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1.
Cell Death Dis ; 5: e1208, 2014 May 08.
Article in English | MEDLINE | ID: mdl-24810044

ABSTRACT

Osteopontin (OPN) is a multifunctional protein involved in hepatic steatosis, inflammation, fibrosis and cancer progression. However, its role in hepatic injury induced by ischemia-reperfusion (I-R) has not yet been investigated. We show here that hepatic warm ischemia for 45 min followed by reperfusion for 4 h induced the upregulation of the hepatic and systemic level of OPN in mice. Plasma aspartate aminotransferase and alanine aminotransferase levels were strongly increased in Opn(-/-) mice compared with wild-type (Wt) mice after I-R, and histological analysis of the liver revealed a significantly higher incidence of necrosis of hepatocytes. In addition, the expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNFα), interleukin 6 (IL6) and interferon-γ were strongly upregulated in Opn(-/-) mice versus Wt mice after I-R. One explanation for these responses could be the vulnerability of the OPN-deficient hepatocyte. Indeed, the downregulation of OPN in primary and AML12 hepatocytes decreased cell viability in the basal state and sensitized AML12 hepatocytes to cell death induced by oxygen-glucose deprivation and TNFα. Further, the downregulation of OPN in AML12 hepatocytes caused a strong decrease in the expression of anti-apoptotic Bcl2 and in the ATP level. The hepatic expression of Bcl2 also decreased in Opn(-/-) mice versus Wt mice livers after I-R. Another explanation could be the regulation of the macrophage activity by OPN. In RAW macrophages, the downregulation of OPN enhanced iNOS expression in the basal state and sensitized macrophages to inflammatory signals, as evaluated by the upregulation of iNOS, TNFα and IL6 in response to lipopolysaccharide. In conclusion, OPN partially protects from hepatic injury and inflammation induced in this experimental model of liver I-R. This could be due to its ability to partially prevent death of hepatocytes and to limit the production of toxic iNOS-derived NO by macrophages.


Subject(s)
Hepatocytes/metabolism , Liver/blood supply , Liver/metabolism , Osteopontin/deficiency , Reperfusion Injury/metabolism , Adenosine Triphosphate/metabolism , Alanine Transaminase/blood , Animals , Apoptosis , Aspartate Aminotransferases/blood , Cell Line , Disease Models, Animal , Hepatocytes/immunology , Hepatocytes/pathology , Inflammation Mediators/metabolism , Interferon-gamma/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Liver/immunology , Liver/pathology , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Necrosis , Nitric Oxide Synthase Type II/metabolism , Osteopontin/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA Interference , Reperfusion Injury/genetics , Reperfusion Injury/immunology , Reperfusion Injury/pathology , Transfection , Tumor Necrosis Factor-alpha/metabolism , Warm Ischemia
2.
Arch Pediatr ; 19(5): 484-7, 2012 May.
Article in French | MEDLINE | ID: mdl-22463958

ABSTRACT

Post-traumatic small-bowel obstructions are rare and late complications following blunt abdominal trauma. Timely diagnosis is frequently impeded because of nonspecific associated symptoms, and furthermore, the degree of urgency is frequently underestimated due to the accidental cause. During the last 6 years (2005-2011), we have observed only 2 cases (4 and 10 years old) with post-traumatic small-bowel obstruction. On admission the patients had a contusion on the abdominal wall, duodenal hematoma and a Chance fracture of the lumbar spine on the computed tomography (CT) scan. Although early clinical improvement was noted, progression of the disorder was observed for the following 15 days like an occlusive syndrome (abdominal distension, nausea, emesis). Abdominal ultrasound and computed tomography scan revealed small-bowel obstruction. At laparotomy, jejunal stenosis was found associated with mesenteric tears, which was resected with end-to-end anastomosis. Six to 8 months of follow-up ascertained the therapeutic efficacy of the procedure. Post-traumatic small-bowel obstructions are rare; the clinical presentation is unspecific and appears with a time lag following the trauma. Echography and computed tomography scan can establish both the diagnosis and therapeutic choice.


Subject(s)
Abdominal Injuries/complications , Intestinal Obstruction/etiology , Jejunal Diseases/etiology , Child , Child, Preschool , Humans , Male , Retrospective Studies
3.
J Pediatr Urol ; 5(6): 466-71, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19428305

ABSTRACT

PURPOSE: To evaluate our results with a new method of intravesical ureteric reimplantation using laparoscopic pneumovesicum in children. MATERIALS AND METHODS: Seventy-two patients (mean age 4.2 years, range 0.5-20 years) with primary vesicoureteral reflux (VUR) underwent a laparoscopic transtrigonal ureteric reimplantation with CO(2) pneumovesicum. Ports were inserted suprapubically - 5mm for the camera and two 3-5-mm working ports. Having mobilized the ureter(s) intravesically, a submucosal tunnel is created and ureteric reimplantation performed with 5/0 and 6/0 absorbable sutures. Bladder drainage was maintained for 2-3 days postoperatively. Patients were followed up with clinical assessment and renal ultrasonography+/-voiding cystourethrogram. RESULTS: Ninety percent had VUR grade > or =3. A total of 113 ureters were reimplanted. The mean operative time was 82min for unilateral and 130min for bilateral reimplantation. Four cases (6%) were converted. Three patients presented with temporary ureteric dilatation without symptoms on follow-up renal ultrasound. Seven patients had postoperative urinary tract infection without persistent reflux on cystography. Follow-up cystogram was performed in 50 patients (81 ureters). Reflux persisted in four patients (8%). CONCLUSIONS: Laparoscopic ureteric reimplantation with CO(2) pneumovesicum is technically feasible with a high success rate (92%). The role of this new technique in the treatment of VUR remains to be determined.


Subject(s)
Laparoscopy , Ureter/surgery , Vesico-Ureteral Reflux/surgery , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Urinary Bladder , Urologic Surgical Procedures/methods , Young Adult
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