Low density lipoprotein catabolism is enhanced by the cleaved form of alpha-1-antitrypsin

The frequent occurrence of hypocholesterolaemia following inflammatory processes is well known but unexplained. Elevated plasma levels of serine proteinase inhibitors (serpins) and their complexes with target enzymes have been demonstrated in inflammatory, malignant and infectious diseases which are also often accompanied by low plasma cholesterol levels. Under inflammatory conditions, uncomplexed, but cleaved inactive serpins arising from slow deacylation of the serpin-proteinase complex may be present in the circulation. To determine the influence of native and cleaved forms of serpins, such as alpha-1-antitrypsin (AAT), on lipoprotein metabolism, we investigated the effect of these forms on low density lipoprotein (LDL) catabolism in human HepG2 cell line. We have found that the cleaved form of AAT in concentrations from 125 to 2000 nmol l-1 stimulates LDL binding to the HepG2 cells, by up to 49% with a subsequent increase in LDL uptake and degradation of up to 79 and 65% respectively. Native AAT was also found to increase LDL binding and internalization by 20-25%, independently of the amount of AAT added, an effect most probably due to the cleaved form of AAT produced by local proteolysis of native AAT incubated in the cell culture. Moreover we have shown that the cleaved form of AAT interacts with LDL in vitro, and that such an interaction abolishes AAT ability to stimulate LDL binding and internalization. This study for the first time describes the ability of the cleaved form of AAT to stimulate LDL binding and internalization in HepG2 cell culture, and provides evidence that hypocholesterolaemia occurring during inflammatory processes may be mediated by cleaved forms of serpins.     

Emission Of Volatile And Semivolatile Organic Compounds From Waterborne Paints – The Effect Of The Film Thickness

A waterborne paint was applied to tin plated steel sheets with three different film thicknesses. The emission of volatile and semivolaile organic compounds ((S) VOCs) from the samples was measured in small climatic chambers under standard conditions over a two-week period. The purpose of the study was to evaluate the effect of the film thickness on the emission rate decay. First order decay models, including sink effects for the high boiling (S) VOCs, were fitted to the concentration versus time data. The results showed that the first order rate constants decrease with increasing film thickness. In uddition, the results indicated that the emissions of the (S)VOCs in the waterborne paint film seemed to be controlled by evaporation. The thicknesses of paint films used in climatic chamber tests to estimate emission rates for product compurison or emission prediction must be known in order to prevent erroneous conclusions     

Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas

ND10 are recently characterized nuclear domains that are composed of 0.5 microm sized, precisely circumscribed dots in cultured human cell lines. To investigate the distribution and number of ND10 on various types of normal and neoplastic human tissues, we carried out immunostaining and immunoprecipitation analyses with monoclonal antibodies 138 and 1150. The number of ND10 varied from 1 to 10 or more in various tissues as did their size. ND10 were diffusely located in early embryonic and normal tissues, except for the exocrine and endocrine cells of the pancreas and for hepatocytes. In normal squamous mucosa, basal cells had more ND10 than did differentiated superficial squamous cells. The number and size of ND10 were markedly increased in malignant neoplasms but were similar in benign tumors and corresponding normal tissues. Sex hormone-related normal tissues, such as the endometrium or myometrium, and neoplasms strongly stained for ND10. The distribution pattern of ND10 in human tissues indicates that they are conserved nuclear substructures that are closely associated with cellular differentiation, hormonal stimulation, and oncogenesis.     

An antinociceptive effect of the intraperitoneal injection of nifedipine in rats, measured by tail-flick test

The tail-flick (TF) technique was used to assess the antinociceptive properties of nifedipine (NIF) given intraperitoneally (i.p.). First, the most suitable intensity of the noxious stimulus (temperature of the bulb) has been ascertained and used in the main study. Male Sprague-Dawley rats received NIF, dissolved in dimethyl sulfoxide (DMSO) at the doses of 0.0, 0.5, 2, 5, 10 and 15 mg/kg, or control with no injection. For the main study, the noxious stimulus was limited to 15 sec (cut-off time) and TF latencies were recorded up to 120 min. The antinociceptive response was expressed as the area under the curve for each rat and analyzed by one-way ANOVA. The antinociceptive response to the lower doses of NIF (0.5 and 2 mg/kg) did not differ from control (no injection) and DMSO alone. Significance was found at 5, 10 and 15 mg NIF with no difference among the doses. However, there was an increasing tendency of the mean values from 0.5 to 15 mg NIF resulting in a positive correlation. The correlation coefficient was 0.32483 (p = 0.015) and regression equation Y = (19.37) x dose + 1320. Our data suggest that spinal mechanisms are involved in NIF-induced antinociception.     

The Danish Twin Apartment Study – Part II: Mathematical modeling of the relative strength of sources of indoor air pollution

Abstract This study deals with the modeling of air pollution in apartments from laboratory measurements of source strengths, using formaldehyde and Total Volatile Organic Compounds (TVOCs) as model pollutants. The sources in two test apartments were grouped into two: building-related sources and occupant-related sources. The measured source strengths and ventilation rates were used for the prediction of concentrations expected in the apartments. These predictions were compared to measurements in the apartment over 12 months. The conclusions were that the model predictions based on emission rates measured in the laboratory can be used to predict the long-term concentration of the two model pollutants in the apartments. Considering the measured differences in ventilation between the apartments, an occupant emission rate of between 0.2 and 0.3 mg/h/kg body weight could be estimated. Based on previous suggested limits of acceptable exposures of humans to VOCs, an acceptable average emission rate of VOCs from building materials in general was estimated to be about 30 (μ/m²/h. The modeling showed that during the first 200 days, building materials dominated the emissions. After this, sources relating to the occupants dominated. On average about half of the VOC pollution originated from the building materials.     

Effects of cholestanol feeding and cholestyramine treatment on the tissue sterols in the rabbit

Rabbits were fed diets enriched with cholestanol or cholestereol (3.5 g/wk) for 4–12 weeks. During cholestanol feeding, the concentration of cholestanol in blood serum, liver, heart and aorta increased 15–30 times. In serum and liver, the concentration of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally seen in rabbits receiving cholestanol for eight weeks or less. During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis.     

Pain threshold values during periodontal probing: assessment of maxillary incisor and molar sites

Probing pain threshold (PPT) assessments were conducted in the facial and oral sulci of maxillary central incisors and first molars of 10 periodontally healthy adults. All subjects were systemically healthy, free of pain, and reported no current medication usage. A computer-linked electronic probe, modified to deliver steadily increasing forces up to 200 grams, was used to collect the data. The system contained a subject operated "off-switch" which, upon activation, signaled the computer to record the subject's PPT. Assessments of each subject's PPTs were conducted on 3 separate occasions at 7-day intervals. Results indicated that the facial sulci of the incisors were the most pain sensitive. They displayed a mean PPT of 50.9 +/- 26.6 grams. The oral sulci of the incisors exhibited a mean PPT of 76.5 +/- 45.2 grams. Facial and oral sulci of the molars evidenced mean PPT values of 102.6 +/- 52.1 grams and 113.5 +/- 51.3 grams, respectively. These data suggest that sulci associated with incisor teeth are nearly twice as pain sensitive as sulci associated with molar teeth. In addition, facial sulci are significantly more pain sensitive than oral sulci. Data did not indicate a visit effect nor a side-of-mouth effect on PPT values.     

An index for paresis and defective healing--an easily applied method for objectively determining therapeutic results in facial paresis (author's transl)

Residuals of facial paralysis consist of a great variety of cosmetic and functional anomalies which differ in quality and/or quantity. An internationally standardized evaluation of such defects is mandatory for the assessment of the results of different therapeutic procedures. In the present study, a system has been developed to record the results of facial paralysis following therapy. Such a system does not require specialized training, instrumentation or require significant time for completion. A clearly-defined "Yes-No" evaluation criteria is established which creates a high interscorer reliability. The usefulness of this scoring system was tested by three examiners on 42 patients following facial nerve surgery, with an obtained interscorer reliability of 93%.