Evidence of PCDD/Fs and PCBs contamination in trees grown in forests far from their production and contamination-free areas.

Polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in trees grown in pathless forests were analyzed to investigate their dispersal patterns in the atmosphere. The pg/g levels of 23 PCCD, 22 PCDF, and 54 PCB congeners were identified. The total amount of PCDDs in the red pine tree sample (95.8 pg/g) was approximately 7 times that in the beech tree sample (13.2 pg/g). The total amount of PCDFs in the red pine tree sample (71.1 pg/g) was also approximately 7 times that in the beech tree sample (11.1 pg/g). The total amounts of PCBs in the red pine tree and beech tree samples were 1,380 and 1,150 pg/g, respectively. The (Cl1-Cl3)-PCBs comprised 63.1 % and 67.6 % of total PCBs in the red pine and in the beech, respectively. The results of the present study indicate that PCDD/Fs and PCBs are transferred over long distances in the atmosphere and accumulated in the contamination-free areas.

Central PACAP mediates the sympathetic effects of leptin in a tissue-specific manner.

We previously demonstrated that the peptidergic neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) affects the autonomic system and contributes to the control of metabolic and cardiovascular functions. Previous studies have demonstrated the importance of centrally-mediated sympathetic effects of leptin for obesity-related hypertension. Here we tested whether PACAP signaling in the brain is implicated in leptin-induced sympathetic excitation and appetite suppression. In anesthetized mice, intracerebroventricular (ICV) pre-treatment with PACAP6-38, an antagonist of the PACAP receptors (PAC1-R and VPAC2), inhibited the increase in white adipose tissue sympathetic nerve activity (WAT-SNA) produced by ICV leptin (2µg). In contrast, leptin-induced stimulation of renal sympathetic nerve activity (RSNA) was not affected by ICV pre-treatment with PACAP6-38. Moreover, in PACAP-deficient (Adcyap1-/-) mice, ICV leptin-induced WAT-SNA increase was impaired, whereas RSNA response was preserved. The reductions in food intake and body weight evoked by ICV leptin were attenuated in Adcyap1-/- mice. Our data suggest that hypothalamic PACAP signaling plays a key role in the control by leptin of feeding behavior and lipocatabolic sympathetic outflow, but spares the renal sympathetic traffic.

Effect of nanoparticles on the male reproductive system of mice.

The effects of nanoparticles toward on the male reproductive system of mice were investigated. Three sizes (14, 56 and 95 nm) of carbon black nanoparticles were intratracheally administered (0.1 mg/mouse for 10 times every week) to ICR male mice to investigate their adverse effects on the reproductive function. The serum testosterone levels were elevated significantly in the 14- and 56-nm carbon nanoparticles-exposed groups. Histological examination showed partial vacuolation of the seminiferous tubules. In addition, the effects of particle number towards the male reproductive system were investigated. The particle number controlled 14-nm nanoparticles-exposed group (14 N group, which has approximately the same particle number per unit volume as the 56-nm nanoparticles) showed fewer effects than did the 56-nm nanoparticles-exposed groups. These results suggest that carbon nanoparticle-exposure has adverse effects on the mouse male reproductive function. Furthermore, the effects of nanoparticles on the male reproductive system depend on particle mass rather than particle number.

The effects of microbial materials adhered to Asian sand dust on allergic lung inflammation.

Asian sand dust (ASD) containing microbiological materials, sulfate (SO(4)(2)), and nitrate (NO(3)(-) ) derived from air pollutants in East China, reportedly cause adverse respiratory health effects. ASD aggravates ovalbumin (OVA)-associated experimental lung eosinophilia. In this study, the toxic materials adsorbed onto ASD were excluded by heat treatment at 360 degrees C for 30 min. The effects of nonheated ASD or heated ASD (H-ASD) toward the allergic lung inflammation were compared in murine lungs. ICR mice were administered intratracheally with normal saline (control), H-ASD, ASD, OVA, OVA + H-ASD, and OVA + ASD, four times at 2-week intervals. ASD only increased neutrophils in bronchoalveolar lavage fluids (BALFs) along with pro-inflammatory mediators, such as keratinocyte chemoattractant (KC). H-ASD and ASD enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. The two ASDs synergistically increased interleukin-5 (IL-5), monocyte chemotactic protein-3 (MCP-3), and eotaxin, which were associated with OVA, in BALF. The enhancing effects were much greater in ASD than in H-ASD. The two ASDs induced the adjuvant effects to specific IgE and IgG1 production by OVA. In the in vitro study using RAW264.7 cells, ASD increased the expression of Toll-like receptor 2 (TLR 2) mRNA but not TLR4 mRNA. H-ASD caused no expression of either TLR mRNA. These results suggest that the aggravated lung eosinophilia by ASD may be due to activation of Th2-associated immune response via the activation of TLR2 by microbial components adhered to ASD.

Hepatic pre-sinusoidal vessels contract in anaphylactic hypotension in rabbits.

AIM: The purpose of this study was to determine whether anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction, and the effects of anaphylaxis on hepatic segmental vascular resistances and liver weight in isolated perfused rabbit livers. METHODS: The rabbits were sensitized by subcutaneous injection of antigen of 2.5 mg ovalbumin with complete Freund's adjuvant three times at 1 week interval. One week after sensitization, anaphylaxis was induced by an injection of 2.5 mg ovalbumin into the jugular vein of pentobarbital anaesthetized rabbits or the perfusate of rabbit livers perfused via the portal vein at a constant flow. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre- (R(pre)) and post-sinusoidal (R(post)) resistances were calculated for the isolated perfused livers. RESULTS: An antigen injection into the sensitized rabbits caused not only a decrease in systemic arterial pressure from 79 +/- 2 to 40 +/- 4 mmHg, but also an increase in portal venous pressure (P(pv)) from 9.5 +/- 2.2 to 24.1 +/- 3.9 cmH(2)O. Portal hypertension persisted for 8 min after the antigen injection. An injection of antigen into the perfusate caused a marked increase in P(pv) from 5.4 +/- 0.1 to 28.6 +/- 2.4 cmH(2)O at 6 min, but only a slight increase in double occlusion pressure from 2.2 +/- 0.2 to 3.8 +/- 0.2 cmH(2)O, resulting in a selective increase in R(pret) rather than R(post). Concomitant with the hepatic pre-sinusoidal constriction, liver weight loss occurred. CONCLUSION: Anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction which is characterized by pre-sinusoidal contraction.

Murine strain differences in 8-hydroxy-deoxyguanosine formation in hepatic DNA induced by oxidized lard and dietary oils.

Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.

Analytical methods for trace levels of reactive carbonyl compounds formed in lipid peroxidation systems.

Analysis of trace levels of reactive carbonyl compounds (RCCs), including formaldehyde, acetaldehyde, acrolein, malonaldehyde, glyoxal, and methyl glyoxal, is extremely difficult because they are highly reactive, water soluble, and volatile. Determination of these RCCs in trace levels is important because they are major products of lipid peroxidation, which is strongly associated with various diseases such as cancer, Alzheimer's disease, aging, and atherosclerosis. This review covers the development and application of various derivatives for RCC analysis. Among the many derivatives which have been prepared, cysteamine derivatives for formaldehyde and acetaldehyde; N-hydrazine derivatives for acrolein, 4-hydroxy-2-nonenal, and malonaldeyde; and o-phenylene diamine derivatives for glyoxal and methyl glyoxal were selected for extended discussion. The application of advanced instruments, including gas chromatograph with nitrogen-phosphorus detector (GC/NPD), mass spectrometer (MS), high performance liquid chromatograph (HPLC), GC/MS, and LC/MS, to the determination of trace RCCs in various oxidized lipid samples, including fatty acids, skin lipids, beef fats, blood plasma, whole blood, and liver homogenates, is also discussed.

Formation and inhibition of genotoxic malonaldehyde from DNA oxidation controlled with EDTA.

The attack of DNA by reactive oxygen species, such as hydroxyl radical, causes several types of damage, which subsequently promote diseases. Determination of oxidized products, such as malonaldehyde (MA), from DNA would provide theoretical and practical information on the mechanisms of DNA oxidation following DNA damage and this information could be used to prevent DNA damage caused by oxidation. In the present study, calf thymus DNA was oxidized by Fenton's reagent/EDTA with or without natural antioxidants-flavonoids and anthocyanins-and synthetic antioxidants, Trolox and 2H-pyrrole, 3,4-dihydro-2,2-dimethyl-, 1-oxide (DMPO). Amounts of MA formed, which was determined by gas chromatography, in oxidized DNA with the presence of antioxidants, ranged from 7.35+/-0.88 nmol/mg (2''-O-GIV) to 12.6+/-0.24 nmol/g (cyanidin). Except for cyanidin, all antioxidants tested inhibited MA formation. DMPO and Trolox inhibited MA formation by 12.4% and 27.3%, respectively from oxidized DNA. The decreasing order of inhibitory effect by the anthocyanins was callistephin (30.2%)>keracyanin (27.3%)>Pelargonindin (10.1%)>cyanidin (0%). The decreasing order of inhibitory effect by the flavonoids was 2''-O-GIV (42.7%)>catechin (8.8%)>quercetin (36.4%)>apigenin (34.4%). It is hypothesized that EDTA controlled formation of hydroxyl radicals via trapping Fe(II) ions reversibly.

Liver carcinogenesis and formation of 8-hydroxy-deoxyguanosine in C3H/HeN mice by oxidized dietary oils containing carcinogenic dicarbonyl compounds.

Oxidized dietary oils (lard, soybean oil, and sardine oil) were orally administered to C3H/HeN male mice. After 6 months, benign hepatocellular adenoma was observed in the mice treated with all three oxidized dietary oils. After 12 months, malignant hepatocellular carcinoma and hepatoblastoma were observed in addition to the benign tumor. Oxidized sardine oil caused the highest tumor incidence (35%) and malignant tumors (27.5%) among the oxidized dietary oils tested. Mice treated with oxidized lard and sardine oil exhibited a significant increase of 8-OH-dG in the livers. The amounts of 8-OH-dG found in the mice treated with oxidized sardine oil correlated with the rates of tumor incidence. After 6 months, mRNA decreased in the case of oxidized lard and sardine oil, whereas it increased in the case of oxidized soybean oil, either in 8-oxoguanine-DNA glycosylase (OGG1) or in 8-oxo-dGTPase. On the other hand, there was no appreciable change in mRNA, in either OGG1 or 8-oxo-dGTPase, after 12 months. Oxidized sardine oil contained the highest level of malonaldehyde (MA) (713+/-91.1 nmol/g) and glyoxal (33.3+/-5.2 nmol/g) among three oxidized oils. The malignant tumor incidence correlated with the high level of MA and glyoxal found in the dietary oils tested.

Different hepatic vascular response to noradrenaline and histamine between guinea-pig and rat.

AIM: Hepatic xenotransplantation from guinea-pig to rat has not been established. This failure is partly ascribed to differences in hepatic vascular characteristics between two species. However, the differences in hepatic vascular resistance distribution and responses to vasoconstrictors are not known. The present study was designed to determine basal levels of segmental vascular resistances and the responses to histamine and noradrenaline in isolated guinea-pig and rat livers. METHODS: The livers were haemoperfused (Hct 8.3%) via the portal vein at a constant flow. The sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. RESULTS: There was no significant difference in basal total hepatic vascular resistance (Rt) between two species, whereas Rpre in rat (69% of Rt) was significantly greater than that in guinea-pig (61% of Rt). The responses to noradrenaline were similar; Rpre increased in a greater magnitude than Rpost, and liver weight was reduced. However, the noradrenaline-induced increase in Rt was greater in rats than in guinea-pigs. In contrast, histamine increased predominantly Rpost over Rpre, and increased liver weight in guinea-pig, while it affected no haemodynamic variables in rat. CONCLUSION: There exist species differences in the hepatic vasculature between rat and guinea-pig. Basal pre-sinusoidal resistance in rat is greater than that in guinea-pig. Although noradrenaline predominantly contracts pre-sinusoidal vessels in both species, histamine causes predominant post-sinusoidal vasoconstriction in guinea-pig liver, while it has no vasoactive effects on rat liver.

Inhibition of malonaldehyde formation from blood plasma oxidation by aroma extracts and aroma components isolated from clove and eucalyptus.

The inhibitory effect of aroma extracts isolated from clove buds [Syzygium aromaticum (L.) Merr. et Perry] and eucalyptus leaves (Eucalyptus polyanthemos Schauer) on malonaldehyde (MA) formation from horse blood plasma oxidized with Fenton's reagent was determined by gas chromatography. Aroma chemicals such as eugenol, thymol and benzyl alcohol, identified in the aroma extracts, were examined for their inhibitory effect on the same system. Between the two aroma extracts tested, clove exhibited the most potent antioxidant activities. Extracts of eucalyptus and clove inhibited MA formation by 23 and 48%, respectively, at the level of 400 microg/ml, whereas, alpha-tocopherol and BHT inhibited MA formation by 52 and 70%, respectively, at the same level. Eugenol, thymol and benzyl alcohol inhibited MA formation by 57, 43 and 32%, respectively, at the level of 400 microg/ml.

Effects of growth hormone following chronic angiotensin-converting enzyme inhibition in chronic heart failure: their relation to infarct size.

Growth hormone (GH) has been attracted as a possible adjunctive treatment for severe heart failure. However, its treatment effects have been still controversial. To assess severity of basal cardiac disease states in which GH might be effective, we analyzed the relation of treatment effects of GH following chronic angiotensin-converting enzyme (ACE) inhibition on cardiac function and structures to infarct size in rat model of chronic heart failure after myocardial infarction. One day after coronary occlusion, rats were randomized to either an ACE inhibitor, temocapril (T) (80 mg/L in drinking water) or placebo for 12 weeks. The animals received concomitant recombinant human (rh) GH (2 mg/kg/day, SC) (T + GH) or vehicle during the final 2 weeks. Compared with the T group, the T + GH group with large MI had smaller increments of left ventricular (LV) dP/dt(max) (0 vs 17%) and cardiac output (9 vs 49%), less improvement of LV relaxation (tau) (-3 vs 29%) and systemic vascular resistance (8 vs 29%), and a greater increase in LV end-diastolic pressure (123 vs -5%) than did the T+GH group with moderate MI. In the T + GH group when compared with the T group, these functional alterations were associated with a 12% reduction in the LV capillary density and a 21% increase in hydroxyproline contents in rats with large MI, whereas a 12% increase in the density and similar collagen contents were found in rats with moderate MI. Thus, prominent beneficial cardiovascular effects of the additive short-term, high-dose GH to chronic high-dose ACE inhibition were obtained in rats with moderate MI, whereas little additional benefit or even detrimental effects of GH were found in rats with large MI. The present study may provide an insight into the therapeutic strategy of GH given late after MI in the presence of chronic ACE inhibition in congestive heart failure.

Seasonal and spatial studies on pesticide residues in surface waters of the Shinano river in Japan.

Water samples collected once a week from early April 1996 to the end of August 1996 from four sites on the Shinano River in Japan were analyzed for pesticides and their metabolites using a gas chromatograph-mass spectrometer. Among the total of 53 chemicals found, 22 were herbicides, 15 were insecticides, 11 were fungicides, and 5 were metabolites. The concentrations of chemicals found ranged from 3 ng/L (bromobutide) to 8200 ng/L (isoprothiolane). Herbicides were found primarily during May and June at all four sites. Insecticides and fungicides were found primarily during July and August at all four sites. The presence of pesticides in the river water correlated with the time of pesticide application to the rice fields near the river.

Antioxidative activity of volatile chemicals extracted from beer.

Volatile chemicals obtained from a commercial beer by liquid-liquid continuous extraction were evaluated for antioxidant activity. The inhibitory ability of this extract toward the conversion of hexanal to hexanoic acid was monitored over a 35-day period. The volatile extract demonstrated >99% effectiveness at inhibiting hexanal oxidation at 50 microg/mL, comparable to that of the natural antioxidant alpha-tocopherol (vitamin E). Volatile compounds contained in the extract were isolated and identified by gas chromatography-mass spectrometry (GC-MS). From the volatile constituents identified in beer extract, phenylethyl alcohol, maltol, and 2-furanmethanol were examined for antioxidative activities. At a concentration of 500 microg/mL, maltol and 2-furanmethanol demonstrated approximately 95 and 100% inhibition of hexanal oxidation over 35 days, respectively. Phenylethyl alcohol did not show any appreciable level of inhibition of hexanal oxidation. Heterocyclic compounds, some of which are known to possess antioxidative activities, were also identified in the volatile extract.

Formation of dioxins during the combustion of newspapers in the presence of sodium chloride and poly(vinyl chloride).

Exhaust gases from the combustion of newspaper alone, from branches of London plane tree alone, and from newspapers mixed with sodium chloride (NaCl), polyethylene, or poly(vinyl chloride) (PVC) were collected. The samples were analyzed for dioxins by gas chromatography/mass spectrometry. Total amounts of dioxins found in the samples were 0.186 ng/g from newspapers alone, 1.42 ng/g from the branches of London plane, 102 ng/g from newspapers impregnated with sodium chloride (CI wt % = 3.1), 101 ng/g from newspapers impregnated with sodium chloride mixed with PVC (Cl wt % = 2.6), and 146 ng/g from newspapers mixed with PVC (Cl wt % = 5.1). Samples with a higher chloride content produced more dioxins, and there is a clear correlation between dioxin formation and chloride content. The amount of dioxins formed in the samples according to the number of chlorides was Cl5 > Cl4 > Cl6 > Cl7 > Cl8 in PCDD isomers and Cl4 > Cl5 > Cl6 > Cl7 > Cl8 in PCDF isomers, except in the case of newspapers alone. Benzofurans composed 78-92% of the total dioxins formed in the exhaust gases. The higher the number of the chlorides, the lower the production of benzofuran observed. NaCl vaporized at the temperature of the flame used for combustion of the samples (760-1080 degrees C). The results indicate that NaCl and PVC contribute significantly to dioxin formation from waste materials combusted in incinerators.