Toll-like receptor-9 in Spanish multiple sclerosis patients: an association with the gender.

BACKGROUND AND PURPOSE: Toll-like receptor-9 (TLR9) is a potent inducer of innate immune system triggered by infection with viruses, some of them previously related to multiple sclerosis (MS). The aim of this study was to analyze the possible association of two TLR9 single nucleotide polymorphisms (SNPs; rs352162 and rs187084) with susceptibility to MS. METHODS: Two independent cohorts of MS patients and controls were included: 574 clinically definite relapsing-remitting MS patients (367 females) and 807 healthy controls (418 females) for the first cohort; and 366 relapsing-remitting MS patients (238 females) and 224 healthy controls (160 females) for the second cohort. Genotyping was performed by TaqMan assays. RESULTS: The AT haplotype was found to be significantly higher in women than in men (P = 0.013 and P = 0.044). CONCLUSIONS: Here two possible genetic markers are proposed that could be also associated with the differences observed in the clinical course of MS in both genders. Further studies with larger cohorts should be performed to confirm these results.

Fear and/or anxiety of children and parents associated with the dental environment.

AIM: To assess levels of anxiety in children concerning different dental instruments and equipment and to relate them with parents' anxiety levels moments before the appointment. MATERIALS AND METHODS: Fifty children from 4 to 12 years of age (average of 10±3.07) and their respective parents were evaluated. A facial scale was used to assess children's anxiety levels, while the Dental Anxiety Scale (DAS) was used to assess parents. Friedman test was applied to check any differences in children's anxiety levels relative to the equipment/instruments, and this was complemented by the use of the Wilcoxon test for two-by-two comparison. In order to assess correlation between parents' and their children's anxiety levels, the study used Spearman correlation coefficient. RESULTS: With regard to parents' anxiety levels, 4% resulted as null, 18% were low, 56% were moderate, and 22% were exacerbated; children's anxiety level results were: 52% light, 44% intermediate, and 4% intense. Anxiety levels related to instruments/equipment were, in descending order: carpule syringe > paediatric forceps > dental explorer > x-ray machine > rubber dam punch > high speed handpiece > rubber dam forceps > mouth mirror > clinical tweezers > dental chair. No correlation was found between parents' anxiety levels and those of their children (p=0.546). CONCLUSION: The instruments/equipment used in the assessment generated different anxiety levels in the children. No correlation was found between parents' anxiety levels and those of their children.

Use of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase in wound healing in diabetic rats.

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.

Reaching task performance is associated to neuromuscular junction adaptations in rats with induced diabetes mellitus.

Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student's t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.

Endocrine dysfunction in leprosy.

Leprosy is still an endemic disease, especially in Third World countries, and, because of migration, it still persists in Europe and the United States. The disease affects the peripheral nerves, skin, and multiple internal organs, making its clinical recognition difficult. In particular, the endocrine manifestations caused by leprosy have been underestimated, even by specialists. The endocrine changes present in leprosy include hypogonadism, sterility, and osteoporosis. In addition, the spectral immune nature of leprosy offers an attractive model to investigate the pathogenetic correlation between the patterns of inflammation in the poles of its spectrum and the hormonal disarrangements observed in this disease. It is important that those involved in leprosy management be aware of the potential endocrine changes and their treatment to address the disease in all of its aspects. In this article, we review the findings on endocrine dysfunction in leprosy, including a survey of the literature and of our own work.

First-trimester maternal serum tumor necrosis factor receptor-1 and pre-eclampsia.

OBJECTIVES: To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-alpha (TNF-R1) at 11-13 weeks of gestation in pregnancies that subsequently develop pre-eclampsia is different from that in women without this complication. METHODS: The concentration of TNF-R1 at 11 + 0 to 13 + 6 weeks was measured in samples from 128 cases that subsequently developed pre-eclampsia and 569 controls with no pregnancy complications. TNF-R1 and uterine artery pulsatility index (UtA-PI) values were expressed as multiples of the median (MoM) adjusted for maternal factors. The distributions of log TNF-R1 MoM and log UtA-PI MoM in the control and pre-eclampsia groups were compared. Logistic regression analysis was used to determine whether a significant contribution is provided by maternal factors, TNF-R1 and UtA-PI in predicting pre-eclampsia. The performance of screening was determined by analysis of receiver-operating characteristics curves. RESULTS: Median TNF-R1 and UtA-PI were significantly higher in the pre-eclampsia group (TNF-R1, 1.062 MoM; UtA-PI, 1.301 MoM) than in the control group (TNF-R1, 0.996 MoM; UtA-PI, 1.037 MoM). There was no significant association between TNF-R1 and gestational age at delivery, birth weight percentile or UtA-PI. Logistic regression analysis demonstrated significant contributions to the detection of pre-eclampsia from maternal factors and UtA-PI but not from TNF-R1. CONCLUSIONS: In pregnancies developing pre-eclampsia the maternal serum TNF-R1 concentration at 11-13 weeks of gestation is increased, but the level of TNF-R1 is not associated with the degree of impairment in placental perfusion or the severity of pre-eclampsia. Measurement of serum TNF-R1 does not improve the prediction of pre-eclampsia provided by screening based on a combination of maternal factors and UtA-PI.

Decreased muscle strength is associated with proinflammatory cytokines but not testosterone levels in men with diabetes.

The aim of this study was to compare muscle strength in male subjects with type 2 diabetes mellitus (DM2) with and without low plasma testosterone levels and assess the relationship between muscle strength, testosterone levels, and proinflammatory cytokines. Males (75) aged between 18 and 65 years were divided into 3 groups: control group that did not have diabetes and had a normal testosterone plasma level (>250 ng/dL), DnormalTT group that had DM2 with normal testosterone levels, and the DlowTT group that had DM2 and low plasma testosterone levels (<250 ng/dL). The age (means±SD) of the groups was 48.4±10, 52.6±7, and 54.6±7 years, respectively. Isokinetic concentric and isometric torque of knee flexors and extensors were analyzed by an isokinetic dynamometer. Plasma testosterone and proinflammatory cytokine levels were determined by chemiluminescence and ELISA, respectively. Glycemic control was analyzed by glycated hemoglobin (HbA1C). In general, concentric and isometric torques were lower and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß plasma levels were higher in the groups with diabetes than in controls. There was no correlation between testosterone level and knee torques or proinflammatory cytokines. Concentric and isometric knee flexion and extension torque were negatively correlated with TNF-α, IL-6, and HbA1C. IL-6 and TNF-α were positively correlated with HbA1C. The results of this study demonstrated that muscle strength was not associated with testosterone levels in men with DM2. Low muscle strength was associated with inflammatory markers and poor glycemic control.

Use of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase in wound healing in diabetic rats

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.

Cytokine profile and lymphocyte subsets in type 2 diabetes.

Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

Reaching task performance is associated to neuromuscular junction adaptations in rats with induced diabetes mellitus

Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student's t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.

Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency.

17 alpha-Hydroxylase deficiency (17-OHDS) is a peculiar type of adrenal insufficiency because of elevated corticosterone (B) production. Episodic and circadian ACTH secretion and the responses to ovine CRH and metyrapone were examined in a female with 17-OHDS under conditions of normal sodium (NSI) and low sodium (LSI) intake. Plasma ACTH and B were higher on LSI than on NSI (mean +/- SD: ACTH, 58 +/- 20 vs. 33 +/- 14 pmol/L; B, 508 +/- 107 vs. 381 +/- 69 nmol/L). ACTH pulses were concomitant with or followed by B pulses. An increase in the amplitude, but not the number, of ACTH and B pulses was found on LSI. Circadian ACTH and B rhythms persisted on LSI. Aldosterone levels were higher on LSI than on NSI. After metyrapone, plasma B decreased in the afternoon (NSI, 220 +/- 10; LSI, 275 +/- 35 nmol/L) and rose on the following morning. Plasma ACTH increased substantially on the following morning (NSI, 135 +/- 47; LSI, 307 +/- 77 pmol/L). The ACTH peak levels after ovine CRH increased after metyrapone administration. These data indicate that B may also have a negative feedback effect at the pituitary level. In all maneuvers, there were no changes in PRA, plasma sodium and potassium, or cortisol. We conclude that in 17-OHDS, in the absence of cortisol production, ACTH and B may interact to modulate the brain-pituitary-adrenocortical system.

Cytoprotective actions of estrogens against tert-butyl hydroperoxide-induced toxicity in hepatocytes.

Estrogens are effective antioxidants in diverse biological systems. Despite their antioxidant activities, it is not known yet whether estrogens prevent or alleviate liver toxicity induced by oxidative stress. In the present work, we studied this possibility by examining in vitro the protective potential of different estrogen compounds (17beta-estradiol, 2-hydroxyestradiol, and diethylstilbestrol) against tert-butyl hydroperoxide-induced hepatocyte damage. Various parameters such as cell viability, lipid peroxidation, adenine nucleotide content, and thiol status were measured as an index of cytotoxicity. The protective effects of estrogens were compared to those of the iron chelator deferoxamine. The molecules tested prevented oxidant-induced cell death differently, showing variable degrees of protection. Deferoxamine was the most potent agent, followed by diethylstilbestrol and 2-hydroxyestradiol, 17beta-estradiol being the least efficient. The inhibitory effects on lipid and thiol oxidations paralleled the effects on cell viability. The molecules also reduced the oxidant-induced ATP depletion, except for 17beta-estradiol which had no effect on the decreased ATP levels. Our results suggest that the mechanisms of the preventive actions of estrogens may be related not only to their antioxidant activity against free radicals, but also and to a lesser extent to the maintenance of the normal redox status of the cell, which partially recovers the intracellular GSH levels.

Diurnal variation of the pituitary-adrenal and AVP responses to stress in rats under food restriction.

In the present study plasma corticosterone (B), ACTH and vasopressin (AVP) were determined in 2 groups of Wistar rats, a control group (C) with free access to food, and a food restricted group (FR) with access to food only from 0900 to 1100 h for 14 days. Blood samples were collected by decapitation under unstressed (basal) conditions and immediately after 30 minutes of immobilization stress applied at AM (0800 h) and at PM (2000 h). The basal plasma B concentrations in C group presented diurnal variation with higher values at PM than at AM. The restricted feeding regimen resulted in a 12 hour shift of peak B values. Basal plasma ACTH rhythm in group C is parallel to diurnal B variation, attaining higher levels at PM. Rats under food restriction presented higher basal plasma ACTH levels at AM than C group, however there was no AM-PM difference. In both groups after stress plasma B concentrations increased in comparison to those in the unstressed rats. There was no significant AM-PM difference in the absolute B values attained in C or FR groups. The stress-evoked ACTH response was higher at AM than at PM in group C. In the FR group the ACTH response was similar in the morning and evening, although the ACTH concentrations achieved in the morning was lower than in group C. Basal plasma AVP levels were similar at AM and PM in both C and FR groups. Immobilization stress evoked no plasma AVP response in neither groups. Our results indicate that long term food restriction is able to modify the diurnal rhythms of both basal secretion and stress responsiveness of pituitary-adrenal axis by an as yet uncharacterized mechanism.

Circadian variations of plasma atrial natriuretic peptide and corticosterone in rats with continuous or restricted access to food.

In the present study plasma Atrial Natriuretic Peptide (ANP) and Corticosterone (B) levels were determined in 2 groups of Wistar rats, a Control group (C) with free access to food, and a Food Shift group (FS) with access to food only from 0900 to 1100 h for 2 weeks. Blood samples were collected by decapitation at 4 hour intervals. ANOVA indicated that B varied over time in both groups (F (6.46) = 10.14, p < 0.0001 for C and F (6.5) = 5.10, p = 0.0005 for FS). There was also time variation in plasma ANP levels in both groups (F (6.54) = 3.78, p = 0.003 for C and F (6.48) = 2.73, p = 0.02 for FS group). Plasma B presented circadian variations from 78 +/- 17 nmol/l (mean +/- SEM) at 0800 h to 339 +/- 79 nmol/l at 2000 h. The day peak plasma ANP level (pmol/l) was also attained at 2000 h (68 +/- 19). This value was higher than all others measured throughout the day. The restricted feeding regimen resulted in a 12 hour shift of peak B values (395 +/- 39 vs 125 +/- 24). The FS rats presented the highest ANP level at 0800 h. The present study indicates similar circadian variations of plasma ANP and B in rats on an ad lib or restricted feeding regimen. ANP and B secretion may occur in anticipation of the feeding period or day activity.

Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes.

In the present study, the antioxidant effects of estradiol (E2) and 2-hydroxyestradiol (2-OHE2) on microsomal lipid peroxidation induced by Fe3+/ADP/NADPH and Fe2+/ascorbate are described. The extent of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS) detection, low-level chemiluminescence, and oxygen consumption. 2-OHE2 had a potent antioxidant activity, which in all cases was higher than that of E2. In the Fe2+/ascorbate model, 2-OHE2 showed a similar pattern of inhibition, irrespective of the presence of NADPH or the functionality of microsomes. However, E2 produced only a slight inhibition when either denatured microsomes or native microsomes without NADPH were used, whereas its protective effect increased considerably when microsomal E2 metabolism was favored. During enzymic Fe3+/ADP/NADPH-induced lipid peroxidation, both E2 and 2-OHE2 were found to provide good protection. Results underline the importance of the chemical structure of these compounds and the role of estradiol metabolism in its antioxidant effects.

Protective effect of estrogens and catecholestrogens against peroxidative membrane damage in vitro.

The antioxidant effects of natural estrogens (estrone, E1; 17 beta-estradiol), synthetic estrogens (17 alpha-ethynylestradiol, EE2; mestranol, MES; diethylstilbestrol, DES) and catecholestrogens (2-hydroxyestradiol; 4-hydroxyestradiol, 4-OHE2) on lipid peroxidation induced by different means in rat liver microsomes were investigated. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances. Prooxidants included Fe3+/ADP/reduced NADPH, Fe2+/ascorbate, tert-butyl hydroperoxide (t-BOOH) and 2,2'-azobis(2-amidinopropane) (AAPH). Estrogens and catecholestrogens decreased lipid peroxidation in all four systems tested. In the iron/ascorbate model it was shown that (i) 4-OHE2 and DES had analogous patterns of inhibition, irrespective of the presence of NADPH or the functional integrity of the microsomes, and (ii) the antioxidant activities of E1, EE2 and MES were dependent on the assay conditions with the activity being markedly higher when estrogen metabolism was favored. When peroxidation was initiated by the peroxyl radical generator AAPH, the inhibitory effects observed were least pronounced. Our data also showed that, in each of the systems, all inhibitors displayed the same order of inhibitory potency with DES and catecholestrogens being the most potent antioxidants under all experimental conditions used. The present results confirm earlier findings and point toward a link between estrogen metabolism and estrogen antioxidant activity. The data also indicate that estrogens and catecholestrogens interact with the peroxidative process at different levels with their interactions with iron or the metal-derived species being the most important modes of inhibition.

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis.

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

Atrial natriuretic peptide and feeding activity patterns in rats.

This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways.

[Urinary lithiasis]. / A litiase urinária.

The introduction of extracorporeal shock wave lithotripsy (ESWL) and the development of "minimally invasive" endourological procedures have completely changed the management of urinary calculi. Nevertheless, some aspects in this field still remain controversial. Conservative management is the first option, when the stone can pass spontaneously. The majority of the patients can be successfully treated with ESWL without anaesthesia and in an ambulatory setting or with a 24 H admission. ESWL failures (1 to 2%) and some difficult calculi (cystine calculi, staghorn calculus, stones of great volume and some ureteral stones) can benefit with endourological or percutaneous procedures alone or in association with ESWL. The classical indication for open surgery has changed significantly and surgery is now considered only in some difficult cases and with the failure of minimally invasive procedures. Uric acid calculi, that usually respond to medical treatment, must be treated with alkalinization therapy as the first option.

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats.

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-ß superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin ßA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.