Time-course comparison of pulmonary inflammation induced by intratracheal instillation of four different nickel oxide nanoparticles in male Fischer rats

Occupational exposure to nickel oxide (NiO) is an important cause of respiratory tract cancer. Toxicity is known to be associated with the dissociated component, i.e. nickel (II) ions. To address the relationship between physicochemical properties, including solubility in artificial lysosomal fluid, of NiO and time-course changes in the pulmonary response, we conducted an intratracheal instillation study in male Fischer rats using four different well-characterized NiO products, US3352 (NiO A), NovaWireNi01 (NiO B), I small particle (NiO C), and 637130 (NiO D). The NiOs were suspended in purified water and instilled once intratracheally into male F344 rats (12 weeks old) at 0 (vehicle control), 0.67, 2, and 6 mg/kg body weight. The animals were euthanized on days 3, 28, or 91 after instillation, and blood analysis, bronchoalveolar lavage fluid (BALF) testing, and histopathological examination were performed. The most soluble product, NiO B, caused the most severe systemic toxicity, leading to a high mortality rate, but the response was transient and surviving animals recovered. The second-most-soluble material, NiO D, and the third, NiO A, caused evident pulmonary inflammation, and the responses persisted for at least 91 days with collagen proliferation. In contrast, NiO C induced barely detectable inflammation in the BALF examination, and no marked changes were noted on histopathology. These results indicate that the early phase toxic potential of NiO products, but not the persistence of pulmonary inflammation, is associated with their solubility.     

The palliative efficacy of modified Mohs paste for controlling canine and feline malignant skin wounds

In veterinary medicine, the management of malignant skin wounds is highly challenging. We conducted a study on seven case animals (four dogs and three cats) which presented with malignant skin wounds. All seven animals had signs and symptoms which were controlled following treatment with a modified Mohs paste. Upon obtaining informed consent from their owners, the animals requiring management of malignant wounds were enrolled in this study. The modified Mohs paste was prepared by mixing zinc chloride, zinc oxide starch powder, glycerin, and distilled water. The modified Mohs paste was topically applied to and left to remain on the malignant wounds for one hour, under controlled conditions. Once the paste was removed, the wounds were irrigated with a solution of sterile saline. At the first examination, the wounds of each animal were observed for signs of exudate, malodor, and bleeding. In every case, visible improvement was observed immediately after the modified Mohs paste treatment. Specifically, the size of the malignant wounds, and the number of times the dressing gauze required changing, significantly decreased (p < 0.05 and p < 0.01, respectively). The open malignant skin wounds caused by mammary gland tumors disappeared in two cases. The Mohs paste has been shown to be a viable option for the palliative treatment in canine and feline malignant skin wound management.     

Impaired female fertility in tubulointerstitial antigen-like 1-deficient mice

Tubulointerstitial nephritis antigen-like 1 (Tinagl1, also known as adrenocortical zonation factor 1 [AZ-1] or lipocalin 7) is a matricellular protein. Previously, we demonstrated that Tinagl1 expression was restricted to extraembryonic regions during the postimplantation period and detected marked expression in mouse Reichert’s membranes. In uteri, Tinagl1 is markedly expressed in the decidual endometrium during the postimplantation period, suggesting that it plays a physical and physiological role in embryo development and/or decidualization of the uterine endometrium during pregnancy. In the present study, in order to determine the role of Tinagl1 during embryonic development and pregnancy, we generated Tinagl1-deficient mice. Although Tinagl1^–/– embryos were not lethal during development to term, homologous matings of Tinagl1^–/– females and Tinagl1^–/– males showed impaired fertility during pregnancy, including failure to carry pregnancy to term and perinatal lethality. To examine ovarian function, ovulation was induced with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG); the number of ovulated oocytes did not differ between Tinagl1^–/– and Tinagl1^flox/flox. In vitro fertilization followed by embryo culture also demonstrated the normal developmental potential of Tinagl1-null embryos during the preimplantation period. Our results demonstrate that Tinagl1 deficiency affects female mice and results in subfertility phenotypes, and they suggest that although the potential of Tinagl1^–/– oocytes is normal, Tinagl1 is related to fertility in adult females but is not essential for either fertilization or preimplantation development in vitro.     

Estrone sulfate and progesterone profiles during late gestation in recipient cows transferred embryos produced by nuclear transfer and in vitro fertilization

The aim of present experiment was to evaluate the plasma concentrations of estrone sulfate (E(1)S) and progesterone (P(4)) during late gestation in recipient cows transferred embryos produced by nuclear transfer (NT) and in vitro fertilization (IVF). Blood samples were collected from recipients transferred embryos produced by NT (n=9) and IVF (n=13) at 160, 220, 240, 260 and 270 d of gestation and then at 5 d intervals until parturition. Plasma samples were analyzed for E(1)S and P(4) by ELISA. One NT and three IVF cows aborted between days 220 and 260 of gestation. Two NT and one IVF cow had prolonged gestation (over 290 d). One IVF cow had an overweight fetus (50 kg) after abortion (257 d). The patterns of changes in the concentrations of E(1)S during late gestation in the NT and IVF cows were almost identical. The NT and IVF cows that aborted had prolonged gestation and much higher E(1)S concentrations than the average. One NT cow aborted after 220 d of gestation and had a sudden high increase in its E(1)S concentration from 160 d to 220 d of gestation. The NT and IVF cows that had prolonged gestation also had significantly higher (P<0.05) P(4) concentrations than the average. These results raise the possibility that the E(1)S and P(4) profiles can be used to monitor some late gestational problems, such as higher birth weight, abortion and prolonged gestation.     

Immunohistochemical analysis of pseudorabies virus spread through neurons innervating the eyeball

Pseudorabies virus (PRV) was inoculated intraocularly into BALB/c mice, and the distribution pattern of cells positive for several neurotransmitters and viral antigens in the eyeball, trigeminal nerve ganglia, and superior cervical ganglia was examined immunohistochemically to clarify the neural route of the virus spread. In the eyeball, substance P (SP)- and calcitonin gene-related peptide (CGRP)-positive cells were detected in the ipsilateral iris and ciliary body, neuropeptide tyrosine (NPY)-positive cells were detected in the choloid membrane, and tyrosine hydroxylase (TH)-positive cells were detected in the ipsilateral inner nuclear layer of the retina; all these cells contained viral antigens. In the superior cervical ganglia, viral antigen-positive cells containing TH or NPY were found at bilateral sites. In the trigeminal nerve ganglia, viral antigen-positive cells containing SP or CGRP were found at bilateral sites. These findings indicated that the SP- and CGRP-positive ganglion cells of the trigeminal nerve ganglia innervating the iris or ciliary body, and the NPY-positive ganglion cells of the superior cervical ganglia innervating the iris, ciliary body, and choroid membrane served as the route for the virus spread. These findings also suggested that dopaminergic neurons, such as the TH-positive retinal cells and TH-positive ganglion cells of the superior cervical ganglia, served as the route for virus spread.     

Bovine herpesvirus-1 (BHV-1) recombinant expressing pseudorabies virus (PrV) glycoproteins B and C induces type 1 immune response in BALB/c mice

Bovine herpesvirus 1 (BHV-1) attached poorly and penetrated into a mouse cell line, BALB 3T3/A31, but a recombinant BHV-1/TF7-6, which expresses pseudorabies virus (PrV) gB and gC genes, did attach and penetrated into cells more efficiently. In this study the gene green fluorescent protein (GFP) has been integrated into genome of BHV-1/TF7-6 and its parental line of BHV-1. When the mouse mesenteries were incubated in vitro and infected with BHV-1/TF7-6/GFP, strong fluorescence was observed while BHV-1/GFP infection hardly demonstrated fluorescence, suggesting that BHV-1 recombinant expressing PrV gB and gC can infect mouse tissue cells more efficiently than the parental BHV-1 does. When BALB/c mice were inoculated with purified BHV-1/TF7-6 or its parental BHV-1, the former induced lower level of anti-BHV-1 immunoglobulin G (IgG) than the latter did. When sub-classes of anti-BHV-1 IgG were analyzed, it was found that mice immunized with BHV-1/TF7-6 or the parental BHV-1 demonstrated the same level of IgG2a. Since anti-BHV-1 IgG1 level was lower in mice inoculated with BHV-1/TF7-6, the IgG2a:IgG1 ratio was higher in BHV-1/TF7-6 inoculated mice than in the parental BHV-1 inoculated ones. These results indicate that BHV-1/TF7-6 induces type 1 predominant immune to BALB/c mice.     

Effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers

The purpose of the present paper was to investigate the effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers. Four crossbred beef steers walked on a treadmill during a 6 week exercise period (1.2 km/h, 1 h/day and 5 days/week). The changes in plasma glucose and insulin levels following glucose infusion were analyzed immediately prior to (bodyweight: 260.4 ± 24.2 kg) and after (295.7 ± 30.1 kg) the exercise period. The basal levels of plasma glucose (86.4 vs. 82.0 mg/dL, P = 0.040) and insulin (24.5 vs. 14.3 μU/mL, P = 0.016) were significantly lower after the exercise period. Further, the increase in the levels of plasma glucose (420.4 vs. 280.8 mg/dL, P < 0.001) and insulin (94.5 vs. 73.1 μU/mL, P = 0.028) following the glucose infusion decreased after the exercise period. The area under the curve of plasma glucose (108.8 vs. 62.9 mg/dL per min, P < 0.001) and insulin (53.6 vs. 29.7 μU/mL per min, P = 0.018) indicated more rapid clearance of exogenous glucose and less insulin secretion for glucose clearance after the exercise period. These results suggest that regular exercise improves glucose tolerance, with lower insulin response to glucose infusion in growing steers, as observed in rodents and humans.