Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis

Transferrin receptor 2 (TfR2) is a membrane glycoprotein that mediates cellular iron uptake from holotransferrin. Homozygous mutations of this gene cause one form of hereditary hemochromatosis in humans. We recently reported that homozygous TfR2(Y245X) mutant mice, which correspond to the TfR2(Y250X) mutation in humans, showed a phenotype similar to hereditary hemochromatosis. In this study, we further analyzed the phenotype as well as iron-related gene expression in these mice by comparing the TfR2-mutant and wild-type siblings. Northern blot analyses showed that the levels of expression of hepcidin mRNA in the liver were generally lower, whereas those of duodenal DMT1, the main transporter for uptake of dietary iron, were higher in the TfR2-mutant mice as compared to the wild-type siblings. Expression of hepcidin mRNA in the TfR2 mutant mice remained low even after intraperitoneal iron loading. In isolated hepatocytes from both wild-type and TfR2 mutant mice, interleukin-6 and lipopolysaccharide each induced expression of hepcidin mRNA. These results suggest that up-regulation of hepcidin expression by inflammatory stimuli is independent of TfR2 and that TfR2 is upstream of hepcidin in the regulatory pathway of body iron homeostasis.     

Wound repair during arm regeneration in the red starfish Echinaster sepositus

Starfish can regenerate entire arms following their loss by both autotomic and traumatic amputation. Although the overall regenerative process has been studied several times in different asteroid species, there is still a considerable gap of knowledge as far as the detailed aspects of the repair phase at tissue and cellular level are concerned, particularly in post‐traumatic regeneration. The present work is focused on the arm regeneration model in the Mediterranean red starfish Echinaster sepositus; to describe the early cellular mechanisms of arm regeneration following traumatic amputation, different microscopy techniques were employed. In E. sepositus, the repair phase was characterized by prompt wound healing by a syncytial network of phagocytes and re‐epithelialisation followed by a localized subepidermal oedematous area formation. Scattered and apparently undifferentiated cells, intermixed with numerous phagocytes, were frequently found in the wound area during these first stages of regeneration and extensive dedifferentiation phenomena were seen at the level of the stump, particularly in the muscle bundles. A true localized blastema did not form. Our results confirm that regeneration in asteroids mainly relies on morphallactic processes, consisting in extensive rearrangement of the existing tissues which contribute to the new tissues through cell dedifferentiation, redifferentiation, and/or migration.     

Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts. METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133(+) progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts. RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133(+) progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.     

Gallbladder disease in patients with primary sclerosing cholangitis

BACKGROUND/AIMS: Gallbladder abnormalities may be part of the spectrum in primary sclerosing cholangitis (PSC). The aim of the present study was to evaluate the occurrence and prognostic importance of gallbladder abnormalities in patients with PSC. METHODS: Presence of gallbladder abnormalities was assessed in 286 patients with PSC treated at the Liver Unit, Karolinska University Hospital, Huddinge, between 1970 and 2005. RESULTS: One or more gallbladder abnormalities were found in 41% of the patients. Gallstones were found in 25% and cholecystitis in 25%. Cholecystitis among patients with extrahepatic involvement of PSC (30% (65/214)) was significantly higher than among those with intrahepatic involvement (9% (6/70)) (P<0.0001). A gallbladder mass lesion with a mean size of 21 (+/-9) mm (S.D.) was found in 18 (6%) patients, in 56% (10/18) of whom it constituted gallbladder carcinoma. In 9 patients without a gallbladder mass lesion, histological re-evaluation disclosed epithelial dysplasia of the gallbladder. CONCLUSIONS: Gallbladder disease is common in patients with PSC. Dysplasia and carcinoma are commonly found in gallbladder epithelium, suggesting that regular examination of the gallbladder in PSC patients could be of value for early detection of a gallbladder mass lesion. Cholecystectomy is recommended when such a lesion is detected, regardless of its size.     

Isolated Roux loop pancreaticojejunostomy versus pancreaticogastrostomy after pancreaticoduodenectomy: a prospective randomized study

Objectives

The optimal strategy for the reconstruction of the pancreas following pancreaticoduodenectomy (PD) is still debated. The aim of this study was to compare the outcomes of isolated Roux loop pancreaticojejunostomy (IRPJ) with those of pancreaticogastrostomy (PG) after PD.

Methods

Consecutive patients submitted to PD were randomized to either method of reconstruction. The primary outcome measure was the rate of postoperative pancreatic fistula (POPF). Secondary outcomes included operative time, day to resumption of oral feeding, postoperative morbidity and mortality, and exocrine and endocrine pancreatic functions.

Results

Ninety patients treated by PD were included in the study. The median total operative time was significantly longer in the IRPJ group (320 min versus 300 min; P = 0.047). Postoperative pancreatic fistula developed in nine of 45 patients in the IRPJ group and 10 of 45 patients in the PG group (P = 0.796). Seven IRPJ patients and four PG patients had POPF of type B or C (P = 0.710). Time to resumption of oral feeding was shorter in the IRPJ group (P = 0.03). Steatorrhea at 1 year was reported in nine of 42 IRPJ patients and 18 of 41 PG patients (P = 0.029). Albumin levels at 1 year were 3.6 g/dl in the IRPJ group and 3.3 g/dl in the PG group (P = 0.001).

Conclusions

Isolated Roux loop PJ was not associated with a lower rate of POPF, but was associated with a decrease in the incidence of postoperative steatorrhea. The technique allowed for early oral feeding and the maintenance of oral feeding even if POPF developed.