L-carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial.

Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6-18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89-60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99-134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97-16.03; p = 0.01) and 6MWT distance (95% CI 5.88-75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.

Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress.

Fatigue is a pervasive public health and safety issue. Common fatigue countermeasures include caffeine or other chemical stimulants. These can be effective in limited circumstances but other non-pharmacological fatigue countermeasures such as non-invasive electrical neuromodulation have shown promise. It is reasonable to suspect that other types of non-invasive neuromodulation may be similarly effective or perhaps even superior. The objective of this research was to evaluate the efficacy of cervical transcutaneous vagal nerve stimulation (ctVNS) to mitigate the negative effects of fatigue on cognition and mood. Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham for the duration of the study. CtVNS could be a powerful fatigue countermeasure tool that is easy to administer, long-lasting, and has fewer side-effects compared to common pharmacological interventions.

Anti-fatigue property of the oyster polypeptide fraction and its effect on gut microbiota in mice.

We aimed to evaluate the anti-fatigue effects of the oyster polypeptide (OP) fraction and its regulatory effect on the gut microbiota in mice. Our exhaustive swimming experiment showed that the swimming time of the low-, middle- and high-dose groups of the OP fraction was increased by 1.82, 2.18 and 2.44 times compared with the control group, respectively. Besides, the liver glycogen levels of the three groups were increased by 19.3%, 42.02% and 65.07%, while the lactate levels were decreased by 18.85%, 21.18% and 28.74%, respectively. Moreover, administration of the OP fraction upregulated the expressions of PEPCK and AMPK, but downregulated the TNF-α expression. Correlation analysis between the gut microbiota and fatigue-related biochemical indicators showed that Faecalibacterium, Desulfovibri and Intestinibacter were negatively correlated with the swimming time, blood lactate, blood urea nitrogen, liver glycogen and muscle glycogen, while Yaniella and Romboutsia were positively correlated. Therefore, the OP fraction had anti-fatigue effects, and could regulate the abundance of gut microbiota and maintain its balance.

Fatigue in multiple sclerosis: The role of thalamus.

Fatigue is very common in multiple sclerosis (MS) and is often considered as its most disabling symptom. Over the last 20 years, an increasing number of studies have evaluated the pathogenetic bases of MS-related fatigue. Converging evidence from neurophysiology and neuroimaging research suggests that a dysfunction in a cortico-subcortical pathway, centered on thalamus, is involved in the pathogenesis of fatigue. However, type and significance of such dysfunction remain unknown, and some studies reported an increase in the activity and connectivity within the thalamic network, whereas others suggested its reduction. Hereby, we review the results of neuroimaging studies supporting the different hypotheses about the role of thalamic network in the pathophysiology of MS-related fatigue and discuss limitations and shortcomings of available data, highlighting the key challenges in the field and the directions for future research.

Post-stroke fatigue as an indicator of underlying bioenergetics alterations.

Approximately half of stroke survivors suffer from clinically significant fatigue, contributing to poor quality of life, depression, dependency, and increased mortality. The etiology of post-stroke fatigue is not well understood and treatment is limited. This study tested the hypothesis that systemic aerobic energy metabolism, as reflected by platelet oxygen consumption, is negatively associated with fatigue and systemic inflammation is positively associated with fatigue in chronic ischemic stroke survivors. Data on self-reported level of fatigue, platelet oxygen consumption rates (OCR) and plasma inflammatory markers were analyzed from 20 ischemic stroke survivors. DNA copy number for two mitochondrial genes was measured as a marker of platelet mitochondrial content. Basal and protonophore-stimulated maximal platelet OCR showed a biphasic relationship to fatigue. Platelet OCR was negatively associated with low to moderate fatigue but was positively associated with moderate to high fatigue. DNA copy number was not associated with either fatigue or platelet OCR. Fatigue was negatively associated with C-reactive protein but not with other inflammatory markers. Post-stroke fatigue may be indicative of a systemic cellular energy dysfunction that is reflected in platelet energy metabolism. The biphasic relationship of fatigue to platelet OCR may indicate an ineffective bioenergetic compensatory response that has been observed in other pathological states.

Inverse relationship between reduced fatigue and severity of anemia in oncology patients treated with integrative medicine: understanding the paradox.

OBJECTIVE: To assess the impact of integrative medicine (IM) on cancer-related fatigue in patients undergoing chemotherapy for early and advanced breast and gynecological (ovarian, endometrial, and cervical) cancer. METHODS: Patients reporting significant levels of fatigue (on the Edmonton Symptom Assessment Scale (ESAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), or Measure Yourself Concerns and Wellbeing questionnaire (MYCAW)) were offered complementary and integrative medicine (CIM) treatments in addition to standard supportive care. Patients who did not undergo IM treatments were designated as controls. Attending at least five CIM treatments less than 30 days between each session was considered as high adherence to integrative care (AIC). RESULTS: Of 258 eligible patients reporting significant fatigue, follow-up assessment at 6 and 12 weeks was considered optimal for 120 patients in the intervention group and for 64 controls; 88 of treated patients found to be adherent to the IM intervention. At 12 weeks, ESAS (P < 0.001) and EORTC (p = 0.001) scores for fatigue improved more significantly in treated patients, with a higher percent with optimal relative dose intensity in the AIC subgroup, both at 6 weeks (P = 0.002) and at 12 weeks (P < 0.001). IM treatment was paradoxically associated with a greater decrease in hemoglobin levels at 12 weeks (P = 0.016), more so in the AIC subgroup (P = 0.024). CONCLUSION: Integrative medicine program may alleviate cancer-related fatigue in patients with breast and gynecological cancer undergoing chemotherapy.

Antifatigue Functions and Mechanisms of Edible and Medicinal Mushrooms.

Fatigue is the symptom of tiredness caused by physical and/or psychological stresses. As fatigue is becoming a serious problem in the modern society affecting human health, work efficiency, and quality of life, effective antifatigue remedies other than pharmacological drugs or therapies are highly needed. Mushrooms have been widely used as health foods, because of their various bioactive constituents such as polysaccharides, proteins, vitamins, minerals, and dietary fiber. This paper reviews the major findings from previous studies on the antifatigue effects, the active components of mushrooms, and the possible mechanisms. Many studies have demonstrated the antifatigue effects of edible and medicinal mushrooms. These mushrooms probably mitigate human fatigue through effects on the functional systems, including the muscular, cardiovascular, hormone, and immune system. The bioactive constituents that contribute to the antifatigue effects of mushrooms may include polysaccharides, peptides, nucleosides, phenolic compounds, and triterpenoids. Further research is still needed to identify the active ingredients and to investigate their mechanism of action on the antifatigue effects. Since most previous studies have been carried out in animal models, more human trials should be performed to verify the antifatigue function of edible and medicinal mushrooms.

Mindfulness-based cognitive therapy for severely fatigued multiple sclerosis patients: A waiting list controlled study.

BACKGROUND: Fatigue is the most common symptom in multiple sclerosis. Evidence-based treatment options are scarce. OBJECTIVE: To study the feasibility and potential effectiveness of mindfulness-based cognitive therapy in severely fatigued multiple sclerosis patients. METHODS: Non-randomized pilot study with a wai-ting list control period including 59 multiple sclerosis patients with severe fatigue. PRIMARY OUTCOME MEASURE: fatigue severity subscale of the Checklist Individual Strength-20. Secondary measures: Hospital Anxiety and Depression Scale, Life Satisfaction Questionnaire, subscale sleep of the Symptom Checklist-90, Cognitive Failure Questionnaire, Fatigue Catastrophizing Scale, Coping Inventory of Stressful Situations, and Five Facet Mindfulness Questionnaire-Short Form. Measurements were taken before treatment (double baseline), after treatment, and at follow-up (3 months). RESULTS: Adherence rate was 71%. Eight out of 10 participants who completed the intervention were satisfied with the intervention. Significant time effects were found for 7 out of 11 outcome measures (p = 0.006 to < 0.001). The effect size was moderate for all outcome measures that were significant post-treatment and/or at follow-up (È ² = 0.10-0.17). Improvements were maintained at follow-up. Of the completers, 46% showed a clinically relevant change regarding fatigue. CONCLUSION: Mindfulness-based cognitive therapy is feasible in severely fatigued multiple sclerosis patients and has positive results in the reduction of severe fatigue and several psychological factors.

Antifatigue Effects of Antrodia cinnamomea Cultured Mycelium via Modulation of Oxidative Stress Signaling in a Mouse Model.

Antrodia cinnamomea, a folk medicinal mushroom, has numerous biological effects. In this study, we aim to assess whether the antifatigue effects of A. cinnamomea mycelia (AC) and its underlying mechanisms are related to oxidative stress signaling using behavioral mouse models and biochemical indices detection. Mice were orally treated with AC at doses of 0.1, 0.3, and 0.9 g/kg for three weeks. AC had no effect on the spontaneous activities of mice indicating its safety on central nervous system. Furthermore, results obtained from weight-loaded forced swimming test, rotary rod test, and exhausted running test confirmed that AC significantly enhanced exercise tolerance of mice. Biochemical indices levels showed that these effects were closely correlated with inhibiting the depletion of glycogen and adenosine triphosphate stores, regulating oxidative stress-related parameters (superoxide dismutase, glutathione peroxidase, reactive oxygen species, and malondialdehyde) in serum, skeletal muscle, and liver of mice. Moreover, the effects of AC may be related with its regulation on the activations of AMP-activated protein kinase, protein kinase B, and mammalian target of rapamycin in liver and skeletal muscle of mice. Altogether, our data suggest that the antifatigue properties of AC may be one such modulation mechanism via oxidative stress-related signaling in mice.

Involvement of hypothalamic nitric oxide signaling in the modulation of a rat's exercise capacity.

PURPOSE: The aim of this study was to explore the effect of nitric oxide (NO) in some regions of the hypothalamus on exercise capacity. MATERIALS AND METHODS: To assess the role of central NO in exercise capacity, L-arginine (L-Arg, a precursor of NO synthesis), NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), or placebo saline was injected into the lateral cerebral ventricle of rats once a day for 4 consecutive days. Thereafter, an one-time exhaustive treadmill exercise was performed, and the levels of nitrate/nitrite, as a marker of NO production, in blood plasma and hypothalamus were assayed. Neuronal nitric oxide synthase (nNOS)-expressing cells were immunohistochemically stained and analyzed in the paraventricular nucleus (PVN), the dorsomedial hypothalamus (DMH), and the ventromedial hypothalamus. Exercise time to exhaustion and total workload were determined. RESULTS: Compared with the rats in the saline group, the exercise time to exhaustion and total workload increased 50% in the L-Arg group and decreased 50% in the L-NAME group. The nitrate/nitrite level of hypothalamus in the L-Arg group increased 50% and decreased 29.4% in the L-NAME group. The number of nNOS-positive cells was significantly increased, 56.5%, in PVN and, 119%, in DMH, but not in ventromedial hypothalamus. No significant changes in nNOS-positive cells were found in L-NAME-treated rats. CONCLUSION: These results show that the modulation of hypothalamic NO signaling can affect the rat's running performance during a treadmill exercise and that enhanced NO signaling by induction of nNOS in PVN and DMH plays a role in improving exercise capacity after central administration of L-Arg. NO signaling in PVN and DMH may be a useful target for the pharmacological intervention of exercise performance or capacity.

Efficacy of Ginseng Supplements on Fatigue and Physical Performance: a Meta-analysis.

We conducted a meta-analysis to investigate the efficacy of ginseng supplements on fatigue reduction and physical performance enhancement as reported by randomized controlled trials (RCTs). RCTs that investigated the efficacy of ginseng supplements on fatigue reduction and physical performance enhancement compared with placebos were included. The main outcome measures were fatigue reduction and physical performance enhancement. Out of 155 articles meeting initial criteria, 12 RCTs involving 630 participants (311 participants in the intervention group and 319 participants in the placebo group) were included in the final analysis. In the fixed-effect meta-analysis of four RCTs, there was a statistically significant efficacy of ginseng supplements on fatigue reduction (standardized mean difference, SMD = 0.34; 95% confidence interval [CI] = 0.16 to 0.52). However, ginseng supplements were not associated with physical performance enhancement in the fixed-effect meta-analysis of eight RCTs (SMD = -0.01; 95% CI = -0.29 to 0.27). We found that there was insufficient clinical evidence to support the use of ginseng supplements on reducing fatigue and enhancing physical performance because only few RCTs with a small sample size have been published so far. Further lager RCTs are required to confirm the efficacy of ginseng supplements on fatigue reduction.

Ibuprofen ameliorates fatigue- and depressive-like behavior in tumor-bearing mice.

AIMS: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. MAIN METHODS: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. KEY FINDINGS: Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1ß and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. SIGNIFICANCE: Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF.

Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation.

PURPOSE: This guideline presents screening, assessment, and treatment approaches for the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment. METHODS: A systematic search of clinical practice guideline databases, guideline developer Web sites, and published health literature identified the pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for Survivorship. These three guidelines were appraised and selected for adaptation. RESULTS: It is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management. For those who report moderate to severe fatigue, comprehensive assessment should be conducted, and medical and treatable contributing factors should be addressed. In terms of treatment strategies, evidence indicates that physical activity interventions, psychosocial interventions, and mind-body interventions may reduce cancer-related fatigue in post-treatment patients. There is limited evidence for use of psychostimulants in the management of fatigue in patients who are disease free after active treatment. CONCLUSION: Fatigue is prevalent in cancer survivors and often causes significant disruption in functioning and quality of life. Regular screening, assessment, and education and appropriate treatment of fatigue are important in managing this distressing symptom. Given the multiple factors contributing to post-treatment fatigue, interventions should be tailored to each patient's specific needs. In particular, a number of nonpharmacologic treatment approaches have demonstrated efficacy in cancer survivors.

Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model.

This study investigated the antifatigue effects of rutin, a flavonoid extracted from the ethyl acetate extract of S. involucrata. Mice were subjected to a weight-loaded forced swim test (WFST) on alternate days for 3 wk. Rutin was administered orally to the mice for 7 days in dosages of 15, 30, and 60 mg/kg body weight, and several biomarkers of physical fatigue were evaluated: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, and the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). On Day 7, the rutin-treated mice had a 3-fold longer exhaustive swimming time than the control mice, as well as significantly reduced blood LA concentrations. The 15, 30, and 60 mg/kg body weight rutin-supplemented groups displayed 11.2%, 22.5%, and 37.7% reduced malondialdehyde (MDA) concentrations, respectively, in brain and muscle tissues compared with the control exercised group. Our results indicated that the administration of rutin protected the mice against the depletion of SOD and GPx activities significantly. Following 7 days of rutin treatment, we sacrificed the mice and analyzed their soleus muscle and brain for peroxisome proliferator-activated receptor-α coactivator (PGC-1α) and sirtuin 1 (SIRT1) mRNA expression. We observed that rutin treatment increased PGC-1α and SIRT1 mRNA and protein expression. The changes in these markers of mitochondrial biogenesis were associated with increased maximal endurance capacity. The application of 2D gel electrophoresis to analyze the rutin-responsive protein profiles in the WFST mouse brain further revealed the upregulation of the CB1 cannabinoid receptor-interacting protein 1, myelin basic protein, Rho GDP dissociation inhibitor (GDI) alpha, and TPI, indicating that rutin might inhibit anxiety through the upregulation of the expression of anxiety-associated proteins. Western blot analysis of MAPK expression further confirmed the antianxiety effects of rutin. Our study results thus indicate that rutin treatment ameliorates the various impairments associated with physical fatigue.

Evaluation of anti-fatigue activity of total saponins of Radix notoginseng.

BACKGROUND & OBJECTIVES: Several biological activities of total saponins of Radix notoginseng (TSRN), a traditional Chinese medicine, have been reported. The present study was carried out to investigate anti-fatigue activity of TSRN in male Kunming mice. METHODS: Mice were divided into four groups. The first group designated as control group was administered with distilled water by gavage every day. The second, third and fourth groups designated as TSRN treatment groups were administered with TSRN of 20, 40 and 80 mg/kg body weight/day, respectively. The treatment continued for 28 days. Exhaustive swimming time, blood lactate and tissue glycogen contents of mice after swimming were determined. RESULTS: TSRN extended exhaustive swimming time of mice, effectively delayed the increase of lactate in the blood, as well as increased the tissue glycogen contents. INTERPRETATION & CONCLUSIONS: TSRN showed promising anti-fatigue activity in animal model. However, further study is needed to elucidate the mechanism of the effect of TSRN on fatigue.

Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation.

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n=10) and in healthy control subjects (n=67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.

Effect of bacoside extract from Bacopa monniera on physical fatigue induced by forced swimming.

The antifatigue effect of bacoside extract (BME) from Bacopa monniera (L.) Wettst. was investigated. Rats were subjected to weight-loaded forced swim test (WFST) every alternate day for 3 weeks. The BME at a dosage of 10 mg/kg body weight was administered orally to rats for 2 weeks in order to evaluate the following biomarkers of physical fatigue: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) and blood parameters, namely blood urea nitrogen (BUN) and creatine kinase (CK). The exhaustive swimming time was increased by 3-fold in the BME supplemented group compared with that of the control group on day 13. The BME treatment lowered malondialdehyde (MDA) levels in brain, liver and muscle tissues by 11.2%, 16.2% and 37.7%, respectively, compared with the control exercised group (p < 0.05). The BME also reduced the LA, serum BUN and CK activities significantly compared with that of the control. Administration of BME significantly protected the depletion of SOD and CAT activities. The HSP-70 expression studies by western blot also confirmed the antifatigue property of BME. The present study thus indicates that BME ameliorates the various impairments associated with physical fatigue.

Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study.

PURPOSE Effects of specific antineoplastic therapies on progression of cancer-associated wasting remain uncharacterized. We selected a targeted therapy, sorafenib, because of its reported association with weight loss. PATIENTS AND METHODS Patients with metastatic renal cell cancer (RCC) who were resistant to standard therapy (N = 80) received sorafenib 400 mg twice daily or placebo in a randomized, double-blinded clinical trial. Computed tomography image analysis, which has high precision and specificity for evaluation of specific muscles and adipose tissues, was used to define change in total skeletal muscle and adipose tissue. Results At inclusion, 51% of patients were overweight or obese (ie, body mass index [BMI] > 25 kg/m(2)). Only 5% were underweight. Advanced muscle wasting (ie, sarcopenia) was present in 72% of patients with BMI less than 25 and in 34% of those with a BMI greater than 25. Patients received placebo for an average of 6 months and received sorafenib for 1 year. Patients in the placebo group had stable body weight during 6 months (0.8 kg +/- 0.7 kg), with no significant alteration of muscle or fat. Patients who received sorafenib lost 2.1 kg +/- 0.6 kg (P < .01) in 6 months and lost 4.2 kg +/- 0.7 kg (P < .01) by 1 year. Sorafenib-treated patients lost skeletal muscle progressively at 6 months (decrease of 4.9%; P < .01) and 12 months (decrease of 8.0%; P < .01). CONCLUSION Sarcopenia is prevalent in patients with metastatic RCC and is an occult condition in patients with normal or high BMI. Muscle loss is specifically exacerbated by sorafenib, consistent with the evidence for a role of kinases in regulating muscle mass. Muscle loss is a sorafenib adverse effect that may relate to asthenia, fatigue, and physical disability.

Hypothalamic involvement assessed by T1 relaxation time in patients with relapsing-remitting multiple sclerosis.

Recent work in multiple sclerosis, focusing on neuropathological abnormalities, found a frequent and severe hypothalamic involvement. The possible clinical implications are disturbances in sleep and sexual activity, depression, memory impairment and fatigue. Despite this there are no magnetic resonance imaging studies focusing on in vivo hypothalamic pathology in multiple sclerosis. Our objective was to investigate magnetic resonance imaging-detectable abnormalities related to pathological changes in the hypothalamus of patients with multiple sclerosis, and to subsequently explore the relationship with fatigue. We used T1 relaxation time as a sensitive measure of pathology. Using region of interest analysis, median T1 values in the hypothalamus were measured in 44 relapsing-remitting multiple sclerosis patients and in 13 healthy controls. Fatigue was assessed using the Fatigue Severity Scale, and patients were divided in two subgroups, fatigued and non-fatigued, according to Fatigue Severity Scale scores. We found a significantly higher T1 relaxation time in the hypothalamus of multiple sclerosis patients compared with controls (p = 0.027). There was a significant correlation between T1 values and fatigue severity (rho 0.437, p = 0.008), and median T1 values were different among the study groups. Our results show that pathological involvement of the hypothalamus in relapsing-remitting multiple sclerosis is detectable using magnetic resonance imaging, and that the pathology measured by quantitative T1 might reflect fatigue.

[Protective effects of salidroside on oxidative damage in fatigue mice].

OBJECTIVE: To study the protective effects of salidroside on oxidative damage in fatigue mice. METHODS: Thirty-two male Kunming mice were randomly divided into four groups based on body weight: normal control group, salidroside group, training group and salidroside plus training group. The mice in the normal control group and the training group were given distilled water and mice in the salidroside group and the salidroside plus training group were given 180 mg/ (kg * d) salidroside for 15 days. At 30 min after the last administration, the mice in the training group and the salidroside plus training group were forced to swim for 120 min. Finally, all the mice were killed. The activities of lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-myocardial band isoenzyme (CK-MB) in plasma were determined by an auto-biochemistry analyzer. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malonaldehyde (MDA) in liver tissue were also detected. The changes of ultrastructures of the skeletal muscle and cardiac muscle were observed under an electron microscope. RESULTS: Compared with no swimming, long-time swimming could significantly increase the activities of LDH, CK and CK-MB in plasma (P < 0.05, P < 0.01), while salidroside could significantly decrease the activities of CK and CK-MB in plasma induced by long-time swimming (P < 0.05, P < 0.01). There existed interactions in LDH, CK and CK-MB activities between salidroside and long-time swimming (P < 0.05). Compared with no swimming, long-time swimming could significantly decrease the SOD and GSH-Px activities and increase the MDA content in liver tissue (P < 0.01). Salidroside could significantly increase the GSH-Px and SOD activities and decrease the MDA content in liver tissue (P < 0.05, P < 0.01). However, there were no interactions in GSH-Px activity and MDA content between salidroside and long-time swimming (P < 0.05). After long-time swimming, more ultrastructural lesions were found in the cardiac muscle and skeletal muscle in the training group than in the salidroside plus training group. CONCLUSION: Salidroside may play a role in protecting the mice from oxidative damage caused by long-time endurance training.