Exercise training delays cardiac remodeling in a mouse model of cancer cachexia.

AIMS: We aimed to investigate the impact of cancer cachexia and previous aerobic exercise training (AET) on cardiac function and structure in tumor bearing mice. MAIN METHODS: Colon adenocarcinoma cells 26 (CT26) were subcutaneously injected in BALB/c mice to establish robust cancer cachexia model. AET was performed on a treadmill during 45 days, 60 min/5 days per week. Cardiac function was evaluated by echocardiography and cardiac morphology was assessed by light microscopy. The protein expression levels of mitochondrial complex were analyzed by Western blotting. The mRNA levels of genes related to cardiac remodeling and autophagy were analyzed by quantitative Real-Time PCR. KEY FINDINGS: Our data confirms CT26 tumor bearing mice as a well-characterized and robust model of cancer cachexia. CT26 mice exhibited cardiac remodeling and dysfunction characterized by cardiac atrophy and impaired left ventricle ejection fraction paralleled by cardiac necrosis, inflammation and fibrosis. AET partially reversed the left ventricle ejection fraction and led to significant anti-cardiac remodeling effect associated reduced necrosis, inflammation and cardiac collagen deposition in CT26 mice. Reduced TGF-ß1 mRNA levels, increased mitochondrial complex IV protein levels and partial recovery of BNIP3 mRNA levels in cardiac tissue were associated with the cardiac effects of AET in CT26 mice. Thus, we suggest AET as a powerful regulator of key pathways involved in cardiac tissue homeostasis in cancer cachexia. SIGNIFICANCE: Our study provides a robust model of cancer cachexia, as well as highlights the potential and integrative effects of AET as a preventive strategy for reducing cardiac damage in cancer cachexia.

Accuracy of quick sequential organ failure assessment score to predict mortality in hospitalized patients with suspected infection in an HIV/AIDS reference centre in Rio de Janeiro, Brazil.

OBJECTIVES: To compare the discriminatory capacity of the quick sequential organ failure assessment (qSOFA) vs. the systemic inflammatory response syndrome (SIRS) score for predicting 30-day mortality and intensive care unit (ICU) admission in patients with suspicion of infection at an HIV reference centre. METHODS: We performed a prospective cohort study including consecutive adult patients who had suspected infection and who were subsequently admitted to the medical ward. Variables related to qSOFA and SIRS were measured at admission. The performance (area under the receiver operating curve, AUROC) of qSOFA (score ≥2) and SIRS (≥2 criteria) as a predictor of 30-day mortality and ICU admission was evaluated. RESULTS: One hundred seventy-three patients (mean ± standard deviation age, 42.6 ± 12.4 years) were included in the analysis; 107 (61.8%) were male, and 111 (64.2%) were HIV positive. Respiratory and gastrointestinal infections occurred in 49 (28.3%) and 23 (13.3%), respectively. The 30-day mortality rate was 9 (5.2%) of 173. The prognostic performance of qSOFA was similar compared to SIRS, with an AUROC of 0.68 (95% confidence interval, 0.55-0.81) and 0.69 (95% confidence interval, 0.53-0.86) (p 0.96). Twenty patients (11%) were admitted to the ICU; qSOFA and SIRS had a similar discriminatory capacity for ICU admission (AUROC 0.63 (95% confidence interval, 0.51-0.75) and 0.63 (95% confidence interval, 0.50-0.76)), respectively). CONCLUSIONS: We found a poor prognostic accuracy of the qSOFA to predict 30-day mortality in hospitalized patients suspected of infection in a setting with a high burden of HIV infection.

Detection of virulence-associated genes in pathogenic and commensal avian Escherichia coli isolates.

Poultry colibacillosis due to Avian Pathogenic Escherichia coli (APEC) is responsible for several extra-intestinal pathological conditions, leading to serious economic damage in poultry production. The most commonly associated pathologies are airsacculitis, colisepticemia, and cellulitis in broiler chickens, and salpingitis and peritonitis in broiler breeders. In this work a total of 66 strains isolated from dead broiler breeders affected with colibacillosis and 61 strains from healthy broilers were studied. Strains from broiler breeders were typified with serogroups O2, O18, and O78, which are mainly associated with disease. The serogroup O78 was the most prevalent (58%). All the strains were checked for the presence of 11 virulence genes: 1) arginine succinyltransferase A (astA); ii) E.coli hemeutilization protein A (chuA); iii) colicin V A/B (cvaA/B); iv) fimbriae mannose-binding type 1 (fimC); v) ferric yersiniabactin uptake A (fyuA); vi) iron-repressible high-molecular-weight proteins 2 (irp2); vii) increased serum survival (iss); viii) iron-uptake systems of E.coli D (iucD); ix) pielonefritis associated to pili C (papC); x) temperature sensitive haemaglutinin (tsh), and xi) vacuolating autotransporter toxin (vat), by Multiplex-PCR. The results showed that all genes are present in both commensal and pathogenic E. coli strains. The iron uptake-related genes and the serum survival gene were more prevalent among APEC. The adhesin genes, except tsh, and the toxin genes, except astA, were also more prevalent among APEC isolates. Except for astA and tsh, APEC strains harbored the majority of the virulence-associated genes studied and fimC was the most prevalent gene, detected in 96.97 and 88.52% of APEC and AFEC strains, respectively. Possession of more than one iron transport system seems to play an important role on APEC survival.

Long-term globular adiponectin administration improves adipose tissue dysmetabolism in high-fat diet-fed Wistar rats.

Adiponectin administration to obese or type 2 diabetic patients is still far off, due to its expensive costs and absence of studies demonstrating the effectiveness of its chronic administration. We performed long-term globular adiponectin administration, testing its usefulness in improving adipose tissue metabolism. Adiponectin (98 υg/day) was administered through a subcutaneous minipump with continued release (28 days) to Wistar rats fed a high-fat diet. Adiponectin decreased body weight and adipocyte size, while decreasing circulating leptin levels. More, adiponectin was able to increase IkappaBalpha and PPARgamma levels and to prevent high-fat diet-induced impairment of insulin signalling, especially in epididymal adipose tissue. This resulted in improved glucose profile. High-fat diet caused an impairment of lipolysis in epididymal adipose tissue, which was partially restored by adiponectin treatment. Long-term globular adiponectin administration was able to improve pathways of insulin signalling and lipid storage in adipose tissue of high-fat diet-fed rats, contributing to a better metabolic profile.

High blood pressure is one of the symptoms of paraquat-induced toxicity in rats.

This study investigated whether paraquat (Pq)-induced lipidic peroxidation (LP) is accompanied by changes in blood pressure and heart rate (HR) in rats. Groups of adult male Wistar rats were studied 2 and 12 h after Pq (35 mg/kg, i.p.) administration. The LP was evaluated by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, liver and lungs, and validated by including a group treated with an antioxidant, superoxide dismutase (CuZnSOD 50,000 IU/kg), in the study. The TBARS levels were significantly higher (p<0.05) in the kidneys of the rats studied 2 h after Pq than in their respective controls. Similarly, systolic and diastolic blood pressure (DBP) were higher (p<0.05), while HR was lower (p<0.05) than basal levels 2 and 12 h after Pq administration. In contrast, the group treated simultaneously with Pq and CuZnSOD exhibited lower levels of TBARS (p<0.05) in all studied organs compared to the control group, while the mean arterial pressure and HR did not differ from those seen in the control group. These findings indicate that acute Pq poisoning symptoms include high blood pressure.

A novel pathway to enzyme deactivation: the cutinase model.

Cutinase in aqueous solution at pH 4.5 deactivates following a parallel pathway. At 53 degrees C, 88% of the cutinase molecules are in the unfolded conformation, which can aggregate with a reaction order of 3 if the protein concentration is high (>/=12 microM). The aggregates show a sixfold increase in size as determined by dynamic light scattering. This aggregation process is the first phase observed during a deactivation experiment; however, after significant cutinase depletion and maturation of the aggregates, a first-order step starts to dominate and a second phase independent of the protein concentration is observed. Kinetic partitioning between aggregation and first-order irreversible changes of the unfolded conformation can occur during enzyme deactivation when the equilibrium between the native and the unfolded conformation is shifted and kept toward the unfolded conformation.

Effect of zinc on the tuberculin response of children exposed to adults with smear-positive tuberculosis.

The tuberculin test (PPD) is used frequently in the diagnosis of tuberculosis. PPD, however, relies on an intact cell-mediated immunity and infected children often have false negative results. This study assessed whether a single oral zinc supplement modifies the PPD induration size and its association with nutritional status in Brazilian children. Ninety-eight children below 15 years of age who had been exposed to adults with smear-positive pulmonary TB in 1998 were tested by PPD in 1998 and 2000. Children were randomised in 2000 to receive a single oral dose of zinc sulphate or a placebo at the time of administering the PPD. Forty-three (44%) children were PPD-positive in 1998 and 54 (55%) in 2000. A higher proportion of children were classified as PPD-positive in 2000 in the zinc-supplemented group (57.1%) than in the placebo group (53.1%). PPD indurations were larger in children receiving zinc (mean 18.5 and 15.5 mm in the zinc and placebo groups, respectively) (p < 0.03). Mean induration sizes in 2000 were larger in zinc-supplemented children, regardless of their nutritional status. Our study demonstrates that zinc increases the PPD induration size in children irrespective of nutritional state. Zinc supplementation could work by correcting asymptomatic or marginal zinc deficiencies or as a non-specific booster of immunological mechanisms (whether or not there is a deficiency).

Use of purified protein derivative to assess the risk of infection in children in close contact with adults with tuberculosis in a population with high Calmette-Guérin bacillus coverage.

SETTING: Household contacts <15 years of age of adults with tuberculosis (TB) attending a reference center in Aracaju, Sergipe, Northeast Brazil. OBJECTIVE: To assess the use of purified protein derivative (PPD) and frequency of infection in children with high Calmette-Guérin bacillus (BCG) coverage who were recently exposed to TB. DESIGN: Cross-sectional study of 141 exposed household contacts <15 years of age and 506 nonexposed neighborhood controls. Children were examined and assessed for degree of exposure to index cases, BCG vaccination and scar and were tested with PPD. RESULTS: Exposed children were younger and less up to date in their vaccination schedule than controls (P < 0.05). BCG had been given to 95.6% of exposed children and 97.4% of controls, but only 80.9% of exposed vs. 88.5% of controls had a scar (P < 0.05). Scar sizes of exposed children were smaller (medians, 4.5 and 7 mm, respectively; P < 0.05). Children had lower weight for age z scores and height than the National Center for Health Statistics standards. Exposed children had lower weight for age z scores than controls (P < 0.05). Sixty-seven (47.5%) exposed children and 18 (3.6%) controls had PPD readings of >10 mm. Positivity and induration sizes increased with age, although this was significant only in the controls. The presence of a BCG scar was not associated with having a positive PPD. The degree of exposure was an important factor for PPD positivity; 66 (60.6%) of the 109 children with close exposure were positive compared with 1 (3.1%) of 32 with less intimate exposure. PPD indurations among close contacts were also larger than those with restricted exposure and controls (16.3, 11 and 9.4 mm, respectively; P < 0.05). PPD positivity was associated with the quantification of acid-fast bacilli in the adult; 38.5% of contacts with adults with sputum with (+) were positive, compared with 42.3% of those with (++) and 58.4% with (+++) (P < 0.05). CONCLUSION: PPD is a useful test to identify children infected with TB independently of whether they had received BCG or not. Children exposed to adults with TB are at high risk of infection. The risk of infection is associated with the intimacy of contact and the number of bacilli expectorated in sputum.

Regional Brazilian diet-induced low birth weight is correlated with changes in renal hemodynamics and glomerular morphometry in adult age.

Number of nephrons, renal hemodynamics, and glomerular morphometry were assessed in rats submitted to a multideficient diet which was developed from a basic regional diet consumed in a Brazilian region of sugarcane cultivation. We evaluated three groups of male Wistar rat offspring: (1) from dams fed a standard diet throughout mating, pregnancy and lactation (control group) and (2) from dams fed the multideficient diet during mating and pregnancy (MalN1 group) or (3) throughout mating, pregnancy, and lactation (MalN2 group). At adult age, the animals were anesthetized to measure mean arterial blood pressure and renal hemodynamics. The MalN1 group, as compared with the control group, showed unaltered body and kidney weights, nephron deficiency, a high mean arterial blood pressure, glomerular hypertrophy, and renal vasoconstriction. The MalN2 group showed the same nephron deficiency and mean arterial blood pressure levels as the MalN1 group. These animals exhibited lower body and kidney weights and no glomerular hypertrophy. In conclusion, the alterations induced by intrauterine malnutrition are compatible with the development of chronic renal failure.