Role of polychlorinated dibenzofuran in yusho (PCB poisoning)

In the blood of 15 patients with yusho or "polychlorinated biphenyl poisoning" that occurred in 1979 in Taiwan, was found polychlorinated dibenzofurans (14 of 15) and polychlorinated quaterphenyls (15 of 15), as well as polychlorinated biphenyls (15 of 15). The mean concentration ratio of these substances was approximately 1 : 160 : 500. Based on the following evidence, we propose that polychlorinated quaterphenyls were major pathogenic substances in the development of yusho: (1) Clinical manifestations and course of yusho patients are disproportionately severe and persistent for the observed blood levels of polychlorinated biphenyls, while patients who were occupationally exposed to pure polychlorinated biphenyls take characteristically mild and benign clinical course despite polychlorinated biphenyl levels often much higher than those noted in yusho patients; (2) Polychlorinated debenzofurans show a marked tendency to accumulate in the liver, which might explain frequent presence of jaundice and other abdominal symptoms in yusho, which are, again, not observed in those with occupational polychlorinated biphenyl poisoning; (3) Toxicity of polychlorinated dibenzofurans is a hundred to ten thousand times greater than that of polychlorinated biphenyls and polychlorinated quaterphenyls in animal experiments.     

Behavioural hyperactivity in rats following postnatal exposure to sub-toxic doses of polychlorinated biphenyl congeners 153 and 126

Over the years, both government and the private sector have used a mix of regulatory controls and competitive market incentives to reduce the rate of spending and minimize excess capacity in health services. Despite these efforts, this study finds an oversupply of five medical technologies in Pennsylvania, which adds costs and raises concern over the quality of care provided by underused facilities. Moreover, as providers compete for network selection, many continue to expand their service capabilities. These findings emphasize the importance of ongoing assessment of the appropriate application, supply, and use of medical services.     

Cytochromes P450, P420 & mixed-function oxidases as biomarkers of polychlorinated biphenyl (PCB) exposure in harbour seals (Phoca vitulina)

Hepatic microsomal cytochrome P450, EROD and ECOD activity were investigated as biomarkers of PCB exposure in harbour seals (Phoca vitulina). Due to the difficulty of obtaining undegraded seal liver samples, standard spectrophotometric methodology was adapted to investigate P420 (degraded P450) as a PCB biomarker with partially degraded samples. Total PCB burdens in both blubber and liver had positive correlations with P450, P420 and MFO activity levels. The use of P420 biomarkers in this study supports the inclusion of samples from by-caught marine mammals for future biomonitoring studies. P450 isozymes CYP1A (P4501A) and CYP2B (P4502B) in conjunction with MFO activity were investigated as "specific" biomarkers of PCB exposure. They were found to reliably reflect levels of [MC] and [PB]-type PCB exposure in harbour seal liver.     

Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.     

Comparison of gas chromatography and mineralization experiments for measuring loss of selected polychlorinated biphenyl congeners in cultures of white rot fungi

Two methods were used to compare the biodegradation of six polychlorinated biphenyl (PCB) congeners by 12 white rot fungi. Four fungi were found to be more active than Phanerochaete chrysosporium ATCC 24725. Biodegradation of the following congeners was monitored by gas chromatography: 2,3-dichlorobiphenyl, 4,4'-dichlorobiphenyl, 2,4',5-trichlorobiphenyl (2,4',5-TCB), 2,2',4,4'-tetrachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, and 2,2',4,4',5,5'-hexachlorobiphenyl. The congener tested for mineralization was 2,4',5-[U-14C]TCB. Culture supernatants were also assayed for lignin peroxidase and manganese peroxidase activities. Of the fungi tested, two strains of Bjerkandera adusta (UAMH 8258 and UAMH 7308), one strain of Pleurotus ostreatus (UAMH 7964), and Trametes versicolor UAMH 8272 gave the highest biodegradation and mineralization. P. chrysosporium ATCC 24725, a strain frequently used in studies of PCB degradation, gave the lowest mineralization and biodegradation activities of the 12 fungi reported here. Low but detectable levels of lignin peroxidase and manganese peroxidase activity were present in culture supernatants, but no correlation was observed among any combination of PCB congener biodegradation, mineralization, and lignin peroxidase or manganese peroxidase activity. With the exception of P. chrysosporium, congener loss ranged from 40 to 96%; however, these values varied due to nonspecific congener binding to fungal biomass and glassware. Mineralization was much lower, 相似文献   

Crystallization and preliminary crystallographic analysis of a 2,3-dihydroxybiphenyl dioxygenase from Pseudomonas sp. strain KKS102 having polychlorinated biphenyl (PCB)-degrading activity

A study of the clinical, radiological, and pathological correlations in 43 patients with solitary cysticercus granuloma and epilepsy focused on factors that might help in predicting the presence of the parasite in the granuloma and those that might influence the formation of oedema around the granuloma. The duration of symptoms (< six months and > or = six months) and CT morphology of the granuloma (ring and disc, type A; nodular lesion, type B) were studied as factors that could possibly predict the presence of the parasite in the granuloma. The influence of sex of the patient and the presence of a neutrophilic response in the granuloma on the intensity of oedema around the lesion as seen on CT was also studied. The pathological features were studied in the excised granulomas. The intact or degenerated form of the cysticercus was evident in 22 of 43 specimens. Neither the duration of seizures (P = 0.17) nor the type of lesion on CT (P = 0.16) was predictive of the presence of the parasite in the granuloma. The sex of the patient (P = 0.51) and the neutrophilic response in the specimen (P = 0.73) did not correlate with the degree of oedema on CT indicating that neither of these host factors was a major determinant of oedema production. The findings point to the varied and unpredictable natural history of solitary cysticercus granulomas and the complex nature of host-parasite interactions in individual patients. The inability to predict the presence of the parasite in the granuloma on the basis of the clinical or radiological features precludes a selection of patients with such lesions for cysticidal drug treatment.     

Effects of oxysterols upon macrophage and lymphocyte functions in vitro

Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell responses to different stimuli. The action of oxysterols on macrophage functions and macrophage-lymphocyte interaction has been poorly investigated. In this work, the effects of 25-hydroxycholesterol (25-OHCh) and 7-ketocholesterol (7-KCh) upon some functions of murine peritoneal macrophage (PM), such as generation of reactive oxygen intermediates (ROI), secretion of neopterin and interleukin-1 (IL-1)-like activity, Fc-receptor (FcR) activity, and murine and human lymphocyte functions, participating in lymphocyte-macrophage interactions, such as macrophage-activating factor (MAF) and Ia-inducing factor (IaIF) secretion, were studied in vitro. 7-KCh in concentration of 5 micrograms/mL culture medium only, but not 25-OHCh, significantly inhibited ROI generation by zymosan-stimulated PM. Pretreatment of PM for 22 h with 25-OHCh and 7-KCh led to the decrease of IL-1-like activity secretion. 25-OHCh and 7-KCh inhibited both FcR-dependent binding and phagocytosis of sheep red blood cells (SRBC). Oxysterols did not change both spontaneous and lipopolysaccharide-stimulated secretion of neopterin by PM. 25-OHCh dose-dependently and more efficiently than 7-KCh inhibited murine splenocyte secretion of MAF, which activity was determined by the ability of splenocyte-conditioned medium to stimulate ROI generation in PM. Both 25-OHCh and 7-KCh inhibited significantly proliferative activity of human mixed lymphocyte culture (MLC), as well as lymphocyte secretion of IaIF, which stimulates the expression of HLA antigens in cultured human monocytes. Purified Ch did not alter these parameters. These data showed, that some inflammatory functions of macrophages and lymphocytes may be modified by such environmental conditions as the presence of oxysterols.     

Use and health effects of Aroclor 1242, a polychlorinated biphenyl, in an electrical industry

Aroclor 1242, a chlorinated biphenyl, is widely used as a dielectric medium in transformers and capacitors. In this survey, thirty-four occupationally exposed workers were examined. Complaints consisted of a burning sensation of the face and hands, nausea, and a persistent body odor. One had chloracne, and five suffered from an eczematous rash on the legs and hands. Although hepatic function tests were normal, the mean blood Aroclor level in the exposed group (approximately 400 ppb) was significantly higher than in the control group. A tentative value of 200 ppb is suggested for Aroclor 1242 as an acceptable level for occupationally exposed workers. The use of an efficient exhaust ventilation to maintain air concentrations below the threshold limit value, and the regular measurements of hepatic function and of blood Aroclor concentrations in exposed workers are recommended.     

In vitro lymphocyte-differentiating effects of thymulin (Zn-FTS) on lymphocyte subpopulations of severely malnourished children

The success of the cardiothoracic surgery residency program in Chapel Hill is due to a number of contributing factors. The first important ingredient is the faculty. Their ability, stability, and dedication, with each faculty member developing an area of expertise, has contributed greatly to the success of our program. The second important aspect is the program design itself--all three years: the first to allow the resident time to reflect on educational priorities and do some innovative thinking; the second and third as chief resident on their respective services--for an entire, continuous year. The third and most important aspect of our program is the quality of the residents we have been able to attract--uniformly a splendid group of individuals who regularly gave more than they received and who continue to be a source of inspiration, hope, and pride for those of us who have been privileged to be their teachers.     

Elimination of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) from human blood in the Yusho and Yu-Cheng rice oil poisonings

The pharmacokinetics of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in humans was studied by monitoring the blood concentrations of individuals who ingested a contaminated rice oil in Japan (yusho) in 1968 and in Taiwan (yu-cheng) in 1979. Sixteen yusho patients were followed from 1982 to 1990 and three yu-cheng individuals from 1980 to 1989. From the three yu-cheng patients, blood lipid values for the two persistent toxic congeners, 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HxCDF), varied from 50 micrograms/kg at first sampling to about 1 micrograms/kg at last sampling corresponding to half-lives for elimination (t1/2) of 2-21/2 years. The blood lipid values for the same PCDF congeners in yusho patients varied from 5 micrograms/kg down to 0.1 micrograms/kg. The calculated t1/2 were more variable with median values closer to 10 years. Planar PCBs #126 and #169 were present at lower concentrations than the PCDFs. For seven of the other PCB congeners, half-lives for elimination in the yu-cheng individuals varied from 1.2 up to 4.6 yr depending on the degree of chlorination. For the yusho patients, the elimination for the PCBs was longer. These results show that clearance of the toxic PCDFs and PCBs in humans is non-linear with faster elimination at higher exposure followed by slower decreases as background levels are approached. Such a clearance pattern can best be explained by a two compartment liver and fat pharmacokinetic model.     

Additional inhibitory effects of intravenous immunoglobulins in combination with cyclosporine A on human T lymphocyte alloproliferative response in vitro

Intravenous immunoglobulins (IvIgG) are often used in patients receiving a basic immunosuppressive therapy with CsA either for prevention of infectious complications or as an additional prophylaxis of graft versus host disease in clinical bone marrow transplantation. As far as we know, the combined in vitro immunosuppressive effects of these 2 drugs have not been investigated yet. In this study, we compared the effect of CsA, IvIgG, and CsA combined with IvIgG on the proliferative capacity of peripheral blood mononuclear cells in a mixed lymphocyte culture system. The concentration-dependent inhibition of peripheral blood mononuclear cell proliferation in the mixed lymphocyte culture system by CsA is a well established phenomenon. By adding IvIgG to the cultures (n=20) containing CsA, we were able to show a significantly (P<0.0002) higher inhibition compared with the inhibitory capacity of CsA alone. Cyclosporine A was added to the cultures at concentrations ranging from 25 to 400 ng/ml, and IvIgG was added in 3 different fixed concentrations: 1.25, 2.5, and 5 mg/ml. These are all concentrations which one usually obtains in patients during therapy with these drugs. Even with a minimal concentration of CsA (25 ng/ml) plus IvIgG (1.25 mg/ml), we achieved a mean inhibition of 77.7 +/- 7.9%, which is in the range of the mean inhibition (84.3 +/- 4.7%) with the highest concentration of CsA (400 ng/ml tested. Our in vitro results could suggest that the additional therapy with IvIgG in patients receiving CsA might cause a CsA sparing effect. This might lead to a combined therapeutic regimen with a good immunosuppressive efficacy and minimal drug associated adverse effects.     

Comparative metabolism of bis(2-methoxyethyl)ether in isolated rat hepatocytes and in the intact rat: effects of ethanol on in vitro metabolism

The metabolism of the reproductive and developmental toxicant bis(2-methoxyethyl)ether (diglyme) was studied in isolated rat hepatocytes and in the intact rat. Male Sprague-Dawley rats (190-220 g) were used in both studies. Hepatocytes, isolated by a two-step in situ collagenase perfusion of the liver, were cultured as monolayers and incubated with [14C]diglyme at 1, 10, 30, and 50 microM for up to 48 h. For the in vivo study, rats were given single oral doses of [14C]diglyme at 5.1 mmol/kg body wt, and urine was collected for up to 96 h. Radioactive compounds in the culture medium or in the urine were separated by high performance liquid chromatography and quantified with an in-line radioactivity monitor. Metabolites were identified by comparison of their chromatographic retention times and their mass spectra with those of authentic compounds. The principal metabolite from hepatocytes and in the urine was (2-methoxyethoxy)acetic acid (MEAA). This metabolite accounted for approximately 36% of the radioactivity in the 48-h culture medium and about 67% of the administered dose in the 48-h urine. Other prominent metabolites common to both systems included 2-(2-methoxyethoxy)ethanol, methoxyacetic acid (MAA), 2-methoxyethanol, and diglycolic acid. The diglyme metabolite profiles from urine and from hepatocytes were qualitatively similar, demonstrating that, in the rat, hepatocytes serve as a good model system for predicting the urinary metabolites of diglyme. Moreover, MEAA was shown to be the metabolite best suited for use as a short-term biological marker of exposure to diglyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of effect of cimetidine on lymphocyte subsets in patients infected with human immunodeficiency virus type 1

Cimetidine, widely used for peptic ulcer disease, blocks type 2 histamine receptors present on immune cells, including T cells, B cells, and monocytes. As an earlier published study showed evidence of increases in CD4 cell counts due to this drug, we conducted a randomized, placebo-controlled, 8-week trial of oral cimetidine (400 mg p.o. t.i.d.) in a study involving 182 patients infected with human immunodeficiency virus (HIV). Overall, cimetidine-treated patients had a decline in CD4+ cell counts that was no different from the decline for placebo-treated persons, neither during the first 8 weeks of the trial (mean drop, 7.1% [standard error, 12.1-1.8] vs. 6.7% [standard error, 11.6-1.5]) nor during the subsequent 8 weeks of open-label administration of cimetidine. No differences were evident between the treatment groups in terms of the percentage reactive to p24 antigen at baseline, and p24 antigen concentrations did not change from baseline to the end of week 8. In summary, cimetidine is well tolerated by HIV-infected individuals but alters neither CD4+ cell counts nor at least one quantitative measure of viral load, HIV p24 antigen levels.     

Lack of developmental and reproductive toxicity of 2,3,3'',4, 4''-pentachlorobiphenyl (PCB 105) in ring-necked pheasants

BACKGROUND/AIMS: The number connection tests A and B are regarded as sensitive psychometric measures for the assessment of early hepatic encephalopathy. Review of the studies dealing with the diagnostic sensitivity of the number connection tests, however, shows that the scoring of the number connection tests results differs between studies. Most groups define the limits of the normal range by studying small control groups. Others use scores given in the literature without ensuring the comparability of the test versions used. Thus, there is a need for normative data for the number connection test results and for re-evaluation of the sensitivity of the tests using valid scores. METHODS: In this study the number connection tests A and B were administered to 249 healthy volunteers (age: 18 to 76 years) to analyze the influence of age, education and occupation on their results. In addition, the age-corrected normative data were applied to 169 patients with grade 0-I hepatic encephalopathy. The specificity and sensitivity of age-corrected and age-independent normative data of the number connection tests were compared. RESULTS: There was a significant influence of age and education on the number connection test results, but only a negligible effect of occupation. Application of the age-corrected normative data to the test results of the patients with grade I hepatic encephalopathy significantly decreased the sensitivity of the number connection tests for hepatic encephalopathy compared to widely used age-independent normal ranges, but also increased the specificity. CONCLUSION: The use of standardized versions of the number connection tests and age-related normative data is recommended.     

Effect of co-planar polychlorinated biphenyl on the hepatic glutathione peroxidase redox system in rats and guinea pigs

The effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on hepatic glutathione peroxidase (GPx) redox system was studied in vivo in rats and guinea pigs. PCB 126 treatment caused significant reduction of Se-dependent and -non-dependent GPx activity in rats. In agreement with this, the content of glutathione (GSH) and the activities of GSH reductase (GR) and gamma-glutamyl transpeptidase (gamma-GTP) were also decreased in this species. On the contrary, guinea pig liver Se-non-dependent GPx activity was significantly enhanced by PCB 126 treatment, while no effect on Se-dependent activity was observed. Neither the content of GSH nor the enzyme activities responsible for GSH supply in guinea pig liver was affected by PCB 126. These result suggested that the damage on GPx redox system is, at least, one of mechanisms by which co-planar PCB induces the toxicity in rats. However, in guinea pigs, this is not the case, and different mechanism from the damage on active oxygen quenching system is likely to be involved.