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Transaminases, γ-GT and alcalic phosphatase are classically termed as liver enzymes, however they can be found in almost every organ. Elevated levels of the transaminases ALAT (alanin-aminotransferase) and ASAT (aspartat-aminotransferase) are signs of disturbed permeability of the cells, in which these enzymes can be found. In contrast to ALAT, which is mainly liver-specific, the ASAT is found in other organs as well, e.g. heart and skeletal muscle. At a mild elevation of these enzymes a reevaluation is recommended, however if an elevation persists and is suspicious for a liver disease, a specific work up is necessary. In this manuscript, we discuss often overlooked problems and provide a diagnostic algorithm for the workup of elevated liver enzymes. [ABSTRACT FROM AUTHOR]

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1·73 m2] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1·73 m2) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from − 1·05 ml/min per month to − 0·15 ml/min per month ( P = 0·024) and proteinuria decreased from 2·4 g/l to 1·0 g/l ( P = 0·015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5·2 years (median; range 0·4–8·8) after the first IVIg pulse, and after 1·3 years (median; range 0·8–2·4) in the control group ( P = 0·043). In Kaplan–Meier analysis, the median renal survival time with IVIg was prolonged by 3·5 years (IVIg 4·7 years versus control 1·2 years; P = 0·006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN. [ABSTRACT FROM AUTHOR]

Deeper insight into pathogenetic pathways and into the biological effects of immunomodulatory agents will help to optimize or adopt therapeutic strategies for atopic disorders. In this article, we highlight selected findings of potential therapeutic relevance that emerged from recent mechanistic studies with focus on molecular and cellular aspects of allergic inflammation. Furthermore, the often complex mechanisms of action of pleiotropic immunomodulatory agents, such as glucocorticoids, vitamin D, or intravenous immunoglobulin ( IVIG), are discussed, as their dissection might reveal targets for novel therapeutics or lead to a more rational use of these compounds. Besides reporting novel evidence, this article points to areas of current debate or uncertainty and aims at stimulating scientific discussion and experimental work. [ABSTRACT FROM AUTHOR]

Introduction The relevance of tissue oxygenation in the pathogenesis of organ dysfunction during sepsis is controversial. We compared oxygen transport, lactate metabolism, and mitochondrial function in pigs with septic shock, cardiogenic shock, or hypoxic hypoxia. Methods Thirty-two anaesthetized, ventilated pigs were randomized to faecal peritonitis ( P), cardiac tamponade ( CT), hypoxic hypoxia ( HH) or controls. Systemic and regional blood flows, lactate, mitochondrial respiration, and tissue hypoxia-inducible factor 1 alpha ( HIF-1α) were measured for 24 h. Results Mortality was 50% in each intervention group. While systemic oxygen consumption ( VO2) was maintained in all groups, hepatic VO2 tended to decrease in CT [0.84 (0.5-1.3) vs. 0.42 (0.06-0.8)/ml/min/kg; P = 0.06]. In P, fractional hepatic, celiac trunk, and portal vein blood flows, and especially renal blood flow [by 46 (14-91)%; P = 0.001] decreased. In CT, renal blood flow [by 50.4 (23-81)%; P = 0.004] and in HH, superior mesenteric blood flow decreased [by 38.9 (16-100)%, P = 0.009]. Hepatic lactate influx increased > 100% in P and HH, and > 200% in CT (all P < 0.02). Hepatic lactate uptake remained unchanged in P and HH and converted to release in CT. Mitochondrial respiration remained normal. Muscle adenosine triphosphate ( ATP) concentrations decreased in P (5.9 ± 1.4 μmol/g wt vs. 2.8 ± 2.7 μmol/g wt, P = 0.04). HIF-1α expression was not detectable in any group. Conclusion We conclude that despite shock and renal hypoperfusion, tissue hypoxia is not a major pathophysiological issue in early and established faecal peritonitis. The reasons for reduced skeletal muscle tissue ATP levels in the presence of well-preserved in-vitro muscle mitochondrial respiration should be further investigated. [ABSTRACT FROM AUTHOR]