Melatonin restores muscle regeneration and enhances muscle function after crush injury in rats.

The goal of this study was to provide evidence that melatonin improves muscle healing following blunt skeletal muscle injury. For this purpose, we used 56 rats and induced an open muscle injury. After injury, all animals received either daily melatonin or vehicle solution intraperitoneally.

Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting.

Small animal fracture models have gained increasing interest in fracture healing studies. To achieve standardized and defined study conditions, various variables must be carefully controlled when designing fracture healing experiments in mice or rats. The strain, age and sex of the animals may influence the process of fracture healing.

HMGB-1 induces c-kit+ cell microvascular rolling and adhesion via both toll-like receptor-2 and toll-like receptor-4 of endothelial cells.

High-mobility group box 1 (HMGB-1) is a strong chemo-attractive signal for both inflammatory and stem cells. The aim of this study is to evaluate the mechanisms regulating HMGB-1-mediated adhesion and rolling of c-kit(+) cells and assess whether toll-like receptor-2 (TLR-2) and toll-like receptor-4 (TLR-4) of endothelial cells or c-kit(+) cells are implicated in the activation of downstream migration signals to peripheral c-kit(+) cells. Effects of HMGB-1 on the c-kit(+) cells/endothelial interaction were evaluated by a cremaster muscle model in wild-type (WT), TLR-2 (-/-) and Tlr4 (LPS-del) mice.

N-terminal domain of alphaB-crystallin provides a conformational switch for multimerization and structural heterogeneity.

The small heat shock protein (sHSP) αB-crystallin (αB) plays a key role in the cellular protection system against stress. For decades, high-resolution structural studies on heterogeneous sHSPs have been confounded by the polydisperse nature of αB oligomers. We present an atomic-level model of full-length αB as a symmetric 24-subunit multimer based on solid-state NMR, small-angle X-ray scattering (SAXS), and EM data.

Impact of portal branch ligation on tissue regeneration, microcirculatory response and microarchitecture in portal blood-deprived and undeprived liver tissue.

Partial ligation of portal branches leads to atrophy of the deprived lobes and hypertrophy of the intact lobes. In this study we investigated the microcirculatory response and their consequences on tissue regeneration after left-sided portal branch ligation (PBL) in Sprague-Dawley rats. At day 1 and 3 after PBL the hepatic microcirculation was assessed by intravital microscopy (IVM).

[Pathophysiological basis of surgery-linked sepsis].

Infection or injury, including surgical procedures, induces an inflammatory response of the host organism. This immune response must be finely tuned and precisely regulated, because deficiencies or excesses of the inflammatory response cause morbidity and shorten the lifespan. Activated receptors of the innate immune system (pattern recognition receptors, PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) including injured tissue-associated intracellular proteins (alarmins), lead to an exaggerated immune response.

Regulation of hepatic blood flow: the hepatic arterial buffer response revisited.

The interest in the liver dates back to ancient times when it was considered to be the seat of life processes. The liver is indeed essential to life, not only due to its complex functions in biosynthesis, metabolism and clearance, but also its dramatic role as the blood volume reservoir. Among parenchymal organs, blood flow to the liver is unique due to the dual supply from the portal vein and the hepatic artery.

Mutation of mitochondrial ATP8 gene improves hepatic energy status in a murine model of acute endotoxemic liver failure.

Aims: Mitochondria not only generate and modulate bioenergy but also serve as biosensors for oxidative stress, and eventually become effector organelles for cell viability. Therefore, the implications of mitochondrial (dys)function in the development of multiple organ failure are profound. We investigated whether a mutation in the ATPase subunit-8 gene affects the course of endotoxemic acute liver failure.

Intestinal ischemia/reperfusion: microcirculatory pathology and functional consequences.

Background: Intestinal ischemia and reperfusion (I/R) is a challenging and life-threatening clinical problem with diverse causes. The delay in diagnosis and treatment contributes to the continued high in-hospital mortality rate.

Results: Experimental research during the last decades could demonstrate that microcirculatory dysfunctions are determinants for the manifestation and propagation of intestinal I/R injury.

Erythropoietin as additive of HTK preservation solution in cold ischemia/reperfusion injury of steatotic livers.

Background: Organ shortage in liver transplantation has justified usage of marginal donor livers to expand the donor organ pool. The particular susceptibility of steatotic livers to I/R injury necessitates optimal preservation conditions in order to minimize preservation-reperfusion injury for successful transplantation.

Methods: The effect of erythropoietin (EPO) as additive to HTK preservation solution was studied in a mouse model.

Uncoupling protein-2 deficient mice are not protected against warm ischemia/reperfusion injury of the liver.

Background: Uncoupling protein-2 (UCP2) might play an important role in mediating ischemia/reperfusion (I/R) injury due to its function in uncoupling of oxidative phosphorylation and in the proton leak-associated increase of reactive oxygen species (ROS) production. The aim of this study was to elucidate the role of UCP2 in hepatic I/R injury.

Materials And Methods: UCP2 wild type and UCP2 deficient mice were subjected to I/R of the left liver lobe.

Temporary angiogenic transformation of the skin graft vasculature after reperfusion.

Background: In the era of tissue engineering, the physiologic process of skin graft revascularization remains unclear, preventing the successful development of skin substitutes. Therefore, the authors developed a new in vivo model with which to visualize the process of engraftment and its microvascular architecture. The aim of this study was to specifically investigate the vascular transformations within the skin graft to gain applicable knowledge on how vascular processes during engraftment occur.

Darbepoetin-α inhibits the perpetuation of necro-inflammation and delays the progression of cholestatic fibrosis in mice.

Biliary obstruction and cholestasis result in hepatocellular necro-inflammation and lead to the development of liver fibrosis. The objective of this study was to analyze whether the multiple tissue-protective properties of erythropoietin are salutary in an experimental model of liver fibrosis. For this purpose, C57BL/6J mice underwent common bile duct ligation (BDL) and were treated with either darbepoetin-α (10 μg/kg i.

Tumour growth following portal branch ligation in an experimental model of liver metastases.

Background: Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases.

Methods: CT26.

Oxidative stress-associated rise of hepatic protein glycation increases inflammatory liver injury in uncoupling protein-2 deficient mice.

Mitochondrial dysfunction seems to be intrinsically involved in the pathogenesis of multiple organ failure because of enhanced production of reactive oxygen species and induction of oxidative damage. Chronic oxidative stress in turn causes an accumulation of advanced glycation end products (AGEs). To investigate whether mitochondrial dysfunction-associated oxidative stress leads to increased formation and accumulation of AGE, we studied hepatic glycation in uncoupling protein-2 (UCP2-/-) knockout mice.

Genistein does not affect vascularization and blood perfusion of endometriotic lesions and ovarian follicles in dorsal skinfold chambers of Syrian golden hamsters.

Genistein has previously been shown to cause regression of endometriotic lesions. In the current study, we investigated whether this observation is due to the antiangiogenic activity of genistein. Endometrial fragments and ovarian follicles were transplanted into dorsal skinfold chambers of hamsters, which were treated with genistein (50 and 200 mg/kg) or vehicle (control).

Splenectomy improves survival by increasing arterial blood supply in a rat model of reduced-size liver.

Prevention of acute portal hyperperfusion in small-for-size livers by inflow modulation results in beneficial postoperative outcome. The objective of this study was to unravel the underlying mechanism, emphasizing the intimate relationship between portal venous (PV) and hepatic arterial (HA) blood flow (BF). Rats underwent partial hepatectomy (pHx), splenectomy before pHx or splenectomy and ligation of the A.

Kupffer cell depletion reduces hepatic inflammation and apoptosis but decreases survival in abdominal sepsis.

Objective: During abdominal sepsis, the activation of hepatic Kupffer cells (KC) and its consequences are of central interest. This study evaluates the impact of selective KC depletion on hepatic microcirculation, cytokine release, and systemic alterations in the colon ascendens stent peritonitis (CASP), a model of polymicrobial abdominal sepsis.

Methods: For KC depletion clodronate liposomes were injected 24 h before CASP surgery in female C57BL/6N mice.

Genetic control of leucocyte--endothelial cell interaction in collagen-induced arthritis.

Objective: Despite considerable work on defining disease pathways, several aspects of collagen-induced arthritis (CIA) remain poorly defined, in particular those contributing to the initiation phase of the disease. It is thought that in CIA the activation of circulating leucocytes, their interaction with the endothelial lining followed by subsequent transendothelial migration and infiltration into tissue represents the first and determining step in a complex sequence of processes mediating tissue injury. In this study we attempted to define the genetic basis of this stage of disease using genetic linkage studies, in-vivo imaging and expression profiling.

[Does experimental surgery still exist?].

During the last two decades research in surgery has changed from a specific to an interdisciplinary approach. Accordingly, the research approaches in surgery show marked overlap with those of other disciplines, such as oncology, immunology, gastroenterology, cardiology and intensive care medicine. This questions the need of experimental surgery in the future.

Acute and chronic response of the right ventricle to surgically induced pressure and volume overload--an analysis of pressure-volume relations.

We aimed to determine the response of the right ventricle (RV) to surgically induced pressure and volume overload in both acute and chronic settings. Four-month-old sheep were operated via left anterior thoracotomy. Pressure overload of the RV was established by banding of the pulmonary trunk.

Open blunt crush injury of different severity determines nature and extent of local tissue regeneration and repair.

Insufficiency of skeletal muscle regeneration is often accompanied with functional deficiencies. The goal of our study was to assess the restoration of peripheral muscle upon injury of different severity. Blunt crush injury of the soleus muscle in rats was induced by a clamp and stepwise amplified in severity by rising the locking level of the clamp, resulting in three different groups (1x lock; 2x lock; 3x lock; n = 30 animals per group).