Azole resistance in Malassezia pachydermatis has been reported in isolates from canine skin worldwide. Decreased susceptibility of M. pachydermatis to azoles has been hypothesized to potentially result from mutations in the ERG11 gene, which encodes lanosterol 14α-demethylase. To sequence the mutation hotspots of ERG11 in the isolates, we prepared primers (MPERG11hot2S and MPERG11hot2R) based on the conserved sequences of M. pachydermatis ERG11. DNA samples from azole-resistant and -susceptible strains were amplified by PCR using the primer pair. PCR amplicons were sequenced and analyzed for single-nucleotide polymorphisms (SNPs) in the target gene. Seven of the tested azole-resistant strains (16 strains) harbored ERG11 SNPs at nucleotide 904 (G→A) or 905 (C→T), resulting in the replacement of Ala 302 with Thr or Val (Ala302Thr or Val). None of the tested azole-susceptible strains had a mutation at either of those residues. Our PCR method detected SNPs at the nucleotide-905 (C→T) hotspot mutation site in M. pachydermatis ERG11. Moreover, we discovered an additional hot spot site at nucleotide 904 (G→A).

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Previous studies suggest that nonhuman animals form concepts that integrate information from multiple sensory modalities such as vision and audition. For instance, Adachi, Kuwahata, and Fujita (2007) demonstrated that form auditory-visual cross-modal representation of their owner. However, whether such multi-modal concepts would expand to more abstract, or collective, ones remains unknown. To answer the question, we tested whether were sensitive to congruence of human genders suggested by the voice and the face of an unfamiliar person. We showed to the a photograph of a male or female human face on the monitor after playing a voice of a person either matching or mismatching in gender. looked at the photograph for longer duration when the auditory stimuli were incongruent than when they were congruent; that is, expectancy violation was suggested. This result suggests that spontaneously associate auditory and visual information to form a cross-modal concept of human gender. This is the first report showing that cross-modal representation in nonhuman animals expands to an abstract social category.

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Indomethacin (IMC) suspended in soybean oil was microencapsulated in a gelatinacacia system by a modified phase separation method from aqueous solution. The microcapsules were hardened with formaldehyde without the use of sodium hydroxide. Average particle diameter of the microcapsules was 111μm, and the content of IMC in the microcapsules was more than 80% of the initial amount of IMC. The in vitro dissolution of IMC from the microcapsules was slower than that of intact IMC, and this indicated that the walls of the microcapsules affected the drug dissolution. The bioavailabilities in beagle of the IMC microcapsules and of a soybean oil suspension of IMC administered in capsules were larger than that of intact IMC.

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Dissolution profiles of sulfamonomethoxine (SMM)/18-crown-6 (1, 4, 7, 10, 13, 16-hexaoxacyclooctadecane) complex, SMM anhydrate and SMM hydrate were investigated by dispersed amount method and stationary disk method, and also in vivo absorption study of these compounds in was carried out in comparison with the data of the dissolution behaviors. According to the dispersed amount method, the concentration of SMM rose quickly and then decreased gradually when the complex was dispersed. On the other hand, a characteristic convex dissolution curve was observed in the case of the anhydrate. This result indicated that the dissolution rate of complex was extremely large, but its decomplexation accompanying the change to the hydrate form in water was also rapid compared with that of the anhydrate. The rate constant of phase change for the complex to the hydrate form, which was calculated by stationary disk method, was extremely large compared with that for the anhydrate. It was observed that the plasma levels of SMM increased extremely by the administration of the anhydrate form. An increase of plasma levels was also observed in the case of the complex.

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An apparent oral toxicity of 18-crown-6 (1, 4, 7, 10, 13, 16-hexaoxacyclooctadecane) and sulfamonomethoxine (SMM)/18-crown-6 complex in was investigated following the bioavailability study of SMM/18-crown-6 complex which the authors reported already. When 18-crown-6 or SMM/18-crown-6 complex was administered orally to healthy beagle , the following symptoms appeared : a tremulous movement, a salivation and a paralysis of hind legs at 2-12 hr after administration. These symptoms disappeared at 24 hr after administration.

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are known to be extremely sensitive to human behavior. They use human gestures such as pointing as a cue better than great apes. A question here is whether this wonderful human companion simply reads apparent "behavior" of us, or, like humans, more deeply some sort of indirect information the behavior implies. In three separate tests, including pointing games with a non-trustworthy person, inference of the door function from human behavior toward it, and third-party affective evaluation of human interactions, we show that often utilize more than superficial actions they observe. are at least somewhat "cognitivists" rather than pure "behaviorists" that learn everything by simple association with observable stimuli.

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We have already recognized that Zn-DTPA (diethylenetriaminepentaacetic acid) is less toxic than Ca-DTPA when they are administered orally to rats. In this study, in order to estimate exactly the safety of Zn-DTPA by the oral administration in humans, by evaluating the degrees of damages in the different animal species between beagle and rats, we examined the toxicity of Zn-DTPA in beagle according to the same methods as the rat, and then the results were compared with those in the rat. Zn-DTPA was administered daily to beagle for 1 month, with the doses of 30, 150, 300μmol/kg body weight. The decreases of body weight, hemorrhage and congestion, and vascular expansion of the lamina propria mucosa and under the serious membrane of the small intestine, and the slight damages of kidney were observed. These changes were similar to those in rats at the same dose.
As a result, it is recognized that there are almost no differences on the Zn-DTPA toxicity between and rats, therefore the safety of orally administered Zn-DTPA in humans might be estimated from the results obtained in the animal experiments without considering the remarkable species differences.

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Recently, detection of canine primary adrenal mass has increased owing to progress in diagnostic imaging. Adrenocortical adenoma, adrenocortical carcinoma, and pheochromocytoma are representative primary adrenal masses; the latter two may invade intravascularly and metastasize to other organs. We encountered a dog exhibiting progressive hindlimb paraplegia. Multimodal imaging including computed tomography (CT) and magnetic resonance imaging (MRI) revealed that the cause of the paraplegia was infiltration of a left adrenal pheochromocytoma into the spinal canal. In addition, MRI detected small liver metastatic lesions that were not detected by CT.

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Optimal bone filling materials that act as a scaffold for the repair of bone defects should possess, histocompatibility, and afford conduction of new bone formation without toxicity or allergic factors. In addition, the materials should ultimatedly be resolved and replaced by new bone. In this study, to develop new bone filling materials that promote bone formation and bone growth, we implanted coral in bone defects and observed the newly-formed bone by confocal laser scanning microscopy (CLSM).
In 3 adult male beagles, bone defects were made in the right and left femora and tibiae under general anesthesia. These defects were either filled with coral blocks or left without any filling material. After 4 weeks, calcein was administered. One week later, the animals were euthanized under general anesthesia, and the femora and tibiae were removed and fixed in formalin. The specimens were divided into two portions: one is for CLSM observation and the other for histopathological observation.
The formation of bone and bone marrow was seen in holes without filling, but only slight bone growth, i.e., increase in bone mass was seen. In the holes with coral filling materials, they were resorbed by giant cells. Furthermore, new bone and bone growth were noted, while lymphocyte infiltration was slight in all holes. Since resorption of the coral inserted into the bone defect was observed, we concluded that coral could be useful for bone regeneration.

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2頭のゴールデン・レトリーバーが全身の被毛減量と尾の脱毛を主訴に来院した。犬種と特徴的な臨床所見の他に, 雄の症例ではT₄値と治療試験から, 雌の症例ではT₄fT₄c-TSHの各検査値からともに甲状腺機能低下症と診断した。2症例ともレボチロキシンナトリウムの投与により症状は著しく改善された。

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2015年から2018年にアジア盲導犬繁殖ネットワークで実施された盲導犬の適性試験の記録（693個体）から推定された3つの形質（落ち着き，ハンドラーへの集中，ストレスコントロール）の量的遺伝パラメーターを用いて，相対希望改良量を達成するための8つの選抜指数を設定した．これらの選抜指数を各形質に達成される遺伝的改良量に基づいて比較した．「落ち着き」と「ストレスコントロール」の間の負の遺伝的関連性に対処するためには，「ストレスコントロール」の遺伝的変化を正に保ったうえで，「落ち着き」の遺伝的改良量を最大化する選抜指数が最も望ましい結果を与えた．この指数の有効性は，2018年に適性試験を受験した個体について推定された育種価を用いた机上選抜でも確認された．

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Inclusion complex of digoxin with γ-cyclodextrin (γ-CyD) in 1 : 4 molar ratio was prepared, and its dissolution and absorption behaviors were compared with those of digoxin alone. The dissolution rate of digoxin in water was found to be markedly in creased by γ-CyD complexation. Bioavailability of digoxin following the oral administration of γ-CyD complex to was 5.4 times as much as that of digoxin alone. The present data did indicate the improvement of dissolution and absorption characteristics of digoxin by inclusion complexation, suggesting the decrease in dose in oral digoxin therapy.

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A variety of spontaneous lesions found histologically in control Beagle (males: 91, famales; 97) used in toxicity studies that were conducted at the Biosafety Research Center, Foods, Drugs and Pesticides during a 10 year period, are described. All animals were exsanguinated by incision of the axillary artery under sodium pentobarbital anesthesia at the end of each study.
Neoplastic lesions included fibrosarcoma of the heart in a female dog at approximately 27 weeks of age (1.0%) and hemangioendothelioma of the spleen in a male dog, also at approximately 27 weeks of age (1.1%).
The most common non-neoplastic changes in both male and famale were deposits of amorphous masses at the renal papilla (males; 68.1%, females ; 80.4%) and fetal glomerulus in the kidney (males; 53.8%, females; 50.5%). Fatty changes in the renal tubular epithelium of female occurred at an incidence of greater than 50%. Pigment deposition in the spleen, guranulation of the liver, atrophy in the thymus, C-cell hyperplasia of the thyroid gland, and pituitary cysts in male and female were evident at an incidence of greater than 10%. In addition, multinucleated giant cells in the testes, eosinophilic bodies in the renal tubular epithelium in males, cellular infiltration of the parotid gland, and deposits of calcium in the spinal cord of females were seen at incidences of greater than 10%. Atrophy of the thymus and C-cell hyperplasia of the thyroid increased with age. Fetal glomerulus of kidney decreased with age.
Other rare, but interesting lesions included: ectopic stomach tissue in the ileum, ductro-insular proliferation of the pancreas, deposits of calcium at the beginning portion of the aorta and in the spinal cord, and hemangiectasis at the atrioventriclar valve of the heart.

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Of 164 used in routine toxicity studies, seven male and three female Beagle 6 to 17 months of age were found to have spontaneous proliferation of pancreatic endocrine cells. The changes consisted of various combinations of irregular-shaped islets, the budding of endocrine cells from ductal epithelia, beta cell nesidioblastosis composed of a few beta cells, focal adenomatous proliferation of endocrine cells, and prominent ductulo-insular complexes. The proliferated endocrine cells were slightly enlarged containing numerous minute granules in their cytoplasm and were interspersed with ductular cells. Immunocytochemically, a moderate increase was seen in beta and delta cells, and pancreatic polypeptide cells were frequently observed in the nesidioblastic lesions, suggesting that nesidioblastosis might have occurred as a regenerative change stimulated by the destruction of exocrine tissue.

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A retrospective review has been performed of Acceptable Daily Intakes (ADI) for pesticide residues in Japan where dog studies have provided the pivotal data for their derivation.  A set of 46 ADIs which are based on the results of dog toxicity studies (normally 1-year) were examined and reassessed under the assumption that the 1-year dog study had not been conducted , thus  requiring the derivation of the ADI from an alternative toxicology study. A resulting ADI up to 2 times higher was not considered to be a real difference and was found in 36 of the 46 data sets (78.3%). An ADI 2-5 times higher was found in another 6/46 data sets (13%), but is potentially  not   a toxicologically
relevant difference or requiring additional studies, while for 3/46 data sets (6.5%) there may be a real difference. Only 1/46 data sets (2.2%) showed an ADI higher than 5 times.
The incidences of 3/46 plus 1/46 should not only be assessed within the specific data set investigated, but against the total of all registrations of conventional pesticides in Japan, a number exceeding 400 active substances. Accordingly, the absence of a 1-year dog study would not influence the ADI derivation in a relevant manner for more than 98% of these pesticides.
Therefore the standard requirement to conduct a 1-year dog study in addition to the 3-month study cannot be justified.

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A rare spontaneous hepatic leiomyosarcoma with osteosarcomatous differentiation was observed in a female beagle dog and its morphological and immunohistochemical characteristics were examined. Upon necropsy, an endoceliac mass originating from the liver was detected, which was composed of hematoid fluid-filled cysts and white to grayish solid tissue. There were no macroscopic findings in other organ systems. Histopathologically, the hepatic mass consisted of two different mesenchymal components. One form was spindle cells arranged in interlacing fascicles immunohistochemically positive for smooth muscle actin (SMA) and smoothelin, indicating leiomyosarcomatous differentiation. The other form was composed of short spindle cells positive for S-100 and was producing various amounts of eosinophilic osteoid and trabecula-like matrices positive for osteocalcin, indicating osteosarcomatous differentiation. In addition, invasive growth in the hepatic parenchyma and cell atypia were observed. Based on these findings, the mass was diagnosed as hepatic leiomyosarcoma with osteosarcomatous differentiation (malignant mesenchymoma), which might be derived from undifferentiated mesenchymal cells.

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実験胃癌の研究は, 1967年杉村らがラノト腺癌をN-Methy-N'-Nitro-N-Nitrosoguamdme (MNNG) の経口投与により発生せしめたことに端を発し, 1974年栗原らのN-Ethyl-N'-Nitro-N-Nitrosoguamidime (ENNG) の経口投与によるイヌ胃癌の発生実験の成功により, 実験イヌ胃癌作製工方法はほぼ完成された.現在実験胃癌の研究は, その治療実験へと進められている.しかし癌発生部位を的確に予想出来ない従来の作製方法は, 治療実験を行い病変の変化を経時的に観察する上で改善の余地を残している.
今回われわれは, ENNG含有ペレットをイヌ胃粘膜下に埋没しさらにENNGを経口投与して埋没部に他部位より高頻度に癌が発生する事を期し, 加えて発癌期間を短縮せしめ, これを治療実験モテルにする目的で実験を行い, 若干の知見を得たので報告する.

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Brain infarction confined to the anterior half of the thalamus can be produced in by simultaneously occluding 4 main arteries ipsilaterally at the base of the brain (the internal carotid, the anterior cerebral, the middle cerebral, and the posterior communicating arteries). Using this “thalamic infarction model in the dog”, hemorrhagic infarction following recirculation was investigated.
In animals undergoing 6-12 hour occlusion, a high incidence of hemorrhagic infarction was found following recirculation. Notably, in brains autopsied 1 hour after recirculation, hemorrhagic infarction was seen in all (100%) of the .

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