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Biomedical subjects

G Siest

Publications and source records attributed to G Siest.

At least 433 records · Page 24Linked to original sources
PubMedDate not supplied

Decreased high-density lipoprotein cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer's disease.

Serum apolipoprotein (apo) AI concentration was studied in 98 Alzheimer's disease (AD) patients (77.56+/-8.83 years) and 59 healthy, elderly controls (75.37+/-5.27 years). ApoAI levels were significantly lower (p<10(-7)) in AD patients. An apoAI cutoff value of 1.50 g/L, could distinguish between the two groups with a sensitivity of 71% and a specificity of 69%. ApoAI levels were highly correlated with mini-mental state (MMSE) scores of patients (p<0.0001). These relationships remained significant after adjustment for multiple testing. Our findings raise the question of the potential implication of apoAI in the etiopathology of AD and bring serum apoAI concentration to the fore as an important biochemical marker.

Aged↗
PubMedDate not supplied

Biochemical values of immigrant groups in north-east France.

Laboratory-test results for a population of immigrants living in north-east France revealed differences between the concentration of the blood constituents of immigrants and native French people. By immigrants we mean persons now living in France but coming from other geographical locations such as Italy, the Iberian Peninsula, northern or central Europe, northern Africa, or the Near or Middle East. Multiple regression analysis confirmed the need to establish reference limits in immigrants for many blood constituents because of a significant shift of the curve relative to that for the French population. We have determined appropriate reference limits, for some ten blood constituents in each group of immigrants.

Adolescent↗
PubMedDate not supplied

[Apolipoprotein E polymorphism in a Moroccan population: allele frequency and relation to plasma lipid concentrations].

To date, no data are available on relationship between apolipoprotein E (apo E) polymorphism and lipid levels in Moroccan population. The present work reports an apo E polymorphism repartition in Moroccan population and relationship between this polymorphism and the levels of plasma cholesterol, triglycerides, apo A1, B and E. Blood samples from 168 healthy Moroccan individuals from Rabat area (90 men and 78 women), aged from 20 to 50 years (32 9 years), were analysed for serum apo E, A1 and B, triglycerides, and total cholesterol. In parallel, genotyping by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed. The apo E allelic frequencies were 11% for epsilon4, 84% for epsilon3 and 5% for epsilon2. There were correlation between apo E alleles and serum lipid concentrations, E2/E3 carriers had significantly higher level of apo E than E3/E3, and E4/E3 carriers had significantly higher total cholesterol apo B and triglycerides than E3/E3 and E2/E3 carriers. The total cholesterol and apo B concentrations are significantly higher in women than in men but the triglycerides are lower. The apo A1 concentration is independent of both sex and apo E genotype. Thus, the results demonstrate an influence of apo E alleles on serum cholesterol, triglycerides, apo E and apo B concentrations among healthy Moroccan.

Adult↗
PubMedDate not supplied

Differential effects of human recombinant interleukin-1 beta on cytochrome P-450-dependent activities in cultured fetal rat hepatocytes.

The immunomodulator interleukin-1 beta (IL-1) is one of the major inflammatory mediators. In vivo, it has been reported to depress some rat liver cytochromes P-450 (cytochrome P-450). Our aim was to study those effects in vitro, using cultured fetal rat hepatocytes as a model. Testosterone 6 beta-hydroxylase (cytochrome P-450 IIIA family activity) was not depressed by IL-1 treatments, but its induction by dexamethasone was prevented. The effect was time- and dose-dependent. Ethoxyresorufine-O-deethylase (cytochrome P-450 IA1 activity) decreased after IL-1 treatment, and dexamethasone partially prevented this inhibition. Acute phase effects of IL-1 were assayed by albumin and transferrin secretions. The cell's sensitivity to glucocorticoids was determined by tyrosine-aminotransferase activity. Our data demonstrate that IL-1 was able to prevent the glucocorticoid induction of cytochrome P-450 IIIA involving at least two different mechanisms. This is in agreement with the theory suggesting that the induction of CYPIIIA family by glucocorticoids requires the presence of the glucocorticoid receptor and some other regulatory elements. Other cytochrome P-450-dependent activities (IIA1, IIB1/2, and IIC11) were inhibited by IL-1 treatments, depending on dose and time, but some were also protected by dexamethasone.

Albumins↗
PubMedDate not supplied

[Glutathione S-transferases genetic polymorphisms and human diseases: overview of epidemiological studies].

Glutathione S-transferases (GST), xenobiotic-metabolising enzymes, are involved in the metabolic detoxification of various environmental carcinogens. Particular genetic polymorphisms of these enzymes have been shown to influence individual susceptibility against various pathologies including cancer, cardiovascular and respiratory diseases. The results from the meta-analysis indicate that GSTM1*0 null allele was associated with enhanced risk for lung (OR (95% IC) = 1,17 (1,07-1,27)), bladder (OR = 1,44 (1,23-1,68) and larynx cancer (OR = 1,42 (1,10-1,84)). GSTT1 null genotype was associated with increased astrocytomas (OR = 2,36 (1,41-3,94)) and meningiomas (OR = 3,57 (1,82-6,92)) cancer risk. GSTP1 allelic polymorphism influence the development of bladder cancer in smokers (OR = 2,40 (1,12-4,95)) and occupational asthma (OR = 3,5 (2,7-4,6)). Finally, GSTM1*0 null allele and GSTT1*1 functional allele were associated with increased risk for coronary heart diseases in smokers (OR = 2,30 (1,40-9,00)) and OR = 2,5 (1,30-4,80), respectively). The GSTT1*1 functional allele was also significantly associated with increased risk of lower extremity arterial disease (OR = 3,60 (1,40-9,00). These epidemiological data suggest that genetic GST polymorphisms influence the individual susceptibility to these diseases. Contrary to cardiovascular disease, no evidence of interaction between GST genotype and smoking status was found in lung cancer but it has not been studied in other cancers. Consequently, other works are necessary to study the potential interaction between GST genotype and environmental carcinogens including tobacco smoke extract.

Cardiovascular Diseases↗
PubMedDate not supplied

[Inhibition of cytochromes P-450. Biochemical mechanisms and possible therapeutic consequences. I--Inactivation by formation of reversible complexes].

Inactivation of cytochrome P-450 dependent monoxygenases, a major family of hepatic oxidative drug-metabolizing enzymes, has been an area of intensive pharmacological and toxicological investigation. Several classes of drugs are known to be inducers or inhibitors of P-450 isoenzymes. The reversible inhibition of the oxidative microsomal metabolism could be directly related to the ability of the drug to bind cytochrome P-450 as shown by the formation of an inhibitory complex. Such effects result in many drug-drug interactions, affect drug disposition and drug action and could interact with the metabolism of endogenous steroids. This review is concerned primarily with a mechanistic interpretation of the reversible interactions between several classes of therapeutic agents and various P-450 isozymes. The effects of structural modifications on the inhibitory activity were also described.

Animals↗
PubMedDate not supplied

Glucuronidation of 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen by liver microsomes.

Acylglucuronide formation from the 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen, three nonsteroidal anti-inflammatory drugs (NSAIDs), was investigated in rat liver microsomes using an HPLC method and 14C-labeled UDP-glucuronic acid as co-substrate. Pirprofen was the best substrate of UDP-glucuronosyltransferase with a Vmax/Km of 45.4, as compared with 8.0 and 1.6 for flurbiprofen and ibuprofen, respectively. Glucuronidation of the drugs was significantly increased upon treatment of rats with phenobarbital; 3-methylcholanthrene or clofibrate failed to induce the activity. At the dose of 100 mg/kg body weight for 1, 3, and 5 days, pirprofen was unable to induce its own glucuronidation. However, this treatment caused a transient increase, after 1 day, of several isoform activities monitored with 4-nitrophenol, 1-naphthol, 4-methylumbelliferone, terpenes, and testosterone as substrates. After 3 and 5 days these activities were decreased, especially when glucuronidation of 4-nitrophenol and 4-methylumbelliferone was considered, glucuronidation of the terpenes cis-myrtanol, borneol, nopol, and of testosterone being similar to control values. By contrast to clofibrate, administration of pirprofen to rats decreased bilirubin UDP-glucuronosyltransferase in a time-dependent fashion with a maximal decrease of 59% after 5 days. Treatment of rats with pirprofen also decreased markedly the formation of flurbiprofen glucuronide. Comparison of NSAID glucuronidation between several species indicated that it was most potent in monkeys, dogs, and humans. Cats were also efficient in that respect. Gunn rats, which are genetically deficient in bilirubin glucuronidation, were able to form acylglucuronides from the drugs, thus indicating that these 2-arylpropionic acids were not substrates of the bilirubin isozyme.

Aged↗
PubMedDate not supplied

[Changes of plasma and tissue gamma-glutamyltransferase under the influence of drugs].

Measurement of gamma-glutamyltransferase (GGT) activity in plasma is widely used in clinical biology (in order to detect hepatic diseases or to monitor treatment for alcoholism), and also in pharmacology (since this test is the only plasmatic marker for hepatic induction in human). However, the correct interpretation of a high plasmatic activity should take into account the various analytical factors which can affect results, as well as the physiological parameters known to modify this activity. It also requires its comparison to defined reference values. Several mechanisms may be involved in the increase of plasmatic activity as an index of hepatic induction, such as an increase in the protein synthesis, a release of the enzyme from the membrane or a modification in the biliary flux.

Chemical Phenomena↗
PubMedDate not supplied

[Variation in the urinary excretion of 6-beta-hydroxycortisol in humans after administration of the new isoquinoline derivative, PK-11195 (52028 RP)].

Among in vivo tests to assess liver drug metabolizing enzyme induction, urinary 6-beta-hydroxycortisol (6-beta-OHF), plasma gamma-glutamyltransferase (GGT) and urinary D-glucaric acid are most frequently proposed. 6-beta-OHF is the most abundant unconjugated metabolite of cortisol in human urine. We measured its elimination during a clinical trial in 16 human healthy volunteers (men and women), these persons being treated by a new isoquinoleine derivative, 52028 RP (PK-11195). This drug is an antagonist of peripheral type benzodiazepine binding sites. Urinary excretion of 6-beta-OHF increased significantly (3.5 fold, p less than 0.01) on the 5th day of treatment (400 mg/day, orally) and remained increased as long as the treatment was continued (15 days). Control values were again observed 5 days after stopping the treatment. Plasma gamma-glutamyltransferase activity and D-glucaric acid urinary elimination are increased more than 2 fold. The data demonstrated that 6-beta-OHF in the most sensitive among the three tests performed to detect a drug metabolism induction, during this clinical trial.

Adult↗
PubMedDate not supplied

Substrate specificity and enantioselectivity of arylcarboxylic acid glucuronidation.

A general and sensitive HPLC method using a precolumn switching system was developed for the separation and quantification of the individual diastereoisomeric glucuronides of the 2-phenylpropionic acid optical isomers. Kinetic properties of rat liver glucuronidation of several arylcarboxylic acids (1- and 2-naphthylacetic acids, clofibric acid, (R)-(-)- and (S)-(+)-2-phenylpropionic acids) are characterized. The results show that rat liver microsomes glucuronidate 1-naphthylacetic acid more efficiently than its regioisomer (higher Vmax/Km ratio because of a 6-fold lower Km value). Furthermore, 2-phenylpropionic acid glucuronidation occurs stereoselectively and is characterized by an enantiomeric ratio R/S = 1.60. Specific inducers of different UDP-glucuronosyltransferase isoforms and the Gunn rat strain are used to define the substrate specificity of the conjugation reaction towards arylcarboxylic aglycones. Acyl glucuronide formation is induced by phenobarbital. Gunn rats are not deficient in conjugation of these arylcarboxylic acids. These results indicate that these compounds behave similarly to classically defined group 2 substrates. In addition, the stereospecificity of 2-phenylpropionic acid conjugation is unchanged by pretreatment of animals with inducers, in vitro detergent activation, and enantiomeric inhibition. This suggests that the optical isomers of 2-phenylpropionic acid can be either conjugated by the same form or very closely regulated forms of UDPGT.

Animals↗