Sub-acute oral exposure to lowest observed adverse effect level of nivalenol exacerbates atopic dermatitis in mice via direct activation of mitogen-activated protein kinase signal in antigen-presenting cells.

This study investigated the immunotoxic effects of the mycotoxin nivalenol (NIV) using antigen-presenting cells and a mouse model of atopic dermatitis (AD). In vitro experiments were conducted using a mouse macrophage cell line (RAW 264.7) and mouse dendritic cell line (DC 2.4). After cells were exposed to NIV (0.19-5 µmol) for 24 h, the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα) was quantified. To further investigate the inflammatory cytokine production pathway, the possible involvement of mitogen-activated protein kinase (MAPK) pathways, such as ERK1/2, p-38, and JNK, in NIV exposure was analyzed using MAPK inhibitors and phosphorylation analyses. In addition, the pro-inflammatory effects of oral exposure to NIV at low concentrations (1 or 5 ppm) were evaluated in an NC/Nga mouse model of hapten-induced AD. In vitro experiments demonstrated that exposure to NIV significantly enhanced the production of TNFα. In addition, it also directly induced the phosphorylation of MAPK, indicated by the inhibition of TNFα production following pretreatment with MAPK inhibitors. Oral exposure to NIV significantly exacerbated the symptoms of AD, including a significant increase in helper T cells and IgE-produced B cells in auricular lymph nodes and secretion of pro-inflammatory cytokines, such as IL-4, IL-5, and IL-13, compared with the vehicle control group. Our findings indicate that exposure to NIV directly enhanced the phosphorylation of ERK1/2, p-38, and JNK, resulting in a significant increase in TNFα production in antigen-presenting cells, which is closely related to the development of atopic dermatitis.

Isolation, structural determination, and antiviral activities of a novel alanine-conjugated polyketide from Talaromyces sp.

Antiviral agents are highly sought after. In this study, a novel alkylated decalin-type polyketide, alaspelunin, was isolated from the culture broth of the fungus Talaromyces speluncarum FMR 16671, and its structure was determined using spectroscopic analyses (1D/2D NMR and MS). The compound was condensed with alanine, and its absolute configuration was determined using Marfey's method. Furthermore, the antiviral activity of alaspelunin against various viruses was evaluated, and it was found to be effective against both severe acute respiratory syndrome coronavirus 2 and pseudorabies (Aujeszky's disease) virus, a pathogen affecting pigs. Our results suggest that this compound is a potential broad-spectrum antiviral agent.

Trace element concentrations in blood samples from dairy cows with uterine torsion and their neonatal calves.

Background and Aim: Mineral deficiencies can lead to dystocia and abnormalities in neonates. Stillbirth of neonatal calves in dairy cows due to dystocia has become an economic problem. Uterine torsion (UT) is a common form of dystocia observed in dairy cows. However, to the best of our knowledge, there have been no reports on the characteristics of serum trace element concentrations in dairy cows with UT. This study aimed to comprehensively measure serum trace element concentrations in dairy cows with UT and dystocia. Materials and Methods: Dairy cows with (n = 15) and without (n = 27) UT and neonates (n = 9 and n = 26, respectively) were included in this study. Blood samples (10 mL) were collected, and serum trace element concentrations were evaluated using inductively coupled plasma mass spectrophotometry. Results: The mortality rate at birth was significantly higher in calves delivered by cows with UT than those delivered by cows without UT. The odds ratio for mortality rate at birth in dairy cows with UT was 7.85. Serum zinc (Zn) levels were significantly lower in cows with UT than in cows without UT (p = 0.01). The copper: Zn ratio was significantly higher in cows with UT than in cows without torsion (p = 0.05). In contrast, serum Cobalt (Co) concentrations were significantly higher in neonates from cows with UT than in neonates from cows without UT (p = 0.01). Conclusion: Uterine torsion is associated with a high mortality rate at birth and considerable economic losses. Cows with UT had low serum Zn levels, and neonates born to these cows had high serum Co levels.

Repeated-Dose Pharmacodynamics of Pimobendan in Healthy Cats.

The aims of this study were to investigate the effects of repeated and multiple-dose pimobendan on cardiac systolic function and the correlations between changes in cardiac systolic function and plasma concentrations of pimobendan and O-desmethylpimobendan (ODMP). Five clinically healthy cats were subjected to four different medication protocols for 14 days, with a washout period of at least 1 month between each protocol. The protocols were pimobendan 0.5 mg/kg q12h (high dosage [HD] group); pimobendan 0.25 mg/kg q12h (standard dosage [SD] group); pimobendan 0.125 mg/kg q12h (low dosage group); and Biofermin R, one tablet q12h (placebo group). Echocardiography and measurement of plasma concentrations of pimobendan and ODMP were performed prior to medication administration (baseline) and 20, 40, 60, 120, 240, 360, and 480 min after administration, and the correlation between the changes in cardiac systolic function and plasma concentration of pimobendan, ODMP, or the sum of both were examined. The cardiac systolic function increased in the HD and SD groups, and there were significant correlations between the lateral peak systolic myocardial velocity (S') changes and plasma pimobendan, plasma ODMP, and the sum of both. Repeated doses of pimobendan in healthy cats increased cardiac systolic function, and there were significant correlations between cardiac function and plasma concentrations of pimobendan and ODMP. The results of this study highlight the effectiveness of a higher dose of pimobendan.

Preparation of Monoclonal Antibodies Specifically Reacting with the Trichothecene Mycotoxins Nivalenol and 15-Acetylnivalenol via the Introduction of a Linker Molecule into Its C-15 Position.

Nivalenol (NIV) is a trichothecene mycotoxin that is more toxic than deoxynivalenol. It accumulates in grains due to infection with Fusarium species, which are the causative agents of scab or Fusarium head blight. An immunoassay, which is a rapid and easy analytical method, is necessary for monitoring NIV in grains. However, a specific antibody against NIV has not been prepared previously. To establish an immunoassay, we prepared NIV, introduced a linker, and generated antibodies against it. NIV was prepared from a culture of Fusarium kyushuense obtained from pressed barley through chromatographic procedures with synthetic adsorbents and silica gel. NIV was reacted with glutaric anhydride, and the reaction was stopped before mono-hemiglutaryl-NIV was changed to di-hemiglutaryl-NIV. 15-O-Hemiglutaryl-NIV was isolated via preparative HPLC and bound to keyhole limpet hemocyanin (KLH) using the active ester method. Two different monoclonal antibodies were prepared by immunizing mice with the NIV-KLH conjugate. The 50% inhibitory concentration values were 36 and 37 ng/mL. These antibodies also showed high reactivity in a direct competitive enzyme-linked immunosorbent assay and specifically reacted with NIV and 15-acetyl-NIV but not with deoxynivalenol and 4-acetyl-NIV.

Sample Introduction Method in Gas Chromatography.

In this review, we summarize the methods of sample introduction into a gas chromatograph. For volatile organic compounds, headspace measurements and purge-trap methods have been used traditionally. Recently, the trapped headspace method has been used in water quality testing. In addition, various solid-state adsorption methods have been developed, including a method in which the adsorbent is placed inside a needle, while new adsorbents and their applications have also been introduced.

The Bacteriological Properties of Bacillus Strain TM-I-3 and Analysis of the Volatile Antifungal Compounds Emitted by this Bacteria.

Previously, we isolated and examined a bacterial strain designated as TM-I-3, belonging to the genus Bacillus, from soil in Nagasaki, Japan. This bacterium was able to inhibit the growth of molds, without coming into direct contact with them. Non-contact antifungals are capable of providing multidirectional inhibition and may contribute to disease prevention. In this study, we revealed the bacteriological properties of TM-I-3 and evaluated the antifungal activity of the compounds emitted from this bacterium. In addition, we analyzed the antimicrobial substances released from TM-I-3 using GC/MS to elucidate the mechanism of its action. Antimicrobial compounds from strain TM-I-3 were identified as acetic acid, propanoic acid, isovaleric acid, 2-methylbutanoic acid, and benzaldehyde, which are all reported to have antimicrobial activity. TM-I-3 demonstrated possible efficacy in inhibiting the growth of Aspergillus fumigatus, Cladosporium cladosporioides and Penicillium expansum, which may lead to inhibition of common fungal contaminants of household products and prevention of some pulmonary diseases.

Evaluation of the genotoxicity of PM2.5 collected by a high-volume air sampler with impactor.

BACKGROUND: The harmful effects of fine particles with an aerodynamic diameter less than 2.5 µm (PM2.5) on respiratory organs are emphasized in pollution studies because PM2.5 have high deposition rates in the respiratory organs and contain various hazardous compounds. In this study, a sampling method combining a high-volume air sampler (HV) with a PM2.5 impactor was developed for collecting large quantities of PM2.5. The concentrations of elemental carbon (EC), organic carbon (OC), inorganic ions, and polycyclic aromatic hydrocarbons (PAHs) were measured in PM2.5 collected by the high-and low-volume air samplers (LV). RESULTS: Similar results were obtained from the HV and LV methods, with respect to inorganic carbon, organic carbon, sodium ions, ammonium ions, and PAHs with more than four rings. Because of the much larger amount of PM2.5 could be collected by the HV method, the trace constituents, that were difficult to detect by the conventional LV method, were readily detected by the HV method. Furthermore, when the microsuspension method that was modified more sensitive Ames mutagenicity test, was used to test the PM2.5 samples at four sites, mutagenic activities were detected by strains TA100 and TA98. Most of the mutagenic activity was associated with the PM2.5 fraction and mutagenic activity in winter was greater than that in summer. CONCLUSIONS: The HV method produced results similar to those from the conventional LV method with respect to the PM2.5 components present in the atmosphere in relatively high concentrations, but its 40-fold greater flow rate enabled the detection of mutagenic compounds present in only trace concentrations.

Measurement of polynuclear aromatic hydrocarbons in canine lung after alkaline decomposition.

An alkaline decomposition method employing a KOH/alcohol solution was studied, and polynuclear aromatic hydrocarbons (PAHs) contained in particles remaining in canine lung were measured. As a result, BaA, BkF, BaP, and BghiP were found. By this method, PAHs extracted from the lungs of 32 dogs were 13.0-166.0 ng (mean, 63.0 ng) for BaA, 6.6-90.2 ng (mean, 27.4 ng) for BkF, 9.8-167.4 ng (mean 47.2 ng) for BaP, and 10.8-206.0 ng (mean, 61.8 ng) for BghiP. The results showed no correlation between the age and the concentration of PAHs in the lung, but some correlation was found between the age and the lung weight (p<0.01). There were significant correlations among the concentrations of the compounds in the lung (p<0.01). These results suggest that dogs, like humans, are affected by automobile exhaust and other common generation sources of such substances.

[Measurement of hazardous chemical constituents and mutagenic activity in fillers and mainstream smoke from Neo Cedar].

OBJECTIVE: To determine constituents of fillers and mainstream smoke from Neo Cedar. METHODS: Neo Cedar is a second-class over-the-counter (OTC) drug and similar to cigarettes in a number of ways. In particular, the design and usage are very similar to those of cigarettes. For the fillers of the drug, the levels of nicotine, tobacco-specific nitrosamines (TSNA), and heavy metals, and mutagenicity were determined using the methods for cigarette products. For the mainstream smoke, the levels of tar, nicotine, carbon monoxide (CO), TSNA, polycyclic aromatic hydrocarbons (PAH), and carbonyl compounds were also determined using the methods for cigarettes. The mainstream smoke from the drug were collected with a smoking machine using two smoking protocols (ISO and Health Canada Intense methods). RESULTS: The nicotine and total TSNA levels in the fillers of the drug averaged 2.86 mg/g and 185 ng/g, respectively. The nine species of heavy metals were also detected in the fillers of the drug. The levels of nicotine, tar, CO, TSNA, PAH, and carbonyl compounds of mainstream smoke from the drug were higher when determined using the HCI regime than when using the ISO regime. The mutagenicity of the mainstream smoke determined using the HCI regime was also higher than that determined using the ISO regime. CONCLUSION: In this study, all constituents of Neo Cedar were determined by methods for cigarette products. The drug had a ventilation hole on its filter. Thus, its constituents are different from those determined by the smoking protocols. Neo Cedar users should be careful of higher exposure to the hazardous gases owing to smoking patterns.