Squamous cell carcinoma in a digit of the hind limb with systemic metastasis in a 17-year-old female koala

We encountered a case of cutaneous squamous cell carcinoma (SCC) in a 17-year-old female koala at a zoo. A fragile, papillary, elevated mass was found on the third digit of the right hind limb. SCC was identified histopathologically: squamous cell-like polygonal tumor cells showed a nest-like growth pattern with epidermal down growth, central keratinization and necrotic foci, and invaded dermal connective tissues. Metastatic lesions were observed in various organs, including the lung and axillary lymph node: in the lung, multiple metastatic foci similar to the primary lesion, and in the axillary lymph node, individual polygonal tumor cells infiltrated the sinusoids. Immunohistochemistry revealed that the tumor cells were positive for proliferating cell nuclear antigen, which exhibited 32–33% of labeling indices in the tumor cells. To our knowledge, this is the first report of a case of SCC in a digit of a koala.     

Mesh-like vascular changes in copper deficiency-induced rat cardiomyopathy

The pathological effects of copper deficiency (COD) are well known. However, the pathogenesis of cardiomyopathy resulting from COD remains unclear. In this study, aimed to elucidate the pathogenesis of COD-induced cardiomyopathy by examining the morphology of the cardiovascular system in copper-deficient rats using histopathology, immunohistochemistry, and scanning and transmission electron microscopy. Changes detected in the myocardium and interstitium were consistent with those reported for COD. Morphological changes included mesh-like changes in the capillary endothelial cells that appear to be a novel finding in COD-induced cardiomyopathy. These changes are hypothesized to result from abnormal vascular remodeling following damage to the basement membrane and due to the mechanical effects of myocardial contractions. Although cardiomyopathy may be associated with microcirculatory disorders arising from these lesions, further investigations are necessary to demonstrate a causal relationship between the pathogenesis of cardiomyopathy and the contribution of these lesions to disease progression.     

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.     

Programmed Cell Death Induced by (?)-8,9-Dehydroneopeltolide in Human Promyelocytic Leukemia HL-60 Cells under Energy Stress Conditions

(+)-Neopeltolide is a marine macrolide natural product that exhibits potent antiproliferative activity against several human cancer cell lines. Previous study has established that this natural product primarily targets the complex III of the mitochondrial electron transport chain. However, the biochemical mode-of-actions of neopeltolide have not been investigated in detail. Here we report that (−)-8,9-dehydroneopeltolide (8,9-DNP), a more accessible synthetic analogue, shows potent cytotoxicity against human promyelocytic leukemia HL-60 cells preferentially under energy stress conditions. Nuclear morphology analysis, as well as DNA ladder assay, indicated that 8,9-DNP induced significant nuclear condensation/fragmentation and DNA fragmentation, and these events could be suppressed by preincubating the cells with a pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD). Immunoblot analysis demonstrated the release of cytochrome c from the mitochondria and the cleavage of full-length caspase-3 and poly(ADP-ribose) polymerase (PARP). These results indicated that 8,9-DNP induced caspase-dependent apoptotic programmed cell death under energy stress conditions. It was also found that 8,9-DNP induced non-apoptotic cell death in the presence/absence of zVAD under energy stress conditions. Immunoblot analysis showed the intracytosolic release of apoptosis-inducing factor (AIF), although it did not further translocate to the nucleus. It appears most likely that, in the presence of zVAD, 8,9-DNP triggered necrotic cell death as a result of severe intracellular ATP depletion.     

Study on some functional and compositional properties of yak butter lipid

The present experiment was performed to determine some functional properties of yak butter lipids such as lipid class composition; conjugated linoleic acid (CLA) composition, differential scanning calorimetric (DSC) analysis, tyrosinase inhibition activity and antioxidant property. Yak butter lipids composition contained 98% triacylglycerols, 0.9% free fatty acids, 0.32% free sterols and 0.27% phospholipids. The CLA content in yak butter was 2.5% and the major portion was of cis‐9 and trans‐11 (90%). The DSC analysis of yak butter lipids showed a similar path for transition temperature as cow butter lipids, although the enthalpy of yak lipid was higher (40.0 mJ/mg) compared to cow butter lipids (32.0 mJ/mg). Melting point of yak butter was observed at 41°C. Yak butter with lactic acid, NaCl, citric acid and ascorbic acid showed pronounced tyrosinase inhibition activity. Vegetable oils blended with yak butter have extended the oxidation induction time.     

Effect of Low-Dose Human Interferon-alpha on Shipping Fever of Thoroughbred Racehorses

To assess the effect of human interferon-alpha (IFNα) on shipping fever of Thoroughbred racehorses subjected to long-distance transportation, an IFNα preparation was orally administered to 48 horses three times (once daily, 3 successive days) before transportation (IFNα group). In the control group (25 horses), maltose was administered in the same way. These treatments induced no abnormal findings in Thoroughbred racehorses before transportation. Immediately after transportation, significant increases in rectal temperature were observed in both treatment groups, whereas the rectal temperature of the IFNα group tended to be lower than that of the control group. Although WBC, Fbg, and SAA immediately after transportation were significantly increased due to transportation in both groups, the extent of the increases in the IFNα group was significantly smaller than in the control group. Long-distance transportation had a relatively profound impact on Thoroughbred racehorses, which was mitigated by IFNα treatment.     

Mean retention time of digesta in the different segments of the equine hindgut

Six Thoroughbred horses were used to determine the mean retention time (MRT) of digesta in the different segments of the hindgut. The horses were fed timothy hay or silage in equal amounts (1.6% bodyweight [BW]/day) every 3 h/day. Hay or silage labeled with the rare earth elements cerium, dysprosium, neodymium, ytterbium, lanthanum, samarium and praseodymium, were fed to the horses 36, 30, 24, 18, 12, 6 and 3 h before slaughter, respectively. Just after slaughter, digesta samples in the different segments were collected and determined for the contents of the rare earth elements. Using these data, a method to calculate the MRT in the different segments was proposed. There were no significant differences between diets in the MRT of each segment. The averaged MRT of hay and silage in the cecum, right ventral colon, left ventral colon, left dorsal colon, right dorsal colon and small colon was 2.9, 3.1, 5.9, 1.0, 4.0, and 4.0 h, respectively. The dry matter weight of the digesta was related to the MRT in the right ventral colon (r = 0.94, P = 0.005), left ventral colon (r = 0.87, P = 0.03), left dorsal colon (r = 0.98, P < 0.001) and right dorsal colon (r = 0.95, P = 0.004), but it was not related to the MRT in the cecum and small colon.     

Effects of preventing hyperphagia on glycolipid metabolic abnormalities in Spontaneously Diabetic Torii fatty rats

Spontaneously Diabetic Torii (SDT) fatty rats, made by introducing the fa allele of the Zucker fatty rat into the SDT rat genome, represent a new model of obese type 2 diabetes. SDT fatty ^fa/fa (SDT fatty) rats exhibit overt obesity, hyperglycemia, and hyperlipidemia from about six weeks of age, and this is associated with hyperphagia by an induced disorder of leptin action. The present study was conducted to elucidate whether suppression of hyperphagia can improve reduce abnormalities in SDT fatty rats. SDT fatty rats were subjected to pair-feeding with SDT fatty ^{+/ +} (SDT) rats from 6 to 26 weeks of age, and the effects on metabolic parameters and diabetic complications were assessed. Body weights of the pair-fed rats were similar with those of SDT rats during the experimental period. Improvement of hyperglycemia or hypertriglyceridemia was observed from 8 to 16 or 12 weeks of age in the pair-fed rats, but hypercholesterolemia was not entirely improved during the experimental period. We also examined mRNAs expression in liver, and found that the expression associated with glyconeogenesis, such as glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), tended to decrease in the pair-fed rats, and the mRNA expression of hydroxymethylglutaryl-CoA (HMG-CoA) was elevated. Renal parameters, such as blood urea nitrogen and urinary albumin excretion, were improved in the pair-fed rats. The incidence or progression of diabetic complications, such as renal lesions and cataract, was reduced. In conclusion, suppression of hyperphagia in SDT fatty rats was effective in temporally improving hyperglycemia or hypertriglyceridemia, and reducing the incidence or progression of diabetic complications, but was ineffective in reducing hypercholesterolemia.     

Dietary intake of iodine‐enriched eggs decreases the incidence of mouse mammary tumors caused by the activated ErbB2 oncogene

Human epigenetic studies suggest that consumption of seaweed prevents mammary cancer, which possibly is explained by iodine daily intake. In this study, we evaluated the efficacy of dietary intake of iodine‐enriched eggs on mammary tumor incidence caused by the expression of activated type ErbB2. Female transgenic mice were divided into three groups, and fed a basic diet, a diet supplemented with ordinary eggs, or with iodine‐enriched eggs. The number of mammary tumors greater than 5 mm in diameter was recorded in mice at 6 months of age. We report that the average number of mammary tumors per mouse was significantly lower in the iodine‐enriched egg‐added diet group than in either the basic diet or ordinary egg diet groups. These results indicate that iodine intake through livestock‐derived products can reduce the incidence of mammary cancers caused by the expression of activated type ErbB2.