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Y Chihaya

Publications and source records attributed to Y Chihaya.

At least 19 recordsLinked to original sources
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (6)--Six-month repeated oral dose toxicity study in dogs].

A six-month repeated oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) at dose levels of 40, 100 and 250 mg potency/kg/day was conducted in male and female beagle dogs. No toxicologically significant changes were observed in general conditions of all animals. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were observed in all treated groups. Plasma irons showed a tendency to increase in the males and females of the 250 mg potency/kg group. However, as no changes suggesting anemia or hepatic injury were observed in this group, the change of plasma iron was considered to have no toxicological significance. No toxicologically significant changes were observed in other examination items. The plasma S-1090 concentrations increased in a manner less than dose-proportional. Based on the above results, the NOAEL of S-1090 was assessed to be 250 mg potency/kg/day.

Administration, Oral↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (5)--Six-month repeated oral dose toxicity study and supplement study in rats].

Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.

Administration, Oral↗
PubMed1997

[A 26-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in rats followed by a 9-week recovery test].

A 26-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Sprague-Dawley rats. Male and female rats were given the drug orally for 26 weeks at doses of 0 (control), 5, 50 and 500 mg/kg. After discontinuation of the treatment, a 9-week recovery test was also conducted. Two cases of death occurred in the 500 mg/kg group. Mydriasis, salivation and lacrimation were seen in the 50 and 500 mg/kg groups. Alopecia, a suppression of body weight gain and an increase in water consumption were seen in the 500 mg/kg group. Food consumption measurement showed no abnormalities attributable to the treatment. Ophthalmologic examination confirmed mydriasis in the 50 and 500 mg/kg groups. Urinalysis showed an increase in urine volume in the 50 and 500 mg/kg groups, and an increase in urinary protein and decreases in Na+, K+ and Cl- excretions in the 500 mg/kg group. Hematological examination showed decreases in hemoglobin, hematocrit, MCV, MCH, MCHC and lymphocytes in the 500 mg/kg group. Blood chemical examination showed increases in total cholesterol, phospholipid and total protein and decreases in glucose, triglyceride, free T3 and T4 in the 500 mg/kg group. Measurements of liver drug-metabolizing enzymes showed an increase in T4UDP-GT activity in the 50 and 500 mg/kg groups, and an increase in cytochrome P-450 in the 500 mg/kg group. Pathological examination disclosed hepatocellular hypertrophy caused by hyperplasia of smooth-ER in the 50 and 500 mg/kg groups, and a decrease in number of glycogen granules in the 500 mg/kg group. Stimulated thyroid follicles were seen in the 50 and 500 mg/kg groups. Increases in incidence and severity of chronic progressive nephropathy were also observed in the 500 mg/kg group. In this dose group, adrenocortical hypertrophy was also observed. The recovery test showed that the above-mentioned changes were satisfactorily reversible. The serum concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups were increased in a dose-dependent manner. No treatment-related effects were seen in the 5 mg/kg group. These results show that the NOAEL (no observed adverse effect level) of NS-21 is 5 mg/kg for 26-week oral toxicity in rats.

Administration, Oral↗
PubMed1996

[Single and 4-week oral toxicity studies of prulifloxacin (NM441) in aged dogs].

Single-dose and repeated dose toxicity studies of prulifloxacin, a new antibacterial agent, were conducted in aged beagle dogs. I. A single-dose toxicity study Prulifloxacin was administered orally to aged female dogs at a single dose of 2500 and 5000 mg/kg. No death occurred in any group. Vomiting was observed in one of two animals at 2500 mg/kg and in both animals at 5000 mg/kg 3-4 hr after dosing. At 5000 mg/kg, vomiting was observed in both animals after feeding on the day after dosing. One animal also showed soft stool. Thereafter, no abnormalities were observed in any animal. No test article related changes were noted in food consumption, water consumption, body weight or pathological examination in any group. The results show that the lethal dose of prulifloxacin is judged to be greater than 5000 mg/kg in aged female dogs. II. A repeated dose toxicity study Aged male and female dogs were given the test article orally for 4 weeks at doses of 0 (control), 20, 100 and 500 mg/kg. No death occurred in any group. At 500 mg/kg, vomiting was observed every day or intermittently throughout the dosing period and salivation was observed almost every day from day 6 to the end of the dosing onward. Decreases or lack of food and water consumption, and decrease of body weight were noted at 500 mg/kg. At 100 mg/kg, slight decreases in food consumption and body weight were noted in the females. No abnormalities were noted in ophthalmoscopic or electrocardio-graphic examination. In urinalysis, decreases in Na+, K+ and Cl- concentrations and the total excretion amount were noted mostly at 500 mg/kg. A low specific gravity was noted in males at 500 mg/kg. In hematology and serum biochemistry, high GPT, BUN and creatinine, and decreases in WBC were noted in both sexes at 500 mg/kg. A high GOT was noted in males, and low Cl- in females at 500 mg/kg. At 100 mg/kg, a high GPT was noted. Rough surface in the kidney and chronic interstitial nephritis (basophilic change of tubule, atrophy of tubule, thickening of tubular basement membrane, interstitial mononuclear cell infiltration, interstitial focal fibrosis) were increased at 500 mg/kg. No toxicological findings were seen in the 20 mg/kg group. The results show that the NOAEL of prulifloxacin is 20 mg/kg for 4-week repeated dose toxicity in aged dogs.

Administration, Oral↗
PubMed1992

A pathological study of bovine alimentary mycosis.

A 10-year study showed that 45 of 692 cattle aged > 6 months had systemic mycosis and, of these, 38 had alimentary mycosis. The percentages of these 38 cattle with lesions in various sites were: rumen (73.7), omasum (71.1), abomasum (34.2), reticulum (21.1), intestine (15.8), omasoabomasal orifice (7.9) and tongue (2.6). Infections in both the forestomachs and abomasum occurred in 31.6 per cent; mucormycosis was found in 94.7 per cent and aspergillosis in 31.6 per cent; 26.3 per cent (10 cattle) had complicated infections with both Mucorales and Aspergillus and eight of these animals had mixed lesions of both mucormycosis and aspergillosis. Macroscopically, focal haemorrhagic necrosis was seen in all 38 cattle. Histologically, thrombosis, coagulative necrosis and hyphae typical of the order Mucorales or of Aspergillus spp. were found. Many of the cattle were also affected by ruminal acidosis-inducing factors (ruminal atony 81.6 per cent, mastitis 63.2 per cent, "downer cow syndrome" 57.9 per cent and parturition 50.0 per cent), which may have predisposed to alimentary mycosis.

Animals↗
PubMed1992

Disseminated mycoses in cattle. A study on nine autopsy cases.

Nine cases affected with disseminated mucormycosis (1.3% of all autopsy cases and 20.0% of systemic mycosis) were found among bovine systemic mycosis examined from 1975 to 1985. The disseminated lesions were found in the lungs (3 cattle), heart (2 cattle), liver (2 cattle), spleen (1 beef cattle), kidneys (1 cattle), central nervous system (1 cattle) and lymph node (1 cattle). Histological examination revealed granulomatous lesions, necrotic foci including infarcts, and thromboangiitis with the hyphae of a member of the Zygomycetes and neutrophil reaction. Granulomatous lesions with asteroid bodies were found in the liver. Metastatic foci were established from the primary lesions found in the alimentary organ (4 from the forestomach or abomasum and 1 from the tongue). One case resulted from uterine mucormycosis, and no primary lesion was found in the other 3 cattle. Complicated infection with respiratory aspergillosis occurred in 4 cases with alimentary mucormycosis. All of the 9 cattle had predisposing disorders. Six cattle had been manifested with prolonged debilitating conditions. Anemia was present in 4, leukopenia in 2 and lymphopenia in 1 cattle.

Animals↗
PubMed1991

Pathological studies on systemic mycoses in calves.

Systemic mycoses were found in 19 (4.7%) of 406 calves less than 6 months old which were autopsied during the past 10 years. Alimentary mycosis occurred in 12 (63.2%) of 19 cases. In alimentary mycosis, mucormycosis showed the highest rate of occurrence (91.7%, 11/12 calves) followed by aspergillosis 41.7% and candidiasis was 9.3%. Mucormycosis and aspergillosis were characterized by focal hemorrhagic necroses with hyphal proliferation and thrombi in the mucosa and muscular layers of the forestomach, abomasum, and small intestine. Candidiasis was characterized by hyperkeratosis with pseudohyphae and microconidia in the mucosa of the omasum. Four of 12 calves (33.3%) had mixed infections of the alimentary tract consisting of Mucorales and Aspergillus species. Pulmonary aspergillosis was found in 10 (52.6%) of 19 calves. There were micro-abscesses with hyphal proliferation or asteroid bodies in the lungs. Infections involving both the alimentary tract and respiratory organs were noted in 3 (10.5%) of 19 calves. Disseminated mycosis was found only in one calf. In alimentary mycosis, administration of antibiotics for the treatment of diarrhea and early weaning were thought to be an important predisposing factor.

Animals↗
PubMed1990

Poxvirus infection in Nile crocodiles (Crocodylus niloticus).

An outbreak was encountered of numerous yellowish cutaneous nodules in one- to two-year-old farmed Nile crocodiles (Crocodylus niloticus) in Kasaba Bay Crocodile Farm at Lake Tanganyika in Zambia during 1988. Out of 4000 crocodiles of different age groups, 300 yearlings were affected and 82 of those affected died. The lesions were prominent on the head, especially around the eyelids, the nostrils, both sides of the mouth, ventral neck, ventral pale belly, limbs and the root of the tail. Histologically, the epidermal lesions revealed large focal areas of marked acanthosis accompanied by hyperkeratosis and parakeratosis. In the prickle cells, there were multiple small neutrophilic granular inclusions and large eosinophilic homogeneous cytoplasmic inclusions. Electron microscopically, there were numerous poxvirus particles and matrices in the cytoplasm of many prickle cells. Dark blue homogeneous cytoplasmic inclusions in toluidine blue sections consisted of an electron opaque matrix with mature viral particles (160 x 200 x 230 nm). Furthermore, there were clumps of granular matrix containing immature viral particles (200 x 399 nm) in the cytoplasm. Various features of viral developing processes were observed.

Alligators and Crocodiles↗
PubMed1988

Ruminant forestomach and abomasal mucormycosis under rumen acidosis.

Spores of Absidia corymbifera were inoculated orally into sheep with ruminal acidosis produced by feeding barley. Lesions, which developed in forestomachs of all four inoculated cases, included desquamation of superficial layers of the mucosae and focal necrosis from lamina propria to muscular layers. Granulomatous lesions were in the submucosa of three sheep. Lesions in the abomasum (two sheep) included focal necrosis, diffuse hemorrhages, and infiltration of neutrophils. All lesions were accompanied by mycotic proliferation. These results show that A. corymbifera can invade forestomach mucosae through degenerate epithelium resulting from ruminal acidosis.

Abomasum↗