ATSC transplantation contributes to liver regeneration following paracetamol-induced acute liver injury through differentiation into hepatic-like cells.

INTRODUCTION: Drug-induced liver injury (DILI) is a leading cause of acute liver injury (ALI). Acetaminophen (also termed paracetamol), can often be found in drugs that may be abused (i.e., prescription for pain relief). Animal experiments have shown that mesenchymal stem cell transplantation can ameliorate or even reverse hepatic injury. MATERIAL AND METHODS: ALI was induced in Wistar rats using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or intrahepatic route directly onto the liver parenchyma. Histological evaluation was conducted to assess drug-induced injury following transplantation. Fluorescence in situ hybridization (FISH) was used to verify the location of stem cells on the liver parenchyma. The effect of those cells on liver regeneration was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic growth factor (HGF), hepatic nuclear factor 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression. RESULTS: Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P<0.001). HNF4α and HGF mRNA levels were increased on day 7 following transplantation (P<0.001 and P=0.009, respectively). CYP1A2 mRNA levels were also increased (P=0.013) in the intravenous groups, while AFP levels were higher in the intrahepatic groups (P=0.006). ATSC transplantation attenuates ALI injury and promotes liver regeneration. Furthermore, expression of specific hepatic enzymes points to ATSC hepatic differentiation. CONCLUSION: The study showed the positive effects of transplanted adipose tissue stem cells (ATSCs) on liver regeneration (LG) through hepatotrophic factors. Furthermore, increased expression of hepatic specific proteins was recorded in ATSC transplanted groups that indicate stem cells differentiation into hepatic cells.

Distinctive expression profiles of Caveolin-1 and Notch-1 protein in patients with nasal polyps or sinonasal inverted papillomas.

BACKGROUND: Nasal polyposis (NP) and sinonasal inverted papillomas (SIP) are considered benign lesions capable of recurrence or malignant transformation although not with the same prevalence. Since fluctuations of Caveolin-1 and Notch-1 proteins expression have been reported in many pathologies, the current study aimed to investigate their involvement in the epithelial transformation observed in SIPs compared to NP. METHODS: Immunohistochemical expression of Caveolin-1 and Notch-1 proteins was assessed in 104 patients with sinonasal lesions (45 NP, 45 SIP and 14 NP with SIP), semiquantively (percentage times intensity). Proteins expression profiles were evaluated statistically for their correlation with patients demographic and clinicopathological variables (grade of dysplasia, inflammation, recurrence) as well as with markers of proliferation (Ki67) and apoptosis (7-AAD) as determined by flow cytometry analysis. RESULTS: SIP lesions presented increased Caveolin-1 immunopositivity compared to NP (62.2%, vs 40.9%; p = 0.045). Cytoplasmic staining was observed only in epithelium's basal and suprabasal layers. Caveolin-1 positivity was not related to Ki67 expression, apoptosis, inflammation or dysplasia, eventhough 81.8% of highly immunopositive lesions were dysplastic (p = 0.03). Also, smokers presented significantly increased immunopositivy (p = 0.03). In contrast SIP lesions presented reduced Notch-1 expression compared to NP (68.9% vs 100%; p < 0.001). Dysplastic lesions presented low Notch-1 immunopositivity (p < 0.001). Enhancement of Notch-1 gene expression was also associated with inflammation. CONCLUSIONS: The herein presented data suggest that the expression profiles of Caveolin-1 and Notch-1 proteins in sinonasal pathologies are distinctive and that could be explored as potential targets for the development of alternative therapeutic approaches.

Modulation of IL-2 expression after uptake of hepatitis C virus non-enveloped capsid-like particles: the role of p38 kinase.

Hepatitis C virus (HCV) has been shown to actively replicate in cells of the immune system, altering both their function and cytokine expression. Naked nucleocapsids have been reported in the serum of infected patients. We investigated interference of recombinant non-enveloped capsid-like particles with signaling pathways in T cells. HCV non-enveloped particles (HCVne) internalization was verified in Jurkat and Hut 78 T cells, as well as primary human peripheral blood and intrahepatic mononuclear cells. HCVne uptake leads to activation of the MAPKs-p38 signaling pathway. Using specific phosphoantibodies, signaling pathways inhibitors, and chemical agents, it was demonstrated that p38 activation in T cells correlated with IL-2 transcriptional activation and was accompanied by a parallel increase of IL-2 cytokine secretion. c-fos and egr-1, two transcription factors, essential for IL-2 promoter activity, were also found to be elevated. We propose that HCVne uptake by T lymphocytes results in increased MAPKs-p38 activity and IL-2 expression, thus altering the host immune response.

Laparoscopic cholecystectomy in cirrhotic patients with symptomatic gallstone disease.

BACKGROUND: The aim of this study was to evaluate the outcome in patients with liver cirrhosis who underwent laparoscopic cholecystectomy for symptomatic gallstone disease. METHODS: Retrospective analysis of prospectively collected data of 34 patients operated between March 1998 and April 2006. RESULTS: There were 19 male and 15 female patients with a median age of 62 years. Cirrhosis aetiology was viral hepatitis in 25 patients, alcohol in 6, primary biliary cirrhosis in 2 and in 1 patient the cause was not identified. Twenty-three were classified as Child-Pugh-Turcotte stage A and 11 as Child-Pugh-Turcotte stage B. The median Model For End-Stage Liver Disease score was 12. Median operating time was 96 min. In three patients there was conversion to open cholecystectomy. Postoperatively, one patient died and six more patients had complications. Median postoperative stay was 3 days. Patients with acute cholecystitis did not have increased morbidity, but had significantly longer hospital stay. CONCLUSION: Laparoscopic cholecystectomy can be carried out with acceptable morbidity in selected patients with well-compensated Child A and B stages liver cirrhosis. Patients with evidence of significant portal hypertension and severe coagulopathy should avoid surgery.

The use of spray electrocautery to control presacral bleeding: a report of four cases.

Bleeding originating from the presacral venous plexus during pelvic operations is difficult to control, constituting a potentially life-threatening complication. Although suture ligatures, packing, and placement of tacks are established hemostatic techniques, they are often proved to be ineffective. We report a simple novel technique using spray diathermy for managing this severe complication. We have applied our method in four patients, two undergoing low anterior resection, and the others undergoing abdominoperineal resection for rectal cancer, that manifested severe presacral bleeding during rectal mobilization. Electrocautery at spray setting was applied slightly above the target bleeders at the presacral fascia, delivering a high-frequency electrical current in combination with drainage suction. In all cases, the method resulted in successful hemostasis. Applying spray electrocautery is a simple and effective method for controlling presacral bleeding. The advantages of using such a method instead of conventional hemostatic techniques include the option of varying the degree of haemostatic effect by altering the frequency and the volume of electric current.