C-Jun N-terminal kinase 2 promotes liver injury via the mitochondrial permeability transition after hemorrhage and resuscitation

Hemorrhagic shock leads to hepatic hypoperfusion and activation of mitogen-activated stress kinases (MAPK) like c-Jun N-terminal kinase (JNK) 1 and 2. Our aim was to determine whether mitochondrial dysfunction leading to hepatic necrosis and apoptosis after hemorrhage/resuscitation (H/R) was dependent on JNK2. Under pentobarbital anesthesia, wildtype (WT) and JNK2 deficient (KO) mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer's solution. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R, ALT in WT-mice increased from 130 U/L to 4800 U/L. In KO-mice, ALT after H/R was blunted to 1800 U/l (P < 0.05). Necrosis, caspase-3 activity and ROS were all substantially decreased in KO compared to WT mice after H/R. After sham operation, intravital microscopy revealed punctate mitochondrial staining by rhodamine 123 (Rh123), indicating normal mitochondrial polarization. At 4 h after H/R, Rh123 staining became dim and diffuse in 58% of hepatocytes, indicating depolarization and onset of the mitochondrial permeability transition (MPT). By contrast, KO mice displayed less depolarization after H/R (23%, P < 0.05). In conclusion, JNK2 contributes to MPT-mediated liver injury after H/R

Guest Editorial: Special issue Rescuing Legacy data for Future Science

Research and discovery in the natural sciences, particularly for documenting changes in our planet, is empowered by gathering, mining, and reusing observational data. However much of the data required, particularly data from the pre-digital era, are no longer accessible to science. The data are hidden away in investigators’ desks on printed paper records, or are no longer readable as they are on deteriorating or outdated media, and are not documented in a way that makes them re-usable. Special initiatives are required to rescue them and preserve such data so that they can contribute to the scientific debates of today and those of the future. Data rescue efforts are key to making data resources accessible that are at risk of being lost forever when researchers retire or die, or when data formats or storage media are obsolete and unreadable

Varijacije tijekom sezone u izokinetičkom vršnom momentu sile kod mladih nogometaša

The aim of the study was to investigate the seasonal variation in the strength of the knee flexors and extensors in highly trained youth soccer players. The players (n=16; age 16.7±0.7) were measured at the end of the competitive season, at the beginning of the off-season and during the sixth week of a new competitive season. Isokinetic concentric peak torque was measured at 60°•s-1, 180°•s-1, 360°•s-1 in a sitting position. The testing range of motion was set from 10–90° of knee flexion. Players performed a set of six maximal repetitions for both dominant and non-dominant limb. Average values of peak torque significantly changed during the observed periods. Significant differences (p<.05) between the three measurement sessions were noted with respect to the knee flexors at all angular velocities. A post-hoc test confirmed a significant increase between the first and the second measurement for flexion in both dominant (180°•s-1; p=.033) and non-dominant legs (360°•s-1; p=.004). A significant increase was also found between the first and the third session for both limbs during knee flexion at all angular velocities. The results indicate that peak torque values of knee flexors and extensors varied differently in trained youth soccer players depending on muscle group and movement velocity with statistically significant changes in knee flexors only.Cilj je ovog istraživanja bio utvrditi varijacije tijekom sezone u snazi pregibača i opružača potkoljenice vrhunskih treniranih mladih nogometaša. Igrači (n=16; dob 16,7±0,7) su testirani na kraju natjecateljske sezone, na početku prijelaznog perioda te tijekom šestog tjedna nove natjecateljske sezone. Izokinetički koncentrični vršni moment sile mjerio se pri brzinama od 60°/s, 180°/s i 360°/s u sjedećem položaju ispitanika. Opseg pokreta se tijekom testiranja kretao od 10 do 90° fleksije koljena. Igrači su izveli seriju od šest maksimalnih ponavljanja prvo dominantnom, a onda i nedominantnom nogom. Prosječne vrijednosti vršnog momenta sile značajno su se mijenjale tijekom promatranih perioda. Značajne razlike (p<0,05) u snazi pregibača potkoljenice zabilježene su između sva tri mjerenja pri sve tri brzine izveđonja. Post hoc test je također potvrdio značajno povećanje snage pregibača potkoljenice između prvoga i drugog mjerenja za dominantnu (180°/s; p=0,033) i nedominantnu (360°/s; p=0,004) nogu. Značajno povećanje vršnog momenta sile pregibača potkoljenice obje noge pri svim brzinama također je zabilježeno između drugoga i trećeg mjerenja. Rezultati pokazuju da vršni moment sile pregibača i opružača potkoljenice različito varira kod treniranih mladih nogometaša ovisno o mišićnoj grupi i brzini pokreta, sa statističkom značajnošću promjena samo za pregibače potkoljenice

Seasonal variation in isokinetic peak torque in youth soccer players

The aim of the study was to investigate the seasonal variation in the strength of the knee flexors and\ud extensors in highly trained youth soccer players. The players (n=16; age 16.7±0.7) were measured at the end\ud of the competitive season, at the beginning of the off-season and during the sixth week of a new competitive\ud season. Isokinetic concentric peak torque was measured at 60°·s-1, 180°·s-1, 360°·s-1 in a sitting position. The\ud testing range of motion was set from 10–90° of knee flexion. Players performed a set of six maximal repetitions\ud for both the dominant and non-dominant limb. Average values of peak torque significantly changed during\ud the observed periods. Significant differences (p<.05) between the three measurement sessions were noted\ud with respect to the knee flexors at all angular velocities. A post-hoc test confirmed a significant increase\ud between the first and the second measurement for flexion in both the dominant (180°·s-1; p=.033) and nondominant\ud legs (360°·s-1; p=.004). A significant increase was also found between the first and the third session\ud for both limbs during the knee flexion at all angular velocities. The results indicate that peak torque values\ud of knee flexors and extensors varied differently in trained youth soccer players depending on muscle group and movement velocity with statistically significant changes in knee flexors only

Objektiv strukturierte Bewertung einer Hautnaht am Modell : ist die direkte Beobachtung der video-basierten Beobachtung überlegen? ; Poster

Poster Einleitung: OSCEs werden immer häufiger in der Ausbildung von Studierenden eingesetzt. Die Einführung eines OSCEs im fach Chirurgie ist in Planung. Durch die große Anzahl von Studierenden pro Semester oder Studienjahr (400 Studierende in Frankfurt) ist die Durchführung einer OSCE Prüfung mit großem personellen Aufwand verbunden. Vor allem während der Prüfung müssen eine Vielzahl von Chirurgen simultan zu Prüfungszwecken zur Verfügung stehen. Ziel der Studie war es, zu überprüfen, ob eine video-basierte Bewertung einer „Nahtstation“ zu einem späteren Zeitpunkt zu gleichen Ergebnissen in der Bewertung der Leistung der Studierenden führt. Methode: 33 Studierende führten unter standardisierten Bedingungen eine Hautnaht an einem Modell durchzuführen. Die Studierenden wurden während der Prozedur von zwei prüfenden Chirurgen und zwei Studierenden im PJ (praktischen Jahr) beobachtet und anhand einer objektiv strukturierten Checkliste bewertet (Prozessevaluation). Die Prozedur wurde gleichzeitig auf Video aufgezeichnet und zu einem späteren Zeitpunkt zwei weiteren Chirurgen und zwei weiteren Studierenden im PJ zur Bewertung gezeigt. Ergebnisse: Der Vergleich zwischen "live“-prüfenden und "video“-prüfenden Chirurgen zeigt eine signifikant hohe Korrelation (r=0,87; p<0,01) und eine hohe Übereinstimmung (88,2%) in der Bewertung. Ebenso zeigen die prüfenden PJler eine signifikant hohe Korrelation (r=0,84; p<0,01). Die Übereinstimmung ist bei den PJlern mit (82.4%) etwas niedriger als bei den beteiligten Chirurgen. Zusammenfassung: Mit dieser Studie konnte zeigt werden, daß es bei der Beurteilung der Performance von Studierenden bei einer Hautnaht am Modell unter Anwendung von objektiv strukturierten Checklisten möglich ist, eine direkte Beobachtung der Studierenden durch eine video-basierte Beobachtung zu ersetzen. Eine "Nahtstation“ in einem OSCE kann somit während der Prüfungszeit ohne Prüfer auskommen und im Anschluß bewertet werden

Circulating Leukotriene B4 Identifies Respiratory Complications after Trauma

Background. Leukotriene B4 (LTB4), a proinflammatory lipid mediator correlates well with the acute phase of Acute Respiratory Distress Syndrome (ARDS). Therefore, LTB4-levels were investigated to determine whether they might be a useful clinical marker in predicting pulmonary complications (PC) in multiply traumatized patients. Methods: Plasma levels of LTB4 were determined in 100 patients on admission (ED) and for five consecutive days (daily). Twenty healthy volunteers served as control. LTB4-levels were measured by ELISA. Thirty patients developed PC (pneumonia, respiratory failure, acute lung injury (ALI), ARDS, pulmonary embolism) and 70 had no PC (ØPC). Results. LTB4-levels in the PC-group [127.8 pg/mL, IQR: 104–200pg/ml] were significantly higher compared to the ØPC-group on admission [95.6 pg/mL, IQR: 55–143 pg/mL] or control-group [58.4 pg/mL, IQR: 36–108 pg/mL]. LTB4 continuously declined to basal levels from day 1 to 5 without differences between the groups. The cutoff to predict PC was calculated at 109.6 pg/mL (72% specificity, 67% sensitivity). LTB4 was not influenced by overall or chest injury severity, age, gender or massive transfusion. Patients with PC received mechanical ventilation for a significantly longer period of time, and had prolonged intensive care unit and overall hospital stay. Conclusion. High LTB4-levels indicate risk for PC development in multiply traumatized patients

Polyphenols of Camellia sinenesis decrease mortality, hepatic injury and generation of cytokines and reactive oxygen and nitrogen species after hemorrhage/resuscitation in rats

Background: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during hemorrhagic shock and resuscitation (H/R), which may contribute to multiple organ failure. The AIM of this study was to test the hypothesis that green tea (Camellia sinenesis) extract containing 85% polyphenols decreases injury after H/R in rats by scavenging ROS and RNS. Method: S: Female Sprague Dawley rats were given 100 mg polyphenol extract/kg body weight or vehicle 2 h prior to hemorrhagic shock. H/R was induced by two protocols: 1) withdrawal of blood to a mean arterial pressure of 40 mm Hg followed by further withdrawals to decrease blood pressure progressively to 28 mm Hg over 1 h (severe), and 2) withdrawal of blood to a sustained hypotension of 40 mm Hg for 1 h (moderate). Rats were then resuscitated over 1 h with 60% of the shed blood volume plus twice the shed blood volume of lactated Ringer's solution. Serum samples were collected at 10 min and 2 h after resuscitation. At 2 or 18 h, livers were harvested for cytokine and 3-nitrotyrosine quantification, immunohistochemical detection of 4-hydroxynonenol (4-HNE) and inducible nitric oxide synthase (iNOS) protein expression. Results: After severe H/R, 18-h survival increased from 20% after vehicle to 70% after polyphenols (p<0.05). After moderate H/R, survival was greater (80%) and not different between vehicle and polyphenols. In moderate H/R, serum alanine aminotransferase (ALT) increased at 10 min and 2 h postresuscitation to 345 and 545 IU/L, respectively. Polyphenol treatment blunted this increase to 153 and 252 IU/L at 10 min and 2 h (p<0.01). Polyphenols also blunted increases in liver homogenates of TNFalpha (7.0 pg/mg with vehicle vs. 4.9 pg/mg with polyphenols, p<0.05), IL-1beta (0.80 vs. 0.37 pg/mg, p<0.05), IL-6 (6.9 vs. 5.1 pg/mg, p<0.05) and nitrotyrosine (1.9 pg/mg vs. 0.6 pg/mg, p<0.05) measured 18 h after H/R. Hepatic 4-HNE immunostaining indicative of lipid peroxidation also decreased from 4.8% after vehicle to 1.5% after polyphenols (p<0.05). By contrast, polyphenols did not block increased iNOS expression at 2 h after H/R. CONCLUSION: Polyphenols decrease ROS/RNS formation and are beneficial after hemorrhagic shock and resuscitation

Effects of green tea catechins on the pro-inflammatory response after haemorrhage/resuscitation in rats

Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0·1% polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2)mmHg for 60min and resuscitated. Control groups (sham_ctrl and sham_GTE) underwent surgical procedures without H/R. At 2h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P<0·05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P<0·05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanis

Large Scale Structure traced by Molecular Gas at High Redshift

We present observations of redshifted CO(1-0) and CO(2-1) in a field containing an overdensity of Lyman break galaxies (LBGs) at z=5.12. Our Australia Telescope Compact Array observations were centered between two spectroscopically-confirmed z=5.12 galaxies. We place upper limits on the molecular gas masses in these two galaxies of M(H_2) <1.7 x 10^10 M_sun and <2.9 x 10^9 M_sun (2 sigma), comparable to their stellar masses. We detect an optically-faint line emitter situated between the two LBGs which we identify as warm molecular gas at z=5.1245 +/- 0.0001. This source, detected in the CO(2-1) transition but undetected in CO(1-0), has an integrated line flux of 0.106 +/- 0.012 Jy km/s, yielding an inferred gas mass M(H_2)=(1.9 +/- 0.2) x 10^10 M_sun. Molecular line emitters without detectable counterparts at optical and infrared wavelengths may be crucial tracers of structure and mass at high redshift.Comment: 4 pages, accepted for publication in ApJ Letter