Dexamethasone enhances constitutive androstane receptor expression in human hepatocytes: consequences on cytochrome P450 gene regulation.

The barbiturate phenobarbital induces the transcription of cytochromes P450 (CYPs) 2B through the constitutive androstane receptor (CAR; NR1I3). CAR is a member of the nuclear receptor family (NR1) mostly expressed in the liver, which heterodimerizes with retinoid X receptor (RXR) and was shown to transactivate both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element. Because previous studies in rodent hepatocyte cultures have shown that the phenobarbital-mediated induction of CYP2B genes is potentiated by glucocorticoids, we examined the role of activated glucocorticoid receptor in this process.

Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes.

The marked impairment of hepatic drug metabolism during inflammation and infections has been known for many years and shown to result from down-regulation of cytochrome P450s (CYP) by cytokines. However, the mechanism of this repression is unknown. Using primary cultures of human hepatocytes, we show here that interleukin-6 (IL-6) rapidly and markedly decreases the expression of PXR (pregnane X receptor) and CAR (constitutively activated receptor) mRNAs, but does not affect the levels of dioxin receptor and glucocorticoid receptor mRNA.

Specific suppression of interleukin 2 biosynthesis by synthetic antisense oligodeoxynucleotides does not influence allograft rejection.

Background: Interleukin (IL)-2 supplementation can reverse both blood transfusion-induced tolerance to kidney allografts and spontaneous tolerance to liver allografts in rats. Moreover, IL-2 expression is frequently suppressed in models of allograft tolerance. The failure of IL-2 biosynthesis might therefore play a critical role in tolerance induction.

Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators.

In this report we show that submicromolar concentrations of dexamethasone enhance pregnane X receptor (PXR) activator-mediated CYP3A4 gene expression in cultured human hepatocytes. Because this result is only observed after 24 h of cotreatment and is inhibited by pretreatment with cycloheximide, we further investigated which factor(s), induced by dexamethasone, might be responsible for this effect. We report that dexamethasone increases both retinoid X receptor-alpha (RXRalpha) and PXR mRNA expression in cultured human hepatocytes, whereas PXR activators such as rifampicin and clotrimazole do not.

An epithelial cell line that can stimulate alloproliferation of resting CD4+ T cells, but not after IFN-gamma stimulation.

It has previously been shown that IFN-gamma-induced up-regulation of HLA class II on the surface of epithelial cells is not sufficient to induce proliferation of allospecific CD4+ T cells in vitro. To further investigate this phenomenon, a human epithelial bladder carcinoma, T24, was induced to constitutively express HLA class II without IFN-gamma stimulation, by permanent transfection with the full-length class II transactivator (CIITA) gene. Proliferation of allospecific T cells to transfected and wild-type cells with and without prior activation with saturating levels of IFN-gamma for 4 days was examined.

Cardiovascular responses to the isoprostanes iPF(2alpha)-III and iPE(2)-III are mediated via the thromboxane A(2) receptor in vivo.

Background: Isoprostanes (iPs) are free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Several iPs exert biological effects in vitro and may contribute to the functional consequences of oxidant stress. For example, iPF(2alpha)-III (8-iso PGF(2alpha)) and iPE(2)-III modulate platelet function and vascular tone.

[Treatment of common bile duct stones with laparoscopy. Retrospective multicenter study with 612 patients].

Objective: To analyse retrospectively the results of one-stage laparoscopic treatment for common bile duct stones in 19 surgical centers in France.

Patients: From January 1991 to July 1996, 612 patients with choledocholithiasis underwent laparoscopic treatment.

Results: Overall duct clearance was obtained in 489 of the 612 patients (80%): through the cystic duct in 222 of 380 patients (58.

[Elective laparoscopic colectomy for sigmoid diverticulitis. Prospective study of 56 cases].

Objective: The aim of this prospective study was to assess the feasibility and postoperative advantages of the laparoscopic-assisted elective colectomy for diverticular disease.

Patients And Methods: From january 1989 to december 1997, among the 114 patients electively operated on for diverticulitis, 56 patients were treated by laparoscopic approach. Evaluated parameters included: gender, age, weight, size, ASA score, operating time, duration of hospital stay, of analgesic treatment, and of postoperative ileus, morbidity and mortality rate.

In vitro investigation of factors important for the delivery of an integrin-targeted nonviral DNA vector in organ transplantation.

Background: Polylysine-molossin is a 31 amino acid synthetic peptide that has previously been demonstrated to function as a DNA vector in vitro for cell lines and for the cornea. It incorporates the 15 amino acid integrin-binding domain of the venom of the American pit viper, Crotalus molossus molossus as the targeting moiety and a chain of 16 lysines as the DNA-binding moiety. The objective of this study was to evaluate several parameters of importance for in vivo applications.

Tissue-binding properties of a synthetic peptide DNA vector targeted to cell membrane integrins: a possible universal nonviral vector for organ and tissue transplantation.

Background: Gene delivery through a nonviral, receptor-mediated system widely expressed in transplanted tissue would have important advantages in transplantation, where gene delivery is performed ex vivo. Integrins are widely expressed cell surface receptors and can be targeted for gene delivery.

Methods: A synthetic 31 amino acid DNA vector (polylysine-molossin) comprising a 15-amino acid moiety for targeting cellular integrins (derived from the snake venom, molossin) and a 16-amino acid polylysine moiety for DNA-binding, has been evaluated.

Natural killer cell and alphabeta and gammadelta lymphocyte traffic into the liver graft immediately after liver transplantation.

Background: The persistence and migration of donor leukocytes has been well established, but cellular kinetics immediately after revascularization and the potential relevance of these different lymphocyte populations to spontaneous tolerance remain unclear. During the early hours of revascularization, there is a transitory "congestion" of the liver graft, which is evidence of an early phase that we have termed "first cellular contact."

Methods: We have carried out by flow cytometry a prospective comparative study of the peak kinetics of lymphocyte subpopulations contained in: (a) peripheral blood and liver grafts at the time of multi-organ extraction from 14 brain-dead donors, (b) recipient peripheral blood before transplantation, and (c) recipient peripheral blood and liver grafts after (t=2 h) declamping and vascularization of the liver graft.

Human hepatocytes in primary culture predict lack of cytochrome P-450 3A4 induction by eletriptan in vivo.

Eletriptan (Relpax) is a novel 5-hydroxytryptamine (serotonin)(1D/1B) agonist currently in development for the acute treatment of migraine. The aim of this work was to evaluate the relative induction potency of eletriptan in vitro compared with well characterized cytochrome P-450 (CYP) inducers with primary cultures of human hepatocytes and to relate this to the situation in vivo. Eletriptan was a weak inducer of CYP3A4 protein and cyclosporin A oxidation in four of the six cultures used, whereas rifampicin was a potent inducer in all cultures.

Specific vascular complications of orthotopic liver transplantation with preservation of the retrohepatic vena cava: review of 1361 cases.

Objective: The objective of this study was to describe the complications specifically related to orthotopic liver transplantation (OLT) with preservation of the inferior vena cava and to their therapeutic management. This preservation technique has considerably influenced the surgical phases of liver transplantation, increasing hepatectomy time and modifying the number of vascular anastomoses.

Methods: Our retrospective multicentric study, based on data from 1361 adult patients that had undergone orthotopic liver transplantation with preservation of the inferior vena cava in France between 1991 and 1997, analyzed the concomitant surgical complications.

Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice.

Platelet activation is characterized by shape change, induction of fibrinogen receptor expression and release of granular contents, leading to aggregation and plug formation. While this response is essential for hemostasis, it is also important in the pathogenesis of a broad spectrum of diseases, including myocardial infarction, stroke and unstable angina. Adenosine 5'-diphosphate (ADP) induces platelet aggregation, but the mechanism for this has not been established, and the relative contribution of ADP in hemostasis and the development of arterial thrombosis is poorly understood.

Syndrome of body fat redistribution in HIV-1-infected patients: relationships to cortisol and catecholamines.

Objective: Alterations of body fat distribution have been recently reported in HIV-infected patients. We aimed to investigate whether the hormones modulating adipose tissue metabolism could be implicated.

Subjects: We investigated twenty-eight HIV-infected patients who had developed abdominal fat, combined with peripheral lipodystrophy in 25 cases and 'buffalo hump' in 2 cases, but who had otherwise improved on antiretroviral therapies.

Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism.

Background/aims: Alcoholic cirrhosis remains a controversial indication for liver transplantation, mainly because of ethical considerations related to the shortage of donor livers. The aim of this study was to review experience to date, focusing on survival rates and complications, and the effect of alcohol relapse on outcome and alterations in marital and socioprofessional status.

Methods: The results for 53 patients transplanted for alcoholic cirrhosis between 1989 and 1994 were compared with those for 48 patients transplanted for non-alcoholic liver disease.

The relationship among carbon dioxide pneumoperitoneum, vasopressin release, and hemodynamic changes.

Unlabelled: We assessed the role of vasopressin (VP) for the hemodynamic response to pneumoperitoneum in pigs. Four groups of anesthetized pigs were investigated. Nine pigs were intraabdominally insufflated with CO2 and eight were intraabdominally insufflated with argon; eight pigs received an i.

Delayed gastric emptying after pancreaticoduodenectomy and pancreaticogastrostomy.

Objective: To find out which factors influence the development of delayed gastric emptying (DGE) after pancreaticoduodenectomy with pancreaticogastrostomy.

Design: Prospective clinical study.

Setting: University hospital, France.

Treatment of acute neonatal vascular injuries--the utility of multiple interventions.

Background/purpose: Vascular injuries in neonates are a rare complication of the varied invasive procedures performed in these small children. Unfortunately there remains a reluctance to repair these injuries early, often because of the relative small size of the affected vessels and the nature of the patient's underlying medical condition. The authors report a consecutive series of patients treated for arterial and venous injuries early in their course using a variety of microsurgical techniques.

Tissue inhibition of angiotensin-converting enzyme activity stimulates angiogenesis in vivo.

Background: Endothelial cells (ECs) represent the critical cellular element responsible for postnatal angiogenesis. Because ACE inhibitors may favorably affect endothelial function, we investigated the hypothesis that administration of the ACE inhibitor quinaprilat could enhance angiogenesis in vivo.

Methods And Results: Ten days after resection of 1 femoral artery, New Zealand White (NZW) rabbits were randomly assigned to receive recombinant human vascular endothelial growth factor (rhVEGF) administered as a single intra-arterial injection (n=6), quinaprilat (n=8) or captopril (n=7) administered as a daily subcutaneous injection, or no treatment (controls, n=6).

Thoracoscopic approach to posterior mediastinal neurogenic tumors in the adult.

Although neurogenic tumors are the most frequent posterior mediastinal tumors, few reports exist on thoracoscopic resection, and methods are not yet standardized. Two cases of thoracoscopic resection of benign posterior mediastinal schwannomas are presented. We believe that in carefully selected patients, thoracoscopic resection can be performed easily and with minimal morbidity.