The recombinant bifunctional protein αCD133-GPVI promotes repair of the infarcted myocardium in mice.

BACKGROUND: Bone-marrow-derived progenitor cells are important in myocardial repair mechanisms following prolonged ischemia. Cell-based therapy of diseased myocardium is limited by a low level of tissue engraftment. OBJECTIVES: The aim of this study was the development of the bifunctional protein αCD133-glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms. RESULTS: We have generated and characterized a bifunctional molecule (αCD133-GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133(+) progenitor cells with high affinity. αCD133-GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that αCD133-GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with αCD133-GPVI-labeled progenitor cells reduces infarction size and preserves myocardial function. CONCLUSIONS: The bifunctional trapping protein αCD133-GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.

[An unusual complication of chronic pancreatitis]. / Ungewöhnliche Komplikation eines akuten Schubs bei chronischer Pankreatitis.

Atraumatic rupture of the spleen is a rare, but life-threatening complication of pancreatitis. We report a case of an atraumatic spleenic rupture in chronic pancreatitis. A 41 year old man presented in the emergency room with abdominal pain and typical signs of acute pancreatitis. His medical history showed a chronic pancreatitis due to alcoholism with recurrent acute pancreatitic episodes. He denied any trauma in the recent past. In the next few hours he showed clinical signs of a severe hemorrhagic shock. The haemoglobin level fell from 9.4 to 3.0 g/dl. Abdominal ultrasound and abdominal CT scan showed free fluid. In the following laparotomy a splenectomy was performed due to splenic rupture. A histological examination of the spleen revealed no reason, that could explain the splenic rupture. Hence we assumed a spontaneous rupture. The reported case demonstrates that in acute pancreatitis and signs of shock it is necessary to rule out rupture of the spleen e.g. via ultrasound and abdominal CT scan. If there are signs of spleenic rupture, the only therapy of this life-threatening complication is instant operation to save patient's life.

Prevalence and spread of enterohepatic Helicobacter species in mice reared in a specific-pathogen-free animal facility.

Infections with enterohepatic Helicobacter species (EHS) can change the results of animal experiments. However, there is little information about the prevalence of EHS in noncommercial animal facilities. The aim of this study was to investigate the prevalence and the spread of EHS in specific-pathogen-free (SPF) mice. Fecal samples of 40 mouse lines were analyzed for members of the family Helicobacteraceae using a group-specific PCR targeting the 16S rRNA gene. Additional experiments were carried out to evaluate the spread of EHS among mice harbored in different caging systems. Helicobacter species were detected in 87.5% of the mouse lines tested. Five different Helicobacter species were identified: H. ganmani, H. hepaticus, H. typhlonicus, and the putative Helicobacter species represented by the isolates hamster B and MIT 98-5357. Helicobacter infection did not spread between animals in neighboring cages when individually ventilated cages were used; in contrast, when the mice were reared in open-air cages, EHS were found to spread from cage to cage. However, the spread was prevented by adding polycarbonate filter tops to the cages. When Helicobacter-negative and infected mice shared the same cage, transmission of the infection occurred in 100% within 2 weeks. Furthermore, we found that mice from commercial breeding facilities may carry undetected Helicobacter infections. Taken together, we show that infection with EHS may frequently occur and spread easily in mice reared under SPF conditions despite extensive safety precautions. Moreover, there is a high prevalence of rather uncommon Helicobacter species that may be a consequence of the current routine procedures used for health screening of SPF mice.

Randomized, placebo-controlled trial of lazaroid effects on severe acute pancreatitis in rats.

OBJECTIVES: To evaluate the therapeutic potential of lazaroids in severe necrotizing acute pancreatitis and to investigate the association between oxidative stress, protease activation, and local production of proinflammatory cytokines and the severity and lethality of the disease. BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Treatment with antioxidants, however, failed to improve survival in most studies performed so far. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack in vitro. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: Seventy-five anesthetized male Wistar rats (300-350 g). INTERVENTIONS: Severe acute pancreatitis was induced by retrograde injection of 3.5% taurocholate-sodium into the common bile-pancreatic duct. Interventions were performed to mimic the clinical situation, including continuous intravenous fluid substitution and administration of lazaroids in a therapeutic protocol. Therapy was started 1 hr after injection of the bile salt by using three different lazaroids, lactated Ringer's solution (placebo), and methylprednisolone as a corticosteroid control (n = 15 in each group). All the substances were given by continuous intravenous infusion throughout the 20-hr trial period. MEASUREMENTS AND MAIN RESULTS: Pancreatic homogenates and ascites were analyzed for indicators of oxidative stress, antioxidants, proteases, and proinflammatory cytokines. Pancreatic edema, morphologic pancreatitis severity, and pancreatic histopathology also were assessed. All three lazaroids and methylprednisolone diminished pancreatic tumor necrosis factor-alpha concentrations. Lethality was 33% in the placebo group. Neither the lazaroids nor methylprednisolone influenced survival. The local pancreatic and peritoneal concentrations of lipid peroxidation products, antioxidants, and proteases did not differ among the five groups. Nonsurviving rats, however, had a higher total protease activity in the pancreas and higher concentrations of trypsinogen activation peptide in ascites, as compared with surviving animals. There were no differences between survivors and nonsurvivors with regard to variables of oxidative stress and cytokines. CONCLUSIONS: Lazaroid application under clinically relevant conditions (i.e., after induction of fulminant acute pancreatitis) does not influence lethality or biochemical variables relevant to this disease. Protease activation rather than oxidative stress or local pancreatic cytokine production is an important determinant of disease severity and survival in acute pancreatitis. In experimental studies evaluating novel therapeutics, the same strict criteria should be applied as in the human setting.