Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013911 (emaciation)
 1,059 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxicosis was induced in pregnant Holstein-Friesian heifers by giving polybrominated biphenyls a in gelatin capsules at the rate of 25 g/day. Initially, this dosage was approximately 67 mg/kg of body weight. Clinical signs were anorexia, excessive lacrimation and salivation, diarrhea, emaciation, dehydration, depression, and abortion. Fever was not evident during the experiment. Values for serum glutamic-oxalacetic transaminase, lactic dehydrogenase, blood urea nitrogen, and bilirubin were increased. Changes in packed cell volume, hemoglobin content, total erythrocyte and leukocyte counts, and differential leukocyte counts were minimal and reflected dehydration and secondary infection. The principal urine changes were decreased specific gravity and moderate proteinuria. Gross necropsy findings included dehydration; subcutaneous emphysema and hemorrhage; atrophy of the thymus; fetal death with concomitant necrosis of cotyledons; kidneys that were enlarged, pale tan to gray; thickened wall of the gallbladder; inspissated bile; edema of abomasal folds; mucoid enteritis; linear hemorrhage and edema of the rectal mucosa; and secondary pneumonia. Microscopic changes were most marked in the kidneys, gallbladder, and eyelid. In the kidney, the principal changes were extreme dilatation of collecting ducts and convoluted tubules, with epithelial degenerative changes of cloudy swelling, hydropic degeneration, and separation from the basement membrane. Common changes in the gallbladder were moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria. The changes in the eyelids were characterized by hyperkeratosis, with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands. Clinical signs and lesions of toxicosis did not develop in heifers given the polybrominated biphenyls at the rate of 0.25 mg and 250 mg/day for 60 days. Initially these rates were approximately 0.00065 mg/kg and 0.65 mg/kg of body weight, respectively.
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PMID:Pathology of experimentally induced polybrominated biphenyl toxicosis in pregnant heifers. 18 92

A three-month oral subacute toxicity study of mofezolac (N-22), a non-steroidal anti-inflammatory agent, was performed using dose levels of 6, 20, 60 and 200 mg/kg in rats, and recovery was also assessed one month after withdrawal. 1. Toxic signs caused by N-22 administration, observed only in the 200 mg/kg group, were as follows: soiling around the mouth and/or nose, piloerection, anemia, diarrhea, emaciation and decreased spontaneous locomotor activity. Nine males and thirteen females in the 200 mg/kg group excreted bloody diarrhea and died of general exhaustion between weeks four and thirteen of study. 2. In the 200 mg/kg group, decrease in food consumption and suppression of body weight gain were noted in males from about week four and in females from about week six after initiation of administration, and increase in water consumption was noted in males from about week seven. 3. Urinary examination revealed a decline in urinary pH in males of the 20 mg/kg and above groups and elevation of urobilinogen levels in males of the 60 and 200 mg/kg groups. 4. Hematological examination showed decreases in erythrocyte count (RBC), hematocrit value (Ht) and hemoglobin concentration (Hb) and increase in reticulocyte rate in both sexes of the 200 mg/kg group and an increase in neutrophil rate in males of the 200 mg/kg group. 5. Biochemical examination demonstrated a decrease in chloride (Cl-) in males receiving the 20 mg/kg or above doses and a decrease in calcium (Ca++) in males of the 60 and 200 mg/kg groups. Moreover, there were decreases in cholinesterase (ChE) activity, total protein (TP) and albumin (Alb) values, as well as increases in blood urea nitrogen (BUN), uric acid (UA) and potassium (K+) in both sexes of the 200 mg/kg group, along with elevations in GOT and lactate dehydrogenase (LDH) activities in females of the 200 mg/kg group. 6. The absolute and/or relative organ weights for liver, kidneys, spleen and adrenals were increased in the 200 mg/kg group. 7. On pathological examination, perforating ulceration in the jejunum and ileum, turbid ascites, adhesion and inflammatory changes in capsules of the abdominal organs, splenomegaly, mesenteric lymph node hyperplasia and inflammatory changes in the thoracic cavity were observed in dead animals of the 200 mg/kg group. Similar pathological changes were observed in a few survival cases of the 200 mg/kg group. 8. After a one month recovery period, the above-mentioned changes had mostly recovered, indicating that they were reversible.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Three-month oral subacute toxicity study of mofezolac (N-22) in rats]. 223 86

A 28-day oral dosage test of miporamicin (MPM), a new macrolide antibiotic, was performed to assess its toxicologic potential in groups of male and female rats receiving the compound in feed. Five graded dosage levels of 0, 3,200, 8,000, 20,000, and 50,000 ppm were employed for treatment with MPM in feed and the treatment period was followed by a 28-day recovery phase observation period. 1. No deaths occurred throughout the course of the experiment. Animals receiving 50,000 ppm developed signs: ruffled hair coat and emaciation, which disappeared following withdrawal of the drug. 2. The MPM-50,000 group displayed depression of weight gain and decrease of feed and water intake during the treatment period. During the posttreatment recovery phase observation period the animals showed recovery in weight gain rate as well as in feed and water intake. 3. The achieved compound dosage was 273 mg/kg/day in males and 288 mg/kg/day in females in the MPM-3,200 group, 721 and 773 mg/kg/day respectively in the MPM-8,000 group, 1,738 and 1,856 mg/kg/day in the MPM-20,000 group, and 3,405 and 3,611 mg/kg/day in the MPM-50,000 group. 4. Hematological examinations revealed low values for RBC, WBC, hematocrit and hemoglobin concentration and decreased platelet counts in the MPM-50,000 group, which were considered to be due to the decreased feed intake. These changes disappeared or abated following withdrawal. 5. Of various serum biochemical parameters assessed, total protein, albumin, glucose and triglycerides showed lowered values in the MPM-50,000 group. All these changes were considered to be attributable to the decreased feed intake. During the ensuing recovery phase observation period, all these parameters showed restoration or abatement in parallel with the recovery in feed intake. 6. Urine analysis disclosed decrease of urine volume, lowered electrolyte concentration and elevation of urine osmolarity in the MPM-20,000 and the MPM-50,000 groups. These changes were considered to be secondary to cecal enlargement which is commonly seen with antibiotic medication, or to the decreased feed and water intake. Following drug withdrawal, all these changes disappeared with the recovery in feed and water intake and abatement of cecal hyperplasia. 7. At terminal necropsy, diminution of body fat and atrophy of the spleen and thymus that correlated with emaciation were noted in the MPM-50,000 group. Dose-related enlargement of the caecum was also noted in the treated groups. All these changes disappeared or abated following withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Subacute toxicity study of miporamicin in rats by twenty-eight-day administration in feed]. 262 84

Subacute toxicity of captopril by daily oral administration at dose levels of 10 mg/kg, 30 mg/kg, 100 mg/kg, 300 mg/kg, 900 mg/kg and 2700 mg/kg for one month was studied in Sprague-Dawley rats. In the 2700 mg/kg group, 13 of 18 males and 17 of 18 females died with marked emaciation and abdominal distension. In the 900 mg/kg group, 1 of 18 males and 3 of 18 females died also during the administration period. In dead animals, a marked dilatation of gastrointestinal tract was noted showing multiple hemorrhagic erosions and/or ulcers in the glandular stomach. The remainder of these groups exhibited polydipsia and polyuria during the dosage period. In the 300 mg/kg and 100 mg/kg groups, all animals survived throughout the entire experimental period showing polydipsia and polyuria. In the 30 mg/kg and 10 mg/kg groups, all animals survived also throughout the entire dosage period without showing any toxic sign. Regarding plasma analysis, the BUN and creatinine concentration was significantly elevated in the group of 100 mg/kg or more. In the hematological examination, there was a decrease of erythrocyte counts, hemoglobin contents and hematocrit values in the group of 300 mg/kg or more. Pathological examinations revealed a marked thickening of the wall in afferent arterioles and interlobular arteries of the kidney in association with hypertrophy and hyperplasia of juxtaglomerular cells in 100 mg/kg, 300 mg/kg, 900 mg/kg and 2700 mg/kg groups. In these groups, multiple hemorrhagic erosions with or without ulcer were also noted in the glandular stomach. In the spleen, a slight increase of extramedullary hematopoiesis and hemosiderosis was noted in the 100 mg/kg, 300 mg/kg, 900 mg/kg and 2700 mg/kg groups, in which an increase of erythropoietic elements was also noted in the bone marrow. From these results, the maximum nontoxic dose was estimated as about 30 mg/kg/day by oral administration of captopril in the rats.
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PMID:[One month studies on the subacute toxicity of captopril in rats]. 627 83

Paratuberculosis in sheep usually is manifested as emaciation and decreased wool production. Diarrhea occurred in only 18% of affected animals. Significant hematologic changes included decreased RBC count, hemoglobin level and hematocrit. Necropsy revealed pallor, cachexia and serous fluid in body cavities. Staining of intestinal mucosal scrapings and mesenteric lymph node impression smears for acid-fast organisms revealed bright-red clumps of Mycobacterium paratuberculosis bacilli. Fecal examination identified 70% of affected animals, intradermal injection of johnin 60%, and avian tuberculin 39%.
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PMID:Diagnosis of paratuberculosis in sheep. 672 47

Subacute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP) was studied in rats. HBP was percutaneously given to rats with 0.1% and 0.5% creame (0.1% HBP-C, 0.5% HBP-C) and ointment (0.1% HBP-O, 0.5% HBP-O) at the daily dose level of 150 mg per 100 g body weight for 1 month. Rats receiving HBP-C and HBP-O showed some dose-dependent symptoms such as the suppression of body weight gain, emaciation, decrease in the number of white blood cells, hemoglobin, hematocrit, and serum total cholesterol level, regressive changes in adrenals, skin, lymphatic and hematopoietic tissues, which are known as toxic effects of synthetic corticosteroids. These symptoms were comparatively high toxic in male rats and in cream groups, and almost disappeared in rats elapsed recovery time of 1 month after withdrawal of HBP.
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PMID:[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -3. Subacute toxicity in rats by percutaneous administration (author's transl)]. 731 Sep 33

Chronic toxicity of a new synthetic corticosteroid, hydrocortisone 17-butyrate 21-propionate (HBP), was investigated in rats of both sexes. HBP was percutaneously given to rats with 0.1%, 0.5% cream and ointment at the daily dose level of 150 mg per 100 g body weight for 6 months. For the comparison, the percutaneous toxicity with 0.12% betamethasone 17-valerate (BV) cream and ointment, and 0.1% hydrocortisone 17-butyrate (HB) cream and ointment at the daily dose level of 150 mg per 100 g body weight were studied. Rats receiving HBP showed the dose-dependent changes such as the suppression of body weight gain and food intake, emaciation, decrease in the number of white blood cells and lymphocytes, total protein, increase in the number of red cells, hematocrit, hemoglobin, blood sugar and total cholesterol, regressive changes in adrenal cortex, lymphatic and hematopoietic tissues and skin, and gastric erosion, which have been well known as toxic effects of synthetic corticosteroids. These findings were comparatively high toxic in male, and almost disappeared in rats elapsed recovery time of month after withdrawal of HBP. The toxicities of HBP, BV and HB were qualitatively same. However, the grade of effects of HBP toxicity was similar to that of HB, weaker than of BV.
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PMID:[Studies of toxicity of hydrocortisone 17-butyrate 21-propionate -5. Chronic toxicity in rats by percutaneous administration (author's transl)]. 731 Sep 35

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, a 13-week oral repeated dose toxicity study and a recovery study using male and female rats was conducted. Doses of S-1 were adjusted to deliver 1.5, 5, and 15 mg/kg/day as doses of FT, and FT was given at 15 mg/kg/day. The following results were obtained. 1. In clinical observation, edema of the limbs and face or swelling of the auricle of the ear and an anemic appearance were observed in both sexes in the 15 mg/kg/day group as dose of FT. Subsequently, males in this group developed severe anemia, decreased spontaneous motor activity, emaciation, and subnormal skin temperature, and many males died. In the survivors, keratosis of the palm, sole, or tail was observed, with necrosis and loss of the tail tip in the severe cases. 2. Body weight gain was suppressed from about week 2 of treatment in both sexes in the 15 mg/kg/day group as dose of FT, and there was almost no weight gain after week 4-5. Food consumption was consistently less than the control value for males in the 15 mg/kg/day group as dose of FT throughout the treatment period. 3. No marked changes were observed in water intake and on opthalmologic examination. 4. In the fecal test for occult blood, a positive tendency was observed in both sexes in the 15 mg/kg/day group as dose of FT. 5. Urinalysis disclosed a slight increase in protein and decrease in sodium, potassium, and chloride in males, and an increase in protein in females in the 15 mg/kg/day group as dose of FT. 6. Hematologically, both sexes in the 15 mg/kg/day group as dose of FT showed decreases in red blood cell count, hemoglobin, and hematocrit, and increases in platelet count and fibrinogen, with a slight decrease in white blood cell count in males. 7. In the blood biochemical test, abnormal findings included increases in total cholesterol and free cholesterol, and decreases in non-esterified fatty acid and albumin in both sexes in the 15 mg/kg/day group as dose of FT. 8. In organ weight measurement, abnormal changes included a decrease in thymus weight in both sexes in the 5 mg/kg/day or higher dosage groups and a decrease in the testis weight in males and an increase in the liver weight in females in the 15 mg/kg/day group as dose of FT. 9. Histopathologically, both sexes in the 15 mg/kg/day group as dose of FT showed a decrease in the red pulp of the bone marrow, atrophy of the thymus, white pulp of the spleen, and testes. degeneration of the renal tubules, and ulcerative changes of the skin or oral mucosa. 10. The findings were unremarkable in the FT group. 11. During the recovery study, all the toxic effects tended to reverse. 12. The NOAEL of S-1 was estimated to be 1.5 mg/kg/day as dose of FT for both sexes.
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PMID:[A 13-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in rats]. 902 59

Oral single-dose and 13-week repeat-dose toxicity studies of (+/-)-4-ethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride (RCC-36), an active metabolite 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, were conducted in male and female Sprague-Dawley rats. In the single-dose toxicity study, rats were given the drug at doses of 0 (control), 400, 600, 900, 1350 and 2030 mg/kg. In the 13-week repeat-dose toxicity study, rats were given the drug for 13 weeks at doses of 0 (control), 3, 30 and 300 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. In the single-dose toxicity study, death occurred in the 600 mg/kg group and over, and LD50 values were 735 mg/kg in both sexes. The major clinical signs observed following the administration of this drug were mydriasis, salivation, decreased spontaneous locomotor activity, ataxic gait, lacrimation and urorrhea in the 400 mg/kg group and over, hypopnea and soft feces in the 600 mg/kg group and over. In addition, prone or lateral position and tonic or clonic convulsion were observed in the dead animals. Rats showed a decrease in body weight or a suppression of its weight gain in the 400 mg/kg group and over. Macroscopic findings in the dead animals were congestion in lung and retention of foamy mucinous fluid in trachea. The animals alive showed no abnormalities attributable to the treatment. In the 13-week repeat-dose toxicity study, 13 cases of death occurred in the 300 mg/kg group. Main pathological findings in these cases were congestion and edema in lung. Mydriasis was seen in the 30 mg/kg group and over. Lacrimation, salivation, wheezing, emaciation [corrected] wasting and unkempt fur were seen in the 300 mg/kg. A suppression of body weight gain and a decrease in food consumption were observed in the 300 mg/kg group. An increase in water consumption was seen in the 30 and 300 mg/kg groups. Ophthalmologic examination confirmed the mydriasis in the 30 mg/kg group and over. Urinalysis showed an increase in urine volume and a decrease in Na+ excretion in the 30 and 300 mg/kg groups and decreases in K+ and Cl- excretions in the 300 mg/kg group. Hematological examination showed decreases in hemoglobin, hematocrit, MCV and MCH, and an increase in MCHC in the 300 mg/kg group. Blood chemical examination showed decreases in triglyceride and glucose, and an increase in total protein in the 300 mg/kg group. Pathological examination disclosed hepatocellular hypertrophy associated with hyperplasia of smooth-ER, a decrease in number of glycogen granules and an increase in number of lipofuscin in the 300 mg/kg group. Stimulated thyroid follicles were seen in the 300 mg/kg/group. In kidney, an increase in number of hyaline droplets in the proximal tubular epithelium, in which lysosomes and dense bodies were increased, was observed in the 300 mg/kg group. Dense bodies were increased also in the glomerular epithelium. In this dose group, adrenocortical hypertrophy was also observed. The recovery test showed that the above-mentioned changes were satisfactorily reversible or the degree and frequency of these changes were lowered. No treatment-related effects were seen in the 3 mg/kg group. These results show that the NOAEL (no observed adverse effect level) of RCC-36 is 3 mg/kg for 13-week oral toxicity in rats.
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PMID:[Oral single-dose and 13-week repeat-dose toxicity studies of RCC-36, the active metabolite 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]. 917 Jun 4

Signalment, clinical signs, and physical examination and clinicopathologic findings in dogs diagnosed with Hepatozoon canis parasitemia (n = 100) were compared with those in Hepatozoon-negative dogs (n = 180). A subset (n = 15) of Hepatozoon-positive dogs with unusually high (> 800 H canis gametocytes/microL of whole blood) parasitemia was compared with dogs that had low parasitemia (n = 85) and with Hepatozoon-negative dogs (n = 180). Hepatozoon-positive dogs significantly differed from Hepatozoon-negative dogs in body temperature, total red blood cell count, hemoglobin concentration, hematocrit, and platelet count. Dogs with high H canis parasitemia significantly differed from those with low parasitemia in hemoglobin concentration, hematocrit, and total neutrophil count. Clinical findings from dogs with high H canis parasitemia included emaciation, lethargy, hyperglobulinemia, hypoalbuminemia, and increased serum alkaline phosphatase and creatine kinase activities. Findings at necropsy included hepatitis, pneumonia, and glomerulonephritis associated with H canis schizonts and extensive parasitism of bone marrow, spleen, and lymph nodes. Low hemoglobin concentration, low platelet count, and concurrent parvovirus infection together represented the best predictor variables for Hepatozoon positivity in dogs presenting to the hospital.
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PMID:Retrospective case-control study of hepatozoonosis in dogs in Israel. 947 Jan 63


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