Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The progression of effects induced by administration of ochratoxin A were characterized in young male broiler chickens (Hubbard x Hubbard). The experimental design consisted of four dietary treatments of ochratoxin A (0, 1.0, 2.0, and 4.0 micrograms ochratoxin A/g feed) and 11 replicates of 10 broilers/replicate. Broilers were housed in electrically heated batteries with feed and water available ad libitum. Broilers were weighed, bled, killed by cervical dislocation, and necropsied at 3, 6, 9, 12, 15, 18, and 21 days of age. Toxicity of ochratoxin A to broilers was evident as early as 6 days of age, when significant (P less than .05) growth depression occurred at 4.0 micrograms dietary ochratoxin A/g feed. Dietary ochratoxin A significantly increased the relative weights of the liver, kidney, spleen, pancreas, and gizzard. Anemia, characterized by a significant decrease in packed-cell volume and hemoglobin levels, was present during ochratoxicosis. Hepatotoxicity of dietary ochratoxin A was evident through an observed significant reduction in serum levels of total protein, albumin, globulin, cholesterol, triglyceride, and blood urea nitrogen, and a significant increase in the serum activities of gamma glutamyl transferase and cholinesterase. A significant increase in serum uric acid and creatinine levels was indicative of nephrotoxicity. These data provide a description of the progression of ochratoxicosis in broilers that should be useful in diagnosis and in improved understanding of ochratoxicosis.
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PMID:Progression of ochratoxicosis in broiler chickens. 290 99

In previous structure-activity studies, we have demonstrated that attachment of a glucose molecule to the chloroethylnitrosourea cytotoxic group produces a compound with reduced murine bone marrow toxicity and retention of full antitumor activity. To further define this protective role conferred by the glucose moiety in bone marrow cells, we have replaced the nitrosourea cytotoxic group with another class of alkylating agent, a bifunctional nitrogen mustard. In a detailed structure-activity analysis, we have now characterized four analogues, with the mustard cytotoxic group positioned at carbon 2 [1,3,4,6-tetra-O-acetyl-2-(di-2-chloroethyl)amino-2-deoxy-D-glucopyranos e (TGM)], carbon 6, or carbon 1 (D- and L-isomers) of the aminoglucose molecule. On a molar basis, TGM was most toxic to normal BALB/c X DBA/2 F1 mice, with a 10% lethal dose (LD10) of 3.8 mumol/kg. The D- and L-isomers of 2,3,4,6-tetra-O-acetyl-N,N-bis(2-chloroethyl)glucopyranosylamine (C-1) were the least toxic, with an LD10 of 73 mumol/kg for both. Optimal antitumor activity against the murine P388 leukemia (single i.p. administration of the LD10) did not differ significantly among the four analogues, with increased life span ranging from 83-86%. P388 antitumor activity for nitrogen mustard (HN2) was significantly less, 60% increased life span (P = 0.01), while p-di(2-chloroethyl)amino-L-phenylalanine produced an increased life span of greater than 101%. An LD10 of 6-bis-(2-chloroethyl) amino-6-deoxy-D-glucose (C-6) or TGM produced significantly less depression of WBC counts than did an equitoxic dose of the C-1 isomers, HN2, or p-di(2-chloroethyl)amino-L-phenylalanine. The mean nadir WBC count for C-6 equaled 86% of control, and for TGM, 80% of control. Consistent with this sparing effect on the peripheral WBC, C-6 and TGM produced significantly less in vivo murine bone marrow DNA synthesis depression, 77 and 64% of control, respectively, as compared to the depression nadir produced by HN2 (27% of control), the D-isomer of C-1 (17%), the L-isomer of C-1 (18%), and p-di(2-chloroethyl)amino-L-phenylalanine (2%). These structure-activity studies demonstrate that conjugation of the mustard cytotoxic group to carbon 6 or carbon 2 of glucose produces an analogue that retains P388 antitumor activity significantly greater than that of HN2, with a concomitant reduction in murine bone marrow toxicity.
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PMID:Antitumor activity and bone marrow toxicity of aminoglucose mustard anticancer agents in mice. 293 28

1. Ten Friesian male calves of about 100 kg and 3 months old were reared similarly and were worm-free. From 13 weeks of age five calves received a dose of 640 infective larvae (L3) of lungworms (Dictyocaulus viviparus) twice weekly for 8 weeks to simulate continuous infection. Animals not infected were fed to the same level as the infected animals (about 1.2-1.3 kg concentrates and 1.4-1.5 kg good-quality hay/d). 2. Heat production was measured twice weekly during 48 h (days 2 and 3, and days 5 and 6) in each group of experimental animals. 3. Infection caused considerable damage to the lungs, increased respiration frequency and clearly produced antibody titres against D. viviparus. 4. Animals infected with lungworms had on average a lower rate of weight gain, reduced by 70 g/d per animal. Digestibility was not affected. Nitrogen retention was much lower in infected animals (12.0 v. 14.6 g/d per animal in controls). 5. Metabolizability of energy was slightly reduced in infected animals. Heat production as found in infected animals may be associated with an increased maintenance energy requirement of 30 kJ/kg live weight 0.75 per d or reduced partial efficiency of feed conversion above maintenance in animals infected with lungworms (58.5 v. 64.1% in the control animals). 6. It was concluded that the depression in rate of gain was related to reduced intake of feed and to decreased N retention.
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PMID:Effect of infection with lungworms (Dictyocaulus viviparus) on energy and nitrogen metabolism in growing calves. 296 Mar 73

A syndrome of metabolic acidosis of unknown etiology was diagnosed in twelve beef calves 7 to 31 days old. Principal clinical signs were unconsciousness or depression concomitant with weakness and ataxia. Other signs included weak or absent suckle and menace reflexes, succussable nontympanic fluid sounds in the anterior abdomen, and a slow, deep thoracic and abdominal pattern of respiration. The variation in clinical signs between calves was highly correlated (r = 0.87, P less than 0.001) with their acid-base (base deficit) status. Abnormal laboratory findings included reduced venous blood pH, pCO2 and bicarbonate ion concentration as well as hyperchloremia, elevated blood urea nitrogen, increased anion gap and neutrophilic leukocytosis with a left shift. Sodium bicarbonate solution administered intravenously effectively raised blood pH and improved demeanor, ambulation and appetite. All calves did well following a return to a normal acid-base status.
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PMID:Further studies on the clinical features and clinicopathological findings of a syndrome of metabolic acidosis with minimal dehydration in neonatal calves. 302 95

Nutritional modulation is one approach to successful aging. In animals, dietary restriction increases life span. Alterations in the macronutrient and micronutrient constituent of the diet can modulate gene expression. Anorexia is common in elderly persons. The results of studies in animals suggest that aging is associated with a decrease in the opioid feeding drive and an increase in the satiating effect of cholecystokinin. Unrecognized depression is a common, treatable cause of anorexia and weight loss in elderly persons. Protein synthesis decreases in elderly persons; nevertheless, nitrogen balance can be maintained in patients with fairly low intakes of protein. Carbohydrate intolerance is common and may be modulated by nutritional intervention and physical activity. The role of cholesterol in the development of heart disease in very old persons is controversial. Homebound and institutionalized elderly persons often do not expose their skin to sunlight; because the skin of older persons has a decreased ability to form vitamin D, the vitamin D status in these persons is precarious and they are at risk for osteopenia. Vitamins are often abused by elderly persons. Drug administration alters the vitamin requirements of persons. Borderline zinc state has been associated with deteriorating immune function, especially in persons who have diabetes mellitus or who abuse alcohol. Zinc administration appears to protect against the deteriorating vision associated with age-related macular degeneration. Selenium deficiency seems to be associated with an increased prevalence of cancer.
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PMID:Nutrition in the elderly. 305 65

The human carcinogen and nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic to Salmonella and, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels greater than 2.5 micrograms/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in corn oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoeisis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays.
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PMID:Mutagenicity to bacteria, cultured cells, and rodents of the human carcinogen chlornaphazine. 305 19

The clinical course of 24 patients with insulin-requiring diabetes mellitus who had received total parenteral nutrition (TPN) was retrospectively analyzed. Routine nutritional assessment disclosed significant depression of anthropometric indices and secretory protein levels in patients with chronic renal failure complicating juvenile onset diabetes mellitus (JODM). Biochemical complications including hypo- or hyperglycemia were significantly more frequent (p less than 0.001) in JODM than in maturity-onset diabetes and found to a lesser degree in patients with renal failure. The catheter infection rate was substantially higher (17%) than usually encountered in TPN therapy. Positive nitrogen balance was achieved in the majority of patients with an average 84% and 92% of estimated protein and caloric requirements being provided. Close monitoring and a protocol of infusion plus supplemental subcutaneous regular insulin was useful in providing adequate TPN safely to these high-risk patients.
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PMID:Total parenteral nutrition in patients with insulin-requiring diabetes mellitus. 308 5

The relationship between circulating thyroid hormones and nutritional status was studied in sarcoma-bearing inbred C57BL/6J mice and control mice. Supplementation with exogenous thyroxine (T4) was also evaluated. Tumor-bearing animals had depressed levels of circulating thyroid hormones. This was also found in food-restricted (pair-fed and pair-weighed) controls. Plasma levels of thyroid hormones decreased with increased tumor burden. Thyrotropin-releasing hormone caused an increased response of thyroid-stimulating hormone in tumor-bearing animals. Low levels of thyroid hormones in sarcoma-bearing mice were due to depressed hormone production by the thyroid gland rather than to increased clearance rate of hormones. Plasma levels of triiodothyronine (T3) correlated to the amount of whole-body nitrogen among sarcoma-bearing mice and food-restricted controls. Exogenous T4 increased food intake by 20% in sarcoma-bearing mice. The benefit of this was probably counteracted by an increased metabolic rate, since reversal of plasma levels of T3 and free T4 had no net effect on body composition of freely eating sarcoma-bearing mice, although it had a negative effect on body and muscle composition in food-restricted controls. Exogenous T4 did not stimulate tumor growth. The results indicate that low circulating levels of thyroid hormones in experimental cancer cachexia are probably caused by the reduced food intake (anorexia), which is in agreement with findings in clinical cancer. Depression of thyroid hormones is probably a physiological means to reduce energy expenditure and to preserve substrates in progressive cancer disease.
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PMID:Thyroid hormones and experimental cancer cachexia. 309 Mar 41

This study tested the hypothesis that the increased glucose requirement of lactation had effects that were independent of the suckling-dependent inhibition of postpartum endocrine function in beef cows. Mature Hereford cows were either suckled ad libitum and infused with saline iv (n = 9) from d 2 through 4 (d 0 = jugular catherization on d 32 +/- 3 postpartum); were nonsuckled and infused with saline from d 2 through 4 (n = 10); or were nonsuckled and infused with phlorizin (3 g/d) from d 2 through 4 (n = 10). Nonsuckled cows infused with phlorizin had lower (P less than .05) plasma concentrations of glucose and amino acid nitrogen (AAN) on d 2 compared with pre-infusion levels (d 1), but their metabolic profile returned to levels similar to the suckled cows by d 3 and 4. Nonsuckled cows infused with saline had elevated glucose and insulin and lower AAN and free fatty acids (FFA) on d 3 and 4 compared with pre-weaning (d 1) levels (P less than .05). Nonsuckled cows infused with phlorizin did not show this weaning-induced elevation in glucose and insulin. The number of luteinizing hormone (LH) pulses was not affected by treatment. However, in contrast to the large LH pulses observed in the nonsuckled cows infused with saline, both the suckled cows and the nonsuckled cows treated with phlorizin had more small and fewer large amplitude pulses (P less than .01). Treatment did not affect serum concentrations of follicle stimulating hormone, gonadotropin release in response to gonadotropin releasing hormone (25 micrograms) or the number of cows ovulating by 55 d after calving. We conclude that the increased glucose clearance caused by phlorizin infusion or lactation results in depression of LH pulse amplitude in suckled postpartum beef cows.
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PMID:Hypoglycemia alters pulsatile luteinizing hormone secretion in the postpartum beef cow. 310 70

We studied RO 15-1788, a new benzodiazepine receptor antagonist, [ethyl 8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1, 5a) (1, 4) benzodiazepine-3-carboxylate] to determine its effects in a murine model of hemorrhagic shock. Hemorrhaged rats treated with RO 15-1788 maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values compared to rats receiving only the vehicle (final MABP 114 +/- 4 vs 82 +/- 4 mmHg, p less than 0.001). Moreover, RO 15-1788 decreased the release of the lysosomal hydrolase, cathepsin D (p less than 0.02) into the circulation and blunted the plasma accumulation of free amino-nitrogen groups (p less than 0.01). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in RO 15-1788 treated rats subjected to hemorrhagic shock than in those given the vehicle (18 +/- 2 vs 42 +/- 4 U/ml, p less than 0.01). Additionally, in vitro analysis indicated that RO 15-1788 antagonizes PAF induced coronary vasoconstriction and cardiac depression observed in perfused rat hearts, as well as inhibiting PAF induced platelet aggregation in cat platelet rich plasma. Our results suggest that antagonism of PAF actions can contribute significantly to the beneficial effects of RO 15-1788 in hemorrhagic shock.
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PMID:Beneficial actions of RO 15-1788, a benzodiazepine receptor antagonist, in hemorrhagic shock. 311 57


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