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J Gugenheim

Publications and source records attributed to J Gugenheim.

At least 37 records · Page 2Linked to original sources
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↗
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

Hypoxia-reoxygenation differentially stimulates stress-activated protein kinases in primary-cultured rat hepatocytes.

Organ injury after ischemia and reperfusion (I/R) remains one of the most important limiting factors in liver surgery and transplantation. Oxygen-free radical (OFR) generation is considered a major cause of this damage. JNK1/SAPK1, a member of MAPK family, regulates cell adaptation to stressful conditions. The aim of this study was to determine if hypoxia-reoxygenation (H/R) can activate JNK1/SAPK1 and if OFR are involved in this activation. Primary cultured rat hepatocytes isolated from other liver cells and blood flow were submitted to warm and cold H/R phases mimicking surgical and transplant conditions. JNK1/SAPK1 was activated by both warm and cold H/R. Deferoxamine (1 mM), di-phenyleneiodonium (50 microM) and N-acetylcysteine (10 mM) significantly inhibited this kinase activation.

Animals↗
PubMed2000

Possibilities of laparoscopic liver resection.

The aim of this study was to report the results of our experience in liver surgery by laparoscopy. From 1989 to 1996, 30 patients (20 women, 10 men; age, 23-88 years; mean age, 53.9 years) underwent laparoscopic liver surgery at our Institute for the following pathology: 10 for biliary cysts, 7 for polycystic diseases, 8 for benign tumors, 3 for hydatid cysts, 1 for chronic abscess, and 1 for metastasis. The locations of these lesions were: 19 in the left lobe, 4 in the right lobe, and 7 in both lobes. Their average size was 8. 45 cm (range, 2.5-22 cm). The largest lesions were biliary cysts; among benign tumors, the maximum diameter was 8 cm. Surgical treatment was as follows: 17 deroofings, 3 pericystectomies, 7 tumorectomies, and 3 left lobectomies. The mean operative time was 79 min (range, 45-527 min). Three of the 30 laparoscopic procedures (10%) were converted to open surgery, because of bleeding in 2 patients with polycystic disease and because it was impossible to carry out the dissection in 1 patient with liver-cell adenoma adjacent to the left portal branch. There were no deaths in this series and 6 patients showed morbidity: 2 patients with polycystic disease developed ascites and required intensive care unit recovery, 1 patient had phlebitis, 1 had infection of the urinary tract, and 2 had local septic complications. Preliminary findings show that the laparoscopic approach to liver lesions may represent safe and effective treatment in selected patients, on condition that several technical details are respected. Of fundamental importance are the surgical equipment, the presence of two experienced operators to do four-hands surgery, and the careful selection of indications, reserving laparoscopic treatment only for those lesions located in easily accessible areas, mainly in the lateral and anterior hepatic segments.

Adult↗
PubMed2000

Laparoscopic management of benign cystic lesions of the liver.

We present our experience in the laparoscopic management of benign liver cysts. The aim of the study was to analyze the technical feasibility of such management and to evaluate safety and outcome on follow-up. Between September 1990 and October 1997, 31 patients underwent laparoscopic liver surgery for benign cystic lesions. Indications were: solitary giant liver cysts (n = 16); polycystic liver disease (PLD; n = 9); and hydatid cysts (n = 6). All giant solitary liver cysts were considered for laparoscopy. Only patients with PLD and large dominant cysts located in anterior liver segments, and patients with large hydatid cysts, regardless of segment or small partially calcified cysts in a safe laparoscopic segment, were included. Patients with cholangitis, cirrhosis, and significant cardiac disease were excluded. Data were collected prospectively. The procedures were completed laparoscopically in 29 patients. The median size of the solitary liver cysts was 14 cm (range, 7-22 cm). Conversion to laparotomy occurred in 2 patients (6.4%), to control bleeding. The median operative time was 141 min (range, 94-165 min) for patients with PLD and 179 min (range, 88-211 min) for patients with hydatid cysts. All solitary liver cysts were fenestrated in less than 1 h. There were no deaths. Complications occurred in 6 patients (19%). Two hemorrhagic and two infectious complications were noted after management of hydatid cysts. Three patients were transfused. The median length of hospital stay was 1.3 days (range, 1-3 days), 3 days (range, 2-7 days), and 5 days (range, 2-17 days) for solitary cyst, PLD, and hydatid cysts, respectively. Median follow-up was 30 months (range, 3-78 months). There was no recurrence of solitary liver cyst or hydatid cysts. One patient with PLD presented with symptomatic recurrent cysts at 6 months, requiring laparotomy. We conclude that laparoscopic liver surgery can be accomplished safely in patients with giant solitary cysts, regardless of location. The laparoscopic management of polycystic liver disease should be reserved for patients with a limited number of large, anteriorly located cysts. Hydatid disease is best treated through an open approach.

Adult↗
PubMed2000

[Vaccination by suicide gene therapy against a model of hepatic metastasis from colon cancer in the rat].

UNLABELLED: Suicide gene therapy consists of transferring into tumor cells a viral or bacterial gene encoding for an enzyme which converts a non-toxic product into a lethal drug. STUDY AIM: To analyze the therapeutic potential of vaccination with tumor cells expressing the bacterial cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) treatment in a rat liver metastasis model. MATERIAL AND METHOD: We used a rat colon carcinoma cell line which, after subcapsular or intraportal injection in syngenic animals, generates single or multiple experimental liver metastases, respectively. We have shown that introduction of a vector expressing the CD gene in this colon carcinoma cell line results in 5-FC sensitivity (PRObCD). RESULTS: Intrahepatic subcapsular injection of PRObCD tumor cells, followed by 5-FC treatment, induces total regression of a wild-type tumor pre-established in the contralateral liver lobe in 45% of animals with a 96% decrease in mean volume (p < 0.0001), demonstrating the existence of a distant bystander effect. This vaccination significantly increased the survival of rats with single (log-rank p < 0.0001) or multiple (log-rank p = 0.01) liver metastasis CONCLUSIONS: These results suggest that suicide gene-modified tumor cells can act as potent therapeutic vaccines against liver metastasis from colon carcinoma.

Animals↗
PubMed2000

[Surgical treatment of anterior rectoceles in women. The transanal approach].

Anterior rectocele is a herniation of the anterior rectal wall into the vagina, which may be either isolated or associated with other pelvic floor disorders. Rectocele could result in outlet obstruction with dyschezia, manual extraction of faeces and/or false incontinence. Rectocele is diagnosed clinically, and can be confirmed by defecography. Other tests may demonstrate associated causes of constipation. Symptomatic rectoceles can be treated via a transrectal route, with two or three layers of plication of the rectal wall and excision of the redundant mucosal flap. The results of transrectal repair are good: short hospital stay, no mortality, morbidity less than 5%, good short- and mid-term results in approximately 80% of cases. Selection criteria in favour of the transrectal approach have not been clearly identified.

Anal Canal↗
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↗
PubMed2000

Effects of macrolide antibiotics on CYP3A expression in human and rat hepatocytes: interspecies differences in response to troleandomycin.

The effects of various macrolide antibiotics [triacetyloleandomycin (TAO), clarithromycin, azithromycin, roxithromycin, erythromycin base] and the new ketolide HMR3004 on CYP3A expression were evaluated in human and rat hepatocytes. Cells were treated for 3 days with nontoxic concentrations of the drugs, and CYP3A induction was assessed through midazolam hydroxylase activity and Western and Northern blot analyses. In rat hepatocytes, no induction of CYP3A1 expression was observed following exposure to macrolides, even to erythromycin base and TAO (well known in vivo CYP3A1 inducers), whereas dexamethasone and phenobarbital were confirmed to induce this enzyme. In contrast, treatment of fresh and thawed human hepatocytes with TAO, produced an increase of midazolam hydroxylation (4-fold over control). This result was in agreement with the high amount of CYP3A4 protein and mRNA revealed by Western and Northern blot analyses. Other tested macrolides had no induction effect on CYP3A expression. These results confirmed the interspecies variability of CYP3A regulation in hepatocytes and raised the question of its mechanism of induction by macrolides in human liver.

Animals↗
PubMed1999

Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.

BACKGROUND: The cytosine deaminase gene of Escherichia coli converts the nontoxic compound 5-fluorocytosine into 5-fluorouracil (5-FU), thereby acting as a suicide gene when introduced into cancer cells, killing the cells when they are exposed to 5-fluorocytosine. We analyzed the efficacy of using cytosine deaminase-bearing cancer cells as an autologous tumor vaccine in a rat model that mimics liver metastasis from colon carcinoma. METHODS: We introduced a plasmid vector containing the E. coli cytosine deaminase gene into a BDIX rat colon carcinoma cell line. Intrahepatic injection of the modified cells in syngeneic animals generates a single experimental liver "suicide tumor." We then analyzed the effect of 5-fluorocytosine treatment in terms of regression of cytosine deaminase-expressing cells in vivo as well as protection against wild-type cancer cells. RESULTS: Treatment with 5-fluorocytosine induced regression of cytosine deaminase-expressing (CD+) tumors, with seven of 11 treated animals being tumor free at the end of 30 days and a statistically significant difference in tumor volumes between treated and control animals (two-sided P<.0001). Intrahepatic injection of CD+ cells followed by 5-fluorocytosine treatment rendered the treated animals resistant to challenge with wild-type tumor cells, with no (zero of seven) treated animals developing wild-type tumors in contrast to all (four of four) control animals. Moreover, in animals with established wild-type liver tumors, injection of CD+ tumor cells followed by 5-fluorocytosine treatment produced a statistically significant increase in survival time (two-sided P<.0001). In vivo immunodepletion and immunohistologic analysis of experimental tumors indicate that natural killer cells are the major immune component involved in this antitumor effect. CONCLUSIONS AND IMPLICATIONS: Taken together, these results suggest the potential use of suicide gene-modified tumor cells as therapeutic vaccines against liver metastasis from colon carcinoma.

Animals↗
PubMed1999

Comparative effects of rifabutin and rifampicin on cytochromes P450 and UDP-glucuronosyl-transferases expression in fresh and cryopreserved human hepatocytes.

The aim of this study was to evaluate rifabutin (RBT) and rifampicin (RIF) capabilities in inducing various xenobiotic metabolizing enzymes such as cytochromes P450 (CYPs) and UDP-glucuronosyl-transferases (UGTs) in cultured fresh and cryopreserved human hepatocytes. Enzyme induction was assessed through the use of several diagnostic markers, i.e. testosterone, midazolam (MDZ), diazepam (DZP) and 7-ethoxyresorufin for CYP-dependent enzyme reactions; and AZT for UGT-dependent enzyme reactions. RBT concentrations (0.118, 0.708 microM) were selected according to previously published pharmacokinetic data in patients. The known CYP3A4 inducer in humans, RIF, was used as a positive control. At the concentrations used, no sign of cytotoxicity was evidenced. Both compounds were able to dose-dependently induce the overall metabolism of testosterone (approximately 2-fold for RBT, 4-fold for RIF) and the formation of the 6beta-hydroxylated-derivative (up to approximately 4-fold over control for RBT and approximately 10-fold for RIF), which is CYP3A4 dependent. The other hydroxylated metabolites (16alpha-OH and 2alpha-OH) were also enhanced. The metabolism of MDZ, which is specifically metabolized by CYP3A4 in humans, was also investigated following drug's exposure to hepatocytes. DZP one, which is governed by various CYPs, including CYP3A, was also investigated. RBT was shown to increase the biotransformation of both benzodiazepines (approximately 1.9-fold over control). Moreover, the effects of both drugs on ethoxyresorufin O-deethylase activity (EROD), which is representative of CYPIA1/2 isoforms, were tested. Results showed only a moderate induction of this marker (approximately 2-fold over control) when compared to the high effect observed after hepatocyte exposure to 3-methylcholantene (approximately 14-fold over control). Finally, the action of RBT and RIF on UGTs expression was investigated by using AZT as diagnostic substrate: glucuronides formation was not significantly affected by the two rifamycin derivatives. On the whole, exposure of fresh or cryopreserved human hepatocytes to RBT dose-dependently affected the levels of drug metabolizing enzymes in a dose-dependent manner. However, as already demonstrated by in vivo pharmacokinetic studies, its inducing properties towards CYPs, CYP3A in particular, are less pronounced than RIF.

Aryl Hydrocarbon Hydroxylases↗
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

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Female↗
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↗
PubMed1999

Laparoscopic management of benign solid and cystic lesions of the liver.

OBJECTIVE: The authors present their experience in the laparoscopic management of benign liver disease. The aim of the study is to analyze technical feasibility and evaluate immediate and long-term outcome. SUMMARY BACKGROUND DATA: Indications for the laparoscopic management of varied abdominal conditions have evolved. Although the minimally invasive treatment of liver cysts has been reported, the laparoscopic approach to other liver lesions remains undefined. METHODS: Between September 1990 and October 1997, 43 patients underwent laparoscopic liver surgery. There were two groups of benign lesions: cysts (n = 31) and solid tumors (n = 12). Indications were solitary giant liver cysts (n = 16), polycystic liver disease (n = 9), hydatid cyst (n = 6), focal nodular hyperplasia (n = 3), and adenoma (n = 9). Only solid tumors, hydatid cysts, and patients with polycystic disease and large dominant cysts located in anterior liver segments were included. All giant solitary liver cysts were considered for laparoscopy. Patients with cholangitis, cirrhosis, and significant cardiac disease were excluded. Data were collected prospectively. RESULTS: The procedures were completed laparoscopically in 40 patients. Median size was 4 cm for solid nodules and 14 cm for solitary liver cysts. Conversion occurred in three patients (7%), for bleeding (n = 2) and impingement of a solid tumor on the inferior vena cava (n = 1). The median operative time was 179 minutes. All solitary liver cysts were fenestrated in less than 1 hour. There were no deaths. Complications occurred in 6 cases (14.1%). Two hemorrhagic and two infectious complications were noted after management of hydatid cysts. There were no complications after resection of solid tumors. Three patients received transfusions (7%). The median length of stay was 4.7 days. Median follow-up was 30 months. There was no recurrence of solitary liver or hydatid cysts. One patient with polycystic disease had symptomatic recurrent cysts at 6 months requiring laparotomy. CONCLUSION: Laparoscopic liver surgery can be accomplished safely in selected patients with small benign solid tumors located in the anterior liver segments and giant solitary cysts. The laparoscopic management of polycystic liver disease should be reserved for patients with a limited number of large, anteriorly located cysts. Hydatid disease is best treated through an open approach.

Adult↗
PubMed1999

Inhibition of calcium influx during hypoxia/reoxygenation in primary cultured rat hepatocytes.

Calcium has been demonstrated to play an important role in hepatocyte damage during ischemia/reperfusion phases. Calcium influx was determined in primary cultured rat hepatocytes submitted to a succession of warm hypoxia and reoxygenation phases in the presence of diltiazem, gallopamil and a Na+/H+ antiport inhibitor, HOE-694. Only diltiazem significantly inhibited calcium influx with higher potency after reoxygenation than after hypoxia only, suggesting a complex mechanism of action of diltiazem which could act on different physiological functions involved in Ca2+ invasion of hepatocytes after hypoxic insult.

Animals↗