mind the need to reduce the toxicity, promote a sustained release and enhance the body-circulation time of cisplatin, herein novel nanocarriers consisting of core-shell silica-coated iron oxide nanoparticles functionalized with dicarboxylic acid groups were prepared and characterized. Cisplatin was conjugated with the functionalized nanoparticles by surface tethering. Controlled release of cisplatin was observed without burst effect and in a sustained profile for up to 3 days. In vitro studies showed cytotoxic and antiproliferative effects of the cisplatin nanoconjugates against a human pancreatic cancer cell line. Importantly, when compared with free cisplatin, nanoconjugates exhibited lower cytotoxic effects regarding nonmalignant human duct pancreatic cells.

Could we expect new praziquantel derivatives? A meta pharmacometrics/pharmacoinformatics analysis of all antischistosomal praziquantel derivatives found in the literature.

Praziquantel (PZQ) is the first line drug for the treatment of human Schistosoma spp. worm infections. However, it suffers from low activity towards immature stages of the worm, and its prolonged use induces resistance/tolerance. During the last 40 years, 263 PZQ analogues have been synthesized and tested against Schistosoma spp. worms, but less than 10% of them showed significant activity. Here, we propose a rationalization of the chemical space of the PZQ derivatives by a ligand-based approach. First, we constructed an in-house database with all PZQ derivatives available in the literature. This analysis shows a high heterogeneity in the data. Fortunately, all studies include PZQ as a reference, permitting the classification of compounds into three classes according to their activities. Models involving ligand-based pharmacophore and logistic regression were performed. Five physicochemical parameters were identified as the best to explain the biological activity. In the end, we proposed new PZQ derivatives with modifications at positions 1 and 7, we analysed them with our models, and we observed that they can be more active than the previously synthesized derivatives. The main goal of this work was to conduct the most valuable meta-pharmacometrics/pharmacoinformatics analysis with all Praziquantel medicinal chemistry data available in the literature.

Rheological behavior of thermoreversible kappa-carrageenan/nanosilica gels.

The rheological behavior of silica/kappa-carrageenan nanocomposites has been investigated as a function of silica particle size and load. The addition of silica nanoparticles was observed to invariably impair the gelation process, as viewed by the reduction of gel strength and decrease of gelation and melting temperatures. This weakening effect is seen, for the lowest particle size, to become slightly more marked as silica concentration (or load) is increased and at the lowest load as particle size is increased. These results suggest that, under these conditions, the particles act as physical barriers to polysaccharide chain aggregation and, hence, gelation. However, for larger particle sizes and higher loads, gel strength does not weaken with size or concentration but, rather, becomes relatively stronger for intermediate particles sizes, or remains unchanged for the largest particles, as a function of load. This indicates that larger particles in higher number do not seem to increasingly disrupt the gel, as expected, but rather promote the formation of stable gel network of intermediate strength. The possibility of this being caused by the larger negative surface charge found for the larger particles is discussed. This may impede further approximation of neighboring particles thus leaving enough inter-particle space for gel formation, taking advantage of a high local polysaccharide concentration due to the higher total space occupied by large particles at higher loads.

Influence of expiratory positive airway pressure on cardiac autonomic modulation at rest and in submaximal exercise in COPD patients.

The aim of this study was to evaluate the effect of expiratory positive airway pressure (EPAP) on heart rate variability (HRV) indices at rest and during 6-min walk test (6MWT) in chronic obstructive pulmonary disease (COPD) patients. Fifteen moderate to severe COPD patients were randomized and evaluated with and without (Non-EPAP) a 5 cmH2O EPAP device. Respiratory rate (RR) was collected at rest (5 min), during the 6MWT (5 min), and at recovery (5 min). Indices of HRV were computed in the time domain, in the frequency domain, and nonlinear analysis. For EPAP and Non-EPAP during the 6MWT, we found an increased mean heart rate (HR) (P=0.001; P=0.001) while mean RR (P=0.001; P=0.015) and RR tri index decreased (P=0.006; P=0.028). Peripheral oxygen saturation (P=0.019) increased at rest only in the EPAP group. In EPAP, correlations were found between forced expiratory volume in 1 s (FEV1) and low frequency (LF) sympathetic tonus (P=0.05; r=-0.49), FEV1 and high frequency (HF) parasympathetic tonus at rest (P=0.05; r=0.49), lactate at rest and LF during the 6MWT (P=0.02; r=-0.57), and lactate at rest and HF during 6MWT (P=0.02; r=0.56). Through a linear regression model, we found that lactate at rest explained 27% of the alterations of LF during 6MWT. The use of 5 cmH2O EPAP improved autonomic cardiac modulation and its complexity at rest in COPD patients. Although it did not influence the performance of the 6MWT, the EPAP device caused alterations in resting lactate concentration with an effect on sympatho-vagal control during the test.

The influence of Citrate or PEG coating on silver nanoparticle toxicity to a human keratinocyte cell line.

Surface coating of silver nanoparticles may influence their toxicity, in a way yet to decipher. In this study, human keratinocytes (HaCaT cells) were exposed for 24 and 48h to well-characterized 30nm AgNPs coated either with citrate (Cit30 AgNPs) or with poly(ethylene glycol) (PEG30 AgNPs), and assessed for cell viability, reactive oxygen species (ROS), cytokine release, apoptosis and cell cycle dynamics. The results showed that Cit30 AgNPs and PEG30 AgNPs decreased cell proliferation and viability, the former being more cytotoxic. The coating molecules per se were not cytotoxic. Moreover, Ag(+) release and ROS production were similar for both AgNP types. Cit30 AgNPs clearly induced apoptotic death, while cells exposed to PEG30 AgNPs appeared to be at an earlier phase of apoptosis, supported by changes in BAX, BCL2 and CASP-3 expressions. Concerning the impact on cell cycle dynamics, both Cit30 and PEG30 AgNPs affected cell cycle regulation of HaCaT cells, but, again, citrate-coating induced more drastic effects, showing earlier downregulation of cyclin B1 gene and cellular arrest at the G2 phase. Overall, this study has shown that the surface coating of AgNPs influences their toxicity by differently regulating cell-cycle and cell death mechanisms.

The tyrosine kinase inhibitor dasatinib reduces lung inflammation and remodelling in experimental allergic asthma.

BACKGROUND AND PURPOSE: Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in understanding of its pathophysiology, asthma remains a major public health problem, and new therapeutic strategies are urgently needed. In this context, we sought to ascertain whether treatment with the TK inhibitor dasatinib might repair inflammatory and remodelling processes, thus improving lung function, in a murine model of asthma. EXPERIMENTAL APPROACH: Animals were sensitized and subsequently challenged, with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, animals were treated with dasatinib, dexamethasone, or saline, every 12 h for 7 consecutive days. Twenty-four hours after the last treatment, the animals were killed, and data were collected. Lung structure and remodelling were evaluated by morphometric analysis, immunohistochemistry, and transmission electron microscopy of lung sections. Inflammation was assessed by cytometric analysis and ELISA, and lung function was evaluated by invasive whole-body plethysmography. KEY RESULTS: In OVA mice, dasatinib, and dexamethasone led to significant reductions in airway hyperresponsiveness. Dasatinib was also able to attenuate alveolar collapse, contraction index, and collagen fibre deposition, as well as increasing elastic fibre content, in OVA mice. Concerning the inflammatory process, dasatinib reduced inflammatory cell influx to the airway and lung-draining mediastinal lymph nodes, without inducing the thymic atrophy promoted by dexamethasone. CONCLUSIONS AND IMPLICATIONS: In this model of allergic asthma, dasatinib effectively blunted the inflammatory and remodelling processes in asthmatic lungs, enhancing airway repair and thus improving lung mechanics.

Interference of propylene glycol with the hole-board test.

Experimental drugs and/or plant extracts are often dissolved in solvents, including propylene glycol. Nevertheless, there is evidence for psychoactive properties of this alcohol. In this study we found that in the hole-board test 10% propylene glycol did not modify the head-dipping behavior. However, 30% propylene glycol induced an increase in the number of head-dips (46.92 +/- 2.37 compared to 33.83 +/- 4.39, P<0.05, ANOVA/Student-Newman-Keuls), an effect comparable to that obtained with 0.5 mg/kg diazepam (from 33.83 +/- 4.39 to 54 +/- 3.8, P<0.01, ANOVA/Student-Newman-Keuls). These results demonstrate that 30% propylene glycol has significant anxiolytic effects in this model and therefore cannot be used as an innocuous solvent.

Heat shock response reduces mortality after severe experimental burns.

The heat shock response has imparted protective effects in animal models of septic shock and endotoxemia. This study has tested the hypothesis that it could be protective in experimental burns. One hundred and fifteen adult male Fischer rats were randomly divided into four groups. Rats in the first group (n = 12) were anesthetized and shaved. In the second group (n = 15) rats were anesthetized and heated in a 45 degrees C water bath. In the third group (n = 44), rats were anesthetized, shaved and submitted to 26-30% body surface third-degree burns using a brass bar. In the fourth group (n = 44), rats were anesthetized, heated and, 1 day after, they were burnt. Mortality rates were measured at 3, 7, 15 and 25 days. Liver and lung samples were collected from all groups for heat-shock protein 70 detection. Heat-shock protein 70 was positive in heated animals. No animals died in the first or second group. Heated and burnt animals showed significantly decreased mortality at days 3 (p < 0.05, Fischer's exact test) and at days 7, 15 and 25 (p < 0.01) after burns, when compared to unheated burnt animals. In conclusion, eliciting the heat-shock response significantly reduced mortality rates in this model of experimental burns.

Use of acrylic of low polymerization after heminandibulectomy.

Two cases of mandibular reconstruction are presented in which a premolded prosthesis of acrylic of low polymerization covered by silicone rubber was used. We believe that the good results obtained were not only due to the material used, but also because the periosteum and meniscus were preserved in the joint space.

[Calcified abdominal lymph node paracoccidioidomycosis]. / Paracoccidioidomicose ganglionar abdominal calcificada.

The calcified form of the South-american blastomycosis is rarely mentioned in the literature. An observation of intra-abdominal lymphatic and visceral spread with abdominal calcification is accompanied by a radiological record. Are done comments. The pathogenesis and rarity of this complication is discussed.

Risk factors for malnutrition in patients undergoing gastroenterological and hernia surgery: an analysis of 374 patients.

OBJECTIVE: The aim of this study was to assess the nutritional status of 374 surgical patients with gastrointestinal disease and hernias of the abdominal wall; to identify risk factors associated with a poorer nutritional status in this group of patients and to assess awareness of the patient's nutritional status by medical teams. SUMMARY BACKGROUND DATA: Malnutrition is prevalent among surgical patients and is associated with higher surgical complication rates and mortality. The major causes of poor nutritional status are related to the underlying disease, socio-economic factors, age, and length of hospitalization. Despite its high prevalence, medical teams often overlook malnutrition, and screening of these patients is not routine. It is of utmost importance to identify patients at risk for malnutrition in order to prevent related complications. METHODS: The 374 patients evaluated in this study were a subgroup of a larger multicenter, cross-sectional, randomized study that was carried out in 1996. Nutritional status was assessed by using Subjective Global Assessment. RESULTS: Malnutrition was present in 55% of the patients, with 19% of the patients severely malnourished. The presence of cancer, infection, age over 60 years, upper gastrointestinal disease, and longer length of hospital stay all negatively influenced nutritional status. Despite the high prevalence of malnutrition, the medical teams only assessed the nutritional status of a few patients. CONCLUSION: Malnutrition was highly prevalent in this setting of patients. Therefore, patients with the risk factors above presented should routinely undergo nutritional screening and/or assessment in order to be able to early diagnose or prevent malnutrition and its correlated morbidity and mortality.

[Delayed (modified) oral cholecystography in the study of biliary dyskinesia]. / Colecistografia oral retardada (modificada) no estudo da discinesia biliar.

Biliary dyskinesia is difficult to be either diagnosed or treated. A modified oral cholecystography technique has been tested to make it suitable for studying such gallbladder disease. Routine oral cholecystography was performed and then two other roentgenograms were taken both 24 and 48 hours after it. In our opinion, further studies should be performed whenever gallbladder visualization lasts longer than 48 hours even in order to indicate surgery.

[Clinical evaluation of gastric emptying with 50% glucose in patients undergoing truncal vagotomy with partial antrectomy and gastroduodenostomy at the level of the lesser curvature]. / Avaliação clínica do esvaziamento gástrico com glicose a 50% em pacientes submetidos à vagotomia troncular com antrectomia parcial e gastroduodenostomia ao nível da curvatura menor.

The results after an oral glucose provocation test before and after surgery of 32 patients with duodenal chloridropeptic ulcer, who underwent a total vagotomy, partial antrectomy and gastroduodenal anastomosis at level of the lesser curvature ("VAGDPC") are presented. It is concluded that with this surgical procedure, when submitted to the oral glucose provocation test, nobody presented the dumping syndrome with clinical expression.