Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo

Previous results in experimental systems have suggested that hydroxylated PCBs may decrease thyroid hormone levels through associative interaction with transthyretin. In the present paper it was investigated whether this property was also shared by various industrial chemicals, mainly pesticides. In total, 65 compounds from 12 chemical groups were analyzed for direct interference with the T4 binding site of transthyretin using a competitive binding assay. Sixty per cent of the compounds were competitive at a concentration level of 100 M. Relatively strong interactions were observed by several chlorophenols, chlorophenoxy acids and nitrophenols, as well as by individual compounds such as hexachlorobenzene, dicofol, bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups, e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil, also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased plasma TT3 levels. The results suggest the existence of a number of halogenated industrial chemicals with a potential for lowering plasma thyroid hormone levels through interference with hormone transport carriers.     

Comparison of two scoring systems for diagnosing levator ani muscle damage

Introduction and hypothesis

Levator defects are risk factors for pelvic organ prolapse (POP) and its recurrence. The most widely used scoring systems for severity of defects shown on magnetic resonance imaging (MRI) and perineal ultrasound (US) are not identical. The aim of this study was to investigate the differences between these classification systems with regard to levator defects on US and their clinical relevance for recurrence after prolapse surgery.

Methods

Women with previous cystocele repair underwent transperineal 3D US. Levator defects were graded according to the scoring system described with regard to MRI (DeLancey et al.) and perineal US (Dietz et al.). The results were compared using the weighted kappa and receiver operating characteristic (ROC) curves (SPSS version 20.0).

Results

We assessed 152 women. On US classification, more defects were categorized as highest grade compared with MRI classification [n?=?64 (42 %) vs. n?=?41 (28 %), p?<?0.01]. The grades of levator defects on both scoring systems showed very good agreement, with a weighted kappa of 0.82 [95 % confidence interval (CI) 0.75–0.88). The predictive value of scoring systems for cystocele recurrence after prolapse surgery showed an area under the receiver operating curve (AUC) of 0.63 and 0.64, respectively.

Conclusions

Comparison of the two scoring systems showed good agreement but was lowest for the highest-grade defects. There was no difference in predictive value between scoring systems for cystocele recurrence after prolapse surgery.     

Action of n-alkanes on drug-metabolizing enzymes from guinea-pig liver

Treatment of guinea-pig liver microsomal preparations with n-pentane, n-hexane and n-heptane enhanced both p-nitrophenol and o-aminophenol glucuronidation. The apparent K_m values of UDPglucuronate, for both p-nitrophenol and o-aminophenol UDPglucuronyltransferase, and of o-aminophenol were considerably increased, whereas the apparent K_m value of p-nitrophenol was the same after n-pentane treatment. No solubilization of UDPglucuronyltransferase or other microsomal proteins was observed after treatment with the n-alkanes. However, a substantial release of phospholipids from microsomal membranes occurred. The relative capacity of the different alkanes to release phospholipid was the same as the relative activation of UDPglucuronyltransferase. Aniline p-hydroxylation was considerably increased by the alkanes at concentrations of about 15–30 times lower than those necessary for optimal activation of UDPglucuronyltransferase. At these concentrations no activation of the aminopyrine N-demethylation was observed, whereas at higher concentrations a gradual decrease in both N-demethylating and p-hydroxylating activities occurred. n-Heptane, at a concentration which optimally activated aniline p-hydroxylation, markedly increased the rate of NADPH-cytochrome P-450 reduction. This suggests that the increase of the p-hydroxylating rate by n-heptane is related to a reversal of the cytochrome P-450 reduction by aniline.     

Metronidazole concentrations in human plasma, saliva, and gingival crevice fluid after a single dose

Metronidazole concentrations were estimated in four human volunteers after a single dose of 750 mg taken orally. Samples of blood, saliva, and gingival crevice fluid were collected before intake and during the following 24 hours. The concentrations of metronidazole in plasma and saliva were measured by high-performance liquid chromatography (HPLC). The concentrations in gingival fluid were estimated by a capillary agar-diffusion assay. The results of the metronidazole measurements as obtained by both methods were significantly correlated. The peak concentrations of metronidazole in plasma and saliva were in the same range, 8.7-13.8 micrograms/mL, and similar concentrations were found in the gingival fluid samples. It is concluded that metronidazole taken orally has similar pharmacokinetics in both saliva and plasma, and that a single oral dose of 750 mg metronidazole leads to a concentration of the drug in the gingival crevice fluid that exceeds the minimal inhibitory concentration for most anaerobic oral micro-organisms.     

Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats

To examine the effect of the exposure pattern on the inhalation toxicity of carbon tetrachloride (CCl4) two 4-week inhalation studies with this compound were carried out in male rats at basic exposure concentrations of 63 and 80 ppm and basic exposure periods of 6 hours per day, 5 days per week. The two main variables studied were interruption of the daily 6-hour exposures by 1.5 hours (2 X 3-hour exposures with a non-exposure interval of 1.5 hour), and peak loads of 5-7 times the basic concentration with or without 1.5-hour interruption of the daily 6-hour exposures. Adverse effects of CCl4 included abnormal activities of several enzymes in serum and liver, decreased quantity of microsomal proteins in the liver, increased relative liver weight, and hydropic and fatty degeneration of hepatocytes. As compared with uninterrupted, interrupted exposures increased more the activities of glutamic oxalacetic and glutamic pyruvic transaminase in serum; peak exposures only slightly affected these enzyme activities. Uninterrupted exposures caused less severe fat accumulation in and hydropic degeneration of liver cells than interrupted exposures with or without peak loads. In addition, uninterrupted exposure to 63 ppm CCl4 with peak loads resulted in more severe hydropic liver degeneration than uninterrupted exposure to the same concentration without peak loads. It was concluded that interruption of the daily 6-hour exposures by 1.5 hour did not result in less severe but rather in slightly more severe hepatotoxicity, and peak loads superimposed on a fixed concentration only slightly aggravated the toxic effects of CCl4 on the liver.     

Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats

The effects of exposure pattern on the toxicity of acetaldehyde vapour were investigated in 4-week inhalation studies. Male rats were exposed to 500 or 150 and 110 ppm for 6 h per day/5 days per week. One group of animals was exposed without interruption, the exposure of a second group was interrupted for 1.5 h between the first and second 3-h periods, the exposure of a third group was similarly interrupted and for six 5 min periods exposure was increased sixfold. Peak exposures of up to 3000 ppm superimposed on 500 ppm acetaldehyde caused irritation and excitation, and reduced body weight gain. No such effects occurred after interrupted or uninterrupted exposure to 500 ppm acetaldehyde without peak loads. A reduced phagocytotic index of lung macrophages was found in each of the groups exposed to 500 ppm acetaldehyde, the effect being most marked in the group with superimposed peaks of 3000 ppm. Degeneration of the nasal olfactory epithelium was observed in rats uninterruptedly exposed to 500 ppm acetaldehyde. Interruption of the exposure or interruption combined with peak exposure did not visibly influence this adverse effect on the nose. No compound-related effects were seen in rats interruptedly or uninterruptedly exposed to 150 ppm acetaldehyde or interruptedly exposed to 110 ppm with peak loads of 660 ppm. As a consequence 150 ppm acetaldehyde can be considered a 'no-toxic-effect level' in male rats exposed for 6 h/day, 5 days/week, during a 4-week period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Capillary agar diffusion assay for measuring metronidazole in human gingival crevice fluid.

An agar diffusion assay in capillaries, with Fusobacterium nucleatum M2 as the indicator strain, has been developed to measure metronidazole concentrations in gingival crevice fluid. The assay allows the measurement of 1.9 micrograms of metronidazole per ml in sample amounts of 0.6 microliters.     

Immune reactivity of candidate reference materials

Immune reactivity is a key issue in the evaluation of the quality of recombinant allergens as potential reference materials. Within the frame of the CREATE project, the immune reactivity of the natural and recombinant versions of the major allergens of birch pollen (Bet v 1), grass pollen (Phl p 1 and 5), olive pollen (Ole e 1), and house dust mite (Der p 1 and 2, and Der f 1 and 2) was analysed. The IgE binding capacity of the allergens was studied by direct RAST and RAST inhibition, and their biological activity by basophil histamine release, using sera of allergic patients selected across Europe. For birch pollen, rBet v 1 is an excellent mimic of the natural allergen. For grass pollen, rPhl p 1 showed a significant lower IgE reactivity and was not considered a suitable candidate, whereas rPhl p 5a exhibited an immune reactivity closer to that of its natural counterpart. For olive, rOle e 1 had a lower IgE binding capacity in RAST but a higher biological activity in histamine release. For house dust mite, recombinant group 1 allergens were significantly less potent than their natural counterparts, but recombinant group 2 allergens were close mimics of their natural homologues.     

The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification

Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.     

Is the Prospective Link between Parental Stress and Adolescent Snack Intake or Weight Outcome Mediated by Food Parenting Practices?

Parental stress may influence adolescents’ food intake and weight development over time, however, it is largely unknown why this is the case. This study examines whether the link between parental stress and adolescents’ snack intake and weight outcome is mediated by food parenting practices (FPPs). Participants included 400 parents and their adolescent children (aged 12–16) who completed questionnaires. The Perceived Stress Scale (PSS) was used to assess parental general stress levels and the Adolescent Food Parenting Questionnaire (AFPQ) to assess FPPs. Multiple mediation analyses with parallel mediators were performed, with parental general stress as an independent variable and adolescent snack intake and zBMI as dependent variables. FPPs (autonomy support, coercive control, modeling, healthy structure, snack structure) were entered as mediators in the model, adjusted for covariates. Autonomy support mediated the link between parental general stress and adolescent savory snack and sweet snack intake at follow-up. Parents who reported higher stress levels provided less autonomy support, which resulted in more adolescent snacking. None of the other FPPs mediated any link between parental stress and intake or weight outcome, and no significant indirect effects were observed with zBMI as an outcome variable. Further research should replicate this finding and may further examine underlying mechanisms.