Differences in the Contractile Properties of the Biceps Femoris and Semitendinosus Muscles Throughout a Season in Professional Soccer Players.

The aim of this study was to monitor seasonal changes in the mechanical and neuromuscular characteristics of the knee flexor muscles with tensiomyography, the biceps femoris (BF) and semitendinosus (ST) muscles, of 27 soccer players. All male professional soccer players (age 25 ± 4 years) were measured at the beginning of the preseason (second week) and in the competitive season (10 weeks later). The variables contraction time (Tc) and muscle displacement (Dm) showed significant differences in some muscles, and in others they indicated a tendency to change. In general, the BF improved (more explosive and better muscle tone) and the ST worsened (slower and worse muscle tone) its values during the season. The findings of this study suggest that usual daily soccer training and weekly competition might produce antagonistic changes between the knee flexor muscles.

An Autologous Topical Serum Derived from Platelet-Rich Plasma Therapy for the Management of Sensitive Skin Alterations: A Case Series Report.

Background: Although the underlying pathophysiology of sensitive skin remains unknown, it presents clinical symptoms like erythema, burning and dryness associated with other inflammatory dermatoses such as dermatitis or rosacea. Objective: The aim of the present report was to provide preliminary data about the efficacy of Endoret-Serum (ES) as an autologous therapy for the topical management of sensitive skin alterations. Materials and Methods: Five patients underwent a daily topical ES treatment that was maintained for three months. Clinical assessment was carried out using validated dermatological surveys (DLQI, IGA, Likert, PGI-I). Additionally, skin hydration measurement and high-resolution topographic and reflectance confocal imaging analysis were carried out. Results: No adverse events were observed during the treatment. At the end of the follow-up period, surveys highlighted a significant therapeutic effect compared to baseline. Skin hydration was also improved, and topographic images showed a decrease in patient's underlying inflammatory and vascular condition. Conclusion: This preliminary report suggests that Endoret-Serum may be useful in the management of clinical symptoms derived from sensitive skin alterations.

Development of Seed-Oil Based Dried Sausages, Considering Physicochemical and Nutritional Quality and the Role of Food Neophobia.

A growing number of consumers now consider the consumption of processed meat products to be an essentially unhealthy habit. Hence, the reformulation of meat products is crucial. In this regard, the aim of this study is to reformulate "fuet", a traditional Spanish dried sausage, by replacing the pork fat with emulsified seed oils (50-50%, 25-75% and 0-100%). Four seed oils were evaluated, including commercial seeds (poppy and chia) and other seeds considered subproducts (melon and pumpkin). Physical parameters, nutritional quality and consumer evaluation of the reformulated dried sausages were analyzed. Additionally, we considered the effects of food neophobia on consumer evaluation. The resulting fuets had a higher concentration of linoleic and linolenic acids, which varied according to the oil used. In the sensory analysis, non-neophobic consumers showed higher preference for the reformulated fuets, while all consumers gave their highest ratings to the fuets produced with pumpkin seed oil.

Elaboration of Cookies Using Oils and Flours from Seeds and Nuts: Effects on Technological, Nutritional and Consumer Aspects.

The consumption of cookies is widely extended throughout the world, although their formulas contain ingredients such as saturated fats or refined flours that are considered harmful to health. In addition, cookies are generally made from wheat flour, and nowadays there is a growing concern about gluten intolerance, thus the demand for gluten-free products is increasing. In this regard, the aim of the present study is to reformulate traditional cookies by replacing wheat flour and butter by flours and oils from nuts and seeds. Within these seeds, poppy or chia are not commonly consumed ingredients as they can cause rejection by consumers. Thus, a study was performed to evaluate the neophobia level of consumers and the consumer acceptance for the inclusion of these novel ingredients in cookies. The results have been obtained by measuring physical parameters, proximate composition and consumer evaluation of five batches of cookies. By replacing butter and wheat flour with maize flour, almond, walnut, chia or poppy seed flours and oils, an increase of protein, fat and fiber has been observed as well as a decrease in carbohydrate content; thus, the resultant cookies would be a good source of vegetal protein as well as a source of oleic and linoleic acid with potential benefits on health. The cookies in general have similar physical properties and a positive consumer acceptance in texture, taste and external aspect. The Food Neophobia Scale results suggest that non-neophobic consumers gave higher scores than neophobic consumers in all the parameters. The resultant product would be a functional product able to substitute traditional ones not only directed to celiac people but all type of consumers because of their beneficial composition.

Effects of 3 mg/kg Body Mass of Caffeine on the Performance of Jiu-Jitsu Elite Athletes.

The effects of caffeine were investigated in judo, boxing, taekwondo and Brazilian jiu-jitsu. However, this substance was never investigated regarding traditional jiu-jitsu. Therefore, the aim of this research was to analyze the effects of caffeine in the Special Judo Fitness Test (SJFT) and technical variables during combat in traditional jiu-jitsu elite athletes. Methods: Twenty-two young professionals of traditional jiu-jitsu, 11 men and 11 women (age = 22 ± 4 (18−33) years, body mass = 66.6 ± 10.8 (46.2−86.1) kg, height = 1.70 ± 0.9 (1.55−1.85) m) with 15 ± 7 years of experience in traditional jiu-jitsu, participated in a double-blind, counterbalanced, crossover study. In two different conditions, the traditional jiu-jitsu athletes ingested 3 mg/kg body mass of caffeine or a placebo. After 60 min, they performed the SJFT test to measure throwing performance, and subsequently, combat to analyze offensive and defensive hitting techniques. Results: Caffeine had a main effect on the number of throws during the SJFT test (P < 0.01). In addition, it was effective in sets 2 (13 ± 2 vs. 14 ± 2; p = 0.01) and 3 (12 ± 2 vs. 13 ± 1; p = 0.03). There was also a main effect during the test on heart rate when caffeine was ingested (F = 12.48, p < 0.01). The effects of caffeine were similar compared to the placebo condition regarding performance during combat both in offensive and defensive fighting variables Conclusions: the pre-exercise ingestion of 3 mg/kg body mass of caffeine increased performance in the SJFT test, decreased fatigue perception, and increased power and endurance perception in professionally traditional jiu-jitsu athletes. However, it did not seem to improve offensive and defensive technical actions during combat.

Caffeine Doses of 3 mg/kg Increase Unilateral and Bilateral Vertical Jump Outcomes in Elite Traditional Jiu-Jitsu Athletes.

Caffeine increases vertical jump, although its effects on kinetics and kinematics during different phases of bilateral and unilateral jumps remain unclear. The aim of this study was to identify the effects of 3 mg/kg on kinetic, kinematic and temporal variables in the concentric and eccentric phases of bilateral and unilateral countermovement jumps. A total of 16 Spanish national team traditional Jiu-Jitsu athletes took part in two experimental trials (3 mg/kg caffeine or placebo) in a randomized, double-blind crossover study. Sixty minutes after ingestion, bilateral and unilateral jumps were performed on a force platform. Compared to the placebo, caffeine increased bilateral jump height (p = 0.008; Δ% = 4.40), flight time (p = 0.008; Δ% = 2.20), flight time:contraction time (p = 0.029; Δ% = 8.90), concentric impulse (p = 0.018; Δ% = 1.80), peak power (p = 0.049; Δ% = 2.50), RSI-modified (p = 0.011; Δ% = 11.50) and eccentric mean braking force (p = 0.045; Δ% = 4.00). Additionally, caffeine increased unilateral RSI-mod in both legs (Left: p = 0.034; Δ% = 7.65; Right: p = 0.004; Δ% = 11.83), left leg flight time (p = 0.044; Δ% = 1.91), left leg jump height (p = 0.039; Δ% = 3.75) and right leg FT:CT (p = 0.040; Δ% = 9.72). Caffeine in a dose of 3 mg/kg BM in elite Jiu-Jitsu athletes is a recommended ergogenic aid as it increased performance of bilateral and unilateral vertical jumps. These increases were also accompanied by modified jump execution during the different phases of the countermovement prior to take-off.

Mutational profile of skin lesions in hepatocellular carcinoma patients under tyrosine kinase inhibition: a repercussion of a wide-spectrum activity.

BACKGROUND/AIM: Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib. MATERIALS AND METHODS: SL were prospectively collected in 311 HCC patients who started sorafenib. SL from sorafenib cohort were compared to those from a control patient group selected to match SL type and demographics. HRAS, KRAS and BRAF mutations were analyzed by CAST-PCR, mutated p53 and MAPK pathway activation by immunohistochemistry and immune infiltration by hematoxylin-eosin staining. RESULTS: Eighty-eight out of 311 patients developed DAE and 7.4% SL required histological assessment. Most frequent lesions were keratoacanthomas (n = 4), squamous-cell carcinomas (SCC)(n = 5), basal-cell carcinomas (BCC)(n = 3) and seborrheic keratosis (n = 5). HRAS and KRAS mutations were detected in 4 SL, while no mutations showed in control SL. Nuclear pERK immunostaining was identified in 33.3% of cases versus 5.3% of controls. Most SL (90%) from patients with DAE were proliferative with intense immune infiltration (73%). CONCLUSIONS: The onset of SL and their molecular profile did not impact negatively on patient's prognosis, but intense proliferation of SL may reflect compensatory activation of MAPK pathway and warrants their close monitoring.

Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma.

Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy. T, B, Natural Killer cells, and their immune checkpoints expression data were characterized by flow cytometry. Cytokine release and immune-suppression assays were carried out ex vivo. Cox baseline and time-dependent regression models were applied to evaluate the probability of increased risk of eDAEs. DNAM-1, PD-1, CD69, and LAG-3 in T cells, plus CD16 and LAG-3 in NK cells, are significantly associated with the probability of developing eDAEs. While NK DNAM-1+ cells express activation markers, T DNAM-1+ cells induce immune suppression and show immune exhaustion. This is the first study to report an association between immune checkpoints expression in circulating immune cells and the increased incidence of eDAEs. Our results support the hypothesis for an off-target role of sorafenib in immune modulation. We also describe a novel association between DNAM-1 and immune exhaustion in T cells.

Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis.

BACKGROUND & AIMS: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism. METHODS: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells. RESULTS: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes. CONCLUSIONS: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.

New Cosmetic Formulation for the Treatment of Mild to Moderate Infantile Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic cutaneous inflammatory disorder, characterized by skin barrier disruption. Dermacare is a new cosmetic formulation, which enhances moisturization, reinforces and repairs the skin barrier, and prevents cutaneous microbiota imbalance. To demonstrate its safety and efficacy, a prospective, open-label, and multicenter study was carried out on patients diagnosed with mild to moderate AD. Transepidermal water loss (TEWL), clinical severity, Desquamation Index, Patient/Investigator Global Assessments, quality of life index, and tolerance were assessed. Adverse events were recorded. Daily application of the new treatment was well tolerated, and adverse events were absent. After 14 days, TEWL showed a 36.7% significant decrease (p = 0.035). At the end of the 28-day treatment, the Desquamation Index showed a reduction in 70% of patients; Eczema Area and Severity Index were reduced by 70.4% (p = 0.002); and skin irritation showed a significant reduction (p = 0.024). Likewise, Patient and Investigator Global Assessments reported a significant improvement in conditions and an overall global worsening when patients restarted their normal treatment. Parent's Index of Quality of Life Index significantly increased by 36.4% (p < 0.05) with Dermacare. In conclusion, a regular use of this new formulation can reduce the risk of relapse and extend the steroid-free treatment periods.

Quality assessment and transfusion efficacy of buffy coat-derived platelet concentrates washed with platelet additive solution.

BACKGROUND: Transfusion of washed platelet concentrates (W-PC) is recommended for some patients, such as those who have had previous severe allergic transfusion reactions. However, we still lack a standardised method for preparing these products. Here, we assessed the effect of a manual washing procedure on in vitro platelet quality and on the transfusion efficacy of W-PCs. MATERIALS AND METHODS: Buffy coat-derived W-PC in Composol solution were prepared by one-step centrifugation. Platelet activation and function were evaluated before and after washing by means of: (i) CD62 expression by flow cytometry; (ii) platelet aggregation (LTA); and (iii) the VerifyNow® P2Y12 test. A pilot prospective transfusion study was carried out in 11 onco-hematology patients receiving, in a short time, two consecutive transfusions: one with standard PC (S-PC) and one with W-PC. The post-transfusion platelet increment, the 1 h and 24 h corrected count increment (CCI) and occurrence of bleeding events were used as indices of transfusion efficacy. RESULTS: Platelet recovery in W-PC was 84.8±5.4%. Washing slightly increased platelet activation in W-PC vs pre-washed samples (% CD62+ platelets 23.6±7 vs 14.8±1; p=0.03). As compared to prewash samples, platelet reactivity of W-PC as measured by VerifyNow® P2Y12 was significantly lower with ADP (PRU 32.2±37.7 vs 4.2±2.4, p=0.027), but similar using TRAP. Platelet aggregation responses to TRAP, collagen, ristocetin and arachidonic acid were maintained in W-PC. The pilot transfusion trial showed similar 1 h (13.5±5.6 vs 11.5±7.3, p=0.49) and 24 h (11±7.2 vs 9±6.5, p=0.48) CCI for S-PC and W-PC. Transfusion of W-PC was not associated with an increased number of bleeding events. DISCUSSION: We have set up a simple method to obtain buffy-coat-derived W-PC, which has minor effects on in vitro platelet quality and transfusion effectiveness. This procedure can be easily implemented in transfusion centres for on-demand preparation of washed platelets.

Bone marrow biopsy superiority over PET/CT in predicting progression-free survival in a homogeneously-treated cohort of diffuse large B-cell lymphoma.

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B-cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R-CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow-up of 25 months the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB-BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2-microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first-line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.

Physiological Demands of Elite Cross-Country Skiing During a Real Competition.

The aim of this study was to assess different physiological variables before and after a 5-km (women) and 10-km (men) cross-country skiing competition to determine potential mechanisms of fatigue. Fourteen elite-level skiers competed in an official cross-country skiing competition using the classical style (9 men and 5 women). Instantaneous skiing velocity was measured during the race by means of 15-Hz global positioning system devices. Before and after the race, a sample of venous blood was obtained to assess changes in blood lactate and serum electrolyte and myoglobin concentrations. Prerace to postrace changes in blood oxygen saturation, forced vital capacity during a spirometry test, jump height during a countermovement jump, and handgrip force were also measured. Mean race speed was 15.8 ± 2.5 and 15.4 ± 1.5 km·h, whereas mean heart rate was 171 ± 6 and 177 ± 3 b·min for men and women, respectively. There were no significant prerace to postrace changes in jump height, handgrip force, and forced vital capacity in men and women. Blood oxygen saturation was reduced from prerace to postrace in men (95.9 ± 2.1% to 93.1 ± 2.3%, p = 0.02) and women (97.8 ± 1.1% to 92.4 ± 2.1%, p < 0.01), whereas blood lactate concentration increased at the end of the race in men (1.4 ± 0.5 to 4.9 ± 2.1 mmol·L, p < 0.01) and women (1.9 ± 0.1 to 6.9 ± 3.2 mmol·L, p < 0.01). After the race, blood markers of muscle damage were at low concentrations, whereas serum electrolytes remained unchanged. Fatigue in 5- and 10-km cross-country skiing competitions was related to a reduced blood oxygen carrying capacity and presumably increased muscle and blood acidosis, whereas the influence of exercise-induced muscle damage on fatigue was minor.

Predicting race time in male amateur marathon runners.

BACKGROUND: The aim of the study was to analyze the relationship between anthropometry, training characteristics, muscular strength and effort-related cardiovascular response and marathon race time in male amateur runners. METHODS: A total of 84 male amateur marathon runners aged between 23 and 70 years took part in this study (41.0±9.5 years). All of them competed in the 2013 edition of the Madrid Marathon with a finish time between 169.8 and 316 minutes (226.0±28.5 minutes). Age, running experience, number of marathon races finished, mean kilometers run weekly in the last three months, and previous personal best time in the 10 km, half marathon and marathon were recorded. Moreover, anthropometric characteristics, and the results from the Ruffier Test and a whole-body isometric force test were measured. After the marathon, the race time was registered. RESULTS: Training volume (r=-0.479; P=0.001), previous running milestones (marathon r=0.756; half-marathon r=0.812; 10-km r=0.732; P<0.001), cardiovascular fitness (r=0.371; P=0.001) and anthropometric variables (body mass, Body Mass Index, body fat percentage, skinfolds and lower leg volume) were correlated to marathon performance (P<0.05). Two regression models appeared from the data with r2>0.50. The best, including body fat percentage, heart rate change during the recovery after the Ruffier Test and the half-marathon race time, was strongly correlated with real marathon performance (r=0.77; P<0.001). A second regression model was proposed replacing the half-marathon performance with the 10-km race time, reducing the correlation to 0.73 (P<0.001). CONCLUSIONS: Marathon performance could be partially predicted by two different equations, including body fat percentage, recovery heart rate in the Ruffier Test and a half-marathon or 10-km performance.

Successful Continuation of HCV Treatment After Liver Transplantation.

BACKGROUND: Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus before surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is 1 potential solution which has not been investigated widely. METHODS: Patients from 5 clinical centers included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents while awaiting LT were identified retrospectively and followed up prospectively. Fifteen patients who had treatment interruptions around LT were identified. RESULTS: The majority of patients (12/15) received interferon-free regimens, most commonly sofosbuvir + daclatasvir (8/12), for a total of 24 weeks (13/15). Treatment was discontinued temporarily for a median of 5 (range, 2-33) days. Fourteen patients completing 12 weeks of follow-up achieved a sustained virological response. One patient who died before week 12 posttreatment achieved a response at posttreatment week 4. Treatment was generally well tolerated. Serious adverse events were recorded in 2 of 15 patients (anaemia in 1 patient; pneumonia in 1 patient); all arose after LT. CONCLUSIONS: Resumption of direct-acting antiviral agent therapy after a temporary interruption around LT was highly effective, achieving sustained virological response in all patients who completed 12 weeks of posttreatment follow-up. Treatment was generally well tolerated pretransplantation and posttransplantation, with a low rate of serious adverse events. Such a strategy may offer an important new approach to the treatment of patients awaiting LT which may be assessed in future studies.

Respiratory function is associated to marathon race time.

BACKGROUND: The purpose of this study was to analyze the relationship between marathon race time and expiratory pulmonary parameters in a heterogeneous group of amateur marathoners. METHODS: A total of 110 marathon runners (age=41.9±9.4 yr, body mass=74.0±9.1 kg, height=175.0±8.0 cm) volunteered to participate in this study. First, they completed a questionnaire about running experience and best performance time in the 10-km, half-marathon and marathon competitions. Then, they performed a maximal spirometry test following guidelines for standardized spirometry. Measurement included peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC). All these expiratory variables were normalized for the participant's body mass. Within 3 days of the spirometry test, participants competed in an official marathon and race time was measured by a chip-timing. After this, participants were grouped by their marathon race time as follows: <210 min, N.=33; between 210 and 240 min, N.=31; and >240 min, N.=46). RESULTS: Marathon race time correlated to the FVC·kg-1 (r=-0.41; P<0.001), to FEV1·kg-1 (r=-0.40; P<0.001), and PEF·kg-1 (r=-0.50; P=0.005). However, self-reported running experience did not show significant correlations to FVC·kg-1 and PEF·kg-1 (P>0.05). The group of faster marathoners (e.g., <210 min) had greater FEV1·kg-1 (<210 min group: 0.064±0.009; 210-240 min group: 0.058±0.008; >240 min group: 0.057±0.009; P<0.001) and higher FVC·kg-1 (<210 min group: 0.081±0.011; 210-240 min group: 0.075±0.012; >240 min group: 0.072±0.010; P<0.001) than the other two groups of slower runners. CONCLUSIONS: These results suggest a significant relationship between individual pulmonary function and marathon race time. Thus, a higher lung capacity per kg of body mass might be a key variable for marathon performance in amateur runners.

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis.

OBJECTIVE: Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. DESIGN: Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. RESULTS: Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. CONCLUSIONS: p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis.

Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

Changes in Serum Free Amino Acids and Muscle Fatigue Experienced during a Half-Ironman Triathlon.

The aim of this study was to investigate the relationship between changes in serum free amino acids, muscle fatigue and exercise-induced muscle damage during a half-ironman triathlon. Twenty-six experienced triathletes (age = 37.0 ± 6.8 yr; experience = 7.4 ± 3.0 yr) competed in a real half-ironman triathlon in which sector times and total race time were measured by means of chip timing. Before and after the race, a countermovement jump and a maximal isometric force test were performed, and blood samples were withdrawn to measure serum free amino acids concentrations, and serum creatine kinase levels as a blood marker of muscle damage. Total race time was 320 ± 37 min and jump height (-16.3 ± 15.2%, P < 0.001) and isometric force (-14.9 ± 9.8%; P = 0.007) were significantly reduced after the race in all participants. After the race, the serum concentration of creatine kinase increased by 368 ± 187% (P < 0.001). In contrast, the serum concentrations of essential (-27.1 ± 13.0%; P < 0.001) and non-essential amino acids (-24.4 ± 13.1%; P < 0.001) were significantly reduced after the race. The tryptophan/BCAA ratio increased by 42.7 ± 12.7% after the race. Pre-to-post changes in serum free amino acids did not correlate with muscle performance variables or post-race creatine kinase concentration. In summary, during a half-ironman triathlon, serum amino acids concentrations were reduced by > 20%. However, neither the changes in serum free amino acids nor the tryptophan/BCAA ratio were related muscle fatigue or muscle damage during the race.