Consequences of urban pollution upon skin status. A controlled study in Shanghai area.

OBJECTIVE: After preliminary studies aimed at measuring pertinent biochemical parameters, potentially modified in subjects exposed to bad environmental conditions, a dedicated study was performed in Shanghai city to evaluate the effect of Urban pollution upon human skin and to collect feedback from the volunteers under study. METHODS: This study was performed during summer 2008 in two different districts of Shanghai, on 159 local residents: 79 subjects from Xu Jia Hui (a centre Shanghainese area), more exposed to pollution, and 80 subjects from Chong Ming, an agricultural region closely located north of Shanghai (<100 kms) and less exposed to pollution, according to official data. Biochemical parameters were measured on skin, and feedback from volunteers was collected through a graduated 'Likert scale' questionnaire under a point scale (strongly agree, agree, disagree, strongly disagree and none). RESULTS: The study demonstrated significant differences in several biochemical parameters measured in Chong Ming area, as compared to Urban area, with an increased ratio of squalene/lipids, a lower level of lactic acid and a better cohesion of stratum corneum. Both sebum excretion rate and sebum casual levels did not differ between the two districts. The volunteer's feedback evidenced a perceived link between pollution and their skin problems. CONCLUSION: This study demonstrated a significant impact of the pollution upon the skin status, as illustrated by changes in superficial biochemical parameters and volunteers' perception.

Evaluation of the impact of urban pollution on the quality of skin: a multicentre study in Mexico.

OBJECTIVE: After pilot and preliminary studies aimed at identifying pertinent biochemical parameters, a multicenter clinical study was performed to evaluate the effect of pollution on human skin. METHODS: The clinical study was performed in collaboration with the 'Centre Régional de lutte contre le cancer de Montpellier' and the 'National Institute of Public Health of Mexico' on 96 subjects in Mexico City (exposed to pollution) and 93 subjects in Cuernavaca (less exposed to pollution). Both biochemical and clinical skin parameters were studied. RESULTS: The study demonstrated significant quantitative and qualitative modifications of parameters related to sebum excretion in Mexico City compared to Cuernavaca one: An increased level of sebum excretion rate, a lower level of vitamin E and squalene in sebum, an increase of lactic acid and a higher erythematous index on the face of the subjects. In the stratum corneum, a significant higher level of carbonylated proteins and a lower level of IL 1α were noticed, as well as a decrease of ATP concentration with a decrease of chymotrysin like activity, without modifications of corneodesmosin content and trypsin like activity. From a clinical point of view, a higher frequency of atopic and urticarial skins, a higher frequency of red dermographism, an important seborrheic status at the forehead level and a lower level of dandruffs were noted in Mexico City population. The analysis taking into account the sex does not modify the observed results. CONCLUSION: The study demonstrated an important impact of polluted environmental conditions on skin quality, evidencing important modifications of superficial biochemical parameters. The cause/effects relationships of these modifications remain, however, to be further assessed by a complementary in vitro/in vivo approaches.

Modelling the influence of activation-induced apoptosis of CD4+ and CD8+ T-cells on the immune system response of a HIV-infected patient.

On the basis of the human immunodeficiency virus (HIV) infection dynamics model proposed by Adams, the authors propose an extended model that aims at incorporating the influence of activation-induced apoptosis of CD4+ and CD8+ T-cells on the immune system response of HIV-infected patients. Through this model, the authors study the influence of this phenomenon on the time evolution of specific cell populations such as plasma concentrations of HIV copies, or blood concentrations of CD4+ and CD8+ T-cells. In particular, this study shows that depending on its intensity, the apoptosis phenomenon can either favour or mitigate the long-term evolution of the HIV infection.

Cross-polarization/magic-angle-spinning nuclear magnetic resonance in selectively 13C-labeled synthetic eumelanins.

We report a solid-state NMR study of synthetic eumelanins prepared by oxidation of 5,6-dihydroxyindole (DHI) selectively 13C-labeled at positions 2 or 3 of the indole ring. The 13C-1H couplings have been used to quantify the carbons by selecting the non-protonated and protonated carbon resonances. By comparing the data of non-labeled melanin to that obtained using [2-(13)C]- and [3-(13)C]-enriched DHI, it was possible to clearly demonstrate the high chemical reactivity of position 2 and, to a lesser extent, position 3 of the DHI unit. These two sites together are responsible for three-quarters of the proton loss during polymerization. The cross-polarization/magic-angle-spinning spectra likewise point to a partial oxidation of positions 2 and 3 to the carboxyl and carbonyl oxidation states during the formation of melanin. Furthermore, it is shown that 13C-13C dipolar interactions in [2-(13)C]-enriched DHI melanins can be observed using radiofrequency-driven dipolar recoupling (RFDR) 2D experiments. An upper limit of about 4 A for the distance between the C-2 carbons is deduced from the RFDR experiments. This result is in agreement with the basic arrangement of the different atoms expected in the DHI melanins.

Levels of cadmium in kidney and liver tissues among a Canadian population (province of Québec).

In an exploratory study, levels of cadmium in whole-kidney and liver tissues of 314 subjects from the general population of the province of Quebec (Canada) were measured postmortem. Frequency distributions of cadmium concentrations were lognormal. As reported in similar studies, age and especially smoking habits were the main variables affecting cadmium concentrations. The geometric mean of whole kidney concentrations (wet weight) was 17.62 microg/g, with a minimum concentration of 2.25 microg/g and a maximum of 100.61 microg/g. Mean concentrations of cadmium in kidneys increased with age, reaching a plateau in the group 50 to 59 yr (29.49 microg/g), and falling slowly thereafter.

Antioxidant activity in bronchoalveolar lavage fluid from patients with lung cancer.

Glutathione (GSH) is one of the key components of the lung antioxidant defenses. Chronic smokers have higher GSH concentrations in their epithelial lining fluid than do nonsmokers. The aim of this study was to compare antioxidant concentrations in epithelial lining fluid (ELF) from nonsmokers, smokers with, and smokers without non-small-cell lung cancer. The study found that GSH in ELF from patients with lung cancer was significantly greater than in ELF from smokers and nonsmokers, at 1,485.5 +/- 208, 544 +/- 97.6 microM, and 339.3 +/- 112 microM, respectively (p < 0.05). In contrast, superoxide dismutase (SOD) was lower in ELF from patients with lung cancer than in that from smokers and nonsmokers, at 3.52 +/- 0.99, 30.82 +/- 8.2, and 43.91 +/- 10.1 U/ml, respectively (p < 0.05). Spontaneous superoxide anion release by adherent alveolar macrophages (AM) showed no difference between smokers with and without lung cancer. These data indicate that patients with lung cancer have marked modifications in their ELF antioxidant defenses by comparison with those of smokers. It is difficult to distinguish whether changed antioxidant status is a primary disturbance involved in the cancer process or whether it is a consequence of the neoplastic changes in malignancy.

Stimulation of the 92-kD type IV collagenase promoter and enzyme expression in human melanoma cells.

The 92-kD type IV collagenase is a member of the metalloproteinase family which degrades type IV collagen, a major component of basement membrane and is involved in tumor invasion and metastasis. The promoter and adjacent regulatory sequences of the 92-kD type IV collagenase have been identified previously and three cis-acting elements homologous to the binding sites for AP-1, NF-KB and SP-1 proteins contributed to induction of the promoter activity by 12-O-tetradecanoylphorbol 13-acetate (TPA) and tumor necrosis factor (TNF-alpha) in HT1080 cells. To date, no direct correlation between promoter activity and expression of the 92-kD type IV collagenase has been reported in normal or cancer cells. In this study, the effects of the transcriptional stimulation of the 92-kD type IV collagenase gene on the expression of the enzyme in human A2058 melanoma cells was analyzed by zymography experiments. Quantitative immunoblots using a monoclonal antibody that recognized specifically and exclusively the 92-kD type IV collagenase, confirmed that the 92-kD gelatinase was 92-kD type IV collagenase. Stimulation of the promoter activity resulted in increased gelatinase activity in the culture medium of A2058 cells. A direct correlation between TPA- and TNF-alpha-mediated promoter stimulation of the 92-kD type IV collagenase gene and its expression was also demonstrated in the human fibrosarcoma HT1080 cells. Interleukin-1 alpha failed to induce 92-kD gene promoter activity and type IV collagenase expression in melanoma and fibrosarcoma cell lines. Our data demonstrated that TPA- and TNF-alpha-induced 92-kD type IV collagenase promoter stimulation leads to a proportional increase of enzyme expression and secretion and thus could contribute to the activation of the invasive phenotype.

High rate of multiple genital HPV infections detected by DNA hybridization.

Cervical smears collected from 450 patients involved in a clinical follow-up of cervical human papillomaviruses (HPV) infections were screened for the presence of HPV 6b, 11, 16, and 18 DNA by both dot blot and southern blot hybridization methods. Using very high stringency hybridization assays, the four HPV types could be easily distinguished by dot blotting. After a preliminary clinical sorting, 42.9% of the samples were found to be HPV-positive. Among the samples infected by a single HPV, type 16 was the most frequent (25.4% of the positive samples) followed by 6b (19.7%), 11 (8.3%), and 18 (7.2%). Double or even multiple infections by the different HPV types were detected at a very high rate (39.4% of the positive samples).

High-performance liquid chromatographic evaluation of 2-(alpha-thenoylthio)propionylglycine and its two metabolites in biological fluids.

A high-performance liquid chromatographic (HPLC) method for determining 2-(alpha-thenoylthio)propionylglycine (TTPG) and its two main metabolites, thiophenecarboxylic acid and thiopronine, in biological samples was developed. TTPG and its metabolites were extracted by solvent partition and then determined by reversed-phase HPLC with UV detection at 245, 295 and 360 nm. This procedure was validated in order to allow the assay of these compounds in plasma and urine samples with sufficiently low detection limits (50 ng/ml for TTPG and TCA and 100 ng/ml for thiopronine) and with good linearity within the concentration range investigated. It was applied to a comprehensive pharmacokinetic investigation of TTPG in healthy volunteers.

[Pharmacokinetics of sulindac in aged patients presenting with inflammatory joint disease]. / Pharmacocinétique du sulindac chez des patients âgés présentant une pathologie articulaire inflammatoire.

The kinetic of sulindac and its two metabolites (sulfide and sulfone) was investigated in twelve elderly patients, following multiple oral dose administration of 400 mg/d. Data were compared to those obtained previously in ten healthy volunteers who received the same dosage regimen. Following multiple dose administration, accumulation ratios indicate that sulindac do not accumulate either in elderly patients (R = 1.35; R = AUC0-24 J8/AUC0-24 J1) or in healthy young subjects (R = 1.38; R = U0-24 J1). No significant modification of sulindac and sulfide kinetic parameters was observed. The apparent bioavailability of the inactive metabolite, sulfone, was found to be doubled in elderly patients (p less than 0.05). We conclude that there is no need to modify the dosage regimen of Arthrocine (400 mg once a day) in elderly patients.

Mechanisms of chronotropic cardiac effects of alinidine and plasma concentration-response relationships in the conscious dog with chronic atrioventricular block.

The chronotropic cardiac effects of alinidine were studied in the conscious dog with chronic atrioventricular block. Alinidine at 0.5 - 4 mg/kg, i.e., at plasma concentrations between 42 +/- 2 and 1625 +/- 371 ng/ml, initially increased atrial rate dose-dependently. This effect fell off rapidly, but atrial bradycardia was never observed. After atropine and pindolol, which raised basal atrial rate, alinidine (2 mg/kg) decreased atrial rate, whereas after phenoxy-benzamine, yohimbine or phentolamine, it produced atrial effects identical to those observed under basal conditions, i.e., initial tachycardia and no bradycardia. Alinidine dose-relatedly decreased ventricular rate. None of the pretreatments modified the maximal ventricular bradycardia, but interestingly after pindolol or yohimbine this effect developed more rapidly (maximal bradycardia between 3 and 5 against 30 min) and then declined progressively. Alinidine did not modify mean blood pressure at any dose. After atropine, phenoxybenzamine or phentolamine, alinidine remained without effect on mean blood pressure, but after pindolol or yohimbine, a hypotensive effect appeared concomitantly with the reduction of the ventricular bradycardia. These results show that the initial atrial cardioacceleration due to alinidine results from a direct vagolytic action of this drug and that the absence of atrial bradycardia results from buffering by the vagolytic effect and/or a relatively low basal atrial rate. They also suggest that the ventricular bradycardia does not involve either the muscarinic cholinoceptors or the alpha- or beta-adrenoceptors, though the results obtained after pindolol or yohimbine suggest possible involvement of a fall in sympathetic tone by stimulation of presynaptic or central alpha2-adrenoceptors, particularly in the persistence of the bradycardic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Variation in cadmium content of caribou tissues from northern Québec.

Samples of kidney, liver, skeletal muscle, heart, mesentery and rumen wall were collected during 1985-1986 in northern Québec from 121 caribou belonging to the Rivière George herd. Significant seasonal variations were found for cadmium concentration in kidneys, liver and skeletal muscles, the level being higher in winter than in autumn. The concentration in liver and kidneys increased with age, while the effect of this factor was complex in skeletal muscles. Sex-related differences were found in muscle and liver levels of cadmium. According to season, sex and age, mean dry-weight concentrations varied between 5.6 and 51.3 micrograms g-1 in kidneys, 1.7 and 4.0 micrograms g-1 in liver and 0 and 0.27 microgram g-1 in skeletal muscles. Season and sex-related differences could be explained by seasonal variation in cadmium intake and by the annual weight cycle exhibited by caribou kidneys and liver. Because of the relatively high cadmium content, it was recommended not to consume liver and kidneys of free-ranging caribou in Québec; this restriction did not apply to meat, heart, mesentery or rumen wall that contained limited concentrations of this heavy metal.

[Pharmacokinetics of cefatrizine administered in repeated doses]. / Pharmacocinétique de la céfatrizine administrée en doses répétées.

Twelve healthy volunteers received cefatrizine orally at doses equal to 500 mg every 12 h for 5 days. Cefatrizine was assayed by high performance liquid chromatography in plasma and urines collected after the first and/or the last administration. Cefatrizine absorption was rapid; its peak plasma level was reached at time 1.79 +/- 0.07 h following the first dose, it was equal to 7.37 +/- 0.31 micrograms.ml-1. Its apparent elimination half-life was equal to 1.50 +/- 0.05 h, it explains the lack of accumulation with time during multiple administrations every 12 hours. Comparisons between peak plasma concentration and area under curves following the first and last dosing showed significant (p less than 0.01) but weak (close to 15%) reduction of these 2 parameters with time which could be explained by a slight reduction of cefatrizine absorption with time. In conclusion, cefatrizine does not accumulate when administered repeatedly at a dose equal to 500 mg every 12 h in young adult, and its pharmacokinetics is virtually linear with time.

A study of the interaction of roxithromycin with theophylline and carbamazepine.

There have been reports of an interaction when theophylline and macrolides are given together, and also when carbamazepine is given with macrolides. We compared the kinetics of theophylline and carbamazepine, given alone and then in combination with roxithromycin. Roxithromycin had little effect on the pharmacokinetics of theophylline and none on carbamazepine, and roxithromycin can be given with either of the drugs without any need to alter the dose.

Pattern of cadmium contamination in the liver and kidneys of moose and white-tailed deer in Québec.

Samples of moose (N = 431) and white-tailed deer (N = 225) liver and kidneys were collected during the 1985 hunting season from 14 zones south of the 50 degree latitude in Québec. Regional differences in cadmium level in the liver were detected and three homogeneous areas were delineated for each species. Uptake was greater for moose than for deer: in the liver, mean concentrations were 2.9-15.9 mg kg-1 (dry weight) for moose and 0.8-2.6 for deer, depending on the area and sex; in kidneys, means ranged between 31.8-100.5 and 20.9-39.0 mg kg-1, respectively. Female moose had lower levels than bulls. Less affected moose, in eastern Québec, contained cadmium concentrations comparable to the highest values measured in Scandinavia. Cadmium uptake in deer was on the same level or higher than in the United States. Our results indicate a widespread presence of this heavy metal in the environment that may be linked to acid precipitation. We do not recommend consuming wild cervid liver or kidneys in Québec for the moment. Further research is needed on the overall mechanisms involved in the cadmium contamination of the environment and on the actual intake of this metal in the human diet.

Quantitative analysis of S3341 in human plasma and urine by combined gas chromatography-negative ion chemical ionization mass spectrometry: 15 month inter-day precision and accuracy validation.

A new quantitative assay for the determination of S3341, an alpha-2 agonist antihypertensive drug, has been developed using combined gas chromatography-negative ion chemical ionization mass spectrometry. The [M]-. ions from TFA derivatives of S3341 (m/z 276) and the internal standard (2H4)S3341 (m/z 280) are monitored simultaneously by selected ion monitoring. For S3341 concentrations ranging from the limit of detection (0.2 ng ml-1 using 1 ml of plasma) to 5 ng ml-1, the average assay precision (CV) is approximately 7% while the average assay accuracy (percentage of error) is 4%. Validation of the day-to-day precision and accuracy was realized after analysing control plasma samples (n = 295) concurrently with the biological samples collected during the pharmacokinetic studies conducted over 15 months. The average day-to-day precision (CV) and accuracy (percentage of error) are 10% and 6% respectively, thus indicating that this assay procedure routinely provides reliable analytical data.

[Comparative pharmacokinetics of piperacillin in young and elderly subjects]. / Pharmacocinétique comparative de la pipéracilline chez le sujet jeune et le sujet âgé.

One single 4 g dose of piperacillin was administered by intravenous infusion over 30 min to 15 patients aged from 66 to 90 years (mean +/- s.e.m.: 79.8 +/- 2.0 years); the patients mean weight was 53 +/- 4 kg. Fifteen samples of blood were withdrawn from each subject. Plasma piperacillin levels were measured by high performance liquid chromatography with detection in ultraviolet light at 214 nm. Mean plasma piperacillin concentrations in elderly subjects, measured 0.5, 2 and 12 h after dosing, were 168.5 +/- 15.7, 79.9 +/- 11.5 and 1.72 +/- 0.69 microgram.ml-1, as against 146.8 +/- 10.6, 35.5 +/- 3.9 and 0.212 +/- 0.040 microgram.ml-1 in healthy young adults. Plasma piperacillin concentrations versus time curves obtained after the infusion was discontinued were bi-exponential, with half-lives T1/2 (lambda 1) and T1/2 (lambda 2) of 0.65 +/- 0.11 and 1.72 +/- 0.09 h respectively; the corresponding figures in young adults were 0.59 +/- 0.03 and 1.81 +/- 0.13 h respectively). In elderly subjects the mean total clearance of piperacillin (ClT = 2.90 +/- 0.25 ml.min-1.kg-1) was reduced by 15% (NS) and the volume of distribution during steady state (Vdss = 0.337 +/- 0.027 L.kg-1) was increased by 43% (P less than 0.001). As a result, the mean time of piperacillin stay in the body (MRS = Vdss/Cl) was practically doubled in elderly subjects (2.09 +/- 0.15 h as against 1.15 +/- 0.04 h in young adults (P less than 0.01).