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Bisphenol A (BPA), identified as an endocrine disruptor, is an industrially important chemical that is used as a raw material in the manufacture of many products such as engineering plastics (e.g., epoxy resins/polycarbonate plastics), food cans (i.e., lacquer coatings), and dental composites/sealants. The demand and production capacity of BPA in China have grown rapidly. This trend will lead to much more BPA contamination in the environmental media and in the general population in China. This paper reviews the current literature concerning the pollution status of BPA in China (the mainland, Hong Kong, and Taiwan) and its potential impact on human health. Due to potential human health risks from long-term exposure to BPA, body burden of the contaminant should be monitored.

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It has been hypothesized that the symptoms of vertigo in patients with Ménière's disease somehow are related to impaired production and/or transport of endolymph. Antisecretory factor (AF) is a protein known to affect transport processes in the intestine and it has been shown that intake of specially processed cereals (SPC) can increase endogenous AF synthesis. In a prospective open pilot study, 24 patients with severe Ménière's disease (functional level scale 5-6 according to the criteria of AAO-HNS) received SPC for 14-30 days. AF levels in plasma increased by 83% in 20 of the 24 patients studied. The attacks of rotatory vertigo were reduced, to final AAO-HNS functional level scale 1-3, in 12 patients and in three of these hearing was normalized. Twelve patients had no or minor effects of the treatment. The correlation between AF activity after treatment and the final AAO-HNS functional level scale was -0.65, P<0.001. Studies in rats using immunohistochemistry methods showed that AF was localized to the cochlea and the vestibule of the inner ear. The present results suggest that AF might be a new regulator of the endolymph.

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All Finnish license holders aged 70 years (from the cohort born in 1922) who did not renew their driver license, and a corresponding comparison group among those who did renew their license, were contacted by a mail survey. They were asked about their reasons to continue or to stop driving, about their current living conditions and health status, and about some aspects of their driving behavior. The reasons to stop or to continue driving were different for men and women. Male drivers considered more frequently than female drivers the use of private car a necessity. Male respondents who did not renew their license (ex-drivers) were less healthy than those who did renew their license (drivers). The most frequently indicated reason to stop driving among men was deteriorated health. However, only 6.9% of the ex-drivers had received professional advice to stop driving. For most of these cases, this advice had been given by the physician responsible for the treatment of their main illness. The change in health condition was related to a shift in driving activity: those still driving were in best health, followed by those ex-drivers who stopped driving at the age of 70 years, while those who had stopped driving at an earlier age had the highest number of illnesses and had most frequently experienced a deterioration of their health status during the last year. Both male and female ex-drivers reported more feelings of stress in traffic and more frequent avoidance of certain traffic situations than drivers. Women reported more frequently traffic-related stress and avoidance than men as both drivers and ex-drivers.

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OBJECTIVES: To find out if there is an association between DNA indexes and DNA synthesis (S) phase measurements and Dukes' classification and histopathological differentiation in colorectal cancers, and to investigate the interrelationship between DNA indexes and S phase measurements. DESIGN: Prospective open study. MATERIAL: 182 colorectal carcinomas in 181 consecutive patients. INTERVENTION: Tumours biopsied immediately after resection or at rectoscopy or colonoscopy. RESULTS: One or more aneuploid cell populations were found in 113 of 182 carcinomas (62%). There was no correlation between Dukes' stage and either degree of differentiation or S phase measurements, but there were significant correlations between S phase measurements and histological grading (p less than 0.05), and between the percentage of cells in the S phase and the DNA index when values for both diploid and aneuploid tumours were included (p less than 0.001). CONCLUSION: The degree of aneuploidy indicates how far tumour cells have progressed in their cellular disarrangement, and information about a tumour's proliferative capacity is given by the S phase measurements.

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Probabilistic risk assessment (PRA) is an important methodology for assessing the risks of complex technologies. This paper discusses the strengths and weaknesses of PRA. Its application is explored in three different settings: adversarial policy processes, regulatory/licensing procedures, and plant safety audits. It is concluded that PRA is a valuable tool for auditing safety precautions of existing or planned technologies, especially when it is carried out as an interactive process involving designers and plant personnel who are familiar with actual, everyday operations. PRA has not proven to be as well-suited in providing absolute risk estimates in public-policy debates concerning the acceptability of a technology, or for the licensing and regulatory procedures. The reasons for this are discussed.

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Peritoneal lavage performed postoperatively in the treatment of purulent peritonitis was evaluated in a prospective randomized study. Patients with free purulent peritonitis due to perforated appendicitis or colonic perforation were treated with intravenous infusion of cefuroxime and metronidazole. The patients were randomly allocated to treatment with or without continuous postoperative peritoneal lavage. The patients were kept under observation for postoperative septic intra-abdominal complications. Of the 79 patients, 41 were treated with lavage postoperatively and 38 were not. No postoperative abscess or other septic intra-abdominal complication was found in any patient. In ten, the postoperative lavage was interrupted because of technical complications or complaints of discomfort by the patient. In this study, no clinical benefit of continuous peritoneal lavage postoperatively in the treatment of purulent peritonitis was noted. Lavage done postoperatively is expensive and seems to carry a risk of complications. Thorough rinsing of the infected abdominal cavity perioperatively and adequate antibiotic treatment, including an antianaerobic agent, seem to be effective in preventing intra-abdominal septic complications.

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The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8- tetrabromodibenzo -p-dioxin ( TBrDD ), 5-chloro-2-(2,4-dichlorophenoxy)phenol (3-Cl- predioxin ) 4,5,6-trichloro-2-(2,4-dichlorophenoxy)phenol (5-Cl- predioxin ), toxaphene, 3-methylcholanthrene (3-MC) and phenobarbital (PB) on the vitamin A storage, UDP-glucuronosyltransferase (UDPGT) and aryl hydrocarbon hydroxylase (AHH) activities in the liver of Sprague-Dawley rats was investigated. Vitamin A was determined as retinol by high pressure liquid chromatography. UDPGT was measured with p-nitrophenol as an aglycone and AHH with 3,4-benzopyrene as a substrate. Both in TCDD- and toxaphene-treated animals a reduced body weight gain was recorded, but no other overt signs of toxicity were seen in this study. Both the concentration and the total amount of hepatic retinol was significantly reduced in TCDD-, 3-MC-, PB- and TBrDD -treated animals. These compounds were also those which gave the most significant enzyme induction as regards the UDPGT and AHH activities. However, the reduction of hepatic retinol caused by these compounds did not correlate with the enzyme activities studied. When compared on a molecular basis, TCDD and TBrDD were in the order of several magnitudes more potent as reducers of hepatic retinol and likewise as enzyme inducers.

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The long-term results of open-heart valve surgery in Uppsala in the period 1959-1974 were reviewed. The total number of patients operated on was 677 and the mean follow-up time was 10 years (range 5-22 years). The operative mortality was high in the early years, but fell to 11-12% towards the end of the period. The main long-term complication was embolism. The frequency of late reoperation was 10-20%, reflecting the limited durability of the early mechanical valves and of subsequently used biologic valves. The actuarial 10-year survival, calculated as 50%, was approximately equal among the patients with aortic and those with mitral valve disease. The predominant late causes of death (60-75%) were 'cardiac', including myocardial as well as valve-related causes. Follow-up investigation comprised 244 survivors. In general there was considerable functional improvement both in the aortic and in the mitral group. Valvular insufficiency leading to reoperation was detected at follow-up examination in 6-8% of the patients.

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The paper presents a method to test metabolic linear multicompartment models for their mathematical solvability and their power of resolution with respect to individual parameters. The method can be seen as a means of predicting not only the model theoretical identifiability but also the expected quality of estimation before undertaking any actual serial experiments. The compartmental model of human cholesterol metabolism is taken as a demonstrative problem. The analysis shows that it is possible with tracer techniques to measure the cholesterol turnover, the cholesterol fluxes between exchangeable cholesterol pools, the cholesterol masses in individual pools, and the endogenous cholesterol synthesis in individual pools if certain conditions are met. In any complex kinetic situation, performance of a systematic model analysis is recommended before embarking on large-scale experimentation.

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A non-linear multicompartment model with saturation kinetics of binding to plasma and interstitial fluid proteins and with non-saturable binding to tissues has been applied to the absorption of warfarin (8 mg/kg of warfarin sodium) from the rat small intestine in situ. The absorption was best described with two pathways, one into plasma and the other instantaneously into the interstitial fluid. According to the results from the best computerized curve fitting, absorption is rapid, the apparent absorption rate constant being 0.258 min -1. At hypothetical zero time 0.253 of the dose (1.0) would be located in plasma, 0.597 in interstitial fluid 0.150 in tissues.

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The uptake, distribution and excretion of curcumin in Sprague-Dawley rats has been studied. When administered orally in a dose of 1 g/kg, curcumin was excreted in the faeces to about 75%, while negligible amounts of curcumin appeared in the urine. Measurements of blood plasma levels and biliary excretion showed that curcumin was poorly absorbed from the gut. No apparent toxic effects were seen after doses of up to 5 g/kg. When intravenously injected or when added to the perfusate of the isolated liver, curcumin was actively transported into bile, against concentration gradients of several hundred times. The major part of the drug was however metabolized. In suspensions of isolated hepatocytes or liver microsomes 90% of the added curcumin was metabolized within 30 min. In view of the poor absorption, rapid metabolism and excretion of curcumin, it is unlikely that substantial concentrations of curcumin occur in the body after ingestion.

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Male Sprague-Dawley rats, 4 weeks old, were subjected to an ambient temperature of 4 C for periods up to 24 days and fed a synthetic diet containing one of the following oils: peanut oil (PO), rapeseed oil (RO), low erucic acid rapeseed oil (LO), and partially hydrogenated marine oil (HO), each at 20% w/w. A parallel experiment using the same oils was performed at room temperature (23 C). During cold stress, animals on the RO diet showed higher mortality than all other groups; all 20 animals in this group died within 5 days. At room temperature, however, all animals survived. The lipid accumulation in the heart reached its peak in all groups after 3 days and then gradually declined. The accumulation was most pronounced in the RO animals and coincided with the high mortality at 4 C. The fatty acid composition of the cardiac triglycerides reflected that of the diet, while the composition of the cardiac lecithin was only marginally modified.

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Preliminary analysis and linear two-compartment solutions of warfarin plasma concentrations recorded in the rat after intravenous bolus injections of 1, 2, 8 and 40 mg/kg of sodium warfarin revealed marked non-linearities. The half-life of total warfarin concentration in the plasma from 1-12h remained unchanged with all the doses used, but that of free warfarin was shorter with 40 mg/kg, possibly as the result of an increase in the binding of the drug to plasma proteins as the high total warfarin concentration decreased. The apparent volume of distribution generally increased with increasing dose, and differed according to the method used for its calculation. Liver warfarin data could be solved with Langmuir type saturation kinetics, but the saturation phenomena were slight in the concentration range studied. A non-linear multicompartment model was constructed, the physiological spaces of which were plasma, interstitial fluid and tissue. The binding of free warfarin to plasma proteins, interstitial fluid proteins and tissue structures was assumed to occur instantaneously, with saturable binding to plasma and interstitial fluid proteins, and a constant binding to tissues. The fluxes between the free warfarin pools of plasma and interstitial fluid as well as elimination were assumed to be linear. Following parameters were simulated simultaneously, using an analog hybrid computer: two for the above-mentioned fluxes, four for zero time drug mass distribution between plasma and interstitial fluid, and one for tissue binding. According to the best fits, warfarin is preferentially distributed into plasma, interstitial fluid and highly perfused tissues. The solution suggests that non-linearities in the pharmacokinetics of warfarin, a highly plasma protein-bound drug, first occur in plasma and interstitial fluid. Therefore, it is believed that the quantitative non-linear multicompartment approach presented in this paper might be useful in studying the kinetic behaviour of other highly plasma protein-bound drugs, too.

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The purpose of the study was to develop a kinetic method for measurement of different parameters of cholesterol metabolism in man using labeled cholesterol precursors that could initially be incorporated even into the slowly exchangeable cholesterol pool. For this purpose, tritiated water and [2-14C]mevalonate were given to five normocholesterolemic subjects and the activities for serum cholesterol and body water were measured serially for up to eight weeks. Elimination of cholesterol was measured by fecal analysis of neutral and acidic steroids. For comparison, two subjects received a mixture of [4-14C]cholesterol and [2-3H]mevalonate. The data were subjected to multicompartmental analysis by computer, with the assumption that synthesis occurred in two compartments. The rapidly exchangeable cholesterol (pool 1) and the fractional hydrogon transport constant from body water to cholesterol could not be measured directly; therefore, the influence of two different mass transport values was tested. The best fit was obtained with the smaller mass of cholesterol in pool 1 associated with a hydrogen transport constant of 0.700 (32 out of 46 hydrogens originate from water). Kinetic analysis of the data allows estimates of the exchangeable cholesterol mass, flux rates of cholesterol between pools 1 and 2, and synthesis of cholesterol separately in the two pools. The results of computer analysis suggested that, in contrast to what has been assumed earlier on the basis of studies with radiolabelled cholesterol, 22-53% of endogenous cholesterol synthesis took place in pool 2 from body water and that this synthesis tended to correlate with the total body fat mass. The study with [2-3H]mevalonate and [4-14C]cholesterol indicated synthesis in pool 2 to be 20-22% of the total. Up to 50% of the DL[2-14C]mevalonate dose was incorporated into cholesterol. The fractional incorporation of DL-mevalonate into pool 2 was correlated with that of tritiated water, indicating that both precursors studied yielded essentially the same kinetic result.

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The effects of ATP, ADP, AMP and adenosine were studied on the spontaneous mechanical activity of the rat portal vein. 2It was found that STP and ADP, in concentrations higher than 300 mug M, caused a transient tetanus, followed by inhibition, and at lower concentrations an increase in the frequency and amplitude of the spontaneous contractions. AMP and adeosine on the other hand, inhibited spontaneous activity, by reducing the amplitude of contractions and increasing their frequency. The effects were dose-dependent. ATP was found to be 2.2 times more potent than ADP, while AMP and adenosine were equipotent. Weak inhibitory effects were obtained with GMP, guanosine and adenine, while GTP, 3K-cyclic AMP and guanine had no effect. ATP and ADP increased the K-contracture, while AMP and adenosine relaxed it. The effects of ATP were augmented in Mg-free solutions and partially inhibited in Mg-high solutions in the normally polarized muscle, while Mg had no influence on the ATP-induced contraction in the depolarized muscle. Theophylline potentiated the inhibitory response to AMP and adenosine. Adrenergic and cholinergic blockers had no influence on the response to ATP, ADP, AMP or adenosine. It is suggested that the effects of ATP and ADP are linked with Ca++ movements across the membrane, while AMP and adenosine might stimulate intracellular metabolism causing increased intracellular Cs-++ binding.

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