PubMed Health⌕ Search

Biomedical subjects

C Albert

Publications and source records attributed to C Albert.

At least 19 recordsLinked to original sources
PubMed2006

Pregnancy in rheumatology patients exposed to anti-tumour necrosis factor (TNF)-alpha therapy.

OBJECTIVES: Anti-tumour necrosis factor (TNF)-alpha therapies are considered category B drugs for pregnancy. Although sometimes prescribed to women of reproductive age, data in humans are limited with regard to safety for a developing fetus. The objectives of the present article are to report experience of anti-TNF-alpha use in pregnancy, and review the international literature. METHODS: Since 1999 the present authors have used anti-TNF-alpha (infliximab, etanercept, adalimumab) to treat patients with various chronic rheumatic conditions. All patients were prospectively followed during their treatment time and data were systematically collected. RESULTS: In a group of 442 patients treated with anti-TNF, three women with RA unexpectedly became pregnant One treated with etanercept chose a therapeutic termination at two and a half months, despite of any ultrasound anomaly, and satisfactory fetal growth. The other two patients (one with adalimumab exposure and one with etanercept exposure) delivered healthy infants. The following perinatal complications were observed: prematurity, neonatal jaundice, neonatal urinary Escherichia coli infection and adrenal congenital hyperplasia of probable hereditary origin. CONCLUSIONS: To date, there is no evidence that TNF-alpha antagonists are associated with embryo toxicity, teratogenicity or increased pregnancy loss. However, caution should be taken when anti-TNF agents are used during pregnancy, as human experience is still extremely limited, particularly in patients with rheumatic diseases among whom there are several alarming reports. The potential risk should be balanced against the known risks associated with DMARDs and steroid therapy. Large registries will be necessary before firm conclusions can be drawn.

Adalimumab↗
PubMed2006

Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies with concurrent B or C chronic hepatitis.

OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA) and concurrent chronic hepatitis B or C. METHODS: Records concerning 480 outpatients attending the Rheumatology Department of the University Hospital of Nice (France) for RA or SA were retrospectively reviewed for the duration of disease, treatment, serological status and biological data. RESULTS: Six relevant cases were identified: two of RA with chronic hepatitis B; one of SA with chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had received etanercept and one infliximab; two had been given adalimumab after an unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B were also given lamivudine. In none of the cases had changes in serum aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF-alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis B viral infection) appeared to be safe in that it had no effect on serum aminotransferases and/or viral load. However, repeated monitoring is necessary throughout the treatment period.

Adalimumab↗
PubMed2006

Ghrelin gastrokinetic action in patients with neurogenic gastroparesis.

Ghrelin has been shown to accelerate gastric emptying in animals where its effect appeared mediated through the vagus nerve. We aimed to verify the gastrokinetic capacity of ghrelin in human. Patients with gastroparesis attributed to a neural dysregulation by diabetes (n = 5) or surgical vagotomy (n = 1) were evaluated. The emptying of a test meal (420 kcal) was determined by the C13 octanoic acid breath test. Saline or synthetic ghrelin 1-4 microg/kg were given in 1 min bolus at the end of the meal. T-lag and T-1/2 were shorter during ghrelin than during saline administration [33 +/- 5 min versus 65 +/- 14 min (p < 0.01) and 119 +/- 6 min versus 173 +/- 38 min (p < 0.001)]. Ghrelin injection therefore accelerated gastric emptying of a meal in humans even in presence of a deficient gastric innervation.

Adult↗
PubMed2003

Implantation rates after two, three, or five days of embryo culture.

Extended embryo culture together with amelioration of embryo selection methods and embryo culture conditions have allowed a substantial increase on both pregnancy and implantation rates. However, uterine embryo transfers are still performed after 2 to 6 days of egg retrieval. In this paper, we show the results of two studies, one prospective study comparing IVF outcome of day 2 and day 3 embryo transfers, and a retrospective study looking at blastocyst transfers versus day 3 embryo transfers in our egg donation program. Also, we test the predictive value of the presence of three or more seven cell-stage embryos on day 3 of development on blastocyst formation and pregnancy rates. No significant differences were found between day 2 and day 3 embryo transfers in terms of pregnancy, ongoing pregnancy, and implantation rates, as well as in multiple and in high order pregnancy. In general, day 6 embryo transfers resulted in significantly higher ongoing pregnancy and implantation rates compared with day 3 embryo transfers (41.1 per cent and 23.6 per cent versus 50.1 per cent and 38.1 per cent, respectively). No differences were found in terms of multiple gestations despite transferring significantly more embryos on day 3 compared with day 6 transfers. When less than three 7-cell embryos were present in the embryo cohort, day 6 embryo transfers did not improve the rates of ongoing pregnancy with regards to day 3 embryo transfer, although significant high implantation rates were obtained on the group of blastocyst transfer. The presence of three or more 7 cell-stage embryos improved significantly both ongoing pregnancy and rates on blastocyst transfers compared to day 3 embryo transfers (65.6 per cent versus 50.6 per cent and 37.4 per cent vs 24.7 per cent, respectively). In conclusion, at least in egg donation, day 3 embryo transfers do not improve either pregnancy or implantation rates when compared to day 2 transfers. Generally speaking blastocyst transfers give significantly higher chance of pregnancy and implantation rates per cycle and per transfer than early cleavage stage transfers. However, the absence of a good embryo cohort, that is having less than three 7 cell-stage embryos on day 3, blastocyst transfers will improve implantation rates but not ongoing pregnancy rates.

Adult↗
PubMed2002

The role of endothelial cells in the pathogenesis of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of treatment with fertility drugs. Using human lung microvascular endothelial cells (HUMEC-L) as an in-vitro model of OHSS, we have tested the hypothesis that the endothelium is a target of HCG in the pathogenesis of OHSS. Since OHSS is characterized by increased capillary permeability, we have investigated the production and action of vasoactive agents. When HUMEC-L were cultured with high doses of estradiol (E(2)), no significant changes were observed in the secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-6 or IL-1 beta. However, the addition of HCG resulted in a significant increase in the secretion of VEGF and IL-6. Time-course experiments showed that VEGF was secreted within minutes of HCG addition, whereas IL-6 was significantly increased only after 48 h in culture. The secretion of IL-1 beta was unchanged by these hormonal conditions. The presence of HCG receptors was demonstrated in HUMEC-L in basal conditions as well as after the addition of E(2). The expression of VEGF receptors was also investigated. High doses of E(2) were unable to increase the expression of KDR, flt-1 and sfl-t, but the addition of HCG significantly upregulated the KDR concentration in endothelial cells, while no change was observed for flt. Permeability assays demonstrated that while E(2) alone did not change the arrangement of HUMEC-L in vitro, the presence of HCG caused changes in the actin fibres corresponding to increased capillary permeability. Anti-human VEGF antibodies were able to overcome these changes. In conclusion, these experiments show that the endothelium may be a primary target of HCG, causing an acute release of VEGF and a significant increase in IL-6 and resulting in an autocrine-paracrine action that may increase vascular permeability.

Actins↗
PubMed2001

Sudden cardiac death, genes, and arrhythmogenesis: consideration of new population and mechanistic approaches from a National Heart, Lung, and Blood Institute workshop, Part II.

This is Part II of a 2-part article dealing with malignant ventricular arrhythmias, which are the leading mechanism of death in common cardiac diseases. Genetic population studies directed at discovering common proximal sources of inherited molecular risk most directly linked to arrhythmia initiation and propagation would appear to have considerable potential in helping reduce cardiovascular mortality.

Arrhythmias, Cardiac↗
PubMed2001

Sudden cardiac death, genes, and arrhythmogenesis : consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I.

Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.

Arrhythmias, Cardiac↗
PubMed2001

Expression, production, and secretion of vascular endothelial growth factor and interleukin-6 by granulosa cells is comparable in women with and without endometriosis.

OBJECTIVE: To investigate the production and secretion of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) mRNA and protein by granulosa luteal cells (GCs) in vivo and in vitro in women with and without endometriosis. DESIGN: Prospective study. SETTING: A private, university-affiliated assisted reproduction unit and a university center. PATIENT(S): Women with severe endometriosis (n = 6) or without the disease (n = 14) after laparoscopy, undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer. INTERVENTION(S): GCs were obtained from each aspirate. MAIN OUTCOME MEASURE(S): Intracellular and secreted protein, as well as mRNA for both VEGF and IL-6 in GCs. RESULT(S): The expression of VEGF and IL-6 mRNAs in vivo and in vitro was similar in both groups. Also, GCs from patients with endometriosis produced and secreted equal amounts of these proteins compared with controls without the disease, either in freshly isolated cells or in 24-hour cultures. CONCLUSION(S): The GC function in terms of VEGF and IL-6 production does not seem to be altered in patients with endometriosis in comparison with those without this condition.

Cells, Cultured↗
PubMed2001

Isolation and characterization of the monkey UDP-glucuronosyltransferase cDNA clone monUGT1A01 active on bilirubin and estrogens.

Although enzymes that catalyze the formation of steroids are well known, less information is available about the enzymes involved in the metabolism of these hormones. Steroid glucuronidation, by UDP-glucuronosyltransferase enzymes, is one mechanism by which steroid hormones can be metabolized and eliminated from a tissue. Previous results suggest that the monkey represents the most appropriate animal model for studying the physiologic relevance of steroid glucuronidating enzymes. The monkey UGT1A01 cDNA clone was isolated by RT-PCR amplification of the liver RNA. The cDNA contains an open reading frame of 1599 bp encoding a protein of 533 residues. The primary structure of monkey UGT1A01 is 95% identical to human UGT1A1. To compare monkey and human UGT1A1 enzymes, both cDNA clones were transfected into HK293 cells and stable cell lines expressing each UGT1A1 protein were established. Western blot analysis of the monUGT1A01-HK293 and hUGT1A1-HK293 cell lines using a anti-UGT1A polyclonal antibody (RC-71) revealed expression of exogenous 55 kDa UGT1 proteins. The transferase activities of monkey and human UGT1A1 proteins were tested with over 60 compounds and were demonstrated to be active on the same compounds. For endogenous compounds only bilirubin and C18 steroids were glucuronidated by these enzymes. Using microsome preparation (from HK293 cell expressing monkey UGT1A01), the apparent K(m) values were 13, 5 and 6 microM for the conjugation of estradiol, 2-hydroxyestradiol and 2-hydroxyestrone, respectively, and were very similar to the values obtained with human UGT1A1. Specific RT-PCR analysis demonstrated the expression of monkey and human UGT1A1 transcripts in several tissues including liver, kidney, intestine, prostate, testis and ovary suggesting a contribution of this isoenzyme to estrogen metabolism in the cynomolgus monkey as in human.

Amino Acid Sequence↗
PubMed2001

An analysis of spontaneous hatching in a human endometrial epithelial coculture system: is assisted hatching justified?

PURPOSE: To evaluate spontaneous embryo hatching in an endometrial epithelial coculture system, and compare it with cases where coculture was performed because of maternal age, previous repeated implantation failures, or both. To clarify in which cases assisted hatching would be appropriate. METHODS: Individual human embryos were cocultured on an endometrial epithelial cell monolayer until Day 6. RESULTS: Blastocyst hatching rate at Day 6, depending on maternal age, was 9.1% (age <37 years) and 3.4% (age > or = 37 years). However, blastocyst hatching rates depending on number of previous IVF failures were similar. CONCLUSIONS: Maternal age and previous implantation failures are factors affecting the ability of human embryos to reach the blastocyst stage in coculture. However, assisted hatching is not justified in these populations because of the absence of hatching rate differences between blastocysts obtained from these two groups and the control group.

Blastocyst↗
PubMed2001

In vivo higher glucuronidation of mycophenolic acid in male than in female recipients of a cadaveric kidney allograft and under immunosuppressive therapy with mycophenolate mofetil.

Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ transplantation to prevent rejection, is being used increasingly in association with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The concentrations of MPAG in serum are many times the concentrations of MPA. Although MPAG has not shown immunosuppressant activity, it was postulated that it could displace MPA from its binding sites on albumin and hence increase the biologic effects of MPA. This effect could be important for patients with acute renal failure; under this condition, MPAG was shown to accumulate. The goal of this study was to document the MPAG/MPA concentration ratio in 100 renal transplant patients under a mixed immunosuppressive therapy. Further, the study addressed the question of whether MPAG can displace MPA in vivo from bound albumin in a representative renal transplant patient population under immunosuppressive therapy. Levels of MPAG and MPA were measured by high-performance liquid chromatography. The distribution of the ratios was not parametric as it tailed toward elevated values. After a square root transformation of the data, parametric analysis was possible. The average MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated with MMF and tacrolimus showed a lower ratio than patients treated with MMF and cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA. Further, it was determined that at physiologic concentrations, MPAG does not increase the amount of free MPA. Because MPAG can favor the elimination of MPA, it can be concluded that gender differences and cotreatment with tacrolimus must be taken into consideration when MMF is being administered.

Adult↗
PubMed2001

Glucuronidation of the nonsteroidal antiestrogen EM-652 (SCH 57068), by human and monkey steroid conjugating UDP-glucuronosyltransferase enzymes.

EM-652 (SCH 57068) is a new orally active antiestrogen that demonstrates pure antagonistic effects in the mammary gland and endometrium. In vivo studies have shown that EM-652 is primarily glucuronidated at the 7-hydroxy position in rats and that the metabolite is present in the plasma of female monkeys and human subjects after EM-800 (SCH 57050) or EM-652.HCl oral administration. Using hepatic microsomes from rat, monkey, and human, the formation of two EM-652 monoglucuronides at positions 4' and 7 was demonstrated by a liquid chromatographic tandem mass spectrometric method. Although no difference in EM-652 conjugation was observed between male and female monkey livers, an interindividual variation of hepatic EM-652 glucuronidation was shown with female human donors. Using microsome preparations from human embryonic kidney 293 cells stably expressing each of the 12 human and 11 monkey UGT enzymes cloned to date, the two EM-652-monoglucuronides were detected after incubation with microsomes containing human UGT1A1, UGT1A3, UGT1A8, UGT1A9, and monkey monUGT1A01, monUGT1A03, and monUGT1A09. Despite human UGT1A1 and monkey monUGT1A09 favored formation of EM-652-7-glucuronide, other active UGT1A enzymes formed both 4'- and 7-glucuronide derivatives in equal amounts. Kinetic analysis of EM-652 glucuronidation by these enzymes showed Michaelis constant (K(m)) values between 36 and 302 microM for EM-652-4'-glucuronide and 19 and 233 microM for EM-652-7-glucuronide. The present results demonstrate the importance of UGT1A isoforms, mainly UGT1A1, for EM-652 metabolism in humans.

Animals↗
PubMed2000

Distribution of uridine diphosphate-glucuronosyltransferase (UGT) expression and activity in cynomolgus monkey tissues: evidence for differential expression of steroid-conjugating UGT enzymes in steroid target tissues.

Based on the similarity of pathways and enzymes involved in steroid metabolism, simians represent a relevant animal model to study steroid elimination by glucuronidation. In this study the tissue distribution of UDP-glucuronosyltransferase (UGT) transcripts, proteins, and enzymatic activities were examined in 24 different cynomolgus monkey tissues. RT-PCR and Western blot analysis on total RNA and microsomal proteins demonstrated the presence of UGT1A and UGT2B transcripts and proteins in a wide range of tissues including steroid target tissues. Glucuronidation activity on eugenol, 5alpha-androstane-3alpha,17beta-diol, androsterone, and 4-hydroxyestradiol was measured using tissue homogenates and radiolabeled [14C]UDP-glucuronic acid. All tissues contained conjugation activity on these substrates, but glucuronidation rates were significantly lower in steroid target tissues than in liver, kidney, or gut. However, the ratio of steroid glucuronidation vs. eugenol glucuronidation was higher in steroid target tissues, suggesting a differential expression of steroid-conjugating enzymes in these tissues. Taken together, these results clearly demonstrate the presence of steroid glucuronidation enzymes in extrahepatic steroid target tissues and support the hypothesis that steroid glucuronidation is an important intracrine pathway involved in termination of steroid signaling.

Animals↗