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The inhibitory effects of ketoconazole (KCZ) and miconazole (MCZ), imidazole containing antimycotics, on the hydroxylations of testosterone as a model for endogenous steroids, and the N-demethylation of aminopyrine and the hydroxylation of aniline as models for xenobiotics were compared with those of cimetidine in mouse hepatic microsomes. In vitro, both KCZ and MCZ inhibited these enzyme activities in a dose-dependent manner. The inhibitory potencies of KCZ and MCZ for testosterone hydroxylations and aminopyrine N-demethylation were much greater, with 50% inhibition concentration (IC50) values 2-3 orders of magnitude lower than those of cimetidine, while the potencies of these antimycotics for aniline hydroxylation were similar to that of cimetidine. Although KCZ, MCZ and cimetidine produced type II difference spectra, the difference between the antimycotics (405 nm) and cimetidine (392-405 nm) was found in the trough position of the difference spectra. Spectral dissociation constants (Ks) of these antimycotics (2.2×10-7-5.4×10-6M) were also 1-2 orders of magnitude lower than those of cimetidine (1.3×10-5-1.6×10-4M), and both KCZ and cimetidine had two kinds of Ks, while MCZ had a single Ks. Pentobarbital sleeping time was prolonged in a dose-dependent manner by the i.p. administration of 10-50 mg/kg of KCZ, MCZ or cimetidine, and the potencies for the prolongation of sleeping time decreased in the order of MCZ>KCZ>cimetidine. These results indicated that the inhibitory potencies of KCZ and MCZ for the cytochrome P-450-mediated oxidative metabolism of testosterone and xenobiotics in hepatic microsomes were greater than those of cimetidine, and that the affinities of KCZ and MCZ for some cytochrome P-450 species in hepatic microsomes differed from one another.

When male ddY mice were treated with consecutive doses of 10 and 100 mg/kg of miconazole (MCZ) or ketoconazole (KCZ), imidazole-containing antimycotics, once a day for 3 d, a dose-dependent shortening of pentobarbital sleeping time was observed for MCZ, while no change in the sleeping time was observed for KCZ. Even at a low dose (10 mg/kg), MCZ significantly increased cytochrome P-450 content and reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase activity. Simultaneously, hydroxylase activities of testosterone as a model of endogenous steroids, and aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities were increased, while KCZ lacked inducing properties even at a high dose (100 mg/kg). The change in hepatic oxidative metabolism of cortisol (F) in a patient before, during and after treatment with progressively increasing doses of 2-10 mg/kg/d of MCZ for 14 d was examined by monitoring urinary 6 beta-hydroxycortisol (6 beta-OHF), an oxidative metabolite of F. The ratio of 6 beta-OHF to F in 24-h urine decreased by 15% from the original level on day 1, and then it began to increase on day 7 to reach 2.4 times the original level on day 14. These results suggest that MCZ, but not KCZ, has inducing activity for hepatic cytochrome P-450-dependent oxidative metabolism of steroids and xenobiotics, in addition to its known inhibitory activity.

Histological and histochemical examinations were carried out on the muscular lesions in a newborn calf with hydranencephaly. The muscular lesions were composed of the fascicles of atrophic muscular fibers histologically. Histochemical examination revealed that the groups of histochemically uniform muscular fibers (fiber-type grouping) were present in the lesions, suggesting that the muscular lesion of this case was a neurogenic disorder.

The in vitro effects of diltiazem (DTZ), a coronary vasodilator, deacetyldiltiazem (D-M1), one of the metabolites of DTZ, and pentoxifylline (PTF) which is known to improve erythrocyte deformation, on the viscosity of platelet poor blood were compared. Furthermore the change in the viscosity of whole blood from patients with effort angina after intravenous administration of DTZ was examined ex vivo. The addition of DTZ into platelet poor blood at 37 degrees C caused a rapid reduction in blood viscosity and an enhancement of erythrocyte deformability within 5 min, which then diminished in a time-dependent manner. Similar effects were also found by adding D-M1. On the other hand, the effects of PTF appeared after an incubation period of more than 60 min and were enhanced in a time-dependent manner. These actions of PTF, but not those of DTZ and D-M1, paralleled the increase of erythrocyte adenosine-triphosphate content. DTZ and D-M1, but not PTF, had biphasic effects on the osmotic behavior of erythrocytes. Whole blood viscosity was reduced significantly during the period 5-30 min after intravenous administration of 10 mg of DTZ, which diminished with the elimination of plasma DTZ. In conclusion, the action mechanisms involved in the effect of DTZ and D-M1 on blood rheological properties appeared to be different from that of PTF. These effects of DTZ are clinically significant in improving the flow properties of blood in vascular diseases.

ヨーネ病は牛・緬山羊などの反幻獣を侵す慢性の伝染病で,わが国では過去に二三の牧場においてその発生が報告されている.今回,著者らは帯広近郊の2つの牧場において,牛の本症例に遭遇したので,これを臨床・病理・細菌および血清学的に検討した.第1例は1968年10月アメリカより輸入された5才の乳牛である.臨床的には,1969年11月から8カ月間にわたる頑固な下廂を主徴とし,元気・食欲・被毛光沢を欠き,極度に削痩し,予後不良の判断で殺処分された.剖検所見では,腸管各部の粘膜が肥厚し,特徴的な皺襞形成が観察された.組織学的には,腸管粘膜固有層および粘膜下織に多数の抗聚菌を寅食した類上皮細胞の著明な集積をみた.細菌学的検査では,腸管各部粘膜と腸間膜リンパ節の塗抹標本で多数の集塊状抗酸菌を認め,同材料のSmit11培地での培養において,ヨ一ネ菌を分離した.血清反応では,発病牛がCF2.PHA抗体1:16,同居牛20頭中1頭がCF,PHA抗体1:4~l:8を示し,約10カ月間にわたって持?続し,本病の感染を示唆した.第2例も,1964年にアメリカより輸入された10・才の乳牛である.1969年8月から10カ月間にわたる下痢が認められ,元気,食欲なく,削痩著しく,殺処分された.病理所見は前例にほぼ等しく,また腸管部の塗抹標本では,多数の集塊状抗:酸菌がみられた.同材料のSmith培地での培養・で,ヨーネ菌が分離された.わが国におけるヨーネ病の発生状況を文献に基づいて整理したところ,過去のすべての発生例.は,今回の成績と同様に,輸入動物か,またはこれらと密接な関連にあった動物に限られていることが明らとかなった.

The activity of urinary peptidases in normal and various diseased states, both in man and experimental animals, was determined using l -leucine-β-naphthylamide, l -glutamyl-β-naphthylamide and synthetic isoleucine-5-angiotensin II as substrate. The increased activity of urinary enzymes hydrolysing β-naphthylamides was seen most characteristically in patients with renal tubular lesions, and was not necessarily coincident with increased activity of serum enzymes. Among the organs the kidney —especially the renal cortex — contains the highest activity, located histochemically in the proximal tubular cells. The urinary enzymes migrated with an electrophoretic mobility identical with that of the kidney enzymes, but different from the mobility of serum enzymes, indicating that these urinary enzymes come from renal tubular cells, but not from serum. These two enzymes were also capable of inactivating isoleucine-5-angiotensin II. In addition to these, however, normal urine was found to contain a further fraction which inactivates angiotensin II and migrates with the electrophoretic mobility of γ-globuhn.

This investigation was carried out in order to know the morphological features ofcoccidia in the intestinal tissue of field chickens. The materials used for it consisted of96 birds of various breeds ranging from 20 days to more than one year of age. Of them, 56 birds were affected concurrently with so-called avian leukosis and 1 bird with Gumborodisease. In principle, the duodenum, jejunum, ileum, cecum and rectum were examinedhistologically in each bird.In consequence, 17 birds were infected mainly with Eimeria acervulina (Table 1), 32 mainly with E. tenella (Tables l -3), 29 mainly with E. necatrix (Tables 2, 4), and 18mainly with E. maxima (Table 5). Twenty-three of all the birds harbored one or two ofthe species of Eimeria mentior?ed above in addition.Parasites in various sexual phases of development were observed within the epi-thelial cells of the intestine (duodenum, jejunum, ileum and cecum), and those invarious asexual phases of development in the lamina propria of the intestine, which maybe a matter of course. As to the morphology of the life cycle of Eimeria, no discrepancieswere found out between the findings obtained by the present authors and those fromexperimental studies by TYZZER6) and TYZZER et aI.7).The identification of coccidial species parasitizing the intestinal tissue will not alwaysbe difficult, if the morphology of the parasites in various stages of development and thelocalization of them in the intestinal tissue and within infected cells are understoodthoroughly.Furthermore, the following findings were pointed out in this study. Birds whichwere accompanied by another species of Eimeria in addition were comparatively numer-ous. A large number of birds had a small number of developing parasites. Retrogres-sive schizonts were fairly frequently found out. These results must be taken into con-sideration in the investigation of coccidial infection in field chickens.

Silver nanoparticle (Ag NP)/chitosan (Ch) composites with antiviral activity against H1N1 influenza A virus were prepared. The Ag NP/Ch composites were obtained as yellow or brown floc-like powders following reaction at room temperature in aqueous medium. Ag NPs (3.5, 6.5, and 12.9 nm average diameters) were embedded into the chitosan matrix without aggregation or size alternation. The antiviral activity of the Ag NP/Ch composites was evaluated by comparing the TCID50 ratio of viral suspensions treated with the composites to untreated suspensions. For all sizes of Ag NPs tested, antiviral activity against H1N1 influenza A virus increased as the concentration of Ag NPs increased; chitosan alone exhibited no antiviral activity. Size dependence of the Ag NPs on antiviral activity was also observed: antiviral activity was generally stronger with smaller Ag NPs in the composites. These results indicate that Ag NP/Ch composites interacting with viruses exhibit antiviral activity.