Combined low-carbohydrate diet and long-term exercise in hypoxia in type 2 diabetes: A randomized controlled trial protocol to assess glycemic control, cardiovascular risk factors and body composition.

Background: Cardiovascular disease is the leading cause of mortality associated with diabetes, which is characterized by chronic hyperglycemia. Low-carbohydrate diet has gained popularity as an intervention in patients with type 2 diabetes mellitus, acting to improve glycemic profile and serum lipids. In its turn, exercise in hypoxia induces specific adaptations, mostly modulated via hypoxia-induced transcription factor signaling cascade, which increases with exposure to altitude, and promotes angiogenesis, glycogen supply, glucose tolerance, and raises GLUT-4 expression. Aim: Given that hyperglycemia decreases HIF-1α and it is better controlled when following a low-carbohydrate diet, this study aims to examine the hypothesis that a combination of both low-carbohydrate diet and chronic exercise in hypoxia in type 2 diabetes mellitus is associated with improved glycemic control and cardiovascular parameters, whose protocol is described. Methods: Patients with type 2 diabetes mellitus (n = 48) will be recruited and randomized into one of the three groups: (a) Control group: Control diet (low-fat and moderate-carbohydrate diet) + exercise in normoxia; (2) exercise in hypoxia group: Control diet + exercise in hypoxia; (3) intervention group: Low-carbohydrate diet (low-carbohydrate and high-fat diet) + exercise in hypoxia. Before and after 8 weeks of interventions, cardiopulmonary tests (Bruce protocol), body composition and blood pressure will be evaluated. Blood samples will be collected to measure hypoxia-induced transcription factor, C-reactive protein, glycemic and lipid profiles. Summary: This will be the first trial to examine the isolated and combined effect of chronic exercise in hypoxia and low-carbohydrate diet in type 2 diabetes mellitus. This trial will help to fill a significant research gap, guide future research and contribute to the combined nutrition and exercise approach to type 2 diabetes mellitus.

Sulfated Oligomers of Tyrosol: Toward a New Class of Bioinspired Nonsaccharidic Anticoagulants.

Sulfated phenolic polymers have extensively been investigated as anticoagulant agents in view of their higher bioavailability and resistance to degradation compared to heparins, allowing for increased half-lives. In this frame, we report herein the preparation of sulfated derivatives of tyrosol, one of the most representative phenolic constituents of extra virgin olive oil, by different approaches. Mild sulfation of OligoTyr, a mixture of tyrosol oligomers, that has been reported to possess antioxidant properties and osteogenic activity, afforded OligoTyrS I in good yields. Elemental analysis, NMR, and MALDI-MS investigation provided evidence for an almost complete sulfation at the OH on the phenylethyl chain, leaving the phenolic OH free. Peroxidase/H2O2 oxidation of tyrosol sulfated at the alcoholic group (TyrS) also provided sulfated tyrosol oligomers (OligoTyrS II) that showed on structural analysis highly varied structural features arising likely from the addition of oxygen, derived from water or hydrogen peroxide, to the intermediate quinone methides and substantial involvement of the phenolic OH group in the oligomerization. In line with these characteristics, OligoTyrS I proved to be more active than OligoTyrS II as antioxidant in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays and as anticoagulant in the classical clotting times, mainly in prolonging the activated partial thromboplastin time (APTT). After intraperitoneal administration in mice, OligoTyrS I was also able to significantly decrease the weight of an induced thrombus. Data from chromogenic coagulation assays showed that the anticoagulant effect of OligoTyrS I was not dependent on antithrombin or factor Xa and thrombin direct inhibition. These results clearly highlight how some structural facets of even closely related phenol polymers may be critical in dictating the anticoagulant activity, providing the key for the rationale design of active synthetic nonsaccharidic anticoagulant agents alternative to heparin.

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0-700 µM). Colostrum co-treated with DEX was executed at 0.1-5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization.

The search for novel anticancer small molecules and strategies remains a challenge. Our previous studies have identified TXA1 (1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H- thioxanthen-9-one) as a hit compound, with in vitro antitumor potential by modulating autophagy and apoptosis in human tumor cell lines. In the present study, the mechanism of action and antitumor potential of the soluble salt of this molecule (TXA1.HCl) was further investigated using in vitro and mouse xenograft tumor models of NSCLC. Our results showed that TXA1.HCl affected steroid biosynthesis, increased RagD expression, and caused abnormal cellular cholesterol localization. In addition, TXA1.HCl treatment presented no toxicity to nude mice and significantly reduced the growth of human NSCLC cells xenografts in mice. Overall, this work provides new insights into the mechanism of action of TXA1, which may be relevant for the development of anticancer therapeutic strategies, which target cholesterol transport.

Correction: Kindlovits et al. Eight Weeks of Intermittent Exercise in Hypoxia, with or without a Low-Carbohydrate Diet, Improves Bone Mass and Functional and Physiological Capacity in Older Adults with Type 2 Diabetes. Nutrients 2024, 16, 1624.

In the original publication [...].

Eight Weeks of Intermittent Exercise in Hypoxia, with or without a Low-Carbohydrate Diet, Improves Bone Mass and Functional and Physiological Capacity in Older Adults with Type 2 Diabetes.

In an increasingly aging and overweight population, osteoporosis and type 2 diabetes (T2DM) are major public health concerns. T2DM patients experience prejudicial effects on their bone health, affecting their physical capacity. Exercise in hypoxia (EH) and a low-carbohydrate diet (LCD) have been suggested for therapeutic benefits in T2DM, improving bone mineral content (BMC) and glycemic control. This study investigated the effects of EH combined with an LCD on body composition and functional and physiologic capacity in T2DM patients. Older T2DM patients (n = 42) were randomly assigned to the following groups: (1) control group: control diet + exercise in normoxia; (2) EH group: control diet + EH; (3) intervention group: LCD + EH. Cardiopulmonary tests (BRUCE protocol), body composition (DEXA), and functional capacity (6MWT, handgrip strength) were evaluated. Body mass index (kg/m2) and body fat (%) decreased in all groups (p < 0.001). BMC (kg) increased in all groups (p < 0.001) and was significantly higher in the EH and EH + LCD groups (p < 0.001). VO2peak improved in all groups (p < 0.001), but more so in the hypoxia groups (p = 0.019). Functional capacity was increased in all groups (p < 0.001), but more so in the EH group in 6MWT (p = 0.030). EH with and without an LCD is a therapeutic strategy for improving bone mass in T2DM, which is associated with cardiorespiratory and functional improvements.

Neuromuscular function, hormonal and redox status and muscle damage of professional soccer players after a high-level competitive match.

The main aim was to analyse the impact of an official match on hormonal and redox status, muscle damage and inflammation and neuromuscular function. Seven high-level male soccer players from the same team performed an official match and data were collected 72 h before, 24, 48 and 72 h post-match. Plasma testosterone/cortisol ratio (T/C), creatine kinase (CK), superoxide dismutase (SOD), glutathione peroxidase (GPX) and reductase (GR) activities, myoglobin (Mb), C-reactive protein (CRP), uric acid (UA), protein sulfhydryls (-SH), malondialdehyde (MDA) concentrations and total antioxidant status (TAS) were measured. Sprint, jump and change of direction performance, and maximal isokinetic knee extension and flexion were obtained as neuromuscular functional parameters. Cortisol increased and T/C decreased until 48 h recovery (P < 0.05). Mb, CRP and -SH (P < 0.05) increased at 24 h and CK, TAS, SOD and MDA (P < 0.05) increased up to 48 h recovery. GR increased and GPX decreased at 24 h recovery (P < 0.05). Jump performance decreased 24 h post-match (P < 0.05), but no significant alterations in sprint, change of direction and muscle strength were observed. In conclusion, an official match resulted in changes in plasma biomarkers until 48 h of recovery period, without major impact on performance.

The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment.

Tumor cells are highly resistant to oxidative stress resulting from the imbalance between high reactive oxygen species (ROS) production and insufficient antioxidant defenses. However, when intracellular levels of ROS rise beyond a certain threshold, largely above cancer cells' capacity to reduce it, they may ultimately lead to apoptosis or necrosis. This is, in fact, one of the molecular mechanisms of anticancer drugs, as most chemotherapeutic treatments alter redox homeostasis by further elevation of intracellular ROS levels or inhibition of antioxidant pathways. In traditional chemotherapy, it is widely accepted that most therapeutic effects are due to ROS-mediated cell damage, but in targeted therapies, ROS-mediated effects are mostly unknown and data are still emerging. The increasing effectiveness of anticancer treatments has raised new challenges, especially in the field of reproduction. With cancer patients' life expectancy increasing, many aiming to become parents will be confronted with the adverse effects of treatments. Consequently, concerns about the impact of anticancer therapies on reproductive capacity are of particular interest. In this review, we begin with a short introduction on anticancer therapies, then address ROS physiological/pathophysiological roles in both male and female reproductive systems, and finish with ROS-mediated adverse effects of anticancer treatments in reproduction.

Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model.

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 µg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 µg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.

Pd2Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice.

Pd2Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd2Spm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd2Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd2Spm was observed in MDA-MB-231 cells (IC50 values of 7.3-8.3 µM), with at least 10-fold lower activity in MCF-12A cells (IC50 values of 89.5-228.9 µM). Pd2Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd2Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd2Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd2Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia.

Associations between nutrition, energy expenditure and energy availability with bone mass acquisition in dance students: a 3-year longitudinal study.

Three years of study showed that female and male vocational dancers displayed lower bone mass compared to controls, at forearm, lumbar spine and femoral neck. Energy intake was found to positively predict bone mass accruals only in female dancers at femoral neck. Vocational dancers can be a risk population to develop osteoporosis. PURPOSE: To determine whether risk factors normally associated with low bone mass in athletic populations (i.e. nutrition intake, energy expenditure and energy availability) are significant predictors of bone mass changes in vocational dance students. METHODS: The total of 101 vocational dancers (63 females, 12.8 ± 2.2 years; 38 males, 12.7 ± 2.2 years) and 115 age-matched controls (68 females, 13.0 ± 2.1 years; 47 males, 13.0 ± 1.8 years) were monitored for 3 consecutive years. Bone mass parameters were measured annually at impact sites (femoral neck, FN; lumber spine, LS) and non-impact site (forearm) using DXA. Nutrition (3-day record), energy expenditure (accelerometer), energy availability and IGF-1 serum concentration (immunoradiometric assays) were also assessed. RESULTS: Female and male vocational dancers had consistently reduced bone mass at all anatomical sites (p < 0.001) than controls. IGF-1 did not differ between male vocational dancers and controls, but female dancers showed it higher than controls. At baseline, calcium intake was significantly greater in female vocational dancers than controls (p < 0.05). Male vocational dancers' fat and carbohydrate intakes were significantly lower than matched controls (p < 0.001 and p < 0.05, respectively). Energy availability of both female and male vocational dancers was within the normal range. A significant group effect was found at the FN regarding energy intake (p < 0.05) in female dancers. No significant predictors were found to explain bone mass differences in males. CONCLUSION: Our 3-year study revealed that both female and male vocational dancers displayed lower bone mass compared to controls, at both impact and non-impact sites. The aetiology of these findings may be grounded on factors different than those usually considered in athletic populations.

Bovine Colostrum Supplementation Improves Bone Metabolism in an Osteoporosis-Induced Animal Model.

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.

Impact of Loughborough Intermittent Shuttle Test versus soccer match on physiological, biochemical and neuromuscular parameters.

The aim of the present study was to analyze the impact of Loughborough Intermittent Shuttle Test (LIST) versus soccer match on heart rate (HR), muscle damage, redox status, blood leukocytes and neuromuscular function throughout 72 h recovery. Sixteen male soccer players (21.3 +/- 1.1 years; 175.0 +/- 6.0 cm; 70.7 +/- 6.3 kg) completed LIST and performed a soccer match separated by 2 weeks and data were collected before, 30 min, 24, 48 and 72 h after LIST and match. HR, plasma creatine kinase (CK) activity, myoglobin (Mb), uric acid (UA), protein sulfhydryls (-SH), malondialdehyde (MDA) contents, total antioxidant status (TAS), blood leukocyte counts, delayed onset muscle soreness, 20 m sprint and jump performances, and maximal isokinetic knee extension and flexion were analyzed. HR after LIST was significantly lower than after the match. Post-match TAS was lower and UA was higher than after LIST. Thirty minutes and 24 h after soccer MDA was higher and -SH was lower than after LIST (P < 0.05). LIST and soccer match induced elevation in total leukocytes and a reduction in lymphocytes at 30 min. This reduction in blood lymphocytes 30 min after match was lower than after LIST. In conclusion, the impact of both exercises did not differ regarding the observed muscle damage markers and some neuromuscular parameters, although soccer requires higher cardiac demand and induced higher changes on redox status, adenine nucleotide metabolism and on lymphocyte counts than LIST, which should be taken into account when using LIST to simulate a match to study these type of physiological and biochemical-related endpoints.

Endocrine parameters in association with bone mineral accrual in young female vocational ballet dancers.

Less is known on bone mass gains in dancers involved in vocational dance training. The present study found that, as young vocational dancers progress on their professional training, their bone health remains consistently lower compared to non-exercising controls. Endocrine mechanisms do not seem to explain these findings. PURPOSE: Little is known on bone mass development in dancers involved in vocational training. The aim of the present study was to model bone mineral content (BMC) accruals and to determine whether circulating levels of oestrogens, growth hormone (GH), and insulin-like growth factor I (IGF-1) explain differences in bone mass gains between vocational dance students and matched controls. METHODS: The total of 67 vocational female dancers (VFDs) and 68 aged-matched controls (12.1 ± 1.9 years and 12.7 ± 2.0 years at baseline, respectively) were followed for two consecutive years (34 VFD and 31 controls remained in the study for the full duration). BMC was evaluated annually at impact [femoral neck (FN); lumbar spine (LS)] and non-impact sites (forearm) using DXA. Anthropometry, age at menarche (questionnaire), and hormone serum concentrations (immunoradiometric assays) were also assessed for the same period. RESULTS: VFD demonstrated consistently reduced body weight (p < 0.001) and BMC at all three anatomical sites (p < 0.001) compared to controls throughout the study period. Menarche, body weight, GH, and IGF-1 were significantly associated with bone mass changes over time (p < 0.05) but did not explain group differences in BMC gains at impact sites (p > 0.05). However, body weight did explain the differences between groups in terms of BMC gains at the forearm (non-impact site). CONCLUSION: Two consecutive years of vocational dance training revealed that young female dancers demonstrate consistently lower bone mass compared to controls at both impact and non-impact sites. The studied endocrine parameters do not seem to explain group differences in terms of bone mass gains at impact sites.

Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle.

In the present study, the effect of vitamin E (alpha-tocopherol) on mice skeletal muscle mitochondrial dysfunction and oxidative damage induced by an in vivo acute and severe hypobaric hypoxic insult (48 h at a barometric pressure equivalent to 8500 m) has been investigated. Male mice (n=24) were randomly divided into the following four groups (n=6): control (C), hypoxia (H), vitamin E (VE; 60 mg/kg of body weight intraperitoneally, three times/week for 3 weeks) and hypoxia+VE (HVE). A significant increase in mitochondrial protein CGs (carbonyl groups) was found in the H group compared with the C group. Confirming previous observations from our group, hypoxia induced mitochondrial dysfunction, as identified by altered respiratory parameters. Hypoxia exposure increased Bax content and decreased the Bcl-2/Bax ratio, whereas Bcl-2 remained unchanged. Inner and outer mitochondrial membrane integrity were significantly affected by hypoxia exposure; however, vitamin E treatment attenuated the effect of hypoxia on mitochondrial oxidative phosphorylation and on the levels of CGs. Vitamin E supplementation also prevented the Bax and Bcl-2/Bax ratio impairments caused by hypoxia, as well as the decrease in inner and outer mitochondrial membrane integrity. In conclusion, the results suggest that vitamin E prevents the loss of mitochondrial integrity and function, as well as the increase in Bax content, which suggests that mitochondria are involved in increased cell death induced by severe hypobaric hypoxia in mice skeletal muscle.

Indoor climbing elicits plasma oxidative stress.

PURPOSE: Indoor climbing is a worldwide sport with particular physiological and physical demands. The purpose of this study was to analyze the effect of sustained indoor climbing until exhaustion on plasma oxidative stress markers, and to relate it to whole-body dynamic exercise performed at the same percentage of maximal oxygen uptake (VO2max). METHODS: Fourteen male indoor climbers continuously climbed a competition-style route until exhaustion. Oxygen consumption and heart rate were continuously monitored during the climbing exercise. One week later, subjects performed a treadmill running protocol with the same duration and percentage of VO2max as that of climbing exercise. Blood samples were collected at rest, immediately after, and 1 h after both exercise protocols to analyze plasma levels of reduced (GSH) and oxidized (GSSG) glutathione, malondialdehyde (MDA), protein sulfhydryl (-SH) and carbonyl (CG) groups, total antioxidant status (TAS) and uric acid (UA), and total blood leukocytes, neutrophil, and lymphocyte counts. RESULTS: Compared with running, climbing significantly increased the %GSSG, MDA, CG, TAS, and UA and decreased the GSH and -SH content. Blood counts of total leukocytes and neutrophils increased immediately after and 1 h after both running and climbing (P<0.05), although counts were higher in climbing than in running (P<0.05). Lymphocytes significantly increased from baseline to 0 h, although they decreased below baseline 1 h after climbing (P<0.05). CONCLUSION: Data demonstrate that indoor climbing induces plasma oxidative stress. Moreover, results suggest that an ischemia-reperfusion prooxidant-based mechanism related to climbers' sustained and intermittent isometric forearm muscle contractions might have significantly contributed to observed plasma oxidative stress.

Effect of off-road competitive motocross race on plasma oxidative stress and damage markers.

AIM: To analyse the effect of an off-road motocross heat on plasma levels of oxidative stress and damage, blood leucocyte counts and urine catecholamine concentration. METHODS: Plasma contents of total, reduced and oxidised (GSSG) glutathione, %GSSG, malondialdehyde (MDA), protein carbonyl and sulphydryl groups, total antioxidant status (TAS), uric acid, and blood neutrophil and lymphocyte counts were evaluated in 10 male top-level riders before, immediately after (0 h) and 1 h after a simulated competitive motocross race. 24-h urine adrenaline, noradrenaline and dopamine concentrations were also measured. RESULTS: The motocross heat resulted in an increase in plasma oxidative stress and damage (p<0.05). This was shown by a significant increase in %GSSG, TAS, MDA and carbonyls, and by a decrease in sulphydryl groups after the race. There was a significant increase in both plasma uric acid and urine catecholamine concentration after the race (p<0.05). Blood neutrophil counts increased at 0 and 1 h after exercise (p<0.05). Lymphocyte count increased from baseline to 0 h, although it decreased from baseline and 0 to 1 h after exercise (p<0.05). CONCLUSION: The data reinforce the marked metabolic and hormonal demands imposed by motocross, resulting in a condition of enhanced plasma oxidative stress and damage.

Bone mass of female dance students prior to professional dance training: A cross-sectional study.

BACKGROUND: Professional dancers are at risk of developing low bone mineral density (BMD). However, whether low BMD phenotypes already exist in pre-vocational dance students is relatively unknown. AIM: To cross-sectionally assess bone mass parameters in female dance students selected for professional dance training (first year vocational dance students) in relation to aged- and sex-matched controls. METHODS: 34 female selected for professional dance training (10.9yrs ±0.7) and 30 controls (11.1yrs ±0.5) were examined. Anthropometry, pubertal development (Tanner) and dietary data (3-day food diary) were recorded. BMD and bone mineral content (BMC) at forearm, femur neck (FN) and lumbar spine (LS) were assessed using Dual-Energy X-Ray Absorptiometry. Volumetric densities were estimated by calculating bone mineral apparent density (BMAD). RESULTS: Dancers were mainly at Tanner pubertal stage I (vs. stage IV in controls, p<0.001), and demonstrated significantly lower body weight (p<0.001) and height (p<0.01) than controls. Calorie intake was not different between groups, but calcium intake was significantly greater in dancers (p<0.05). Dancers revealed a significantly lower BMC and BMD values at all anatomical sites (p<0.001), and significantly lower BMAD values at the LS and FN (p<0.001). When adjusted for covariates (body weight, height, pubertal development and calcium intake), dance students continued to display a significantly lower BMD and BMAD at the FN (p<0.05; p<0.001) at the forearm (p<0.01). CONCLUSION: Before undergoing professional dance training, first year vocational dance students demonstrated inferior bone mass compared to controls. Longitudinal models are required to assess how bone health-status changes with time throughout professional training.

Endurance training limits the functional alterations of rat heart mitochondria submitted to in vitro anoxia-reoxygenation.

BACKGROUND: Studies analysing the effect of endurance training on heart mitochondrial function submitted to in vitro anoxia-reoxygenation (A-R) are missing. The present study aimed to investigate the effect of moderate endurance treadmill training (14 weeks) against rat heart mitochondrial dysfunction induced by in vitro A-R. METHODS: Respiratory parameters (state 3, state 4, ADP/O and respiratory control ratio-RCR) and oxidative damage markers (carbonyl groups and malondialdehyde) were determined in isolated mitochondria before and after 1 min anoxia followed by 4 min reoxygenation. Levels of heat shock protein 60 kDa (HSP60) and 70 kDa (HSP70) were measured before A-R in mitochondria and whole muscle homogenate, respectively. RESULTS: A-R significantly impaired the rate of state 3 and state 4 respiration, as well as the RCR and ADP/O in the sedentary group. However, mitochondrial state 3 respiration was significantly higher in trained than in the sedentary group both before and after A-R. The impairments in RCR, ADP/O ratio and state 4 induced by A-R in sedentary group were significantly attenuated in endurance-trained group. The inhibition of state 4 induced by GDP was significantly higher in trained than in sedentary group. Oxidative modifications of mitochondrial proteins and phospholipids were found in sedentary group after A-R, although limited in trained group. Increased levels of mitochondrial HSP60 and tissue HSP70 accompanied the lower decrease in the respiratory function after A-R observed in trained group. CONCLUSION: We therefore concluded that endurance training limited the impairments on rat heart mitochondria caused by the oxidant insult inflicted by in vitro A-R.

Acute and severe hypobaric hypoxia increases oxidative stress and impairs mitochondrial function in mouse skeletal muscle.

Severe high-altitude hypoxia exposure is considered a triggering stimulus for redox disturbances at distinct levels of cellular organization. The effect of an in vivo acute and severe hypobaric hypoxic insult (48 h at a pressure equivalent to 8,500 m) on oxidative damage and respiratory function was analyzed in skeletal muscle mitochondria isolated from vitamin E-supplemented (60 mg/kg ip, 3 times/wk for 3 wk) and nonsupplemented mice. Forty male mice were randomly divided into four groups: control + placebo, hypoxia + placebo (H + P), control + vitamin E, and hypoxia + vitamin E. Significant increases in mitochondrial heat shock protein 60 expression and protein carbonyls group levels and decreases in aconitase activity and sulfhydryl group content were found in the H + P group when compared with the control + placebo group. Mitochondrial respiration was significantly impaired in animals from the H + P group, as demonstrated by decreased state 3 respiratory control ratio and ADP-to-oxygen ratio and by increased state 4 with both complex I- and II-linked substrates. Using malate + pyruvate as substrates, hypoxia decreased the respiratory rate in the presence of carbonyl cyanide m-chlorophenylhydrazone and also stimulated oligomycin-inhibited respiration. However, vitamin E treatment attenuated the effect of hypoxia on the mitochondrial levels of heat shock protein 60 and markers of oxidative stress. Vitamin E was also able to prevent most mitochondrial alterations induced by hypobaric hypoxia. In conclusion, hypobaric hypoxia increases mitochondrial oxidative stress while decreasing mitochondrial capacity for oxidative phosphorylation. Vitamin E was an effective preventive agent, which further supports the oxidative character of mitochondrial dysfunction induced by hypoxia.