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Altered fucosylation of glycoproteins is associated with development of hepatocellular carcinoma (HCC). Lectins have been commonly used to assay changes in fucosylation of plasma glycoproteins. In the present study a recombinantly engineered form of the fucose binding lectin Aleuria aurantia (AAL) consisting of a single binding site for fucose (S2), was used to construct a reverse lectin ELISA method. Microtiter plates coated with the S2 lectin were used to capture glycoproteins from plasma samples followed by antibody detection of S2-bound fucosylated α1-acid glycoprotein (S2-bound AGP). The method was used to compare the level of S2-bound AGP in serum samples from a small cohort of patients with hepatitis, cirrhosis or HCC. Using the reverse S2 lectin ELISA it was shown that the levels of S2-bound AGP was significantly higher in HCC patients compared to non-cancer patients and that there was also a significant elevation of S2-bound AGP in HCC patients compared to cirrhosis patients. There was no correlation between the level of S2-bound AGP and total AGP concentration. The performance of S2-bound AGP in differentiating HCC from cirrhosis samples or hepatitis samples were compared to other markers. A combination of S2-bound AGP, α-fetoprotein and AGP concentration showed performances giving area under receiver operating curves of 0.87 and 0.95 respectively. [ABSTRACT FROM AUTHOR]

Background and Aim: Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms. Methods: We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, King´s score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC). Results: Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89. Conclusion: The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts. [ABSTRACT FROM AUTHOR]

Unilateral strength training can cause cross-transfer strength effects to the homologous contralateral muscles. However, the impact of the cross-over effects on the muscle tissue is unclear. To test the hypothesis that unilateral muscle overuse causes bilateral alterations in muscle fiber composition and vascular supply, we have used an experimental rabbit model with unilateral unloaded overstrain exercise via electrical muscle stimulation (E/EMS). The soleus (SOL) and gastrocnemius (GA) muscles of both exercised (E) and contralateral non-exercised (NE) legs (n = 24) were morphologically analyzed after 1w, 3w and 6w of EMS. Non-exercised rabbits served as controls (n = 6). After unilateral intervention the muscles of both E and NE legs showed myositis and structural and molecular tissue changes that to various degrees mirrored each other. The fiber area was bilaterally smaller than in controls after 3w of E/EMS in both SOL (E 4420 and NE 4333 µm2 vs. 5183 µm2, p<0.05) and GA (E 3572 and NE 2983 µm2 vs. 4697 µm2, p<0.02) muscles. After 6w of E/EMS, the percentage of slow MyHCI fibers was lower than in controls in the NE legs of SOL (88.1% vs. 98.1%, p<0.009), while the percentage of fast MyHCIIa fibers was higher in the NE legs of GA (25.7% vs. 15.8%, p = 0.02). The number of capillaries around fibers in the E and NE legs was lower (SOL 13% and 15%, respectively, GA 25% and 23%, respectively, p<0.05) than in controls. The overall alterations were more marked in the fast GA muscle than in the slow SOL muscle, which on the other hand showed more histopathological muscle changes. We conclude that unilateral repetitive unloaded overuse exercise via EMS causes myositis and muscle changes in fiber type proportions, fiber area and fiber capillarization not only in the exercised leg, but also in the homologous muscles in the non-exercised leg. [ABSTRACT FROM AUTHOR]

The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement. [ABSTRACT FROM AUTHOR]

The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2–3 days and 7–8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7–8 days than at 2–3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2–3 days to 7–8 days post exercise (lower in 5 of the 6 subjects at 7–8 days than at 2–3 days; p<0.05). Thus, the increased fibre size at 7–8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS. [ABSTRACT FROM AUTHOR]

It is well established that unilateral exercise can produce contralateral effects. However, it is unclear whether unilateral exercise that leads to muscle injury and inflammation also affects the homologous contralateral muscles. To test the hypothesis that unilateral muscle injury causes contralateral muscle changes, an experimental rabbit model with unilateral muscle overuse caused by a combination of electrical muscle stimulation and exercise (EMS/E) was used. The soleus and gastrocnemius muscles of both exercised and non-exercised legs were analyzed with enzyme- and immunohistochemical methods after 1, 3 and 6 weeks of repeated EMS/E. After 1 w of unilateral EMS/E there were structural muscle changes such as increased variability in fiber size, fiber splitting, internal myonuclei, necrotic fibers, expression of developmental MyHCs, fibrosis and inflammation in the exercised soleus muscle. Only limited changes were found in the exercised gastrocnemius muscle and in both non-exercised contralateral muscles. After 3 w of EMS/E, muscle fiber changes, presence of developmental MyHCs, inflammation, fibrosis and affections of nerve axons and AChE production were observed bilaterally in both the soleus and gastrocnemius muscles. At 6 w of EMS/E, the severity of these changes significantly increased in the soleus muscles and infiltration of fat was observed bilaterally in both the soleus and the gastrocnemius muscles. The affections of the muscles were in all three experimental groups restricted to focal regions of the muscle samples. We conclude that repetitive unilateral muscle overuse caused by EMS/E overtime leads to both degenerative and regenerative tissue changes and myositis not only in the exercised muscles, but also in the homologous non-exercised muscles of the contralateral leg. Although the mechanism behind the contralateral changes is unclear, we suggest that the nervous system is involved in the cross-transfer effects. [ABSTRACT FROM AUTHOR]

It is well established that unilateral exercise can produce contralateral effects. However, it is unclear whether unilateral exercise that leads to muscle injury and inflammation also affects the homologous contralateral muscles. To test the hypothesis that unilateral muscle injury causes contralateral muscle changes, an experimental rabbit model with unilateral muscle overuse caused by a combination of electrical muscle stimulation and exercise (EMS/E) was used. The soleus and gastrocnemius muscles of both exercised and non-exercised legs were analyzed with enzyme- and immunohistochemical methods after 1, 3 and 6 weeks of repeated EMS/E. After 1 w of unilateral EMS/E there were structural muscle changes such as increased variability in fiber size, fiber splitting, internal myonuclei, necrotic fibers, expression of developmental MyHCs, fibrosis and inflammation in the exercised soleus muscle. Only limited changes were found in the exercised gastrocnemius muscle and in both non-exercised contralateral muscles. After 3 w of EMS/E, muscle fiber changes, presence of developmental MyHCs, inflammation, fibrosis and affections of nerve axons and AChE production were observed bilaterally in both the soleus and gastrocnemius muscles. At 6 w of EMS/E, the severity of these changes significantly increased in the soleus muscles and infiltration of fat was observed bilaterally in both the soleus and the gastrocnemius muscles. The affections of the muscles were in all three experimental groups restricted to focal regions of the muscle samples. We conclude that repetitive unilateral muscle overuse caused by EMS/E overtime leads to both degenerative and regenerative tissue changes and myositis not only in the exercised muscles, but also in the homologous non-exercised muscles of the contralateral leg. Although the mechanism behind the contralateral changes is unclear, we suggest that the nervous system is involved in the cross-transfer effects.