An oligothiophene compound neutralized influenza A viruses by interfering with hemagglutinin

Background and ObjectivesRecently influenza pandemic outbreaks were caused by emerging H5N1, H7N9 and H1N1 viruses. However, virucidal disinfectants are mainly unspecific and toxic. It is tactical to discover specific virucidal compounds.MethodsThe inhibitory potency was determined in H5N1 pseudovirus system; Interactions of compounds with hemagglutinin (HA) were detected with surface plasmon resonance (SPR) and further calculated with molecular docking. Virucidal effect was also estimated in influenza virus A/Puerto Rico/8/34(H1N1). Prevention efficacy was further estimated in mice model.ResultsOligothiophene compound 4sc was potently virucidal against H5N1 pseudovirus with selective index > 1169 (IC₅₀ = 0.17 ± 0.01 μM). Pseudovirus assay revealed 4sc may interact with HA. However, HA inhibition test indicated 4sc did not interact with receptor pocket in HA. SPR detection revealed 4sc interacted directly with HA and its HA2 subunits. Molecular docking analysis revealed that 4sc interacted with the cavity of HA2 stem region and HA1-HA2 interface which consist of 7 residues: L2₂, K26₂, G47₂ and F110₂ in HA2; M24₁, E25₁ and N27₁ in HA1. 4sc also potently and irreversibly neutralized PR8 (H1N1) virus, causing 10^{5.06 ± 0.26} fold decrease of virus titer after exposure for 10 min. 4sc blocked PR8 transmission to MDCK cells. Amazingly, virucidal effect of 4sc was not significantly reduced even at 4 °C. Furthermore, 4sc blocked viral transmission to mice.ConclusionOligothiophene compound 4sc is a novel selective virucide of influenza virus, which blocks entry by interfering viral hemagglutinin. Due to promising safety profile and stable virucidal effect at 4 °C, 4sc may be useful in disinfecting H5N1 and H1N1 influenza virus.     

Prevalencia de hiperandrogenismo y síndrome de ovario poliquístico en transexuales de mujer a hombre

IntroductionPrevalence of hyperandrogenism (HA), including the polycystic ovary syndrome (PCOS), in female-to-male transsexuals (FMT) is high. This has been related to metabolic syndrome (MS), which appears to increase cardiovascular morbidity and mortality throughout cross-sex hormone (CSH) therapy.ObjectivesTo assess the prevalence of HA and PCOS in FMT patients before the start of CSH therapy, and their association to MS and its components, insulin resistance (IR) and other cardiovascular risk (CVR) factors.Materials and methodsSeventy-seven FMTs underwent clinical and biochemical assessment for HA before the start of CSH therapy. CVR, IR, and other MS parameters were also assessed.ResultsPrevalence of HA was 49.4% (73.7% were cases of PCOS [Rotterdam criteria]), and prevalence of PCOS in the overall sample was 36.4%. Prevalence of MS was 38.4% and 51.7% according to ATP-III and IDF criteria respectively). MS (according to ATP-III and IDF criteria respectively) was found in 36.8% and 57.9% as compared to 25.6% and 41% of patients with and without HA respectively (p < 0.0001 and P < 0.01 respectively). Of total patients, 54.5% had normal weight (body mass index [BMI] 18.5-24.9 kg.m^-2), 26% were overweight (BMI 25-29.9 kg.m^-2), and 19.5% were obese (BMI ≥ 30 kg.m^-2). After adjusting for BMI, the comparison of hormonal, metabolic, and anthropometric parameters showed statistically significant differences in plasma glucose, HOMA-IR, and abdominal circumference (P < 0.001 for all), as well as HDL cholesterol (HDL) (P = 0.033), but not in total testosterone or calculated free testosterone levels. In the total sample, 27.3% had HDL levels less than 50 mg/dL.ConclusionsOverall HA, and PCOS in particular, are highly prevalent in FMTs. HA and PCOS are related to early development of SM, IR, and other CVR factors with unknown consequences in adulthood.     

Mechanical stress regulates osteogenic differentiation and RANKL/OPG ratio in periodontal ligament stem cells by the Wnt/β-catenin pathway

BackgroundThe balance between osteoblastic and osteoclastic activity is critical in orthodontic tooth movement (OTM). Mesenchymal stem cells (MSCs) play an important role in maintaining bone homeostasis, and periodontal ligament stem cells (PDLSCs) are tissue-specific MSCs in the periodontal ligament. However, whether PDLSCs are required for periodontal tissue remodeling during OTM is not fully understood.MethodsHere, we used PDGFRα and Nestin to trace PDLSCs during OTM in rats. We treat human PDLSCs with 100 kpa static pressure for 1 h or 12 h in vitro, and examined the phenotypic changes and expression of RANKL and OPG in these cells.ResultsIn vivo, we found that positive signals of PDGFRα and Nestin in the PDL gradually increased and then decreased on the pressure side to which pressure was applied. In vitro, the osteogenic differentiation of PDLSCs was significantly increased after force treatment for 1 h relative to 12 h. In contrast, the expression ratio of RANKL/OPG was reduced at 1 h and significantly increased at 12 h. Furthermore, we found that the Wnt/β-catenin pathway was dynamically activated in the PDL and in PDLSCs after mechanical stimulation. Importantly, the canonical Wnt pathway inhibitor DKK1 blocked the osteogenesis effect and rescued the ratio of RANKL/OPG in PDLSCs under force treatment for 1 h.ConclusionsOur findings reveal that PDLSCs participate in OTM and that the Wnt/β-catenin pathway maintains bone homeostasis during tooth movement by regulating the balance between osteoblastic and osteoclastic activity.General significanceWe describe a novel potential mechanism related to tooth movement.     

Sharper angle,higher risk? The effect of cutting angle on knee mechanics in invasion sport athletes

IntroductionCutting is an important skill in team-sports, but unfortunately is also related to non-contact ACL injuries. The purpose was to examine knee kinetics and kinematics at different cutting angles.Material and methods13 males and 16 females performed cuts at different angles (45°, 90°, 135° and 180°) at maximum speed. 3D kinematics and kinetics were collected. To determine differences across cutting angles (45°, 90°, 135° and 180°) and sex (female, male), a 4 × 2 repeated measures ANOVA was conducted followed by post hoc comparisons (Bonferroni) with alpha level set at α ≤ 0.05 a priori.ResultsAt all cutting angles, males showed greater knee flexion angles than females (p < 0.01). Also, where males performed all cutting angles with no differences in the amount of knee flexion −42.53° ± 8.95°, females decreased their knee flexion angle from −40.6° ± 7.2° when cutting at 45° to −36.81° ± 9.10° when cutting at 90°, 135° and 180° (p < 0.01). Knee flexion moment decreased for both sexes when cutting towards sharper angles (p < 0.05). At 90°, 135° and 180°, males showed greater knee valgus moments than females. For both sexes, knee valgus moment increased towards the sharper cutting angles and then stabilized compared to the 45° cutting angle (p < 0.01). Both females and males showed smaller vGRF when cutting to sharper angles (p < 0.01).ConclusionIt can be concluded that different cutting angles demand different knee kinematics and kinetics. Sharper cutting angles place the knee more at risk. However, females and males handle this differently, which has implications for injury prevention.     

A simple noninvasive index to predict significant liver fibrosis in patients with advanced schistosomiasis japonica

BackgroundSchistosoma japonicum causes marked liver fibrosis, while lethal syndromes present in advanced schistosomiasis patients. Its management depends on the degree of fibrosis present.Patients and methodsFifty-two patients were recruited to assess the diagnostic value of bio-markers in patients with advanced schistosomiasis japonica. Fibrosis was assessed in liver biopsies using METAVIR system. The correlation between conventional parameters and significant fibrosis (F2-F4) was assessed using univariate analysis and logistic regression. The method of area under receiver operating characteristic curves (AUROCs) was used as a measurement of diagnostic efficacy.ResultsWhite blood cell counts, platelet counts and albumin (all P < 0.05) were significantly lower, while prothrombin time, international normalized ratio (INR), hyaluronic acid (HA), IV collagen and ultrasound fibrosis scores (all P < 0.01) were significantly elevated in F2-F4 patients compared with F0-F1 patients. HA and INR were identified as independent predictors by multivariate analysis (P = 0.023 and P = 0.013, respectively). Of the routine laboratory tests for the diagnosis of significant fibrosis, HA gave the best AUROC of 0.875 (95% confidence interval (CI): 0.701–0.997). We constructed a new simple index (INR × HA/100) to discriminate between F2-F4 patients and F0-F1 patients. It showed the highest AUROC of 0.921 (95% CI: 0.828-1.000), and had better diagnostic values than APRI and FIB-4.ConclusionHA and INR were reliable markers for differentiating significant liver fibrosis in patients with advanced schistosomiasis japonica. And the new simple index can easily predict significant liver fibrosis with a high degree of accuracy.     

The effect of deep hypothermia on the human pulmonary circulation

ObjectiveAcute rises in pulmonary artery pressures following complex cardiac surgery are associated with high morbidity and mortality. We hypothesised that periods of deep hypothermia predispose to elevated pulmonary pressures upon rewarming. We investigated the effect of this hypothermic preconditioning on isolated human pulmonary arteries and isolated perfused lungs.MethodsIsometric tension was measured in human pulmonary artery rings (n=24). We assessed the constriction and dilation of these arteries at 37 °C and 17 °C. Isolated perfused human lung models consisted of lobes ventilated via a bronchial cannula and perfused with Krebs via a pulmonary artery cannula. Bronchial and pulmonary artery pressures were recorded. We investigated the effect of temperature using a heat exchanger.ResultsRewarming from 17 °C to 37 °C caused a 1.3 fold increase in resting tension (p<0.05). Arteries constricted 8.6 times greater to 30 nM KCl, constricted 17 times greater to 1 nM Endothelin-1 and dilated 30.3 times greater to 100 μM SNP at 37 °C than at 17 °C (p<0.005). No difference was observed in the responses of arteries originally maintained at 37 °C compared to those arteries maintained at 17 °C and rewarmed to 37 °C. Hypothermia blunted the increase in pulmonary artery pressures to stimulants such as potassium chloride as well as to H-R but did not precondition arteries to higher pulmonary artery pressures upon re-warming.ConclusionsDeep hypothermia reduces the responsiveness of human pulmonary arteries but does not, however, precondition an exaggerated response to vasoactive agents upon re-warming.     

Valoración de la musculatura isquiosural en personas mayores

Objectiveto evaluate hamstring flexibility in older adults.Materials and methodsa total of 177 subjects (13 men and 164 women) aged between 43 and 80 years old (mean age = 63.4 ± 6.7 years) who attended fitness classes were evaluated. The mean height was 161 ± 10 cm and the mean weight was 74 ± 5.6 kg. Hamstring flexibility was evaluated using the straight leg raise test.Resultsthe mean flexion in the right hip was 72° ± 13.2° and the mean flexion of the left hip was 72.4° ± 13.8°. No significant differences were found in the values obtained from the straight leg raise test in the left and right legs. For the right leg, 48.02% of the subjects’ values were within the normal range, while 28.81% showed grade I shortness, and 23.61% showed grade II shortness. For the left leg, 49.94% showed normal values, 29.94% showed grade I shortness, and 22.03% showed grade II shortness.Conclusionshalf of the adults and elderly individuals that took part in the present study had hamstring shortness, which increased in frequency with age.     

Measurement of coronary bifurcation angle with coronary CT angiography: A phantom study

PurposeAccurate determination of the bifurcation angle and correlation with plaque buildup may lead to the prediction of coronary artery disease (CAD). This work evaluates two techniques to measure bifurcation angles in 3D space using coronary computed tomography angiography (CCTA).Materials and MethodsNine phantoms were fabricated with different bifurcation angles ranging from 55.3° to 134.5°. General X-ray and CCTA were employed to acquire 2D and 3D images of the bifurcation phantoms, respectively. Multiplanar reformation (MPR) and volume rendering technique (VRT) were used to measure the bifurcation angle between the left anterior descending (LAD) and left circumflex arteries (LCx). The measured angles were compared with the true values to determine the accuracy of each measurement technique. Inter-observer variability was evaluated. The two techniques were further applied on 50 clinical CCTA cases to verify its clinical value.ResultsIn the phantom setting, the mean absolute differences calculated between the true and measured angles by MPR and VRT were 2.4° ± 2.2° and 3.8° ± 2.9°, respectively. Strong correlation was found between the true and measured bifurcation angles. Furthermore, no significant differences were found between the bifurcation angles measured using either technique. In clinical settings, large difference of 12.0° ± 10.6° was found between the two techniques.ConclusionIn the phantom setting, both techniques demonstrated a significant correlation to the true bifurcation angle. Despite the lack of agreement of the two techniques in the clinical context, our findings in phantoms suggest that MPR should be preferred to VRT for the measurement of coronary bifurcation angle by CCTA.     

Effect of diagnostic cone-beam computed tomography protocols on image quality,patient dose,and lesion detection

ObjectiveTo evaluate the effect of cone-beam computed tomography (CBCT) image acquisition protocols on image quality, lesion detection, delineation, and patient dose.Methods100-patients and a CTDI phantom combined with an electron density phantom were examined using four different CBCT-image acquisition protocols during image-guided transarterial chemoembolization (TACE). Protocol-1 (time: 6 s, tube rotation: 360°), protocol-2 (5 s, 300°), protocol-3 (4 s, 240°) and protocol-4 (3 s, 180°) were used. The protocols were first investigated using a phantom. The protocols that were found to be clinically appropriate in terms of image quality and radiation dose were then assessed on patients. A higher radiation dose and/or a poor image quality were inappropriate for the patient imaging. Patient dose (patient-entrance dose and dose-area product), image quality (Hounsfield Unit, noise, signal-to-noise ratio and contrast-to-noise ratio), and lesion delineation (tumor-liver contrast) were assessed and compared using appropriate statistical tests. Lesion detectability, sensitivity, and predictive values were estimated for CBCT-image data using pre-treatment patient magnetic resonance imaging.ResultsThe estimated patient dose showed no statistical significance (p > 0.05) between protocols-2 and -3; the assessed image quality between these protocols manifested insignificant difference (p > 0.05). Two other phantom protocols were not considered for patient imaging due to significantly higher dose (protocols-1) and poor image quality (protocol-4). Lesion delineation and detection were insignificant (p > 0.05) between protocols-2 and -3. Lesion sensitivities generated were 81–89% (protocol-2) and 81–85% (protocol-3) for different lesion types.ConclusionData acquisition using protocols-2 and -3 provided good image quality, lesion detection and delineation with acceptable patient dose during CBCT-imaging mainly due to similar frame numbers acquired.     

Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk

PurposePancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated.MethodsA total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field.ResultsCompared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively.ConclusionsOptimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.     

BAPTA-AM,an intracellular calcium chelator,inhibits RANKL-induced bone marrow macrophages differentiation through MEK/ERK,p38 MAPK and Akt,but not JNK pathways

To examine the roles of intracellular calcium in RANKL-induced bone marrow macrophages (BMMs) differentiation, the effects of intracellular calcium chelator BAPTA-AM on RANKL-induced BMMs differentiation, and the activation of its relating signal proteins (MAPKs, and the PI3K/Akt) were studied. BMMs were cultured with various concentrations of BAPTA-AM in the presence of M-CSF (25 ng/ml) and RANKL (25 ng/ml) for 7 days, osteoclastogenic ability, cytosolic free Ca²⁺ concentration, osteoclast survival and the expression of phosphorylated ERK1/2, SAPK/JNK, Akt and p38 MAPK were measured by TRAP staining, spectrofluorometer and Western blotting. BAPTA-AM inhibited osteoclastogenesis and osteoclast survival of BMMs by RANKL induction. In osteoclasts without the pretreatment of BAPTA-AM, the increased response of [Ca²⁺]_i was observed within 15 min and the maximum was about 1.2 times that of control. This response was sustained for 30 min and returned to the control level at 1 h after RANKL-inducing, and the increased response of [Ca²⁺]_i was completely abolished and sustained to at least 8 h by BAPTA-AM. Although immunoblotting data revealed that RANKL could activate the phosphorylation of ERK1/2, SAPK/JNK, Akt and p38 MAPK, the expression of ERK1/2, Akt and p38 MAPK phosphorylation was inhibited by BAPTA-AM dose-dependently. These results revealed that BAPTA-AM inhibit osteoclastogenic ability of BMMs via suppressing the increase of [Ca²⁺]_i which lead to inhibit RANKL-induced the phosphorylation of ERK, Akt and p38 MAPK, but not JNK. This finding may be useful in the development of an osteoclastic inhibitor that targets intracellular signaling factors.     

Optimizing isothermal titration calorimetry protocols for the study of 1:1 binding: Keeping it simple

BackgroundSuccessful ITC experiments require conversion of cell reagent (titrand M) to product and production or consumption of heat. These conditions are quantified for 1:1 binding, M + X ⇔ MX.MethodsNonlinear least squares is used in error-propagation mode to predict the precisions with which the key quantities — binding constant K, reaction enthalpy ΔH°, and stoichiometry number n — can be estimated over a wide range of the dimensionless quantity that governs isotherm shape, c = K[M]₀. The measurement precision σ_q is estimated from analysis of water–water blanks.ResultsWhen the product conversion exceeds 90%, the parameter relative standard errors are proportional to σ_q/q_tot, where the total heat q_tot ≈ ΔH° [M]₀ V₀. Specifically, σ_K/K × q_tot/σ_q ≈ 25 for c = 10 ^− 3 − 10, ≈ 11 c^1/3 for c = 10 − 10⁴. For c > 1, n and ΔH° are more precise than K; this holds also at smaller c for the product n × ΔH° and for ΔH° when n can be held fixed. Use of as few as 10 titrant injections can outperform the customary 20–40 while also improving productivity.ConclusionThese principles are illustrated in experiment design using the program ITC-PLANNER15.General significanceSimple quantitative guidelines replace the “c rules” that have dominated the literature for decades. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.     

Hyaluronic acid production and molecular weight improvement by redirection of carbon flux towards its biosynthesis pathway

Hyaluronic acid (HA) production in Streptococcus zooepidemicus competes for the carbon source along with biomass formation, lactate formation (via glycolysis) and pentose phosphate pathway (PPP). In our studies, increase in HA molecular weight was observed by redirecting the carbon flux towards HA biosynthesis pathway by partially inhibiting the glycolytic pathway. Batch bioreactor (1.2 L) studies showed that with the addition of 25 μM sodium iodoacetate, 5 g/L tryptophan and 10 g/L pyruvate, which are glycolytic inhibitors, HA molecular weight increased to 3.2, 3.2 and 3.1 MDa respectively compared to control run (2.4 MDa). Yield coefficients Y_HA/S and Y_LA/S showed inverse relationship, indicating competition for glucose between HA and lactic acid formation. Addition of 5 g/L glutamine along with 25 μM sodium iodoacetate also increased the HA concentration to 5.0 g/L from 2.0 g/L in control run. Metabolic flux analysis studies show that concentration and molecular weight of HA is increased by decreasing carbon flux towards glycolysis and PPP and increasing carbon flux towards HA precursor formation. It was observed that specific growth rate of the cells correlated positively to the specific HA production rate and negatively to the molecular weight of HA produced. Addition of antioxidant tannic acid also increased molecular weight to 3.0 MDa.     

The eccentric,concentric strength relationship of the hamstring muscles in chronic low back pain

ObjectiveThe objective of this study was to measure hamstring muscle eccentric and concentric strength in individuals with and without low back pain (LBP). Two composite scores for the relative balance of eccentric to concentric strength at the different movement velocities were calculated (the DEC and SEC), to determine whether or not self perceived pain, disability, or fear avoidance measures were associated with hamstring strength characteristics.DesignCross-sectional repeated measures design.SettingUniversity laboratory.ParticipantsFifteen individuals with chronic LBP and 15 matched controls.Main outcome measuresIsokinetic eccentric and concentric strength at 30° s^?1 and 120° s^?1_. Composite scores (DEC and SEC) based on peak torque were calculated to evaluate the relationship between the different muscle actions across the test velocities. Self report measures included the Oswestry disability index, general health and well being, fear avoidance, and pain.ResultsEccentric/concentric strength ratio at 30° s^?1 was higher for the LBP group (F(1,58) = 4.81, p = 0.032). The SEC was also higher for the LBP (F(1,58) = 5.97, p = 0.018). Fear avoidance beliefs and mental well-being were significantly associated with the SEC only in the LBP group (adjusted r² = 0.26, (F(2,27) = 5.8, p = .008). For the control group both the DEC and SEC were associated with self report measures. Matched differences between groups’ for the SEC were best explained by fear avoidance beliefs about work (adjusted r² = 0.12, F(1,28) = 5.1, p = 0.03).ConclusionReduced concentric relative to eccentric strength is best identified by the SEC. The SEC was significantly associated with impaired self report measures of fear avoidance and mental well being in individuals with LBP. Differences between groups for the SEC were best explained by fear avoidance beliefs about work.     

Muscle fatigue and metabolic responses following three different antagonist pre-load resistance exercises

PurposePreload of antagonist muscles can be achieved by reciprocal actions (RAs) or by opposing muscle actions. However, evidence concerning neuromuscular and fatigue responses are scarce.ObjectiveTo compare the effects of different knee flexor (KF) preload methods on knee extension (KE) vastus medialis muscle fatigue, based on EMG-spectral index (FI), load range (LR), total work (TW), blood lactate (LAC) and biceps femoris co-activation (BFc) during resistance exercise.MethodsTwenty-four healthy men (23.5 ± 3.6 yrs) performed three antagonist pre-load isokinetic exercises (4 sets, 10 repetitions, 60° s^?1, 1 min rest between sets): RA (KF contraction immediately followed by KE); Superset (SS; one KF set immediately followed by one KE set); Multiple Set (MS; four KF sets followed by four KE sets).ResultsTotal work was significantly greater in RA. There was no significant decrease in LR between sets in RA. The BFc did not differ between protocols (p = 0.063). However, RA presented greater biceps femoriscoactivation. The FI was greater during SS compared to RA and MS (p < 0.05). The SS had greater LAC when compared to MS and RA (p = 0.005 and p = 0.007, respectively).ConclusionIt is suggested that the RA protocol is more neuromuscular and metabolic efficient during the performance of knee extension resistance exercise.     

Modulation of delta opioid agonist-induced antinociception by repeated morphine pretreatment in rhesus monkeys

AimsRepeated treatment with morphine increases antinociceptive effects of delta opioid agonists in rodents by a mechanism that may involve increased cell-surface expression of delta receptors. The present study evaluated effects of repeated morphine treatment on behavioral effects of the delta agonist SNC80 and the mu agonist fentanyl in rhesus monkeys.Main methodsIn an assay of schedule-controlled responding, three monkeys responded for food reinforcement under a fixed-ratio 30 schedule. In an assay of thermal nociception, tail-withdrawal latencies were evaluated in three monkeys using thermal stimulus intensities of 48 and 54 °C. In both assays, the effects of SNC80 (0.032–3.2 mg/kg) and fentanyl (0.001–0.056 mg/kg) were evaluated after repeated treatment with saline or a regimen of morphine doses modeled on the regimen that enhanced delta agonist antinociception and apparent delta receptor availability in previous rodent studies.Key findingsBoth SNC80 and fentanyl dose-dependently decreased rates of schedule-controlled responding, and repeated morphine treatment did not significantly alter these effects. In the assay of thermal nociception, SNC80 had little effect on tail-withdrawal latencies from water heated to 48 or 54 °C, whereas fentanyl increased tail-withdrawal latencies at both temperatures. Repeated morphine tended to increase the antinociceptive effects of SNC80 and to decrease the antinociceptive effects of fentanyl, but these effects of repeated morphine were small and were significant only at the higher stimulus intensity (54 °C).SignificanceThese results provide limited support for the proposition that prior stimulation of mu receptors selectively increases the antinociceptive effects of delta agonists in rhesus monkeys.     

Tennis players show a lower coactivation of the elbow antagonist muscles during isokinetic exercises

PurposePrevious studies have suggested that muscle coactivation could be reduced by a recurrent activity (training, daily activities). If this was correct, skilled athletes should show a specific muscle activation pattern with a low level of coactivation of muscles which are typically involved in their discipline. In particular, the aim of this study was to verify the hypothesis that the amount of antagonist activation of biceps brachii (BB) and triceps brachii (TB) is different between tennis players and non-players individuals during maximal isokinetic contractions.MethodsTen young healthy men and eight male tennis players participated in the study. The surface electromyographic signals (sEMG) were recorded from the BB and TB muscles during three maximal voluntary isometric contractions (MVC) of elbow flexors and extensors and a set of three maximal elbow flexions and extensions at 15°, 30°, 60°, 120°, 180° and 240°/s. Normalized root mean square (RMS) of sEMG was calculated as an index of sEMG amplitude.ResultsAntagonist activation (%RMSmax) of TB was significantly lower in tennis players (from 14.0 ± 7.9% at MVC to 16.3 ± 8.9% at 240°/s) with respect to non-players (from 27.7 ± 19.7% at MVC to 38.7 ± 17.6% at 240°/s) at all angular velocities. Contrary to non-players, tennis players did not show any difference in antagonist activation between BB and TB muscles.ConclusionsTennis players, with a constant practice in controlling forces around the elbow joint, learn how to reduce coactivation of muscles involved in the control of this joint. This has been shown by the lower antagonist muscular activity of triceps brachii muscle during isokinetic elbow flexion found in tennis players with respect to non-players.     

Stability and activity of Dictyoglomus thermophilum GH11 xylanase and its disulphide mutant at high pressure and temperature

The functional properties of extremophilic Dictyoglomus thermophilum xylanase (XYNB) and the N-terminal disulphide-bridge mutant (XYNB-DS) were studied at high pressure and temperature. The enzymes were quite stable even at the pressure of 500 MPa at 80 °C. The half-life of inactivation in these conditions was over 30 h. The inactivation at 80 °C in atmospheric pressure was only 3-times slower. The increase of pressure up to 500 MPa at 80 °C decreased only slightly the enzyme's stability, whereas in 500 MPa the increase of temperature from 22 to 80 °C decreased significantly more the enzyme's stability. While the high temperature (80–100 °C) decreased the enzyme reaction with short xylooligosaccharides (xylotetraose and xylotriose), the high pressure (100–300 MPa) had an opposite effect. The temperature of 100 °C strongly increased the K_m but did not affect the k_cat to the same extent, thus indicating that the interaction of the substrate with the active site suffers before the catalytic reaction begins to decrease as the temperature rises. Circular dichroism spectroscopy showed the high structural stability of XYNB and XYNB-DS at 93 °C.