In many liver disorders inflammation and apoptosis are important pathogenic components, finally leading to acute liver failure. Erythropoietin and its analogues are known to affect the interaction between apoptosis and inflammation in brain, kidney, and myocardium. The present study aimed to determine whether these pleiotropic actions also exert hepatoprotection in a model of acute liver injury. C57BL/6J mice were challenged with D-galactosamine (Gal) and Escherichia coli lipopolysaccharide (LPS) and studied 6 hours thereafter. Animals were either pretreated (24 hours before Gal-LPS exposure) or posttreated (30 minutes after Gal-LPS exposure) with darbepoetin-␣ (DPO, 10 g/kg i.v.). Control mice received physiological saline. Administration of Gal-LPS caused systemic cytokine release and provoked marked hepatic damage, characterized by leukocyte recruitment and microvascular perfusion failure, caspase-3 activation, and hepatocellular apoptosis as well as enzyme release and necrotic cell death. DPO-pretreated and -posttreated mice showed diminished systemic cytokine concentrations, intrahepatic leukocyte accumulation, and hepatic perfusion failure. Hepatocellular apoptosis was significantly reduced by 50 to 75% after DPO pretreatment as well as posttreatment. In addition, treatment with DPO also significantly abrogated necrotic cell death and liver enzyme release. In conclusion, these observations may stimulate the evaluation of DPO as hepatoprotective therapy in patients with acute liver injury.
BackgroundLiver resection and the use of small-for-size grafts are restricted by the necessity to provide a sufficient amount of functional liver mass. Only few promising strategies to maximize liver regeneration are available. Apart from its erythropoiesis-stimulating effect, erythropoietin (EPO) has meanwhile been recognized as mitogenic, tissue-protective, and anti-apoptotic pleiotropic cytokine. Thus, EPO may support regeneration of hepatic tissue.MethodologyRats undergoing 68% hepatectomy received daily either high dose (5000 IU/kg bw iv) or low dose (500 IU/kg bw iv) recombinant human EPO or equal amounts of physiologic saline. Parameters of liver regeneration and hepatocellular apoptosis were assessed at 24 h, 48 h and 5 d after resection. In addition, red blood cell count, hematocrit and serum EPO levels as well as plasma concentrations of TNF-α and IL-6 were evaluated. Further, hepatic Bcl-xL and Bax protein expression were analyzed by Western blot.Principal FindingsAdministration of EPO significantly reduced the expression of PCNA at 24 h followed by a significant decrease in restitution of liver mass at day 5 after partial hepatectomy. EPO increased TNF-α levels and shifted the Bcl-xL to Bax ratio towards the pro-apoptotic Bax resulting in significantly increased hepatocellular apoptosis.ConclusionsMultiple doses of EPO after partial hepatectomy increase hepatocellular apoptosis and impair liver regeneration in rats. Thus, careful consideration should be made in pre- and post-operative recombinant human EPO administration in the setting of liver resection and transplantation.
BackgroundThere are conflicting reports about the fitness status of European adults, partly due to the lack of a standardized fitness test battery used across Europe. The European Fitness Badge (EFB) was developed in 2017 as an online-based tool to assess the health-related fitness of persons aged ≥ 18 years residing in European countries. We examined the demographic characteristics and fitness status of persons who completed the EFB between June 2017 and May 2019.MethodsWe conducted a multinational study in eight European countries. Participants completed the EFB which includes 11 validated motor tests to measure endurance, strength, coordination, and flexibility performance, under the supervision of an EFB instructor in different settings (e.g., sports club sessions, public events). Two different test batteries [test profiles (TPs)] are available to distinguish between less active (TP1) and active individuals (TP2). We calculated descriptive statistics and conducted analyses of variance to examine sample characteristics and a potential impact of sex, age, body mass index (BMI), physical activity, and posture on fitness as assessed by the EFB.ResultsThe sample included 6,019 adults (68.7% females; mean age 52.7 years; age range 18–89 years). Participants who completed TP1 were older (TP1: 61.4 years; TP2: 44.2 years; p = 0.00), reported a lower level of physical activity (TP1: 3.8; TP2: 4.0; p = 0.00), had a higher BMI (TP1: 25.7; TP2: 24.3; p = 0.00) and a higher frequency of postural abnormalities (TP1: 43%; TP2: 33%; p = 0.00) than TP2 participants. Among 3,034 participants who completed TP2, males had higher performance in endurance, strength, and overall fitness, whereas females performed better in coordination and flexibility tests. In addition, younger age, lower BMI, and higher level of physical activity engagement were associated with better EFB test performance.ConclusionThe EFB can be used to assess the health-related fitness status of individuals aged ≥ 18 years. Our results show that TP1 and TP2 were completed by persons from the respective target groups (i.e., less active vs. active), and also confirm findings from previous studies on potential determinants of fitness such as sex or age.
ZusammenfassungBereits im Kindes- und Jugendalter gilt die motorische Leistungsfähigkeit als wichtiger Gesundheitsmarker. Auf Basis von Daten der Motorik Modul-Studie wird in diesem Artikel längsschnittlich über die Jahre 2003–2017 untersucht, inwieweit sich Sportvereinsmitglieder, die konstant im Sportverein aktiv waren, hinsichtlich ihrer motorischen Entwicklung von denjenigen unterscheiden, die nie im Sportverein aktiv waren. Es wurden Daten aus drei Messwellen untersucht: T1 (2003–2006), T2 (2009–2012) und T3 (2014–2017). Aus insgesamt N = 1092 Teilnehmenden, von denen über T1 bis T3 Daten zur Motorik vorlagen, wurden all diejenigen mit konstanter Mitgliedschaft und Nicht-Mitgliedschaft im Sportverein über drei Messwellen ausgewählt. Das sind 46 % der Gesamtstichprobe (N = 498). Von den N = 498 Teilnehmer*innen (Alter T1: 8,9 ± 3,8 Jahre, T2: 15,1 ± 3,9 Jahre, T3: 20,3 ± 4,0 Jahre) waren 15 % dauerhafte Sportvereinsmitglieder mit Wettkampfengagement, 53 % dauerhafte Sportvereinsmitglieder ohne Wettkampfengagement sowie 32 % dauerhaft Sportvereinsabstinente. Zur Ermittlung der motorischen Leistungsfähigkeit wurden konditionelle und koordinative Fähigkeiten anhand des MoMo-Testprofils erhoben (Kondition: Standweitsprung, Liegestütz, Fahrrad-Ausdauertest, Koordination: Seitliches Hin- und Herspringen, Einbeinstand, Balancieren rückwärts). Die Unterschiede in der Entwicklung wurden anhand von alters- und geschlechtsadjustierten Perzentilen mittels Varianzanalysen mit Messwiederholung berechnet, mit dem Sozialstatus als Kovariate. Innerhalb der Sportvereinsmitglieder waren Teilnehmende mit niedrigem Sozialstatus deutlich unterrepräsentiert. Insgesamt betrachtet, ist die Entwicklung der koordinativen und konditionellen Fähigkeiten bei Sportvereinsmitgliedern als signifikant besser zu beurteilen im Vergleich zu Sportvereinsabstinenten (Modell Koordination * Sportverein: df = 3,870 | F = 2,931 | p = 0,021 | ETA = 0,015 | f = 0,123; Modell Kondition * Sportverein: df = 4 | F = 3,794 | p = 0,005 | ETA = 0,048 | f = 0,225). Die Ergebnisse untermauern die Wichtigkeit der Sportvereine für die motorische Entwicklung von Kindern, Jugendlichen und jungen Erwachsenen in Deutschland.
SUMMARYWe present a case of an XX male with carcinoma of the breast and primary infertility. He was admitted to hospital with recurrent chest pains, but a history of surgery for breast carcinoma, gynaecomastia and the finding of bilaterally atrophied testes, coupled with the fact that he had never fathered children, necessitated further investigations. Chromosomal analysis showed a 46, XX male genotype with a normal X chromosome and an abnormal X chromosome formed by translocation between the short arm of one X chromosome and the Y chromosome. By using fluorescence in situ hybridisation, the patient proved to be SRY positive, the sex‐determining region of the Y chromosome. In this rare genetic abnormality males retain normal phenotype but they are generally of short stature, have gynaecomastia, and may have genital anomalies. They are infertile and at increased risk of developing carcinoma of the breast. This seems to be the first documented case of carcinoma of the breast in an SRY positive XX male. This particular case illustrates the need for all cases of male breast cancer to undergo full endocrinological assessment, especially in the presence of genital anomaly or infertility. (Int J Clin Pract 2003; 57(9): 844–845)
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