Brazil nut consumption reduces DNA damage in overweight type 2 diabetes mellitus patients.

Type 2 diabetes mellitus (T2D) is a metabolic disease, which occurs largely due to unhealthy lifestyle. As oxidative stress is believed to promote T2D, by inducing damage to lipids, proteins, and DNA, appropriate dietary interventions seem critical to prevent, manage, and even reverse this condition. Brazil nuts (Bertholletia excelsa, H.B.K.) are nature's richest source of selenium, a mineral that has shown several health benefits. Therefore, this study aims to assess the effects of selenium consumption, through Brazil nuts, on biochemical and oxidative stress parameters, and genomic instability in T2D patients. We recruited 133 patients with T2D, registered in the Integrated Clinics of the University of Southern Santa Catarina (Brazil). Participants consumed one Brazil nut a day for six months. Blood samples and exfoliated buccal cells were collected at the beginning and the end of the intervention. The glycemic profile, lipid profile, renal profile and hepatic profile, DNA damage and selenium content were evaluated. A total of 74 participants completed the intervention. Brazil nut consumption increased selenium and GSH levels, GPx, and CAT activity while DCF and nitrites levels decreased. Total thiols increased, and protein carbonyl and MDA levels decreased. Levels of baseline and oxidative DNA damage in T2D patients were significantly decreased, as well as the frequency of micronuclei and nuclear buds. The fasting glucose levels, HDL and LDL cholesterol, and GGT levels that increased significantly in patients with type 2 diabetes were significantly reduced with nut consumption. Our results show an increase in antioxidant activity, along with reductions of protein and lipid oxidation as well as DNA damage, suggesting that Brazil nut consumption could be an ally in reducing oxidative stress and modulating the genomic instability in T2D patients.

The involvement of neuroinflammation in an animal model of dementia and depression.

Alzheimer's disease (AD) and depression are inflammatory pathologies, leading to increased inflammatory response and neurotoxicity. Therefore, this study aimed to evaluate the effect of the treatment with fluoxetine and/or galantamine and/or donepezil on the levels of proinflammatory and anti-inflammatory cytokines in a mixed animal model of depression and dementia. Adult male Wistar rats underwent chronic mild stress (CMS) protocol for 40 days and were subjected to stereotaxic surgery for intra-hippocampal administration of amyloid-beta (Aꞵ) peptide or artificial cerebrospinal fluid (ACSF) to mimic the dementia animal model. On the 42nd day, animals were treated with water, galantamine, donepezil, and/or fluoxetine, orally for 17 days. On the 57th and 58th days, the Splash and Y-maze tests for behavior analysis were performed. The frontal cortex and hippocampus were used to analyze the tumor necrosis factor alfa (TNF-α), interleukin 1 beta (IL-1ꞵ), IL-6, and IL-10 levels. The results of this study show that animals subjected to CMS and administration of Aꞵ had anhedonia, cognitive impairment, increased TNF-α and IL-1ꞵ levels in the frontal cortex, and reduced IL-10 levels in the hippocampus. All treatment groups were able to reverse the cognitive impairment. Only donepezil did not decrease the TNF-α levels in the hippocampus. Fluoxetine + galantamine and fluoxetine + donepezil reversed the anhedonia. Fluoxetine reversed the anhedonia and IL-1ꞵ levels in the frontal cortex. In addition, fluoxetine + donepezil reversed the reduction of IL-10 levels in the hippocampus. The results indicate a pathophysiological interaction between AD and depression, and the association of medications in the future may be a possible therapeutic strategy to reduce inflammation, especially the fluoxetine-associated treatments.

The combined treatment of gold nanoparticles associated with photobiomodulation accelerate the healing of dermonecrotic lesion.

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion.Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis.Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema.Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.

Role of Oxidative Stress on Insulin Resistance in Diet-Induced Obesity Mice.

Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.

Green synthesis of gold nanoparticles modulates lipopolysaccharide-induced lung inflammation in Wistar rats.

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.

The effectiveness of treadmill and swimming exercise in an animal model of osteoarthritis.

Introduction: Osteoarthritis (OA) is considered an inflammatory and degenerative joint disease, characterized by loss of hyaline joint cartilage and adjacent bone remodeling with the formation of osteophytes, accompanied by various degrees of functional limitation and reduction in the quality of life of individuals. The objective of this work was to investigate the effects of treatment with physical exercise on the treadmill and swimming in an animal model of osteoarthritis. Methods: Forty-eight male Wistar rats were divided (n=12 per group): Sham (S); Osteoarthritis (OA); Osteoarthritis + Treadmill (OA + T); Osteoarthritis + Swimming (OA + S). The mechanical model of OA was induced by median meniscectomy. Thirty days later, the animals started the physical exercise protocols. Both protocols were performed at moderate intensity. Forty-eight hours after the end of the exercise protocols, all animals were anesthetized and euthanized for histological, molecular, and biochemical parameters analysis. Results: Physical exercise performed on a treadmill was more effective in attenuating the action of pro-inflammatory cytokines (IFN-γ, TNF-α, IL1-ß, and IL6) and positively regulating anti-inflammatories such as IL4, IL10, and TGF-ß in relation to other groups. Discussion: In addition to maintaining a more balanced oxi-reductive environment within the joint, treadmill exercise provided a more satisfactory morphological outcome regarding the number of chondrocytes in the histological evaluation. As an outcome, better results were found in groups submitted to exercise, mostly treadmill exercise.

Effects of diet-induced hypercholesterolemia and gold nanoparticles treatment on peripheral tissues.

Cholesterol is a lipid molecule of great biological importance to animal cells. Dysregulation of cholesterol metabolism leads to raised blood total cholesterol levels, a clinical condition called hypercholesterolemia. Evidence has shown that hypercholesterolemia is associated with the development of liver and heart disease. One of the mechanisms underlying heart and liver alterations induced by hypercholesterolemia is oxidative stress. In this regard, in several experimental studies, gold nanoparticles (AuNP) displayed antioxidant properties. We hypothesized that hypercholesterolemia causes redox system imbalance in the liver and cardiac tissues, and AuNP treatment could ameliorate it. Young adult male Swiss mice fed a regular rodent diet or a high cholesterol diet for eight weeks and concomitantly treated with AuNP (2.5 µg/kg) or vehicle by oral gavage. Hypercholesterolemia increased the nitrite concentration and glutathione (GSH) levels and decreased the liver's superoxide dismutase (SOD) activity. Also, hypercholesterolemia significantly enhanced the reactive oxygen species (ROS) and GSH levels in cardiac tissue. Notably, AuNP promoted the redox system homeostasis, increasing the SOD activity in hepatic tissue and reducing ROS levels in cardiac tissue. Overall, our data showed that hypercholesterolemia triggered oxidative stress in mice's liver and heart, which was partially prevented by AuNP treatment.

Deep Tillage Strategies in Perennial Crop Installation: Structural Changes in Contrasting Soil Classes.

Tillage modifies soil structure, which can be demonstrated by changes in the soil's physical properties, such as penetration resistance (PR) and soil electrical resistivity (ρ). The aim of this study was to evaluate the effect of deep tillage strategies on three morphogenetically contrasting soil classes in the establishment of perennial crops regarding geophysical and physical-hydric properties. The experiment was conducted in the state of Minas Gerais, southeastern Brazil. The tillage practices were evaluated in Typic Dystrustept, Rhodic Hapludult, and Rhodic Hapludox soil classes, and are described as follows: MT­plant hole; CT­furrow; SB­subsoiler; DT­rotary hoe tiller; and DT + calcium (Ca) (additional liming). Analyses of PR and electrical resistivity tomography (ERT) were performed during the growing season and measurements were measured in plant rows of each experimental plot. Undisturbed soil samples were collected for analysis of soil bulk density (Bd) at three soil depths (0−0.20, 0.20−0.40, and 0.40−0.60 m) with morphological evaluation of soil structure (VESS). Tukey's test (p < 0.05) for Bd and VESS and Pearson linear correlation analysis between Bd, ρ, and PR were performed. Soil class and its intrinsic attributes have an influence on the effect of tillage. The greatest effect on soil structure occurred in the treatments DT and DT + Ca that mixed the soil to a depth of 0.60 m. The ρ showed a positive correlation with Bd and with PR, highlighting that ERT may detect changes caused by cultivation practices, although ERT lacks the accuracy of PR. The soil response to different tillage systems and their effects on soil structure were found to be dependent on the soil class.

Behavioral, genetic and biochemical changes in the brain of the offspring of female mice treated with caffeine during pregnancy and lactation.

The intrauterine environment is a critical location for exposure to exogenous and endogenous factors that trigger metabolic changes through fetal programming. Among the external factors, chemical compounds stand out, which include caffeine, since its consumption is common among women, including during pregnancy. Thereby, the aim of the present study was to evaluate the behavioral, genetic, and biochemical parameters in the offspring of female mice treated with caffeine during pregnancy and lactation. Swiss female mice (60 days old) received tap water or caffeine at 0.3 or 1.0 mg/mL during copulation (7 days), pregnancy (21 days) and lactation (21 days). After the end of the lactation period, the offspring were divided into groups (water, caffeine 0.3 or 1.0 mg/mL) with 20 animals (10 animals aged 30 days and 10 animals aged 60 days per group per sex). Initially, the offspring were submitted to behavioral tasks and then euthanized for genetic and biochemical analysis in the brain (cortex, striatum, and hippocampus). Behavioral changes in memory, depression, and anxiety were observed in the offspring: 30-day-old female offspring at 1.0 mg /mL dose presented anxiogenic behavior and male offspring the 0.3 mg/mL dose at 30 days of age did not alter long-term memory. Furthermore, an increase in DNA damage and oxidative stress in the brain were observed in the offspring of both sexes. Furthermore, there were changes in Ape-1, BAX, and Bcl-2 in the female offspring hippocampus at 30 days of life. Thus, with this study, we can suggest genotoxicity, oxidative stress, and behavioral changes caused by caffeine during pregnancy and lactation in the offspring that were not treated directly, but received through their mothers; thus, it is important to raise awareness regarding caffeine consumption among pregnant and lactating females.

Feasibility and Safety of Ipsilateral Ulnar Access in Cases of Impossibility or Failure of Radial Access for Coronary Angiography or Percutaneous Coronary Intervention.

OBJECTIVES: To evaluate the feasibility and safety of using the ulnar access in coronary angiography and percutaneous coronary intervention, in the failure or contraindication of ipsilateral radial access. METHODS: We prospectively evaluated, in a quaternary hospital, patients undergoing coronary angiography or percutaneous coronary intervention by transulnar approach, in case of failure or contraindication to the ipsilateral radial access. RESULTS: Between August 2018 and March 2020, of the 5,916 invasive coronary procedures performed, 2.2% were by transulnar approach. In the 130 patients evaluated, the indication for use of the transulnar approach was predominantly the low-amplitude or difficult to palpate radial pulse when compared to the ulnar artery (39.2%), followed by occlusion of the ipsilateral radial artery (33.1%). Complications of using the transulnar approach were superficial hematoma or low-degree muscle infiltration with extension ≤10 cm, in 6 patients (4.5%), and in 5 cases (3.8%) hematoma >10 cm. There was a case of transient ischemia of the hand due to forearm hematoma, treated conservatively. No cases of arterial thrombosis, pseudoaneurysm, arteriovenous fistula, symptomatic ulnar artery occlusion or ulnar nerve injury were observed after 30-day follow-up. CONCLUSION: The use of ipsilateral transulnar access is a feasible and safe alternative in cases where radial access would be impossible. This access site is associated with a low incidence of complications, which, when present, are most commonly associated with the occurance of spasm after the attempted radial puncture.

Metabolic programming in offspring of mice fed fructose during pregnancy and lactation.

Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.

Effects of the intranasal application of gold nanoparticles on the pulmonary tissue after acute exposure to industrial cigarette smoke.

Inhalation of harmful particles appears as a primary factor for the onset and establishment of chronic obstructive pulmonary disease (COPD). Cigarette smoke acutely promotes an exacerbated inflammatory response with oxidative stress induction with DNA damage. Administration of Gold Nanoparticles (GNPs) with 20 nm in different concentrations can revert damages caused by external aggravations. The effects of GNPs in a COPD process have not been observed until now. The objective of this work was to evaluate the therapeutic effects of intranasal administration of different doses of GNPs after acute exposure to industrial cigarette smoke. Thirty male Swiss mice were randomly divided into five groups: Sham; cigarette smoke (CS); CS + GNPs 2.5 mg/L; CS + GNPs 7.5 mg/L and CS + GNPs 22.5 mg/L. The animals were exposed to the commercial cigarette with filter in an acrylic inhalation chamber and treated with intranasal GNPs for five consecutive days. The results demonstrate that exposure to CS causes an increase in inflammatory cytokines, histological changes, oxidative and nitrosive damage in the lung, as well as increased damage to the DNA of liver cells, blood plasma and lung. Among the three doses of GNPs (2.5, 7.5, and 22.5 mg/L) used, the highest dose had better anti-inflammatory effects. However, GNPs at a dose of 7.5 mg/L showed better efficacies in reducing ROS formation, alveolar diameter, and the number of inflammatory cells in histology, in addition to significantly reduced rate of DNA damage in lung cells without additional systemic genotoxicity already caused by cigarette smoke.

Antimicrobial and Toxicity Evaluation of Imidazolium-Based Dicationic Ionic Liquids with Dicarboxylate Anions.

Imidazolium-based dicationic ILs (DILs) presenting antimicrobial activity and relatively low toxicity are highly desirable and are envisioned for use in live tissue to prevent bacterial or fungal infections. In this context, we present here DILs with dicarboxylate anions [Cn(MIM)2[Cn(MIM)2][CO2-(CH2)mCO2], in which n = 4, 6, 8, and 10, and m = 0, 1, 2, 3, 4, and 5. The results showed that DILs with an alkyl chain spacer of ten carbons were active against yeasts and the bacterial strains tested. However, most of the DILs were cytotoxic and toxic at 1 mM. By contrast, DILs with alkyl chains possessing less than ten carbons were active against some specific Candidas and bacteria (mainly S. aureus), and they showed moderate cytotoxicity. The best activity against Gram-positive bacteria was observed for [C4(MIM)2][Pim] toward MRSA. For the DILs described herein, their level of toxicity against C. elegans was lower than that of most of the mono- and dicationic IL analogs with other anions. Our results showed that the presence of carboxylate anions reduces the toxicity of DILs compared to DILs containing halide anions, which is particularly significant to the means of designing biologically active compounds in antimicrobial formulations.

Intra-articular treatment with hyaluronic acid associated with gold nanoparticles in a mechanical osteoarthritis model in Wistar rats.

This study aimed to evaluate the effects of intra-articular treatment with hyaluronic acid (HA) associated with GNPs in a mechanical model of osteoarthritis induced by median meniscectomy (MM). Fifty Wistar rats (2 months weighing between 250 and 300 g) were used, divided into five groups of 10 animals each: Sham, osteoarthritis (OA), OA + HA, OA + gold nanoparticles (GNPs), and OA + HA + GNPs. Intra-articular treatment was started 30 days after the model was induced, with a frequency of 2 weeks for 60 days. Fifteen days after the last application, the animals were euthanized with the removal of the joint tissue for biochemical and histological analysis. The model used was able to mimic osteoarthritis, characterized by the presence of high levels of proinflammatory cytokines, oxidative stress, and degeneration of joint surfaces (Grade III, according to SCORE OARSI). The isolated use of HA or GNPs provided beneficial results to the joint; however, only the group subjected to the association between HA and GNPs showed the attenuation of oxidative stress and reduced proinflammatory markers, with a simultaneous increase in levels of anti-inflammatory cytokines and growth factors. Upon histological analysis, only the OA + HA + GNPs group achieved the restoration of the thickness of the joint cartilage with reduced damage and return to the intact joint surface. The results found demonstrated that the association of GNPs with HA was able to reverse the deleterious effects caused by the model by inhibiting the progressive degeneration of joint surfaces, representing a promising treatment for osteoarthritis.

Cotreatment of Small Gold Nanoparticles Protects Against the Increase in Cerebral Acetylcholinesterase Activity and Oxidative Stress Induced by Acute Ethanol Exposure in the Zebrafish.

Gold nanoparticles (GNP) have emerged as an alternative to biomaterials in biomedical applications. Research has clearly demonstrated the relative safety and low toxicity of these molecules. However, the possible neuroprotective effect of GNP on the central nervous system (CNS) and its relationship with neurological and psychiatric disorders remain unclear. Zebrafish is a reliable model to investigate the impact of ethanol (EtOH) consumption on the CNS, including reward signaling such as the cholinergic neurotransmission system. Here, we investigated whether cotreatment or pretreatment with GNP prevented EtOH-induced changes in acetylcholinesterase activity and oxidative stress in the brain of zebrafish. We exposed adult zebrafish to 2.5 mg·L-1 GNP 1 h prior to EtOH (1% v/v) treatment for 1 h, and cotreated adult zebrafish simultaneously with both substances for 1 h. Pretreatment with GNP did not prevent EtOH-induced increase in the acetylcholinesterase activity, whereas cotreatment with 2.5 mg·L-1 GNP and EtOH protected against this increase. The results also suggested similar protective effect on oxidative stress parameters in the zebrafish pretreated with GNP at 2.5 mg·L-1. GNP significantly decreased the levels of thiobarbituric acid reactive species and dihydrodichlorofluorescein levels when cotreated with EtOH. GNP also prevented EtOH-induced increase in superoxide dismutase and catalase activities, suggesting a modulatory role of GNP in enzymatic antioxidant defenses. Our results showed that GNP was able to modulate the disruption of cholinergic and oxidative homeostasis in the brain of zebrafish. These findings indicate for the first time that zebrafish is an interesting perspective to investigate nanoparticles against disorders related to alcohol abuse.

Co-encapsulation of sodium diethyldithiocarbamate (DETC) and zinc phthalocyanine (ZnPc) in liposomes promotes increases phototoxic activity against (MDA-MB 231) human breast cancer cells.

There has been considerable interest in the development of novel photosensitisers for photodynamic therapy (PDT). The use of liposomes as drug delivery systems containing simultaneously two or more drugs is an attractive idea to create a new platform for PDT application. Therefore, the aim of this study was to evaluate the synergistic effect of diethyldithiocarbamate (DETC) and zinc phthalocyanine (PDT) co-encapsulated in liposomes. The reverse-phase evaporation method resulted in the successful encapsulation of DETC and ZnPc in liposomes, with encapsulation efficiencies above 85 %, mean size of 308 nm, and zeta potential of - 36 mV. The co-encapsulation decreased the cytotoxic effects in mouse embryo fibroblast (NIH3T3) cells and inhibited damage to human erythrocytes compared to free DETC + ZnPc. In addition, both the free drugs and co-encapsulated ones promoted more pronounced phototoxic effects on human breast cancer cells (MDA-MB231) compared to treatment with ZnPc alone. This synergistic effect was determined by DETC-induced decreases in the antioxidant enzyme activity of superoxide dismutase (SOD) and glutathione (GSH).

Effects of cryotherapy on the regeneration process and muscular mechanical properties after lacerative injury model.

Cryotherapy is a therapeutic modality widely used for the treatment of muscle injuries to control pain and inflammatory processes. This study aimed to investigate the effects of cryotherapy on the inflammatory and oxidative stress parameters and mechanical properties of, and pain in, the skeletal muscles of rats with lacerative muscle injury. The rats were anesthetized with 4% isoflurane and subjected to gastrocnemius muscle laceration injury. After injury, all animals in the intervention groups received cryotherapy treatment for 20 minutes using plastic bags containing crushed ice. The protocol comprised three daily applications at 3-hour intervals on the day of injury, with reapplication 24 hours later. Seventy-two male Wistar rats were divided into three groups: sham, muscle injury (MI), and MI + cryotherapy (MI + cryo). Muscle mechanical properties were analyzed by mechanical tensile testing on day 7 after injury. The MI + cryo group showed reduced TNF-α, IFN-γ, and IL1ß levels; elevated IL4, IL6, and IL10 levels; reduced oxidant production and carbonyl levels; and elevated sulfhydryl contents. Animals that underwent tissue cooling showed superoxide dismutase activity and glutathione levels close to those of the animals in the sham group. The MI and MI + cryo groups showed reduced values of the evaluated mechanical properties and lower mechanical thresholds compared to those of the animals from the sham group. Our results demonstrated that the proposed cryotherapy protocol reduced the inflammatory process and controlled oxidative stress but did not reverse the changes in the mechanical properties of muscle tissues or provide analgesic effects within the time frame analyzed.

Anti-Staphylococcus aureus Methicillin-Resistant (MRSA) activity of a novel 3-Chalcogenyl Indole / Atividade Anti-Staphylococcus aureus Meticilina Resistente (MRSA) de um novo composto 3-Calcogenil Indol

Objective: the development of new drugs against Methicillin-resistant Staphylococcus aureus is a priority to the World Health Organization. So, the objective of this study was to evaluate the antibacterial activity and toxicity of 5-bromo-3-((4-methoxyphenyl) sulfenyl)-1H-indole (3b) against MRSA. Methods: minimum inhibitory concentration (MIC) of 3b was determined against S. aureus ATCC 29213 and 43 clinical isolates. The time-kill assay was performed for 9 isolates. Analysis of variance followed by the post hoc Bonferroni test was used for the statistical tests. Results and conclusions: the MIC50 and MIC90 of 3b were 4 µg.mL-1 and 16 µg.mL-1 respectively. In time-kill assay, the 3b showed bactericidal activity to all evaluated isolates at concentrations of 1xMIC and 2xMIC and the re-growth effect was not observed. About the toxicity tests, 3b has not presented cytotoxicity, mutagenicity, or allergenicity. 3b had particularly good activity against MRSA demonstrating high potential for the development of new antimicrobials products.

Objetivo: o desenvolvimento de novos antimicrobianos contra Staphylococcus aureus resistentes à meticilina (MRSA) é uma prioridade para a Organização Mundial da Saúde. Então, o objetivo desse estudo foi avaliar a atividade antibacteriana e a toxicidade do 5-bromo-3-((4-metoxifenil) sulfenil)-1H-indol (3b) contra MRSA. Métodos: a concentração inibitória minima de 3b foi determinada contra S. aureus ATCC 29213 e 43 isolados clínicos. O ensaio de curva de morte foi realizado para nove isolados. Análise de variância seguida pelo teste post hoc Bonferroni foi usada para testes estatísticos. Resultados e conclusões: a MIC50 e MIC90 do 3b foi 4 µg.mL-1 e 16 µg.mL-1, respectivamente. No ensaio de curva de morte, o 3b demonstrou atividade bactericida contra todos os isolados avaliados na concentração de 1xMIC e 2xMIC e o recrescimento não foi observado. Em relação aos testes de toxicidade, 3b não apresentou citotoxicidade, mutagenicidade ou alergenicidade. 3b apresentou atividade particularmente interessante contra MRSA, demonstrando alto potencial para o desenvolvimento de novos produtos antimicrobianos.