Camila S. Padilha

Chronic Blood Pressure Reductions and Increments in Plasma Nitric Oxide Bioavailability

This study analyzed the effects of 12 weeks of resistance training (RT) on resting blood pressure (BP) and plasma levels of nitric oxide metabolites (NOx) in pre- and hypertensive older women, and evaluated the relationship between these 2 parameters. Thirty-five older women (68.2±5.7 years, 70.0±14.4 kg, 157.1±6.4 cm, 28.3±5.0 kg.m-2) were randomly allocated into a training group (TG; n=17), which performed a 12-week RT program, and a control group (CG; n=18), which did not perform any physical exercise. Anthropometry, one repetition maximum (1RM), body composition analysis by dual energy X-ray absorptiometry, blood samples, and resting BP were measured. There was a significant interaction for all variables analyzed, in which reductions of systolic BP (-8.5%), diastolic BP (-8.4%), and mean arterial pressure (-8.5%), and increases of NOx (+35.2%) were observed only for the TG. Moreover, a negative and significant correlation was observed (P<0.05; r=-0.63) between NOx and systolic BP in the TG. Results suggest that a 12-week RT program is sufficient to induce reductions in BP in pre- and hypertensive older women and that the decrease in systolic BP is associated with an increase in plasma NOx concentration.

Effect of Resistance Training Systems on Oxidative Stress in Older Women

The purpose of this study was to investigate the effect of two different resistance training (RT) systems on oxidative stress biomarkers in older women. Fifty-nine older women (67.9 ± 5.0 years) were randomly assigned to one of three groups. Two training groups performed an 8 week RT program either in traditional (TD, n = 20) or a pyramid (PR, n = 20) system 3 times per week, or a control group (CG, n = 19). The TD program consisted of 3 sets of 8-12 RM with constant load for the 3 sets, whereas the PR training consisted of 3 sets of 12/10/8 RM with incremental loads for each set. As compared with the CG, both TD and PR achieved upregulation of the antioxidant system as evidenced by higher (p < .05) values of total radical-trapping antioxidant parameter plasma concentration after intervention (TD= 930.4 ± 160.0 µmolTrolox, PR= 977.8 ± 145.2 µmolTrolox, CG= 794.4 ± 130.2 µmolTrolox). For the protein oxidation adducts, TD and PR presented lower (p < .05) scores compared with CG (TD= 91.2 ± 25.0 µmol/L, PR= 93.0 ± 30.3 µmol/L, CG= 111.0 ± 20.4 µmol/L). However, there were no differences (p < .05) between trained groups in the antioxidant capacity markers and in the protein oxidation adducts markers. The results suggest that 8 weeks of progressive RT promotes an improvement in markers of oxidative stress in older women independent of the load-management RT system.

Solid Ehrlich carcinoma reproduces functional and biological characteristics of cancer cachexia

AIMS Well-characterized animal tumor models of cancer cachexia are warranted to elucidate underlying mechanisms and provide a better approach to the human scenario. We aimed to investigate whether solid Ehrlich carcinoma reproduces clinical, functional and biological conditions of tumor-induced cachexia in mice. METHODS Eight-week old female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells (tumor-bearing, TB group) or vehicle (sham) into the right flank and monitored for 28days. Tumor histopathological features and tumor-host interaction, including tissue weight, muscle structure, strength and biochemical parameters were carried out. KEY FINDINGS Tumor growth curve demonstrated a linear pattern with no difference in final carcass weight between groups. A well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The TB group had reduced handgrip strength, aside from lower cross sectional area (CSA) and critically reduced parametrial fat pads. Plasma parameters of lactate dehydrogenase (LDH), creatine kinase (CK) and tumor necrosis factor-α (TNF-α) were higher in the TB group, suggesting predominance of catabolic and pro-inflammatory activities. Conversely, food intake and tissue weight did not differ between groups. SIGNIFICANCE Our data elucidated that the solid Ehrlich tumor model is feasible and effective in reproducing some of the relevant issues experienced by cancer patients with cachexia. The solid Ehrlich carcinoma emerges as an alternative tool against more aggressive cancer cachexia models during preclinical research.

Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice

Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

Age at menarche and cancer risk at adulthood

Abstract Aim: The aim was to evaluate the association between age at menarche and cancer using a nationally representative sample of Brazilian women. Methods: Data from the Brazilian Health Survey (PNS), a nationally representative survey conducted in 2013 (n = 33,715 women; ≥18 years), were used. Information on cancer diagnosis, age at menarche and other co-variables (chronological age, educational status, skin colour, menopause, leisure-time physical activity and tobacco smoking) were collected via interview. Logistic regression models were used for aetiological analyses. Results: The prevalence of cancer diagnosis was greater among women with early age at menarche [2.6% (2.0–3.5%)] compared to on-time [1.6% (1.4–1.9%)] and late women [2.0% (1.1–3.4%)]. The onset of menarche ≤11 years was significantly associated with cancer risk, regardless of co-variables [OR =2.45 (1.34–4.48)], compared to the late group. Conclusion: Early age at menarche was associated with cancer risk in adulthood, regardless of race, educational status, chronological age, obesity, menopause onset, tobacco smoking or physical activity.

Resistance exercise attenuates skeletal muscle oxidative stress, systemic pro-inflammatory state, and cachexia in Walker-256 tumor-bearing rats

The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers, and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n = 9), tumor-bearing (n = 9), exercised (n = 9), and tumor-bearing exercised (n = 10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails for 6 weeks. The physical activity of control and tumor-bearing rats was confined to the space of the cage. After this period, tumor-bearing and tumor-bearing exercised animals were inoculated subcutaneously with Walker-256 tumor cells (11.0 × 107 cells in 0.5 mL of phosphate-buffered saline) while control and exercised rats were injected with vehicle. Following inoculation, rats maintained resistance exercise training (exercised and tumor-bearing exercised) or sedentary behavior (control and tumor-bearing) for 12 more days, after which they were euthanized. Results showed muscle wasting in the tumor-bearing group, with body weight loss, increased systemic leukocytes, and inflammatory interleukins as well as muscular oxidative stress and reduced mTOR signaling. In contrast, RET in the tumor-bearing exercised group was able to mitigate the reduced body weight and muscle wasting with the attenuation of muscle oxidative stress and systemic inflammatory markers. RET also prevented loss of muscle strength associated with tumor development. RET, however, did not prevent the muscle proteolysis signaling via FBXO32 gene messenger RNA expression in the tumor-bearing group. In conclusion, RET performed prior tumor implantation prevents cachexia development by attenuating tumor-induced systemic pro-inflammatory condition with muscle oxidative stress and muscle damage.