Influence of water activity on the enantioselective esterification of (R,S)-ibuprofen by crosslinked crystals of Candida antarctica lipase B in organic solvent media.

The lipase B from Candida antarctica was purified from a commercial source and crystallized. The microcrystals were crosslinked using glutaraldehyde. The crosslinked crystals were then used to catalyze the esterification of (R,S)-ibuprofen with dodecanol in octane at various water activities. As for the commercial preparation immobilized on acrylic resin, Novozym 435, low water activities foster better enantioselectivity, and the maximum reaction rates are obtained for a(W) = 0.1.

Environmental pesticide exposure as a risk factor for Alzheimer's disease: a case-control study.

The aim of this study was to evaluate the influence of pesticide exposure on the development of Alzheimer's disease (AD), taking into account the potentially confounding factors (genetic, occupational exposure, and sociodemographic). The 1924 study participants (>70 years old) were randomly selected in the Saguenay-Lac Saint-Jean region (Quebec, Canada). The AD diagnosis was established in three steps according to recognized criteria. Sixty-eight cases were paired with a nondemented control for age (+/-2 years) and sex. Structured questionnaires addressed to subjects and proxy respondents allowed a description of the sociodemographic characteristics, lifestyle characteristics, and residential, occupational, familial, and medical histories. Assessment of environmental exposure to pesticides was based on residential histories and the agriculture census histories of Statistics Canada (1971-1991) for herbicide and insecticide spraying in the area. Statistical analyses were performed with a logistic regression, adjusting for potential confounding factors. The results failed to show a significant risk of AD with an exposure to herbicides, insecticides, and pesticides. However, future investigations are needed to establish more precisely the identification, measurement, mobility, and bioavailability of neurotoxic pesticide residues in relation to AD.

Aluminum forms in drinking water and risk of Alzheimer's disease.

The objective of this study was to assess the relation between long-term exposure to different aluminum (Al) forms in drinking water and Alzheimer's disease (AD). The study participants were selected from a random sample of the elderly population (> or = 70 years of age) of the Saguenay-Lac-Saint-Jean region (Quebec). Sixty-eight cases of Alzheimer's disease diagnosed according to recognized criteria were paired for age (+/-2 years) and sex with nondemented controls. Aluminum speciation was assessed using established standard analytical protocols along with quality control procedures. Exposure to Al forms (total Al, total dissolved Al, monomeric organic Al, monomeric inorganic Al, polymeric Al, Al(3+), AlOH, AlF, AlH(3)SiO(2+)(4), AlSO(4)) in drinking water was estimated by juxtaposing the subject's residential history with the physicochemical data of the municipalities. The markers of long-term exposures (1945 to onset) to Al forms in drinking water were not significantly associated with AD. On the other hand, after adjustment for education level, presence of family cases, and ApoE varepsilon4 allele, exposure to organic monomeric aluminum estimated at the onset of the disease was associated with AD (odds ratio 2.67; 95% CI 1.04-6.90). On average, the exposure estimated at the onset had been stable for 44 years. Our results confirm prime the importance of estimation of Al speciation and consideration of genetic characteristics in the assessment of the association between aluminum exposure and Alzheimer's disease.

Shoulder supports revisited: a Canadian follow-up survey.

This paper investigates the use of shoulder supports with stroke patients in Canada and compares the results of two survey questionnaires carried out in 1984 and 1994. It describes which shoulder supports therapists are using with stroke patients and which goals they hope to achieve with specific supports. The Lapboard, Cuff Type Sling, and Arm Trough Support were the most frequently used supports at both time periods. The most frequent goal chosen for each of these three most frequently chosen supports was the same at both time periods but were chosen significantly less frequently in 1994. There was a significant decrease in the use of the Bobath Axial Roll over the ten-year period. This follow up questionnaire documents the limited changes which have occurred in the last ten years in the management of the shoulder following stroke, raises some questions about this area of practice, and outlines some solutions including the need to base occupational therapy practice on more evidence.

Influence of water activity on the enantioselective esterification of (R,S)-ibuprofen by Candida antarctica lipase B in solventless media.

The lipase-catalyzed enantioselective esterification of ibuprofen has been studied in a media, composed only of substrates. When racemic ibuprofen is used, the alcohol-chain length affects the esterification rates of individual enantiomers, but it does not affect the enantioselectivity. Water activity affects the esterification rates of (R)- and (S)-ibuprofen differently, leading to higher enantioselectivity at lower water activities. Experiments were also conducted at various (R)- to (S)-ibuprofen ratios. It appears that the esterification rate of (R)-ibuprofen is always proportional to its concentration, whereas at low water activity the esterification rate of (S)-ibuprofen shows a saturation at higher concentrations. Other 2-phenyl carboxylic acids were studied, and the increase in apparent enantioselectivity at low-water activity was not observed for the molecules tested.

Chiral high performance liquid chromatography resolution of ibuprofen esters.

Two cellulose-based chiral stationary phases (Chiralcel OD and Chiralcel OJ) were compared on their ability to resolve various aliphatic ibuprofen esters. Chiralcel OJ with hexane as the mobile phase allows for the separation of most of the esters. Observed changes in resolution depending on the solute nature (basicity of the solute, esterified alcohol chain length, presence of a double bond) are discussed. An example of the application of this method for following the kinetic resolution of racemic ibuprofen is presented.

[Diagnosis of colitis caused by cytomegalovirus infection in AIDS. Comparative value of total colonoscopy and rectosigmoidoscopy (apropos of 24 cases). AIDS GIT]. / Diagnostic de colite à cytomégalovirus au cours du SIDA. Valeur comparative de la coloscopie totale et de la rectosigmoïdoscopie (à propos de 24 cas). AIDS GIT.

OBJECTIVES: To evaluate the respective diagnostic value of flexible rectosigmoidoscopy and colonoscopy in the cytomegalovirus colitis. METHODS: Twenty-four patients with AIDS were studied retrospectively. The entry criteria were: flexible rectosigmoidoscopy or colonoscopy, with 2 rectal and 2 caecal biopsies, presenting cytomegalovirus inclusions bodies linked to an inflammation at least on one colonic biopsy. RESULTS: Twenty-four patients had 29 colonoscopies. In 16 cases colonoscopy was performed to the caecum. The endoscopic findings of the 16 full colonoscopies were: 7 right colitis, 5 diffuse colitis, 2 bisegmentary colitis, 1 proctitis and 1 non endoscopic lesion. The histologic findings of the 16 full colonoscopies were: 5 cytomegalovirus inclusions on rectal biopsies and 16 on caecal biopsies. For the 13 incomplete colonoscopies, 11 had inclusions on rectal biopsies. So the flexible rectosigmoidoscopy was not sufficient to find inclusions 13 times out of 29. CONCLUSION: Our study indicates that in the cytomegalovirus colitis, inclusions predominate in the caecum, isolated right colitis exists and extra-colonic cytomegalovirus disease is not always found. For these reasons full colonoscopy is necessary for diagnosis in patients with normal flexible rectosigmoidoscopy.

Effects of sulindac and oltipraz on the tumorigenicity of 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone in A/J mouse lung.

The efficacies of the non-steroidal, anti-inflammatory drug sulindac and the schistosomicidal agent oltipraz in inhibiting lung tumorigenesis was measured in A/J mice. Lung tumors (15.7 tumors/mouse) were induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 9.1 mg/mouse) administered in drinking water for 7 weeks. Feeding mice with sulindac (123 mg/kg diet), 2 weeks before carcinogen treatment until they were killed reduced tumor multiplicity by 53%. Oltipraz (250 mg/kg diet), however, has no effect on tumorigenesis. The absorption and metabolism of NNK were compared in the stomachs and intestines isolated from mice fed AIN-76A diet or sulindac + diet. Sulindac had no effect on alpha-carbon hydroxylation, pyridine N-oxidation or carbonyl reduction of NNK. Mouse lung explants were cultured with 4.7 microM [5-3H]NNK for 4 or 8 h. The addition of 1 mM sulindac to the culture medium reduces the alpha-carbon hydroxylation and pyridine N-oxidation of NNK. However, the administration of sulindac in the diet prior to the excision of the lung explants had no effect on these two metabolic pathways. We compared the levels of sulindac and its sulfide and sulfone metabolites in the lungs, livers and plasma of mice fed an AIN-76A diet containing 130 mg sulindac/kg for 2 weeks. The sulfide metabolite was the most abundant of the three compounds in plasma (17.6 pmol/microliters) and liver tissues (17.7 pmol/mg) but it could not be detected in lung tissues. These results show that non-steroidal anti-inflammatory drugs constitute a new class of chemopreventive agents in lung tumorigenesis. The tumor chemopreventive activity of sulindac is not mediated by the sulfide metabolite responsible for its anti-inflammatory activity.

Modulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone demethylation and denitrosation by rat liver microsomes.

The nicotine-derived N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) is abundant in tobacco smoke and is a potent carcinogen in laboratory animals. We have characterized and compared methyl hydroxylation leading to formaldehyde formation (activation pathway) and denitrosation (putative deactivation pathway) of NNK using rat liver microsomes. Methyl hydroxylation was linear between 10 and 50 min and denitrosation was linear between 20 and 65 min. The ratio of nitrite/formaldehyde formation was smaller with 4 mM NNK (0.016) than with N-nitrosodimethylamine (NDMA) (0.037). Liver microsomes exhibited at least two apparent Km values (0.005 and 0.534 mM) for NNK methyl hydroxylation. In vitro methyl hydroxylation of NDMA and NNK were induced by pretreatment of the rat with isopropanol. Butylated hydroxytoluene pretreatment doubled the rate of microsomal denitrosation but did not affect the rate of methyl hydroxylation (+)-Catechin is a flavonoid present in tea, wine and apple skin. We observed that 0.10 mM (+)-catechin inhibited methyl hydroxylation and denitrosation of 4 mM NNK by 40% and 62%, respectively. These results indicated that NNK could be deactivated by denitrosation. Hydroxylation of the NNK methyl group by rat liver microsomes was 34 times more extensive than denitrosation.

Lung tumorigenicity of NNK given orally to A/J mice: its application to chemopreventive efficacy studies.

The ability of five chemopreventive agents to inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice was determined. The carcinogen was administered in the drinking water during 7 weeks (at doses of 9.2 to 3.1 mg/mouse). Three chemopreventive agents: (dose, g/kg diet) ellagic acid (4.0), 2(3)-BHA (5.0), and sulindac (0.13) inhibited the multiplicity of lung adenomas by 52, 88, and 52%, respectively, when compared to NNK controls. beta-Carotene + retinol (2.14 + 0.009), in combination, and selenium (0.0022) were ineffective. NNK was absorbed more rapidly from the duodenum than from the stomach and was metabolized in both tissues. The activation of NNK by alpha-carbon hydroxylation and its deactivation by pyridine N-oxidation was more extensive in the duodenum than in the stomach. Carbonyl reduction of NNK was 10 times higher in the duodenum. Liver microsomes were more active than lung microsomes in the alpha-carbon hydroxylation of NNK, suggesting that some liver isozymes of cytochrome P-450 have a high affinity for NNK. Pyridine N-oxidation was five times more extensive in lung microsomes than in liver microsomes. Collectively, these results demonstrate that NNK given orally to A/J mice provides a suitable model from which to assess the relative activity and mechanisms of action of chemopreventive agents in pulmonary carcinogenesis.