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Biomedical subjects

L Nicod

Publications and source records attributed to L Nicod.

At least 19 recordsLinked to original sources
PubMed2002

Solute complexation degree with human serum albumin: biochromatographic approach.

A mathematical model was developed for the study of the D,L-dansylamino acid retention mechanism in reversed-phase liquid chromatography using a C18 column as a stationary phase and human serum albumin (HSA) as an eluent modifier. The solute retention factor is dependent on the HSA concentration in the eluent as well as the binding constant of the guest-HSA complex. A determination of the degree of complexation n(c) (the percent of the complexed guest) could be carried out. Different Van 't Hoff plot shapes of the degree of complexation were observed with different eluent pH, confirming a change in the solute complexation mechanism for physiological pH (between 7-7.5). Enthalpy-entropy compensation was also analysed in relation to this mathematical model to confirm the solute complexation behavior with HSA. These results finally confirmed that at physiological pH and temperature (approximately 35 degrees C) values the HSA was in a favorable structural conformation for its binding with a great majority of drugs.

Chromatography, High Pressure Liquid↗
PubMed2002

Role of the magnesium cation on antihypertensive molecule-human serum albumin binding: affinity chromatography approach.

The role of the Mg2+ cation on antihypertensive molecule binding on human serum albumin (HSA) was studied by affinity chromatography. The thermodynamic data corresponding to this binding were determined for a wide range of Mg2+ concentrations (c). For the nifedipine molecule, an increase in the Mg2+ concentration produced a decrease in binding due to a decrease in the electrostatic interactions. For verapamil and diltiazem, which have the highest solvent accessible surface area, the solute binding on HSA was divided into two Mg2+ concentration regions. For a low c value below c(c) (approximately 1.6 mmol/l), the binding dependence with c was similar to that of nifedipine. For c above c(c) the hydrophobic effect created in the bulk solvent associated with a decrease in the van der Waals interactions between the solute molecule and the HSA implied a decrease in its binding. These results showed that for patients with hypertension, an Mg2+ supplementation during treatment with these antihypertensive molecules can increase the active pharmacological molecule concentration.

Antihypertensive Agents↗
PubMed2001

Severe pulmonary hypertension: data from the Swiss Registry.

BACKGROUND: Severe pulmonary hypertension (PH) is a rare disease with a dismal prognosis if untreated. Progress in diagnosis and in the development of effective therapeutic options has created new interest in this pathology. There are, however, only limited data on the prevalence of severe PH unrelated to chronic left ventricular failure or COPD, on the associated conditions and on the parameters with a prognostic impact. With the aid of a retrospective registry we have collected data from 5 centres in Switzerland and attempted to answer the above questions. METHODS: Data on patients with PH from 4 university facilities (Zurich, Basle, Geneva and Lausanne) and one well-defined geographical area (Ticino) were retrospectively collected and analysed up to December 1999. Clinical and haemodynamic parameters and associated diseases were noted. We were also interested in the age distribution of the patients and the year of diagnosis of PH. RESULTS: We found 106 patients with severe PH (43 men, 63 women, median age 43 years); 79% were in NYHA class III or IV. There was a steep rise in diagnosis of PH after 1995. In 74% PH was either primary or associated with collagen vascular disease or thromboembolic disease. By the end of the observation period 30% of the patients had died. The best distinguishing parameters between surviving patients and those who eventually died were the 6-minute walking test (363 vs. 235 metres, p = 0.002), the NYHA class (II vs III/IV, p = 0.015), and mixed venous saturation (66.5 vs. 57.9%, p = 0.006). Therapy consisted of calcium antagonists in 18% and of (inhaled) prostanoids, chiefly iloprost, in 33%. Seven patients underwent lung transplantation. CONCLUSIONS: We conclude that PH is diagnosed more often as diagnostic and therapeutic options improve; that primary forms, and those associated with collagen vascular disease and with chronic venous thromboembolism, make up three-quarters of the aetiologies; and that the 6-minute walking test, the functional class and mixed venous saturation are the best prognostic parameters.

Adolescent↗
PubMed2001

Strain difference (WKY, SPRD) in the hepatic antioxidant status in rat and effect of hypertension (SHR, DOCA). Ex vivo and in vitro data.

We assessed the hepatic antioxidant status of spontaneously (SHR) and desoxicorticosterone acetate (DOCA)-induced hypertensive rats and that of respective normotensive Wistar Kyoto (WKY) and Sprague-Dawley (SPRD) rats. For this we evaluated, ex vivo in liver cytosols, reduced glutathione (GSH) content, glutathione-related enzyme (peroxidase, reductase and transferase) activities as well as the rate of lipid peroxidation in 9-11 week-old rats. The antioxidant status and the cytotoxicity of acetaminophen, a radical- and hydrogen peroxide-mediated hepatotoxic compound, were also assessed in vitro in cultured hepatocytes isolated from hypertensive (SHR, DOCA) and normotensive control (WKY, SPRD) rats. Our results suggest that a difference exists in the hepatic antioxidant status between rat strains, with GSH levels being lower (-15%) and lipid peroxidation rate higher (+30%) in WKY compared to SPRD rats. In hepatocyte cultures from WKY rats, both GSH content and catalase activity were lower (-30 and -70% respectively) compared to hepatocyte cultures from SPRD rats. This was associated with a 35% higher cytotoxicity of acetaminophen in cultured hepatocytes from WKY rats compared to that in hepatocytes from SPRD rats. Hypertension in DOCA rats (mmHg: 221+/-9 vs. 138+/-5 in control SPRD rats) was associated with decreases (about 30%) in both glutathione peroxidase (GSH-Px) and catalase activities, ex vivo in livers and in vitro in hepatocyte cultures. Hypertension in SHR (mmHg: 189+/-7 vs. 130+/-5 in control WKY rats) was also associated with decreases (about 50%) in GSH-Px activity, ex vivo in livers and in vitro in hepatocyte cultures but catalase activity was not modified. The IC50 of acetaminophen was also lower in hepatocytes from hypertensive rats compared to respective controls, which could be related to the weakened antioxidant status in hepatocytes from hypertensive rats. Our data thus suggest that hepatocyte cultures are appropriated tools in which to assess hepatotoxicity and hepatoprotection in hypertension.

Acetaminophen↗
PubMed2001

Mitomycin C for control of recurrent bronchial stenosis: a case report.

A 27-year-old patient with cystic fibrosis underwent a bilateral lung transplantation despite the presence of multiresistant Burkholderia cepacia. Postoperatively, the patient presented with bilateral bronchial necrosis. During the 14th week, his FEV(1) dropped to 2.5 L from a baseline level of 3.4 L. A subtotal occlusion of the right mainstem bronchus below the suture was noted. Using argon electrocoagulation, the right upper lobe bronchus, the intermediate bronchus, and the right middle lobe bronchus were reopened. During the period between weeks 20 and 42 post-transplantation, a recurrent stenosis required eight endoscopic interventions combining dilatation and stenting. During the 42nd week, dilatation followed by mitomycin C application stabilized the right lung function. This case report is the first to describe the effectiveness of the local application of mitomycin C to stop recurring extensive bronchial stenosis following bronchial necrosis secondary to lung transplantation.

Administration, Topical↗
PubMed2000

Massive cerebral edema after I.V. cyclosporin overdose.

We describe a patient who accidentally received an infusion of cyclosporin at a rate of 30 mg/hr during 13 hr instead of the prescribed dose of 3 mg/hr and who concomitantly developed massive intracerebral edema with brainstem compression and death. A cyclosporin level as high as 1700 ng/ml could have been reached before the drug was withdrawn. To the best of our knowledge, this is the first case of fatal cyclosporin overdose reported in an adult patient.

Brain Edema↗
PubMed2000

Effects of model inducers on thyroxine UDP-glucuronosyl-transferase activity in vitro in rat and mouse hepatocyte cultures.

Thyroxine (T(4))-UDP-glucuronosyltransferase (UGT) activity was measured directly in cultured male Sprague-Dawley rat and OF-1 mouse hepatocyte monolayers. The activity of T(4)-UGT (pmol/min/g liver) in vitro in hepatocyte cultures was, after 24 hr in culture, equivalent to that previously measured in vivo in rat and mouse liver microsomes (Viollon-Abadie et al., 1999). A progressive decline in T(4)-UGT activity occurred over time in both rat and mouse hepatocyte cultures. Treatment of cultures with various model inducers such as phenobarbital (PB), beta-naphthoflavone (NF) and clofibric acid (CLO) induced a strong increase in T(4)-UGT activity in rat hepatocyte monolayers. In addition, and as expected from available in vivo data, treatment of rat hepatocyte cultures with NF also increased p-nitrophenol (PNP)-UGT activity and treatment with PB or CLO increased bilirubin (Bili)-UGT activity. In contrast, T(4)-UGT activity in mouse hepatocyte monolayers was not affected by the treatments, neither were PNP- and Bili- UGT activities. These in vitro data confirm our previous in vivo observations that these inducers increase rat but not mouse liver T(4)-UGT activities (Viollon-Abadie et al., 1999). The present study thus demonstrates that hepatocyte monolayers are appropriated for the evaluation and inter-species comparison of the effects of xenobiotics on T(4)-UGT activities.

Animals↗
PubMed2000

Antioxidant status, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities in livers from control and DOCA-salt hypertensive male Sprague Dawley rats.

The effects of DOCA-salt hypertensive treatment on hepatic glutathione-dependent defense system, antioxidant enzymes, lipid peroxidation, mixed function oxidase and UDP-glucuronyl transferase activities were investigated in male Sprague Dawley rats. Compared with controls, DOCA-salt hypertensive rats had lower body weights (linked to liver hypertrophy). Mixed function oxidase and p-nitrophenol-UGT activities were not affected by the treatment but a significant lower rate of the glucuronoconjugation rate of bilirubin (p < 0.001) was observed in DOCA-salt hypertensive rats. While cytosolic glutathione contents and glutathione reductase activity were not affected, glutathione peroxidase (p < 0.001), glutathione transferase (p < 0.001) and catalase (p < 0.01) activities were decreased and associated with higher malondialdehyde contents (p < 0.001) in treated rats. The imbalance in liver antioxidant status (increasing generation of cellular radical species), associated with increases in lipid peroxidation, suggests that oxidative stress might be directly related to arterial hypertension in DOCA-salt treated male Sprague Dawley rats.

Animals↗
PubMed2000

Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague Dawley rats--relation with liver antioxidant status.

The effects of 8-week diethylmaleate (DEM) and clofibric acid (CFA) supplemented diet on blood pressure, body and liver weights, liver antioxidant status and nitric oxide synthase (NOS) activity were investigated in 8-week DOCA-salt treated and untreated Sprague-Dawley male rats. It appeared that DEM and particularly CFA treatments were associated with a significant decrease in blood pressure in DOCA-salt treated rats, and an accentuation of the decreases in body weights in both diet supplemented groups. This was not associated with increases in NO production in the liver. In contrast, hepatic lipid peroxidation was significantly decreased in both DOCA-salt treated and untreated groups on DEM and particularly on CFA supplemented diet. The protective effects of CFA and DEM against hepatic cellular damage could be involved in the decreases in blood pressure in DOCA-salt treated rats, where CFA was more efficient than DEM. In CFA supplemented groups, there was a strong increase in hepatic superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), and catalase (CAT) activities and in DEM supplemented groups, increases in SOD and CAT activities and in GSH levels were observed. Our data suggest that normalization of blood pressure in DOCA-salt treated rats by CFA was due to an enhancement of the half-life of NO while DEM increased its availability.

Animals↗
PubMed2000

Peroxisome proliferators induce apoptosis and decrease DNA synthesis in hepatoma cell lines.

We examined the effects of various peroxisome proliferators (PPs) such as the hypolipidaemic agents clofibric acid (CLO), bezafibrate (BEZA), ciprofibrate (CIPRO) and nafenopin (NAFE) and the plasticizer di-(2-ethylhexyl)phthalate (DEHP) on peroxisomal enzyme activities, apoptosis and DNA synthesis in rat FaO and human HepG2 hepatoma cell lines. Both growing and confluent cultures were treated with PPs (250 microM) for 48 or 72 h. In accordance with our previous observations in PP-treated primary hepatocyte cultures of rat and human origin, the various PPs increased peroxisomal enzyme activities in rat FaO cells but not in human HepG2 cells. PPs strongly induced apoptosis in FaO cells. They did not affect TGFbeta-induced apoptosis, with the exception of DEHP and NAFE, respectively blocking and increasing induced apoptosis in confluent cultures. Moreover, PPs produced a minor, but significant, decrease in DNA synthesis in FaO cells. PPs also decreased DNA synthesis in growing HepG2 cells, and CLO, CIPRO and NAFE induced apoptosis in confluent HepG2 cultures. This is in opposition with the effects of PPs on primary hepatocyte cultures, i.e. inhibition of both spontaneous and TGFbeta-induced apoptosis and increases in DNA synthesis in rat hepatocytes, and unchanged mitosis-apoptosis balance in human hepatocytes.

Acyl-CoA Oxidase↗
PubMed1999

Comparison of the effects of various peroxisome proliferators on peroxisomal enzyme activities, DNA synthesis, and apoptosis in rat and human hepatocyte cultures.

Peroxisome proliferators (PPs) are a class of rodent nongenotoxic hepatocarcinogens that cause hepatocyte peroxisome proliferation, increased DNA synthesis, and decreased spontaneous apoptosis. We examined the effects of various PPs such as the hypolipidemic agents clofibric acid (CLO), bezafibrate (BEZA), ciprofibrate (CIPRO), and nafenopin (NAFE) and the plasticizer di-(2-ethylhexyl)phthalate (DEHP) on the various parameters in vitro in rat and human hepatocyte cultures. In rat hepatocyte cultures, after 72 h of treatment with the various PPs at 100-500 microM, a compound-dependent increase in acyl CoA oxidase (ACO) and carnitine acetyl transferase (CAT) activities, markers of peroxisome proliferation, was observed with the following potencies: CIPRO = NAFE > BEZA > CLO > DEHP. A minor (120-150%), but significant, no concentration-dependent increase in DNA synthesis and a marked, no compound-dependent and, with the exception of NAFE, no concentration-dependent 60-80% decrease in spontaneous apoptosis was observed with all tested compounds (50-250 microM) after 48 h of treatment. Inhibition of spontaneous apoptosis in PP-treated versus control rat hepatocyte cultures was also observed morphologically. Furthermore, PPs inhibited transforming growth factor beta (TGFbeta)-induced apoptosis but not tumor necrosis factor alpha (TNFalpha)/alpha Amanitine (alphaAma)-induced apoptosis in rat hepatocyte cultures. In human hepatocyte cultures, the various PPs at 50-500 microM did not affect peroxisomal enzyme activities, DNA synthesis, or spontaneous and induced (TGFbeta or TNFalpha/alphaAma) apoptosis. The compound-dependent peroxisome proliferation but no compound-dependent disruption of the mitogenic/apoptotic balance elicited by PPs in primary rat hepatocyte cultures supports the hypothesis that oxidative stress is directly linked to the hepatocarcinogenic potential of a given PP in rodents and that disruption of the mitogenic/apoptotic balance contributes to the development of PP-induced hepatocarcinogenesis. In addition, the absence of effects of all PPs on both peroxisome proliferation-associated parameters and mitogenic/apoptotic balance supports the hypothesis that human liver cells are refractory to PP-induced hepatocarcinogenesis.

Acyl-CoA Oxidase↗
PubMed1999

Phenobarbital, beta-naphthoflavone, clofibrate, and pregnenolone-16alpha-carbonitrile do not affect hepatic thyroid hormone UDP-glucuronosyl transferase activity, and thyroid gland function in mice.

The effects of representative liver enzyme inducers such as clofibrate (CLO), phenobarbital (PB), pregnenolone-16alpha-carbonitrile (PCN), and beta-naphthoflavone (NF) on hepatic microsomal thyroxin (T4)- UDP-glucuronosyl transferase (UGT) and triiodothyronine (T3)- UGT activities and thyroid function were evaluated in OF-1 male mice after a 14-day po administration. CLO, PB, and PCN induced histological liver hypertrophy, increases in liver weights, in microsomal protein and cytochrome P450 contents as well as increases in specific UGT activities. Despite this, no significant changes in T4-UGT and T3-UGT activities occurred after treatment by any of these compounds. Furthermore, no significant changes in serum T4 and T3 levels were observed and thyroid histology was not affected. NF treatment induced microvacuolation of hepatocytes but did not affect any of the other tested parameters. The results show that, in contrast to the widely described effects in rats, liver enzyme inducers do not affect hepatic thyroid hormone metabolism and thyroid function in mice, suggesting that this species should be less sensitive to thyroid tumor promotion by hepatic microsomal enzyme inducers than rats.

Animals↗
PubMed1999

Human herpes-virus 8 seropositive patient with skin and graft Kaposi's sarcoma after lung transplantation.

Kaposi's sarcoma (KS) has been reported after solid organ transplantation mostly in recipients of renal, liver, heart, and bone allografts. We describe the first case of a patient with lung transplantation who developed KS of the skin, but also of the lung graft. The tumors were localized to places of previous trauma, implying the involvement of a Koebner phenomenon. Moreover, a polymerase chain reaction assay revealed the presence of DNA sequences of herpesvirus 8 (HHV-8) on tissue of the cutaneous KS. Serological tests showed HHV-8 seronegativity of the graft donor and HHV-8 seropositivity of the patient before lung transplantation suggesting that the latter was already infected before the surgery and that immunosuppression resulted in the development of KS. This case report raises the question of the prevalence of HHV-8 in candidates for transplantation and organ donors, and of the value of an antiviral prophylaxis to lower the risk of KS.

Herpesviridae Infections↗
PubMed1999

Treatment of cachexia with recombinant growth hormone in a patient before lung transplantation: a case report.

OBJECTIVES: To describe the effects of recombinant human growth hormone (rhGH) in a severely malnourished patient before lung transplantation. DESIGN: Case study. SETTING: Intensive care unit. PATIENTS: A 38-yr-old severely malnourished (body mass index, 15.1 kg/m2) woman (receiving prednisone) with bronchiolitis obliterans evolving during 10 yrs presented with end-stage lung disease and required continuous noninvasive mechanical ventilation. INTERVENTIONS: Two courses of 35 days of 16 IU/day (0.42 IU/kg/day) rhGH administered subcutaneously, with an interruption of 5 wks between the two courses of rhGH. MEASUREMENTS AND MAIN RESULTS: Weight gain of 14.7% and 12.8% fat-free mass, as measured by 50-kHz bioelectrical impedance analysis, during treatment during a 3.5-month period. Nitrogen excretion decreased from 23.7 g/day before treatment to 8.0 g/day while receiving rhGH. Improvement of pulmonary function was also noted and allowed discharge of the patient from the hospital after the second course of rhGH. She underwent successful lung transplantation 2 months later and reached 48.8 kg of body weight 6 months later. CONCLUSIONS: rhGH treatment is a possible strategy that could be used with malnourished patients who are awaiting lung transplantation to improve the nutritional status and respiratory muscle function to prevent recurring respiratory infection and postoperative complications favored by malnutrition and possibly to decrease the length of hospital stay.

Adult↗
PubMed1998

Metabolic capacities in cultured human hepatocytes obtained by a new isolating procedure from non-wedge small liver biopsies.

A new isolating procedure of human hepatocytes has been developed using two-step collagenase digestion by a non-perfusion procedure (NP) of non-wedge liver biopsies. 1. A yield of 2-7 x 10(6) hepatocytes/g liver, 52-95% viability and 13-75% attachment were obtained from liver biopsies weighing 6-60 g, comparable to that obtained when using the classical perfusion procedure (P) to isolate human hepatocytes from wedge liver samples of 50-150 g. 2. In culture, human hepatocytes obtained by NP remained attached to plastic for up to 5 days and displayed the usual morphological characteristics. Their metabolic capacities, assessed by liver-specific albumin and urea synthesis and by CYP-dependent and conjugation pathways, were equivalent to those of human hepatocytes obtained by P. In addition, they responded adequately to specific CYP inducers, demonstrating that they constitute a model in which human drug metabolism and toxicity studies can be performed.

Adult↗
PubMed1998

Successful combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas.

Pulmonary lymphangioleiomyomatosis (LAM) and renal angiolipomas are rare but distinct clinical entities that share similar morphological features. Lung transplantation is considered as a valuable therapeutic modality in patients with end-stage pulmonary LAM. However, in some patients, renal complications due to bleeding angiomyolipomas and cyclosporin-induced nephropathy have become newly identified problems. This study reports the first case of combined lung and kidney transplantation for pulmonary lymphangioleiomyomatosis and renal angiolipomas. Two years after transplantation, renal and pulmonary function have remained stable and the patient has resumed a normal daily life, including a full-time professional activity.

Adult↗
PubMed1997

Rifampicin and isoniazid increase acetaminophen and isoniazid cytotoxicity in human HepG2 hepatoma cells.

Acetaminophen (APAP) induced a concentration-dependent (0-30 mM) cytotoxic effect in human HepG2 hepatoma cells which was significantly increased when intracellular reduced glutathione (GSH) content was decreased. The cytotoxic effect of APAP (0-30 mM) was significantly lower in a day 3-treated compared to day 1-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 5 microM 3-methylcholanthrene (3MC), 50 microM rifampicin (RFP) or 1 mM isoniazid (INH) significantly increased 15-30 mM APAP cytotoxicity, of about 15-20% for INH and RFP and 35-50% for 3MC. The cytotoxicity of 10 mM APAP was also increased (about 20%) by a 3-day preincubation with INH but was not affected by 3MC and RFP. INH induced a concentration-dependent (0-40 mM) cytotoxic effect in day-1 treated HepG2 cells and not significantly affected by decreases in intracellular GSH concentrations. INH was not cytotoxic in day 3-treated HepG2 cells. A 3-day preincubation of HepG2 cells with 50 mM RFP or 1 mM INH significantly increased 10-40 mM INH cytotoxicity, respectively of about 10% and 10-25%. A 3-day preincubation with 3MC did not modify the cytotoxic effect of INH at these concentrations. This is to our knowledge the first report of increases by INH and RFP of APAP of INH cytotoxicity in vitro in hepatocellular cells of human origin. It is in accordance with clinical observations of severe hepatotoxicity associated with APAP or INH usage in patients receiving multiple drug therapy (INH, RFP) for tuberculosis or in alcoholics.

Acetaminophen↗