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Biomedical subjects

R Cursio

Publications and source records attributed to R Cursio.

At least 19 recordsLinked to original sources
PubMed2006

Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

BACKGROUND: This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver. METHODS: Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion. RESULTS: The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk. CONCLUSION: Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs.

Analysis of Variance↗
PubMed2006

Alterations in protein tyrosine kinase pathways in rat liver following normothermic ischemia-reperfusion.

The phosphoregulation of signal transduction pathways is a complex series of reactions that modulate the cellular response to ischemia-reperfusion (I-R). The aim of this study was to evaluate the effect of normothermic liver I-R on protein tyrosine phosphorylation, production of angiogenic growth factors, and activation of signal proteins in tyrosine kinase pathways. A segmental normothermic ischemia of the liver was induced in rats by occluding the blood vessels (including the bile duct) to the median and left lateral lobes for 120 minutes. Liver extracts from either ischemic or nonischemic lobes were prepared at 0, 1, 3, and 6 hours after reperfusion. Liver tyrosine phosphorylation of proteins was examined by Western blot analysis, whereas vascular endothelial growth factor (VEGF) mRNA was analyzed by Northern blot. In ischemic liver lobes, VEGF mRNA and total protein levels increased at 1 and 3 hours after reperfusion. Tyrosine phosphorylation of the VEGF receptor Flk-1 and the platelet-derived growth factor receptor (PDGF-R) was increased only at 1 hour after reperfusion, while c-Src tyrosine phosphorylation remained increased at 3 hours and remained up to 6 hours after reperfusion. In conclusion, 1-R led to alterations in protein tyrosine phosphorylation and increased expression of VEGF in rat liver.

Animals↗
PubMed2002

Laparoscopic tumorectomy of renal carcinoma recurred in remaining kidney.

Nephron sparing surgery is the standard treatment for small, peripherally located renal cell carcinoma. To reduce the morbidity of nephron sparing surgery laparoscopy was proposed. A case of renal carcinoma recurred in the remaining kidney successfully treated by laparoscopic approach is reported.

Aged↗
PubMed2001

[Ischemia-reperfusion].

IMPORTANCE OF ISCHEMIA-REPERFUSION LESIONS: After transplantation, ischemia-reperfusion lesions are associated with an increased risk of acute rejection, late recovery of liver function, or chronic graft dysfunction. In all, about 20% of the grafts are lost. The importance of prevention is evident. HEME-OXYGENASE: It has been shown that heme-oxygenase, an anti-oxidant reducing apoptosis, reduces the extent of ischemia-reperfusion lesions after liver, heart, kidney or Langerhans islet transplantation. OTHER COMPOUNDS WITH INTERESTING PROPERTIES: Other compounds also have interesting properties for preventing ischemia-reperfusion lesions: a specific metallo-protease inhibitor, L-arginine, a selective agonist of the PGE1 receptor, estrogens, low-dose cyclosporine, and certain immunosuppressors (FTY 720, anti CD28, anti B7-1), and rPSGL-Ig ligand.

Anti-Inflammatory Agents↗
PubMed2001

Intermittent ischemia reduces warm hypoxia-reoxygenation-induced JNK(1)/SAPK(1) activation and apoptosis in rat hepatocytes.

Prolonged liver ischemia followed by reperfusion (I/R) causes functional and structural damage to liver cells, resulting in necrosis and apoptosis. c-jun N-terminal kinase 1/stress-activated protein kinase 1 (JNK(1)/SAPK(1)) is activated during I/R and participates in the onset of the apoptosis program. Excessive blood loss during surgery can hinder postoperative recovery. Intermittent portal triad clamping (PTC) is better tolerated than prolonged continuous ischemia. This study was designed to demonstrate that intermittent ischemia could improve postischemic survival rates by a decrease of JNK(1)/SAPK(1) and caspase 3 activation, which were involved in the apoptosis process. Rats were subjected to intermittent 1-hour ischemia (15-minute ischemia/5-minute reperfusion, 4 times), followed by 220-minute reperfusion, or to continuous ischemia (1 hour), followed by 240-minute reperfusion. Mortality rates were assessed on day 7. Serum aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase levels (LDH) were measured 6 hours after ischemia. This study was completed in primary cultured isolated rat hepatocytes, subjected to the same continuous or intermittent hypoxic conditions. The activation status of JNK(1)/SAPK(1) was evaluated by immunoprecipitation or Western blotting experiments. Apoptosis was assessed by measuring caspase activation and by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) reaction. Eighty percent of the intermittent-ischemia group was alive 7 days after surgery and serum enzyme levels were significantly decreased. Intermittent hypoxia or ischemia did not lead to JNK(1)/SAPK(1) activation, but at least 3 hypoxia-reoxygenation (H/R) sets were necessary to inhibit kinase activation. Consequently, caspase 3 activation and apoptosis were dramatically reduced. Intermittent ischemia is a powerful, protective way to reduce I/R damage of the liver, by reduction of JNK(1)/SAPK(1) activation associated with a down-regulation of caspase 3 activity, which leads to inhibition of hepatocyte apoptosis.

Animals↗
PubMed2001

Successful transarterial embolization of idiopathic renal arteriovenous fistula.

A case of idiopathic renal arteriovenous fistula in a 46-year-old woman presenting intensive right renal colic associated to massive hematuria is reported. The renal arteriography confirmed the diagnosis and embolization of the fistula was performed. The transarterial embolization was successful no recurrence is observed after one year follow-up.

Arteriovenous Fistula↗
PubMed2000

Caspase inhibition protects from liver injury following ischemia and reperfusion in rats.

Normothermic ischemia and reperfusion of the liver results in microcirculatory failure followed by necrosis and cell death. Recently, another type of cell death, apoptosis or programmed cell death, was found to be activated during the early phase of reperfusion after liver ischemia. Caspases are cysteine proteinases specifically involved in the initiation and execution phases of apoptosis. The aim of this study was to demonstrate that inhibition of apoptosis by a specific inhibitor of caspases might protect the liver against ischemia/reperfusion injury. Rats were divided into three groups: group 1, control, PBS administration; group 2, Z-Asp-cmk (Z-Asp-2,6-dichlorobenzoyl-oxymethylketone) treatment; group 3, sham-operated control animals. Z-Asp-cmk (0.5 mg Z-Asp-cmk dissolved in 300 microl PBS solution containing 1% DMSO) was injected intravenously, 2 min prior to induction of 120 min ischemia. Survival rates were compared and serum activities of aspartate aminotransferases and alanine aminotransferases were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver was assessed 6 h after the end of ischemia. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling method (TUNEL method) and by electrophoresis for analysis of DNA fragmentation. Caspase activity was determined by measuring hydrolysis of the CPP32-like substrate Ac-DEVD-pNA and absorption of paranitroaniline. Z-Asp-cmk treatment significantly increased 7-day survival (95%) compared with that in nontreated rats (30%, P < 0.001). Serum activities of aminotransferases and the extent of liver congestion and necrosis were significantly (P < 0.001) decreased after treatment with Z-Asp-cmk. TUNEL-positive cells were detected 3-6 h after reperfusion in the control group. In Z-Asp-cmk pretreated rats, a dramatic decrease in the number of TUNEL-positive cells was observed. Analysis of DNA fragmentation of freshly isolated hepatocytes confirmed these results. Caspase activity was increased 3-6 h after reperfusion in the control group, but significantly (P < 0.001) decreased after treatment with Z-Asp-cmk. These findings demonstrate that liver injury following ischemia and reperfusion can be prevented by inhibition of caspases. Caspase inhibitors may have important implications for therapy in liver disease and after liver transplantation.

Alanine Transaminase↗
PubMed2000

Protein kinase activation by warm and cold hypoxia- reoxygenation in primary-cultured rat hepatocytes-JNK(1)/SAPK(1) involvement in apoptosis.

Ischemia-reperfusion procedures induced severe hepatic damages owing to different processes related to hypoxia and reoxygenation (H/R) phases, including the consecutive oxygen free radical (OFR) release. Stress-activated protein kinases (SAPKs) could be activated by extracellular stimuli. The aim of this study was to show whether H/R stress conditions could stimulate these kinases, and especially c-jun-N-terminal kinase (JNK(1)/SAPK(1)), to reveal a potential role of JNK(1)/SAPK(1) in the control of hepatocyte apoptosis. Primary cultured rat hepatocytes, isolated from other liver cells and blood flow, were subjected to warm and cold hypoxia-reoxygenation phases mimicking surgical and transplant conditions. The activation status of SAPKs was evaluated by immunoprecipitation or Western-blotting experiments, whereas apoptosis was assessed by measuring caspase activation and internucleosomal DNA fragmentation in vitro and by TUNEL reaction, in vivo. Hypoxia, and especially hypoxia-reoxygenation, significantly increased JNK(1)/SAPK(1) activation in cultured hepatocytes. Either in warm or cold conditions, OFR scavengers (N-Acetylcystein, Di-Phenyleneiodonium, Deferoxamine) decreased this stimulation. Warm ischemia-reperfusion also led to JNK activation. Hypoxia and especially hypoxia-reoxygenation induced programmed cell death in vivo and in vitro. This last phenomenon was inhibited when hepatocytes were treated with SB 202190, which was described as a potent inhibitor of p38 and JNK activities. Altogether, these results confirmed that JNK(1)/SAPK(1) was activated during the hypoxia-reoxygenation process, and that this activity participated in the onset of the apoptosis program.

Animals↗
PubMed1999

Increased risk of antibody-mediated rejection of reduced-size liver allografts.

Because of the shortage of liver allografts in children, transplantation of reduced-size liver allografts from adult cadaveric donors or living, related donors is being done more frequently. Reduced-size liver allografts may be used in cases of ABO incompatibility and T-cell warm cross-match positivity. This experimental study in inbred rats was undertaken to determine if reduced-size liver allografts are more sensitive to antibody-mediated rejection than full-size liver allografts. Brown-Norway (BN) (RT1(n)) rats were sensitized by three successive skin grafts at 10-day intervals. Then orthotopic Lewis (LEW) (RT1(1)) liver grafts were transplanted into these BN rats. Full-size liver allografts were compared with reduced-size liver allografts (70% of donor liver). Control groups were composed of full-size and/or reduced-size isografts. Titers of specific antibodies were assayed using a complement-dependent assay before and after orthotopic liver transplantation. Histological and immunofluorescence studies (IgG, IgM, C(3), and fibrinogen deposits) were assessed. Recipients of reduced-size liver allografts died of hyperacute rejection at 36.6 +/- 4.1 h, significantly earlier than recipients receiving full-size liver allografts, which died of accelerated acute rejection at 259.2 +/- 25.2 h (P < 0.001). Either full-size or reduced-size isograft recipients survived indefinitely. A decrease in the titers of donor-specific antibodies was observed in both groups of animals. Slight deposits of IgG, IgM, C(3), and fibrinogen were observed in recipients of reduced-size liver allografts, whereas larger deposits were observed in recipients of full-size liver allografts. Our data demonstrate that there is an increased risk of antibody-mediated rejection of reduced-size liver allografts in sensitized recipients. This may have important clinical implications for partial liver grafting in cases of ABO incompatibility and T-cell warm cross-match positivity.

Animals↗
PubMed1999

A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis.

Apoptosisis activated during the early phase of reperfusion after liver ischemia and after liver transplantation in animals. However, the molecular basis of ischemia-induced cell death remains poorly understood. In this study we show that hepatocytes from ischemic liver lobes undergo apoptosis after reperfusion. In vivo pretreatment of rats with a specific inhibitor of caspases abrogates the apoptotic response in ischemic liver lobes. Inhibition of apoptosis can be accounted for by total inhibition of caspase activation as assessed in an enzymatic assay and by specific affinity labeling. Treatment with a caspase inhibitor fully protects rats from death induced by ischemia/reperfusion. These findings indicate that liver injury after ischemia/reperfusion can be prevented by inhibition of caspases. Thus, caspase inhibitors may have important therapeutic implications in liver ischemic diseases and after liver transplantation.

Animals↗
PubMed1998

Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the role of the pancreas in pro-LPH maturation.

Brush border lactase-phlorizin hydrolase carries two catalytic sites. In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273. The proteolytic processing of pro-lactase-phlorizin hydrolase by (rat) enterocytes stops two amino acid residues short of the N-terminus of 'mature' final, brush border lactase-phlorizin hydrolase. Only these two amino acid residues are removed by luminal pancreatic protease(s), probably trypsin.

Amino Acid Sequence↗
PubMed1998

Improvement of normothermic rat liver ischemia/reperfusion by muramyl dipeptide.

Normothermic ischemia and reperfusion (I/R) of the liver remains a major problem after liver surgery and transplantation. Activation of Kupffer cells (KCs) after normothermic I/R is responsible for a massive release of various monokines such as tumor necrosis factor alpha (TNF-alpha) and a decrease in phagocytic activity. Muramyl dipeptide (MDP) is an immunostimulant that increases phagocytic activity of KCs. The aim of this study was to demonstrate that MDP pretreatment might protect the liver against I/R injury by a modification of KC functions. Rats were divided into three groups: group 1, control, Ringer's lactate administration; group 2, MDP (N-acetyl-muramyl-d-alanyl-d-isoglutamine) treatment; group 3, sham-operated control animals. MDP (500 microg/250 g) was injected intravenously 5 min before the induction of 90 min ischemia. Survival rates were compared and serum activities of TNF-alpha, aspartate aminotransferase, and alanine aminotransferase were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver and KC activity were assessed 6 and 9 h after the end of ischemia, respectively. MDP treatment significantly increased 7-day survival (86.6%) compared with nontreated rats (40%, P < 0.001). Serum activities of TNF-alpha and aminotransferases were significantly decreased after MDP treatment, whereas phagocytic capacity of KCs was partially restored. The extent of liver necrosis was decreased after MDP administration. A significant difference was observed for other histological parameters studied, except for steatosis. Our findings have demonstrated that MDP is able to protect the liver from ischemic insult by modulation of KC activity (TNF-alpha release and phagocytic capacity). Control of macrophage activity may offer a new strategy to reduce ischemic injury of the liver.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Prolongation of discordant heart xenograft survival after liver hemoperfusion: role of nonparenchymal liver cells.

In the discordant guinea pig (GP)-to-rat combination, heart xenografts are hyperacutely rejected. The aim of the present study was to demonstrate that a donor-species-specific extracorporeal liver hemoperfusion can prolong survival of discordant heart xenografts and to specify the role of non-parenchymal cells. GP hearts were grafted into Brown Norway rats (group 1) In group 2, heart xenografting was carried out immediately after a 15-min GP hemoperfusion. In group 3, Kupffer cells of the GP liver were blockaged by intravenous injection of dextran sulfate (4 mg/100 g) 30 min before hemoperfusion. In group 4, Kupffer cells of the liver were activated by intravenous injection of muramyl dipeptide (MDP; 500 micrograms/250 g) 24 h before hemoperfusion. Lymphocytotoxic antibodies were detected according to a complement-dependent antibody assay. A donor-specific liver hemoperfusion can delay hyperacute rejection of heart xenografts (67.6 +/- 47.1 min in group 2 versus 8.0 +/- 2.4 min in group 1; p < 0.01) and reduce the level of lymphocytotoxic antibodies. Deposits of immunoglobulins and complement were significant on the hemoperfused liver and moderate on the transplanted heart. In group 3, after blockade of Kupffer cells with dextran, heart xenograft survival was less prolonged (31.8 +/- 8.2 min) and the decrease in antibody levels was not significant and associated with moderate deposits of immunoglobulins and complement on the hemoperfused liver and significant deposits on heart xenografts. In group 4, after stimulation of Kupffer cells by MDP, a significant decrease in antibody levels was present, and significant deposits were observed. These results show that donor-specific liver hemoperfusion can prolong the survival of discordant heart xenografts and support the hypothesis that nonparenchymal liver cells play a major role by absorption of preformed antibodies and complement.

Animals↗
PubMed1996

[Laparoscopic treatment of appendiceal peritonitis in adults].

UNLABELLED: The aim of this study was to evaluate the results of laparoscopic treatment of appendicular peritonitis. PATIENTS AND METHODS: From January 1991 to December 1994, 32 patients (16 men and 16 women with a mean age of 43 years) underwent emergency laparoscopy for a clinical diagnosis of localized or generalized appendicular peritonitis. All patients had double antibiotic therapy for at least 7 days. The laparoscopic appendectomy technique consisted of:insufflation to 12 mmHg, introduction of 3 trocars, first peritoneal lavage, coagulation of the mesoappendix, ligature of the base of the appendix, no drainage. RESULTS: There were 4 conversions (12.5%). Nine of the 28 cases treated completely by laparoscopy, presented generalized peritonitis and 19 presented localized peritonitis (including 8 abscesses). The operations were performed by 7 surgeons and the mean operating time was 86 minutes. There were no deaths. The postoperative morbidity was 10.7%. The mean duration of postoperative ileus was 2.8 days. The mean hospital stay was 6.8 days. Histological examination concluded on acute suppurative appendicitis 96.4% of cases. There were no bowel obstructions or incisional hernias with a mean followup of 28.5 months. CONCLUSIONS: The laparoscopic treatment of appendicular peritonitis is possible, simple and reproducible, effective, without any specific complications. The advantages of laparoscopic techniques over the traditional large incisions are the absence of parietal complications, the quality of exploration and peritoneal lavage, and improvement of postoperative comfort.

Adolescent↗