The associations between suicide-related behaviors, prefrontal dysfunction in emotional cognition, and personality traits in mood disorders.

Suicide is a serious public health problem, and it is urgent to identify biomarkers associated with suicide to prevent it. We aimed to clarify the association across suicidal behavior, personality traits, and brain activation by emotional stimulation tasks using near-infrared spectroscopy (NIRS) in patients with mood disorders. 11 mood disorder patients with a history of suicide attempt (MDSA), 18 mood disorder patients with no history of suicide attempt (MDNSA), and 17 healthy individuals were studied. The MDSA patients showed significantly high impulsivity and hopeless compared to healthy subjects, great response to the thread word task in the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) compared to MDNSA patients, and the significant correlation between the personality traits and brain activation. The MDNSA did not show the trend. The results suggest that the personality traits and the activation of OFC and DLPFC during the negative emotional cognitive stimuli is associated with suicidal behavior, indicating the findings are involved in the pathophysiology of suicidality in mood disorders.

[A 52-week feeding study of genetically modified soybeans in F344 rats].

A chronic feeding study to evaluate the safety of the genetically modified glyphosate-tolerant soybeans (GM soybeans) was conducted using rats. F344 DuCrj rats were fed diet containing GM soybeans or Non-GM soybeans at the concentration of 30% in basal diet. Non-GM soybeans were closely related strain of GM soybeans. These two diets were adjusted to an identical nutrient level. In this study, the influence of GM soybeans on rats was compared with that of the Non-GM soybeans, and furthermore, to assess the effect of soybeans themselves, the groups of rats fed GM and Non-GM soybeans were compared with a group fed commercial diet (CE-2). General conditions were observed daily and body weight and food consumption were recorded. At the intermediate examination (26 weeks), and at the termination (52 weeks), animals were subjected to hematology, serum biochemistry, and pathological examination. There were several differences in animal growth, food intake, serum biochemical parameters and histological findings between the rats fed the GM and/or Non-GM soybeans and the rats fed CE-2. However, body weight and food intake were similar for the rats fed the GM and Non-GM soybeans. Gross necropsy findings, hematological and serum biochemical parameters, organ weights, and pathological findings showed no meaningful difference between rats fed the GM and Non-GM soybeans. These results indicate that long-term intake of GM soybeans at the level of 30% in diet has no apparent adverse effect in rats.

Antiestrogenic effect of paradichlorobenzene in immature mice and rats.

A significant increase/decrease in uterine and ovarian weights was occasionally seen in immature mice and rats subcutaneously administered paradichlorobenzene (PDCB) at doses of 22-67 mg/kg/day, but the results were not necessarily reproducible. PDCB at a dose of 800 mg/kg/day always reduced uterine and ovarian weights. Intraperitoneal PDCB at doses more than 400 mg/kg/day significantly inhibited the uterotrophic effect of beta-estradiol (E2) in CD-1 (ICR) mice. E2-induced uterotrophy was dose-dependently prevented by 204-400 mg PDCB/kg/day in C57BL/6N (Ah responsive) mice but not DBA/2N (Ah non-responsive) mice. While PDCB did not bind to estrogen receptor (ER(alpha)) up to 10(-3) M. Hepatic ethoxyresorufin-O-deethylase in adult female C57BL/6N mice was induced by i.p. administration of PDCB. Induction activity of PDCB may be 10(5)-10(6) times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest that PDCB is a weak antiestrogenic/antiuterotrophic compound possibly due to ER modulation through arylhydrocarbon receptor.

Flame retardant tetrabromobisphenol A induced hepatic changes in ICR male mice.

Tetrabromobisphenol A (TBBPA) is widely used throughout the world as flame retardant for electronic equipment or building materials, and is detected in air at the dismantling plant, sewage sludge, sediment or human serum samples. In the present study, we examined the effects of TBBPA on the liver when administered to mice for 14 consecutive days. Groups of 7 (control group) or 8 (treated group) Crlj:CD1 (ICR) male mice were given 0 (control), 350, 700 or 1400mg/kg body weight/day TBBPA (99.1% pure) in olive oil for 14 days. The serum concentration of total-cholesterol in high-dose (1400mg/kg BW) group was higher than those of the control group. Absolute and relative liver weights were dose-dependently increased, and were significantly increased in high-dose (1400mg/kg BW) group. The histological findings showed that the slight enlargement of the hepatocytes, inflammatory cell infiltrations and focal necrosis of hepatocytes were more marked in liver of treated groups (from 350mg/kg BW) than in control group. The present data suggest the possibility of inducing hepatic lesion by TBBPA dosing.

Role of mitochondrial membrane permeability transition in N-nitrosofenfluramine-induced cell injury in rat hepatocytes.

The role of mitochondrial membrane permeability transition in N-nitrosofenfluramine-induced cell injury was studied in mitochondria and hepatocytes isolated from rat liver. Mitochondrial permeability transition has been proposed as a common final pathway in acute cell death through mitochondrial dysfunction. In isolated mitochondria, N-nitrosofenfluramine (0.25 to 1.0 mM) in the presence of Ca(2+) (50 microM) elicited a concentration-dependent induction of mitochondrial swelling dependent on mitochondrial permeability transition and the release of cytochrome c, both of which were prevented by pretreatment with a specific inhibitor of mitochondrial permeability transition, cyclosporin A (0.2 microM). The effects of N-nitrosofenfluramine on mitochondria were more potent than those of fenfluramine, which is a sympathomimetic amine with anorectic action. The pretreatment of isolated hepatocytes with cyclosporin A (2 microM) partially but not completely prevented N-nitrosofenfluramine (0.6 mM; a low toxic dose)-induced cell death, loss of cellular ATP, formation of cell blebs and decrease in mitochondrial membrane potential. These results suggest that the onset of N-nitrosofenfluramine-induced cytotoxicity is linked to mitochondrial failure dependent upon induction of mitochondrial permeability transition accompanied by mitochondrial depolarization, the release of cytochrome c and depletion of intracellular ATP through uncoupling of oxidative phosphorylation.

N-Nitrosofenfluramine induces cytotoxicity via mitochondrial dysfunction and oxidative stress in isolated rat hepatocytes.

The cytotoxic effects of fenfluramine, an appetite suppressant, and its N-nitroso derivative, N-nitrosofenfluramine, have been studied in freshly isolated rat hepatocytes and isolated hepatic mitochondria. Exposure of hepatocytes to N-nitrosofenfluramine caused not only concentration (0.25-1.0 mmol L(-1)) and time (0-3 h)-dependent cell death accompanied by the loss of cellular ATP, adenine nucleotide pools, reduced glutathione (GSH), and protein thiols, but also the accumulation of oxidized glutathione and malondialdehyde (MDA), indicating lipid peroxidation. There was a time lag for the onset of the accumulation of MDA after the rapid depletion of ATP. Supplementation of the hepatocyte suspensions with N-acetylcysteine (4 mmol L(-1)), a precursor of intracellular GSH, partially inhibited N-nitrosofenfluramine (1 mmol L(-1))-induced cytotoxicity. In comparative effects based on cell viability and rhodamine 123 retention, an index of mitochondrial membrane potential, fenfluramine was less toxic than N-nitrosofenfluramine. In mitochondria isolated from rat liver, N-nitrosofenfluramine caused an increase in the rate of state-4 oxygen consumption, indicating an uncoupling effect, and a decrease in the rate of state-3 oxygen consumption in a concentration-dependent manner. These results indicate that (a) mitochondria are target organelles for N-nitrosofenfluramine, which elicits cytotoxicity through mitochondrial dysfunction related to membrane potential and/or oxidative phosphorylation at an early stage and subsequently lipid peroxidation at a later stage; and (b) the toxicity of N-nitrosofenfluramine is greater than that of fenfluramine, suggesting participation of the nitroso group in the toxicity.

Distribution of aflatoxin-producing Aspergillus flavus and Aspergillus parasiticus in sugarcane fields in the southernmost islands of Japan.

The distribution of Aspergillus flavus and Aspergillus parasiticus in sugarcane field soils and on harvested sugarcane stems was studied on seven islands of Okinawa and Kagoshima Prefectures, the southernmost prefectures in Japan. With the use of a combination of dilution plate and plant debris plate techniques, the fungi were detected on all seven islands studied and in 74% of 53 soil samples. The fungi were also found on the cut surfaces of sugarcane stems from one of the islands. A. parasiticus was the predominant fungus, although many atypical A. parasiticus isolates that produced metulated conidial heads were also obtained. The proportions of isolates testing positive for aflatoxin production were ca. 89% (146 of 164) of all isolates and ca. 69% of A. flavus isolates. More than 40% of A. flavus isolates also produced G aflatoxins. Scanning electron microscopic observation of conidial wall texture was useful in distinguishing A. parasiticus from A. flavus. Cyclopiazonic acid, an indole mycotoxin, was never synthesized by any of the A. parasiticus or G aflatoxin-producing A. flavus isolates tested.

[Identification of Aloe species by random amplified polymorphic DNA (RAPD) analysis].

Juice and integument of leaves of 3 Aloe species, Aloe vera, A. ferox and A. africana, are not allowed to be used as food according to the Pharmaceutical Affairs Law in Japan. On the other hand, whole leaves of A. arborescens can be used as food. The present study was designed to distinguish Aloe species by random amplified polymorphic DNA (RAPD) analysis. DNA was isolated from fresh and dried leaves of the 4 Aloe species. Five out of 32 different 10-mer primers examined were useful for analysis. By comparison of the characteristic bands of PCR products on agarose gel, it was possible to distinguish the 4 species. Thus, the botanical species of Aloe in commercial food products can be identified by RAPD analysis.

Simultaneous determination of eleven dyes and their aluminum lakes in drugs.

A 3-step extraction method was developed for the simultaneous determination of 11 dyes and their aluminum lakes in drugs. The dyes were first extracted with warm water (approximately 60 degrees C) and were cleaned up by solid-phase extraction with a tC18 cartridge. Aluminum lake dyes that remained in the precipitate were extracted with 0.02M NaOH. Aluminum in the dye lakes was reextracted into the organic layer with acetylacetone-butyl acetate (1 + 9, v/v), as an acetylacetone chelate, and was quantified by atomic absorption spectrometry. The dye portions of the aluminum lakes remained in the aqueous layer and were cleaned up in the same way as the dyes. The dyes and the dye portions of the aluminum lakes were quantified by ion-pair liquid chromatography with a photodiode array detector within 20 min. The recoveries of dyes from drug fortified at 10 microg of each dye per pill were 87.0-102.2%, and the recoveries of dyes from drugs fortified at 50 microg of each dye lake per pill were 82.9-101.6%, except for recoveries of indigo carmine. In 40 ethical and over-the-counter drugs, dyes that were not indicated in the package insert information for drugs were detected in 5 samples. The highest amount of dye found in a drug was 1169.5 microg erythrosine, which was detected in a capsule of antibiotic. Aluminum lake dyes were detected in 8 samples of various dosage forms.

Determination of thyroid hormones in pharmaceutical preparations, after derivatization with 9-anthroylnitrile, by high-performance liquid chromatography with fluorescence detection.

HPLC with fluorescence detection was used for the determination of low levels of liothyronine sodium and levothyroxine sodium in pharmaceutical preparations after fluorogenic derivatization. 9-Anthroylnitrile in dimethyl sulfoxide was used as a precolumn fluorogenic reagent. The 9-anthroylnitrile derivatives of liothyronine sodium and levothyroxine sodium were separated on a reversed-phase column with acetonitrile-0.02 M sodium dodecylsulfate (pH 3.5 with phosphoric acid) as the eluent. The calibration graphs were linear over a sample concentration range of 0.25-2.5 microg/ml. The detection limits for liothyronine sodium and levothyroxine sodium were 0.2 ng per injection. The proposed method was applied to the determination of thyroid hormones in pharmaceutical preparations.

Degradation of Aflatoxins by Food Additives.

Degradation of four aflatoxins (AFB1, AFB2, AFG1 and AFG2) by food additives was investigated. Pure aflatoxins were degraded by treatment with solutions of acidic food additives (hydrochloric acid:HCl and sulfuric acid:H2SO4), alkaline food additives (sodium bicarbonate:NaHCO3, sodium carbonate:Na2CO3, sodium hydroxide:NaOH, sodium sulfite:Na2SO3, and sodium hypochlorite:NaOCl) and neutral food additives (potassium metabisulfite:K2S2O5, sodium bisulfite:NaHSO3, sodium hydrosulfite:Na2S2O4, hydrogen peroxide:H2O2, sodium chlorite:NaClO2, and ammonium peroxodisulfate:(ÑH4)2S2O8). The aflatoxins were treated with these neutral food additives under several conditions, and the effects of treatment temperature, time, and concentration of food additives on aflatoxin degradation were studied. Potassium bromate (KBrO3), potassium nitrate (KNO3), and sodium nitrite (NaNO2) had no effect on aflatoxins. Of the aflatoxin added to corn, 20% AFB, remained after treatment with the solution of NaHSO3 (0.5%, 48 h), but all of the AFB1 was completely degraded by NaClO2 (0.25%, pH 4, 48 h) and (NH4)2S2O8 (0.25%, 48 h) at 60°C. Of the aflatoxins added to butter beans, less than 20 and 5% of AFB1 remained after boiling treatment with a 2 and 0.5% solution of Na2S2O4, respectively. These findings suggested that aflatoxins can be degraded or removed by treatment with food additives during food processing.