Fernando Tadeu Trevisan Frajacomo

Eccentric Exercise in Rehabilitation: Safety, Feasibility and Application

This nonexhaustive mini-review reports on the application of eccentric exercise in various rehabilitation populations. The two defining properties of eccentric muscle contractions--a potential for high muscle-force production at an energy cost that is uniquely low--are revisited and formatted as exercise countermeasures to muscle atrophy, weakness, and deficits in physical function. Following a dual-phase implementation, eccentric exercise that induces rehabilitation benefits without muscle damage, thereby making it both safe and feasible in rehabilitation, is described. Clinical considerations, algorithms of exercise progression, and suggested modes of eccentric exercise are presented.

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL.

Creatine supplementation prevents fatty liver in rats fed choline-deficient diet: a burden of one-carbon and fatty acid metabolism.

AIM To examine the effects of creatine (Cr) supplementation on liver fat accumulation in rats fed a choline-deficient diet. METHODS Twenty-four rats were divided into 3 groups of 8 based on 4 weeks of feeding an AIN-93 control diet (C), a choline-deficient diet (CDD) or a CDD supplemented with 2% Cr. The CDD diet was AIN-93 without choline. RESULTS The CDD significantly increased plasma homocysteine and TNFα concentration, as well as ALT activity. In liver, the CDD enhanced concentrations of total fat (55%), cholesterol (25%), triglycerides (87%), MDA (30%), TNFα (241%) and decreased SAM concentrations (25%) and the SAM/SAH ratio (33%). Cr supplementation prevented all these metabolic changes, except for hepatic SAM and the SAM/SAH ratio. However, no changes in PEMT gene expression or liver phosphatidylcholine levels were observed among the three experimental groups, and there were no changes in hepatic triglyceride transfer protein (MTP) mRNA level. On the contrary, Cr supplementation normalized expression of the transcription factors PPARα and PPARγ that were altered by the CDD. Further, the downstream targets and fatty acids metabolism genes, UCP2, LCAD and CPT1a, were also normalized in the Cr group as compared to CDD-fed rats. CONCLUSION Cr supplementation prevented fat liver accumulation and hepatic injures in rats fed with a CDD for 4 weeks. Our results demonstrated that one-carbon metabolism may have a small role in mitigating hepatic fat accumulation by Cr supplementation. The modulation of key genes related to fatty acid oxidation pathway suggests a new mechanism by which Cr prevents liver fat accumulation.

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol.

The Effects of Acute Exercise and Exercise Training on Plasma Homocysteine: A Meta-Analysis

Background Although studies have demonstrated that physical exercise alters homocysteine levels in the blood, meta-analyses of the effects of acute exercise and exercise training on homocysteine blood concentration have not been performed, especially regarding the duration and intensity of exercise, which could affect homocysteine levels differently. Objective The aim of this meta-analysis was to ascertain the effects of acute exercise and exercise training on homocysteine levels in the blood. Method A review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the online databases PubMed, SPORTDiscus, and SciELO to identify relevant studies published through June 2015. Review Manager was used to calculate the effect size of acute exercise and exercise training using the change in Hcy plasmaserum concentration from baseline to post-acute exercise and trained vs. sedentary control groups, respectively. Weighted mean differences were calculated using random effect models. Results Given the abundance of studies, acute exercise trials were divided into two subgroups according to exercise volume and intensity, whereas the effects of exercise training were analyzed together. Overall, 22 studies with a total of 520 participants indicated increased plasma homocysteine concentration after acute exercise (1.18 μmol/L, 95% CI: 0.71 to 1.65, p < .01). Results of a subgroup analysis indicated that either long-term exercise of low-to-moderate intensity (1.39 μmol/L, 95% CI: 0.9 to 1.89, p < .01) or short-term exercise of high intensity (0.83 μmol/L, 95% CI: 0.19 to 1.40, p < .01) elevated homocysteine levels in the blood. Increased homocysteine induced by exercise was significantly associated with volume of exercise, but not intensity. By contrast, resistance training reduced plasma homocysteine concentration (-1.53 μmol/L, 95% CI: -2.77 to -0.28, p = .02), though aerobic training did not. The cumulative results of the seven studies with a total of 230 participants in exercise training analysis did not demonstrate a significant impact on homocysteine levels in the blood (-0.56 μmol/L, 95% CI: -1.61 to 0.50, p = .23). Conclusions Current evidence demonstrates that acute exercise increases homocysteine levels in the blood independent of exercise duration and intensity. Resistance, but not aerobic training decreases plasma homocysteine levels.

Colon preneoplasia after carcinogen exposure is enhanced and colonic serotonergic system is suppressed by food deprivation

Calorie restriction regimens usually promote health and extend life-span in mammals. This is partially related to their preventive effects against malignancies. However, certain types of nutritional restriction failed to induce beneficial effects. The American Institute of Nutrition defines calorie restriction as diets which have only 40% fewer calories, but provide normal amounts of necessary food components such as protein, vitamins and minerals; whereas, food restriction means 40% less of all dietary ingredients plus 40% less calories. Our study aimed to test the hypothesis that the latter type of food deprivation (40% less food than consumed by standard fed rats) might increase cancer risk instead of reducing it, as is generally assumed for all dietary restrictive regimens. Since the endogenous modulation of the colon serotonergic system has been observed to play a role during the early steps of carcinogenesis we also investigated whether the serotoninergic system could be involved in the food intake modulation of cancer risk. For this, rats were exposed to a carcinogen and subjected to food deprivation for 56 days. Triglyceride levels and visceral adipose tissue were reduced while hepatic and colonic lipid peroxidation was increased. This dietary restriction also decreased serotonin levels in colon, and gene expression of its intestinal transporter and receptors. Finally, the numbers of preneoplastic lesions in the colon tissue of carcinogen-exposed rats were increased. Our data suggest that food deprivation enhances formation of early tumorigenic lesions by suppressing serotonergic activity in colon tissue.

Biomechanical adaptations of mice cortical bone submitted to three different exercise modalities.

Objective To compare the adaptive effects of three non-weight bearing exercise on bone mechanical properties. Methods 24 male Balb/c mice (22-25g), were randomly divided into four groups (n=6): sedentary group (S); swimming group (N) which performed sessions five times per week for 60 min progressively; resistance group (R), which performed climbing exercise with progressive load, three times per week; and combined group (C), which performed the same protocols aforementioned being three times a week according to N protocol and two times a week the R protocol during eight weeks. Biomechanical tests, load until failure and stiffness evaluation of shinbone was performed after animals have been sacrificed. Results Stiffness values were statistically higher only in the isolated modalities groups (N and R, 41.68 ± 10.43 and 41.21 ± 11.38 N/mm, respectively) compared with the S group (28.48 ± 7.34 N/mm). However, taking into consideration the final body mass, relative values, there was no difference in the biomechanical tests among the groups. Conclusion Data from the present investigation demonstrated a favorable influence of muscle contraction in lower impact isolated exercise modalities on absolute stiffness values, i.e.groups N and R, whereas the combined group (C) did not present any statistical significant difference compared to sedentary group. Level of Evidence II, Prospective Comparative Study.

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.

Frequency and Duration Modulate Anticarcinogenic Effects of a Physical Training in the Colon

Physical exercise has proven protective against colon carcinogenesis. We sought to clarify whether the frequency and duration of physical training were key factors for its anticarcinogenic effects on the colon. Either sedentary or physically trained male Wistar rats (n=82) were either exposed or not to the carcinogen dimethylhidrazine (DMH). The first protocol investigated whether swimming for 60 min in different frequencies modulates antipreneoplastic effects of physical training. Another protocol then explored whether the duration for training 5 times a week impacts on the development of colon preneoplastic lesions. After 8 weeks, serum and colon samples were collected and analyzed afterwards. Swimming once a week for 60 min did not promote those anticarcinogenic effects found in rats trained 5 times weekly. Such weekly sustained physical training not only decreased the development of colon preneoplastic, but also epithelial proliferation, and subepithelial cyclooxygenase 2 (COX-2) expression. Interestingly, a 5 time per week training for less than 60 min was not as protective against colon carcinogenesis as swimming for 90 min. This 90 min training indeed reduced serum cholesterol and triglycerides levels, as well as colonic lipid peroxidation in carcinogen-exposed rats. Our collective data suggest anticarcinogenic effects of physical exercises are potentially promoted when training 5 times a week for at least 60 min.