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Biomedical subjects

Louis Merle

Publications and source records attributed to Louis Merle.

8 recordsLinked to original sources
PubMed2005

Predicting and preventing adverse drug reactions in the very old.

The size of the elderly population has been increasing steadily for several years. Individuals in this age group often have several concomitant diseases that require treatment with multiple medications. These drugs, for various reasons and especially as a consequence of potential accumulation, may be associated with adverse reactions. Of the numerous factors that can favour the occurrence of these adverse drug reactions, the most important are the pathophysiological consequences of aging, particularly as these apply to the very old. Although absorption of drugs is not usually reduced in the elderly, diffusion, distribution and particularly elimination decline with age. Furthermore, while hepatic metabolic function is fairly normal, renal function is usually markedly depressed in very old individuals, and this can translate into clinical consequences if it is not taken into account. This is why, before administration of any drug in the elderly, evaluation of glomerular filtration rate is essential. Validated estimations such as those obtained from the classical Cockcroft-Gault formula or from more recent methodologies are required. In addition to reductions in various organ functions, factors connected with very old age such as frailty, falls, abnormal sensitivity to medications and polypathology, all of which tend to be more common in the last years of life, all directly impact on adverse drug reaction occurrence. Given these characteristics of the elderly population, the best way to reduce the prevalence of adverse drug reactions in this group is to limit drug prescription to essential medications, make sure that use of prescribed agents is clearly explained to the patient, give drugs for as short a period as possible, and periodically re-evaluate all use of drugs in the elderly.

Aged↗
PubMed2003

Inhibition of human serum arylesterase by metal chlorides.

The inhibition of arylesterase (paraoxonase, EC 3.1.8.1) by metal chlorides was studied with both pooled human serum (A phenotype) and purified enzyme, using phenyl acetate as substrate. Inhibition data were analysed with the Hill equation. Results obtained with whole serum and purified enzyme were very similar. On the basis of the Hill coefficient, n(H), three groups of inhibitors were distinguished: (1) Cu(2+) and Hg(2+) for which n(H)=1, suggesting a single binding site (probably the free cysteine at position 283); these metals were mixed inhibitors, with more affinity for the free enzyme than for the enzyme-substrate complex; (2) Mn(2+), Co(2+), Ni(2+), Zn(2+), and Cd(2+) for which n(H)>1, suggesting several cooperative binding sites; (3) La(3+), for which n(H)<1. Within groups (1) and (2) the inhibiting potency followed the order of the periodic table. For the 3d elements the inhibiting order followed the Irving-Williams series, with the classical exception of Cu(2+). Only Zn(2+) was inhibitory at its physiological concentration.

Carboxylic Ester Hydrolases↗
PubMed2002

Inhibition of butyrylcholinesterase by phenothiazine derivatives.

The inhibition of horse serum butyrylcholinesterase (EC 3.1.1.8) by 10 phenothiazine or thioxanthene derivatives was studied with a purified enzyme. Most compounds were mixed inhibitors, but for some of them an apparent competitive inhibition was observed. The competitive inhibition constants (K) were in the range 0.05 to 5 microM. The structures of the inhibitors were modeled by geometry optimization with the AM1 semi-empirical molecular orbital method and octanol/water partition coefficients were estimated with the CLOGP software. Quantitative structure-activity relationships identified lipophilicity, molecular volume, and electronic energies as the main determinants of inhibition. This quantitative model suggested hydrophobic and charge-transfer interactions of the phenothiazine ring with a tryptophan residue at the "anionic" site of the enzyme, and a hydrophobic interaction of the lateral chain with nonpolar amino acids.

Animals↗
PubMed2002

Paraoxonase 1 activity: a new vascular marker of dementia?

Paraoxonase 1 (PON1), an A-esterase with peroxidase-like activity present on the surface of HDL, decreases the peroxidation of LDL. Serum PON1 activity (PON1a) decreases with aging and in disorders associated with a high risk of adverse cardiovascular events (acute myocardial infarction, diabetes mellitus, and chronic renal failure). The implication of vascular factors in Alzheimer-type dementia (ATD) is strongly suspected. We measured PON1a by spectrophotometry using the paraoxon substrate in 180 healthy subjects (controls; mean age: 75.3 +/- 8.9 years; 98 women) and 154 patients admitted for cognitive testing. According to criteria, 45 patients had mild cognitive impairments (MCI; mean age: 75.6 +/- 9.3 years; 28 women), 60 had ATD (mean age: 75.6 +/- 8.3 years; 47 women), and 49 had vascular dementia (VaD; mean age: 77.5 +/- 7.2 years; 33 women). Mean PON1a was lower in VaD (0.25 +/- 0.1 U/mL) than in controls or ATD (both 0.41 +/- 0.2 U/mL, p < 0.01). Mean PON1a values in MCI (0.34 +/- 0.2 U/mL) and ATD (0.41 +/- 0.2 U/mL) were not significantly different. In multiple linear regression, PON1a was negatively correlated with male sex, age, and VaD, and positively correlated with ATD (each correlation p < 0.001). As shown in other high-risk cardiovascular disorders, PON1a seems to be a reliable marker of VaD. Its modification in Alzheimer's disease supports the implication of vascular risk factors in this type of dementia.

Aged↗
PubMed2002

Paraoxonase 1 192/55 gene polymorphisms in Alzheimer's disease.

An esterase, paraoxonase 1 (PON1), protects against organophosphate neurotoxicity and decreases lipoprotein oxidation. Two polymorphisms of PON1 [192 (R or Q) and 55 (M or L)] exist and are associated with coronary artery disease. We have previously shown that serum PON1 activity (PON1a) is lower in vascular dementia (VaD) than in Alzheimer's disease (AD), suggesting that PON1a may distinguish VaD from AD. As PON1 polymorphism modifies PON1a, we determined 192 and 55 PON1 polymorphisms by sequence-specific primer PCR in 64 healthy subjects (HS; mean age: 79.5 +/- 6.3 years; 38 women) and in 72 patients (mean age: 80.2 +/- 6.8 years; 51 women) undergoing cognitive evaluations. According to DSM-IV/NINCDS/ADRDA/NINDS/AIREN criteria, 45 patients (mean age: 80.0 +/- 7.2 years, 34 women) had AD and 27 patients (mean age: 79.8 +/- 6.6 years, 16 women) had VaD. We also measured serum PON1a by spectrophotometry. No significant differences in phenotype distributions among the three study groups were detected by chi(2) test. Among the variables, age, sex, and phenotypes 192 and 55, logistic regression selected only polymorphism 192, but not 55, as a discriminating factor between AD and VaD (p < 0.05). Substitution of serum PON1a for genotype yielded a similar result. PON1 polymorphism 192 appears to be a reliable marker to distinguish patients with AD from patients with VaD and from healthy subjects. Changes in 192 polymorphism distributions in AD and in VaD may at least partially explain the significant difference in PON1a in these two types of dementia.

Aged↗
PubMed2002

[Acetaminophen-induced hypothermia, an AIDS related side-effect? About 4 cases].

Hypothermia is an uncommon side effect of acetaminophen. We report 4 cases of HIV-infected patients who developed hypothermia after intravenous injection of propacetamol (the parenteral formulation of acetaminophen). The mechanism of this hypothermia is unknown. AIDS-induced changes in the metabolism of acetaminophen, could be an explanation. AIDS-associated opportunistic diseases may account for part of the mechanism. These hypothermias occur within 6 hours after the injection, are well tolerated and regress spontaneously.

Acetaminophen↗