Oxidative stress, cardiomyocytes premature senescence and contractile dysfunction in in vitro and in vivo experimental models of Chagas disease.

AIMS: The relationship between redox imbalance and cardiovascular senescence in infectious myocarditis is unknown. Thus, the aim of this study was to investigate whether cardiomyocytes parasitism, oxidative stress and contractile dysfunction can be correlated to senescence-associated ß-galactosidase (SA-ß-Gal) activity in Trypanosoma cruzi-infection in vitro and in vivo. METHODS: Uninfected, T. cruzi-infected untreated and benznidazole (BZN)-treated H9c2 cardiomyocytes and rats were investigated. Parasitological, prooxidant, antioxidant, microstructural, and senescence-associated markers were quantified in vitro and in vivo. RESULTS: T. cruzi infection triggered intense cardiomyocytes parasitism in vitro and in vivo, which was accompanied by reactive oxygen species (ROS) upregulation, lipids, proteins and DNA oxidation in cardiomyocytes and cardiac tissue. Oxidative stress was parallel to microstructural cell damage (e.g., increased cardiac toponin I levels) and contractile dysfunction in cardiomyocytes in vitro and in vivo, whose severity accompanied a premature cellular senescence-like phenotype revealed by increased senescence-associated ß-galactosidase (SA-ß-Gal) activity and DNA oxidation (8-OHdG). Cellular parasitism (e.g., infection rate and parasite load), myocarditis and T. cruzi-induced prooxidant responses were attenuated by early BZN administration to interrupt the progression of T. cruzi infection, protecting against SA-ß-gal-based premature cellular senescence, microstructural damage and contractile deterioration in cardiomyocytes from T. cruzi-infected animals. CONCLUSION: Our findings indicated that cell parasitism, redox imbalance and contractile dysfunction were correlated to SA-ß-Gal-based cardiomyocytes premature senescence in acute T. cruzi infection. Therefore, in addition to controlling parasitism, inflammation and oxidative stress; inhibiting cardiomyocytes premature senescence should be further investigated as an additional target of specific Chagas disease therapeutics.

Protective immunity triggered by ectonucleoside triphosphate diphosphohydrolase-based biopharmaceuticals attenuates cardiac parasitism and prevents mortality in Trypanosoma cruzi infection.

Chagas disease is a potentially fatal infection in 21 endemic Latin America countries for which the effectiveness of reference antiparasitic chemotherapy is limited. Thus, we developed three biopharmaceuticals and evaluated the effectiveness of different immunization strategies (recombinant protein NTPDase-1 [rNTPDase-1], DNA plasmid encoding Trypanosoma cruzi NTPDase-1 [TcNTPDase-1] and DNA-NTPDase-1 prime/rNTPDase-1 boost [Prime-boost]) based on the surface ecto-nucleoside triphosphate diphosphohydrolase (ecto-NTPDase) enzyme of T. cruzi in animals challenged with a virulent strain (Y) of this parasite. BALB/c mice were immunized three times at 30 days intervals, challenged with T. cruzi 15 days after the last immunization, and euthanized 30 days after T. cruzi challenge. Our results showed limited polarization of specific anti-ecto-NTPDase immunoglobulins in mice receiving both immunization protocols. Conversely, the Prime-boost strategy stimulated the Th1 protective phenotype, upregulating TNF-α and downregulating IL-10 production while increasing the activation/distribution of CD3+/CD8+, CD4+/CD44hi and CD8+/CD44hi/CD62L cells in immunized and infected mice. Furthermore, IL-6 and IL10 levels were reduced, while the distribution of CD4+/CD44hi and CD3+/CD8+ cells was increased from rNTPDase-1 and DNA-NTPDase1-based immunization strategies. Animals receiving DNA-NTPDase1 and Prime-boost protocols before T. cruzi challenged exhibited an enhanced immunological response associated with IL-17 upregulation and remarkable downregulation of heart parasitism (T. cruzi DNA) and mortality. These findings indicated that NTPDase-1 with Prime-boost strategy induced a protective and sustained Th17 response, enhancing host resistance against T. cruzi. Thus, ecto-NTPDase is a potentially relevant and applicable in the development of biopharmaceuticals with greater immunoprophylactic potential for Chagas disease.

Relationship between time-dependent variability in cardiometabolic risk factors and biochemical markers with cytokine and adipokine levels in hemodialysis patients.

Hemodialysis patients (HP) are exposed to malnutrition, cardiometabolic and pro-inflammatory risk factors. However, limited knowledge of the variability of these risk factors remains a serious barrier to the proper clinical management of HP. From a longitudinal study, we investigated the relationship between time-dependent variability in cardiometabolic risk factors and biochemical markers with cytokine and adipokine circulating levels in HP. Thirty-eight HP (women = 15, men = 23) aged 54.13 ± 16.78 years old underwent three independent anthropometric, nutritional, biochemical and immunological assessments (1, 6 and 12 months). Patient's characteristics (body mass, comorbidities, history of kidney disease and time on hemodialysis) were similar after sex stratification. From grouped data, 31.6-100.0% HP exhibited multiple malnutrition and cardiometabolic risk factors in all time-points evaluated. All anthropometric and nutritional results, and most biochemical markers were similar in 1, 6 and 12 months follow-up, indicating a marked time-dependent stability. Urea, creatinine, total proteins, albumin, adipokines (adiponectin, leptin and resistin) and cytokines (TNF, IL-6 and IL-10) levels were highly variable in 12 months follow-up. Direct correlations between leptin and fat mass, TNF and IL-6 with creatinine and pre-dialysis urea were observed in all time-points (1, 6 and 12 months). Creatinine and pre-dialysis urea were negatively correlated with IL-10 for the entire follow-up. Fat mass, creatinine and pre-dialysis urea were predictive markers of leptin, TNF, IL-6 and IL-10 variability. Our findings indicated that biochemical, nutritional and cardiovascular risk factors exhibit low time-dependent variability in HP under clinical and nutritional monitoring. However, adipokines and cytokines are highly variables, which can potentially be influenced by body adiposity, creatinine and urea clearance. Thus, these parameters can contribute to predict the inflammatory status in HP.

Green Tea Infusion Ameliorates Histological Damages in Testis and Epididymis of Diabetic Rats.

Green tea is a popular drink used for therapeutic purposes to mitigate the consequences of diabetes. In this study, we aimed at evaluating the potential of green tea infusion to ameliorate structural and enzymatic damages caused by hyperglycemia in the testis and epididymis of Wistar rats. For that, nondiabetic and streptozotocin-induced diabetic rats (negative control and diabetes control, respectively) received 0.6 mL of water by gavage. Another set of diabetic animals received 100 mg/kg of green tea infusion diluted in 0.6 mL of water/gavage (diabetes + green tea) daily. After 42 days of treatment, the testes and epididymides were removed and processed for histopathological analysis, micromineral determination, and enzymatic assays. The results showed that treatment with green tea infusion preserved the testicular and epididymal histoarchitecture, improving the seminiferous epithelium and the sperm production previously affected by diabetes. Treatment with green tea reduced tissue damages caused by this metabolic condition. Given the severity of hyperglycemia, there was no efficacy of the green tea infusion in maintaining the testosterone levels, antioxidant enzyme activity, and microminerals content. Thus, our findings indicate a protective effect of this infusion on histological parameters, with possible use as a complementary therapy for diabetes.

High-fat diet and caffeine interact to modulate bone microstructure and biomechanics in mice.

AIMS: Although excessive fat and caffeine intake are independent risk factors for bone microstructural and functional disturbances, their association remains overlooked. Thus, we investigated the impact of high-fat diet (HFD) and caffeine alone and combined on serum lipid profile, bone microstructure, micromineral distribution and biomechanical properties. METHODS: Forty female C57BL/6 mice were randomized into 4 groups daily treated for seventeen weeks with standard diet (SD) or HFD (cafeteria diet) alone or combined with 50 mg/kg caffeine. KEY FINDINGS: The association between HFD and caffeine reduced the weight gain compared to animals receiving HFD alone. Caffeine alone or combined with HFD increases total and HDL cholesterol circulating levels. HFD also reduced calcium, phosphorus and magnesium bone levels compared to the groups receiving SD, and this reduction was aggravated by caffeine coadministration. From biomechanical assays, HFD combined with caffeine increased bending strength and stiffness of tibia, a finding aligned with the marked microstructural remodeling of the cortical and cancellous bone in animals receiving this combination. SIGNIFICANCE: Our findings indicated that HFD and caffeine interact to induce metabolic changes and bone microstructural remodeling, which are potentially related to bone biomechanical adaptations in response to HFD and caffeine coadministration.

Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control.

ETHNOPHARMACOLOGICAL RELEVANCE: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies. AIM: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes. MATERIAL AND METHODS: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney. RESULTS: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment. CONCLUSION: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

Tagitinin F has anti-inflammatory, anti-nociceptive and anti-matrix metalloproteinase properties: An in silico, in vitro and in vivo study.

Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 µM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.

Arsenic induces dose-dependent structural and ultrastructural pathological remodeling in the heart of Wistar rats.

AIM: Arsenic, an environmental contaminant, represents a public health problem worldwide. Studies have shown its association with molecular mechanisms related to cardiomyocytes redox balance. However, the microstructure and ultrastructure of cardiac tissue, as well as the activity of its antioxidant defenses front of disturbances in the mineral bioavailability induced by arsenic are still scarce. Thus, the aim of this study was to evaluate if arsenic exposure might induce structural and ultrastructural damages in cardiac tissue, including pathological remodeling of the parenchyma and stroma. Moreover, its impact on micromineral distribution and antioxidant enzymes activity in heart tissue was also evaluated. MAIN METHODS: Adult male Wistar rats were divided into three groups that received 0, 1 and 10 mg/L sodium arsenite in drinking water for eight weeks. The hearts were collected and subjected to structural and ultrastructural analysis, mineral microanalysis and antioxidant enzymes quantification. Functional markers of cardiac damages were evaluated using serum samples. KEY FINDINGS: Arsenic exposure induced dose-dependent structural and ultrastructural remodeling of cardiac tissue, with parenchyma loss, increase of stroma components, collagen deposition, and pathological damages such as inflammation, sarcomere disorganization, mitochondria degeneration and myofilament dissociation. Moreover, this metalloid was bioaccumulated in the tissue affecting its micromineral content, which resulted in antioxidant imbalance and increased levels of oxidative stress and cardiac markers. SIGNIFICANCE: Taken together, our findings indicate that the heart is a potential target to arsenic toxicity, and long-term exposure to this metalloid must be avoided, once it might induce several cardiac tissue pathologies.

Lipophosphoglycan-3 recombinant protein vaccine controls hepatic parasitism and prevents tissue damage in mice infected by Leishmania infantum chagasi.

AIMS: In this work, we aimed to evaluate the effects of the Leishmania infantum chagasi infection on the liver of vaccinated mice, considering parameters of tissue damage and the inflammatory response elicited by vaccination. MAIN METHODS: We used recombinant LPG3 protein (rLPG3) as immunogen in BALB/c mice before challenge with promastigote forms of L. infantum chagasi. The animals were separated into five groups: NI: non-infected animals; NV: non-vaccinated; SAP: treated with saponin; rLPG3: immunized with rLPG3; rLPG3 + SAP: immunized with rLPG3 plus SAP. The experiment was conducted in replicate, and the vaccination protocol consisted of three subcutaneous doses of rLPG3 (40 µg + two boosters of 20 µg). The mice were challenged two weeks after the last immunization. KEY FINDINGS: Our results showed that rLPG3 + SAP immunization decreased the parasite burden in 99 %, conferring immunological protection in the liver of the infected animals. Moreover, the immunization improved the antioxidant defenses, increasing CAT and GST activity, while reducing the levels of oxidative stress markers, such as H2O2 and NO3/NO2, and carbonyl protein in the organ. As a consequence, rLPG3 + SAP immunization preserved tissue integrity and reduced the granuloma formation, inflammatory infiltrate and serum levels of AST, ALT, and ALP. SIGNIFICANCE: Taken together, these results showed that rLPG3 vaccine confers liver protection against L. infantum chagasi in mice, while maintaining the liver tissue protected against the harmful inflammatory effects caused by the vaccine followed by the infection.

Could biological tissue preservation methods change chemical elements proportion measured by energy dispersive X-ray spectroscopy?

Energy dispersive X-ray spectroscopy (EDS) is a powerful technical tool used in the biomedical field to investigate the proportion of chemical elements of interest in research, such as heavy metal bioaccumulation and the enzymatic cofactors and nanoparticle therapy in various pathologies. However, the correct evaluation of the proportion of the elements is subject to some factors, including the method of sample preservation. In this study, we seek to investigate the effect of biological tissue preservation methods on the proportion of chemical elements obtained by the EDS methodology. For such, we used EDS to measure the proportion of chemical elements with biomedical interest in preserved livers, using three common methods for preserving biological tissues: (a) freezing, (b) paraformaldehyde fixative solution, and (c) Karnovsky solution. We found an increased level of sodium and reduced contents of potassium and copper in samples fixed in fixative solutions, when compared to frozen samples (p < 0.05). Our data indicate that preservation methods can change the proportion of chemical elements in biological samples, when measured by EDS. Frozen preservation should be preferred to retain the actual chemical content of samples and allow a correct assessment of the proportion of their elements.

Fatores associados à autoavaliação negativa da saúde em idosos cadastrados nas unidades básicas de saúde / Factors associated with negative self-assessment of health in elderly enrolled in primary care units

INTRODUÇÃO: A autoavaliação do estado de saúde pode ser considerada um preditor significante e independente de funcionalidade e morbimortalidade em idosos. OBJETIVO: Verificar a associação de indicadores sociodemográficos, de saúde e funcionalidade com a autoavaliação negativa da saúde (AANS) em idosos. MÉTODOS: Estudo transversal, com uma amostra estratificada de idosos comunitários do município de Diamantina (MG), Brasil. Para avaliar a AANS e as variáveis sociodemográficas, de saúde e funcionalidade foi utilizado o Questionário BOAS ­ Brazil Old Age Schedule. Os testes Timed up & go e Functional reach foram aplicados para avaliar funcionalidade e risco de quedas, respectivamente. Para as análises univariadas utilizou-se o teste Qui-Quadrado de Pearson e o teste Qui-Quadrado de tendência linear (p ≤ 0,20). As análises múltiplas foram realizadas por meio de três modelos de regressão logística (p ≤ 0,05). RESULTADOS: 401 idosos participaram deste estudo. As variáveis que apresentaram associação significativa com a AANS foram: idade de 80 anos e mais (OR=1,81; IC95%=1,06-3,08), recurso financeiro insuficiente (OR=2,43; IC95%=1,55-3,78), histórico de quedas (OR=3,24; IC95%=1,71-6,14), hipertensão (OR=3,27; IC95%=1,37-7,81), doença neurológica (OR=2,36; IC95%=1,18-4,71), doença osteomioarticular (OR=2,18; IC95%=1,26-3,78), depressão (OR=3,87; IC95%=1,88-7,75), tempo de doença > 12 anos (OR=2,13; IC95%=1,12-4,03), uso de prótese dentária (OR=0,50; IC95%=0,28-0,89), tempo ≥ 10 segundos para realização do Timed up & go (OR=2,54; IC95%=1,62-3,10), incapacidade em 2 ou mais atividades de vida diária (OR=1,86; IC95%=1,17-2,95) e autorrelato de sentir menos energia (OR=2,60; IC95%=1,57-4,31). CONCLUSÃO: A AANS está associada a fatores sociodemográficos, de saúde e funcionalidade, indicando a necessidade de um cuidado integral à saúde do idoso.

INTRODUCTION: The self-assessment of health might be considered a significant and independent predictor of physical function, morbidity and mortality in older adults. OBJECTIVE: To verify the association between sociodemographic, health and physical functional data with negative self-assessment of health in elderly. METHODS: Cross-sectional study, with a stratified sampling of communitydwelling from Diamantina (MG), Brazil. To evaluate the AANS and sociodemographic, health and functional variables Questionnaire the Brazil Old Age Schedule (BOAS). The Timed up & go test and the Functional Reach test were performed to assess physical function and risk of falls, respectively. Chi-square tests were used to analyze the univariate associations (p≤0.20). Multiple logistic regression models were created to identify the adjusted associated factors (p≤0.05). RESULTS: 401 older adults participated in this study. The variables that showed a significant association with the negative selfassessment of health were: 80 years or more (OR=1.81; IC95%=1.06-3.08), insufficient financial resource (OR=2.43; IC95%=1.55-3.78), history of falls (OR=3.24; IC95%=1.71-6.14), hypertension (OR=3.27; IC95%=1.37-7.81), neurological disease (OR=2.36; IC95%=1.18-4.71), osteomioarticular disease (OR=2.18; IC95%=1.26-3.78), depression (OR=3.87; IC95%=1.88-7.75), time of disease > 12 years (OR=2.13; IC95%=1.12-4.03), use of dental prosthesis (OR=0.50; IC95%=0.28-0.89), time ≥ 10 seconds to perform the Timed up & go (OR=2.54; IC95%=1.62-3.10), disability in two or more activities of daily living (OR=1.86; IC95%= 1.17-2.95) and self-report of less energy (OR=2.60; IC95%=1.57-4.31). CONCLUSION: The negative self-assessment of health was associated with sociodemographic, health and physical function factors, indicating the need of a comprehensive health care for this population. (AU)

Euterpe edulis Extract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Rats.

We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals' diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins.

Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.

Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes.

Diabetic cardiomyopathy is associated with cardiac remodeling, myocardial dysfunction, low-grade inflammation, and reduced cardiac adiponectin in patients with type 1 diabetes mellitus (T1DM). Alternatively, physical exercise is an important strategy for the management of diabetes. This study aimed to investigate the influence of low-intensity swimming training in cardiac cytokines, structural remodeling, and cardiomyocyte contractile dysfunction in growing rats with untreated experimental DM. Thirty-day-old male Wistar rats were divided into four groups (n=14, per group): sedentary control (SC), exercised control (EC), sedentary diabetic (SD), and exercised diabetic (ED). Diabetes was induced by streptozotocin (60 mg kg(-1), i.p.). Animals from exercised groups swam (5 days/week, 90 min/day, loading up to 5% body weight around the animal's chest) for 8 weeks. The left ventricle (LV) was removed for molecular, morphological, and cardiomyocyte mechanical analysis. Diabetic animals presented cardiac remodeling with myocardial histoarchitectural disorganization, fibrosis, and necrosis. The capillary density was lower in diabetic animals. LV cardiomyocytes from diabetic animals exhibited more prolonged time to the peak of contraction and time to half relaxation than those from control animals. The cardiac levels of interleukin 10, nitric oxide, and total and high molecular weight (HMW) adiponectin were significantly decreased in diabetic animals. Exercise training reduced the level of TNF-α, increased capillary density, and attenuated the histopathological parameters assessed in diabetic rats. In conclusion, the cardiac structural remodeling coexists with reduced levels of total and HMW adiponectin, inflammation, and cardiomyocyte contractility dysfunction in experimental DM. More important, low-intensity swimming training attenuates part of these pathological changes, indicating the beneficial role for exercise in untreated T1DM.

Depletion of enteroendocrine and mucus-secreting cells is associated with colorectal carcinogenesis severity and impaired intestinal motility in rats.

This study investigated the relationship between enteroendocrine and mucus-secreting cells distribution, the severity of colonic mucosal injury and intestinal motility in experimental colorectal carcinogenesis. Using a standardized murine model of colorectal carcinogenesis, eight-weeks-old female Wistar rats weighting 147.30 ± 29.15g were randomized into two groups receiving a subcutaneous injection of 0.9% saline (control) or the chemical carcinogen 1,2-dimethylhydrazine (DMH) at 20 mg/kg per week during 10 weeks. Aberrant crypt foci (ACF) were more frequent in DMH group compared to control group (P < 0.001). The number of enteroendocrine and mucus-secreting cells, and intestinal motility was reduced in DMH animals (P < 0.05). The distribution of enteric neurons was similar in both groups. In DMH animals there was a direct correlation between colonic motility and distribution of enteroendocrine (R(2) = 0.68, P < 0.05) and mucus-secreting cells (R(2) = 0.77, P < 0.05). Inverse correlation between the number of ACF, mucus-secreting cells (R(2) = -0.57, P < 0.05), and enteroendocrine cells (R(2) = -0.74, P < 0.05) was also observed. There was inverse correlation between the severity of the mucosal lesion, the number of mucus-secreting cells (R(2) = -0.83, P < 0.05) and enteroendocrine cells (R(2) = -0.96, P < 0.05). There was a direct correlation between nucleolar organizer regions (AgNOR) and ACF number (R(2) = 0.62; P < 0.01). Inverse correlation was also found between AgNOR, the number of mucus-secreting cells (R(2) = -0.76; P < 0.001), and enteroendocrine cells (R(2) = -0.86; P < 0.001). Taken together, the results indicated that colonic malignant transformation is related to depletion of mucus-secreting and enteroendocrine cells, which was a useful indicator of the evolutionary status of intestinal neoplasm, partially explaining the intestinal motility disorders in the early stages of colorectal carcinogenesis.

Prevalência de conjuntivite adenoviral em clínica oftalmológica no município de Viçosa (MG) / Prevalence of adenoviral conjunctivitis at the ophthalmologic clinic on municipality of Viçosa/MG

Objetivo: Avaliar a prevalência de Adenovírus como agente etiológico da conjuntivite, em clínica médica oftalmológica especializada, em Viçosa, Minas Gerais, Brasil. Métodos: Amostras da secreção conjuntival de 91 pacientes clinicamente diagnosticados com conjuntivite foram submetidos à reação em cadeia da polimerase (PCR), utilizando primers degenerados para a região codificadora do gene da proteína estrutural II. Posteriormente as amostras positivas foram submetidas a sequenciamento e genotipagem. Resultados: A análise dos resultados de PCR revelou prevalência de 36,3% de Adenovírus. Não havendo distinção entre os sexos e com maior prevalência na faixa etária de 26 a 65 anos com 60,60% dos casos positivos. O sequenciamento dos casos positivos por Adenovírus revelaram a presença dos sorotipos 3, 4, 7, 8 e 34 circulante na região. Conclusão: No município de Viçosa, dois em cada cinco casos de conjuntivite são de etiologia adenoviral.

Objective: The aim of this study was to evaluate the prevalence of Adenovirus as a etiologic agent of conjunctivitis on a ophthalmic clinic in Viçosa, Minas Gerais, Brazil. Methods: Samples of conjunctival secretion from 91 patients clinically diagnosed with conjunctivitis were subjected to polymerase chain reaction (PCR) using degenerate primers targeted to the gene encoding the structural protein II. Positive samples were subsequently subjected to sequencing and genotyping. Results: PCR results showed 36.3% prevalence of Adenovirus. No differences between the sexes and was found to be higher in the age group 26-65 years with 60.60% of the positive cases. Sequencing of positive cases showed the presence of Adenovirus serotypes 3, 4, 7, 8, and 34 circulating in the region. Conclusion: In Viçosa two in five cases of conjunctivitis has Adenovirus as etiologic agent.

The impact of serum uric acid on the diagnostic of metabolic syndrome in apparently healthy Brazilian middle-aged men / El impacto del ácido úrico sérico en el diagnóstico del síndrome metabólico en brasileños de mediana edad aparentemente saludables

Background: Hyperuricemia is related to Metabolic Syndrome (MetS) and cardiovascular diseases, but the use of serum uric acid (UA) to diagnose MetS is currently ignored in clinical practices. Objectives: To examine the impact of serum UA on the diagnostic of MetS and the relationship of serum UA with cardiometabolic risk factors in apparently healthy Brazilian middle-aged men residents in a city of Minas Gerais. Methods: In a cross-sectional analysis, 289 apparently healthy middle-aged men underwent anthropometric, clinical, sociodemographic and blood serum biochemical evaluation. By using receive operating curve the internal cutoff of serum UA was determined (5.25 mg/dL). Results: Subjects with two or more components of MetS exhibited higher serum UA as compared to those with one or none component. The inclusion of serum UA ≥ 5.25mg/dL as an additional component of MetS increased the occurrence of this syndrome by 13%. Subjects with UA ≥ 5.25mg/dL showed high prevalence for MetS and association with its components (central obesity, hypertriglyceridemia, dyslipidemia and hypertension) as well as atherogenic risk. Conclusions: Serum UA has an important impact on the diagnostic of MetS and is related to cardiometabolic risk factors in apparently healthy Brazilian middle-aged men. Its use in clinical practices could aggregate accuracy to diagnose MetS (AU)

Introducción: La hiperuricemia viene sido asociada con el síndrome metabólico (SM) y las enfermedades cardiovasculares, pero el uso del ácido úrico (AU) en el diagnóstico del SM es comúnmente ignorado en la práctica clínica. Objetivos: Investigar el impacto de las concentraciones de AU en el diagnóstico del SM y la asociación del AU sérico con los factores de riesgo cardiometabólico en brasileños de mediana edad aparentemente saludables residentes en una ciudad de Minas Gerais. Métodos: Por medio de un análisis transversal, 289 hombres de mediana edad aparentemente saludables fueron sometidos a evaluaciones para determinaciones de variables antropométricas, clínicas, sociodemograficos y bioquímicas. Para determinar el mejor punto de corte para la concentración del AU sérico con respecto al diagnóstico del SM (5.25 mg/dL) fue utilizada la curva ROC. Resultados: Sujetos con dos o más componentes del SM han demostrado mayores concentraciones séricas de AU cuando comparados con individuos con uno o ninguno componente. Además, la inclusión del AU > 5.25 mg/dL como un componente adicional en el diagnóstico del SM aumentó la ocurrencia de este síndrome en un 13%. Finalmente, los hombres con AU ≥ 5.25mg/dL presentaron una asociación positiva con componentes del SM (obesidad central, hipertrigliceridemia, dislipemia e hipertensión arterial), así como un mayor riesgo aterogénico. Conclusión: AU serico tiene un relevante impacto en la ocurrencia del SM, así como es asociado a reconocidos factores de riesgo cardiometabólico en brasileños de mediana edad aparentemente saludables y, su uso en la práctica clínica podría añadir en la exactitud del diagnóstico del SM (AU)

Extrato aquoso de Allium sativum potencializa a ação dos antibióticos vancomicina, gentamicina e tetraciclina frente Staphylococcus aureus / Aqueous extract of Allium sativum potentiates action of the antibiotics vancomycin, gentamicin and tetracycline against Staphylococcus aureus

O presente estudo objetivou analisar a influência da atividade do extrato aquoso de Allium sativum na CIM frente S. aureus, in vitro,e seu efeito sinérgico com vancomicina, gentamicina e tetraciclina. Os testes de sinergismo foram realizados através do método de Kirby-Bauer. A associação do extrato com cada antibiótico de forma isolada foi efetiva em inibir o crescimento da cepa S. aureus. A maior evidência do sinergismo foi observada na combinação do extrato com vancomicina. Os resultados dos testes de sinergismo foram submetidos ao teste tde Wilcoxon (p < 0,01). Considerando-se os resultados obtidos no presente estudo, da associação de antibioticoterapia com o extrato de alho, pode-se concluir que o mesmo pode representar uma ferramenta terapêutica promissora para tratamento de doenças bacterianas com possibilidade de diminuição do grau de toxicidade e resistência bacteriana a antibióticos.

The present study aimed to analyze the influence of (Allium sativum) aqueous extract activity in the minimum inhibitory concentration of antibiotics against S. aureus, in vitro, and its synergistic effect with vancomycin, gentamicin, and tetracycline. The synergy tests were performed by Kirby-Bauer method. The association of the extract with each antibiotic in isolation was effective in inhibiting the growth of S. aureus strain. The greatest evidence of synergism was observed in the combination of extract with vancomycin. The synergy tests results were submitted to Wilcoxon’s t-test (p <0.01). Regarding the results obtained in this study, the association of antibiotic therapy with garlic extract can represent a promising therapeutic tool for the treatment of bacterial diseases with possibility of reduction in the toxicity degree and bacterial resistance to antibiotics.