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 chemotherapeutically effective 5:1 combination N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) was investigated to determine any evidence of toxicological potentiation or new toxic signs. It was found that CN 3123 had a very low acute toxicity when administered orally to mice, rats and dogs (oral LD50: mouse greater than 12 000 mg/kg; rat greater than 14 000 mg/kg; dog greater than 1000 mg/kg body weight). The combination was also tolerated by rats and dogs in repeated doses administered over a period of 4 or 26 weeks, that greatly exceeded the therapeutic dose. The only change observed occurred in the thyroid, which in all doses administered exhibited a dose-related increase in weight accompanied by histological changes indicating an activation of thyroid function and a hypersecretion of basophilic thyrotropic cells in the anterior lobe of the pituitary. Six weeks after discontinuation of treatment this condition showed a tendency to reversibility or had already returned to normal. In dogs there was a dose-related increase in iodine uptake by the thyroid and a decrease in serum thyroxine over a period of 6 months under the highest dosage of CN 3123 administered. Whereas the thyroid changes observed under the combination could be reproduced with sulfamoxole, no effect on thyroid weight was observed in rats and dogs in the subacute toxicity phase of a comparative investigation with trimethoprim. Moreover, trimethoprim did not increase the effect of sulfamoxole on the thyroid gland. The effect of sulfamoxole on the thyroid is discussed in detail with a review of the literature. It can be characterized as species-specific for sulfonamides in mice, rats, rabbits and dogs but not in monkeys or in man and appears to be caused by the inhibition of the organic binding of iodine in the thyroid, whereby the predisposing factors must vary considerably from species to species. The thyroid hypertrophy observed is due to the activation of the regulatory cycle via the anterior lobe of the pituitary. The following systemic changes occurred after 600 mg CN 3123/kg, a lethal-toxic dosage and the highest administered in the study: reduced body weight, decreased food consumption leading to cachexia, slightly increased SGPT and alkaline phosphatase, slight thrombocyte depression, enlargement and increased fatty degeneration of the liver, occurrence of necrotic areas in the liver, hemosiderin accumulation in Kupffer's cells, and an increase of reticular cells in the spleen. The acute toxicity of CN 3123 and all major functional and histological changes under repeated administration were due exclusively to sulfamoxole. The combination sulfamoxole/trimethoprim gives no indication of toxicological potentiation or new toxic signs.
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PMID:[Toxicological investigations of the combination sulfamoxole/trimethoprim, a new broad-spectrum chemotherapeutic (author's transl)]. 94 24

The effect of 10 days of total fasting (energy deprivation) on blood polymorphonuclear granulocyte functions, leukocyte numbers, iron and transferrin levels was evaluated in 14 healthy, normal-weight males. Granulocytes from 7 of the subjects were tested in vitro. A statistically significant depression was noted in their bactericidal capacity against Staph. aureus. The 14 subjects showed a marked decrease in the stainable activity of granulocyte alkaline phosphatase and decreases were noted in plasma iron and serum transferrin levels. The iron saturation of serum transferrin was unchanged. Thus, impairment of granulocyte bactericidal functions may occur secondarily to short-term total energy deprivation, in the absence of iron deficiency.
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PMID:Fasting (acute energy deprivation) in man: effect on polymorphonuclear granulocyte functions, plasma iron and serum transferrin. 96 52

Feeding sodium deoxycholate orally to rats for four days caused depression of the activity of the small intestinal enzymes lactase, sucrase, maltase, alkaline phosphatase, and N-acetyl-beta-glucosaminidase. The first four are brush border enzymes, the last a lysosomal enzyme. Alkaline phosphatase activity recovered very rapidly and rebounded to above the normal level within 24 hours. The activity of the three disaccharidases returned to normal within seven days while no recovery was observed within 96 hours of the activity of the lysosomal enzyme, N-acetyl-beta-glucosaminidase, after removing the bile salt from the diet.
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PMID:Deoxycholate depresses small-intestinal enzyme activity. 114 Jun 27

Intestinal disaccharidase activities were determined in 294 jejunal biopsies obtained from 254 children with various disorders of the small bowel, and alkaline phosphatase activity was measured in 251 biopsies. In normal mucosa a broad range of enzyme activity was found corresponding with the data in the literature. A primary disaccharidase deficiency was observed in 5 children with congenital sucrase-isomaltase deficiency and in a 12-year-old Egyptian boy with acquired lactase deficiency. A secondary generalized depression of disaccharidase activity and a diminution of alkaline phosphatase activity existed chiefly in patients who had severe or moderate mucosal damage, also in active coeliac disease and during gluten loading, in protracted diarrhoea of infancy, chronic malabsorption of unknown origin and agammaglobulinemia. During remissions enzyme activities recovered together with mucosal improvement. Low levels of enzyme activities were also seen in some cases of protracted diarrhoea of infancy and chronic malabsorption of unknown origin although only mild mucosal lesions were demonstrated.
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PMID:[Intestinal disaccharidase and alkaline phosphatase activities of jejunal biopsies in small bowel diseases of children (author's transl)]. 127 85

A study of 35 (5 x 7) male, individually housed, albino rats (initial average weight = 50 g) was undertaken to examine the effect of an addition of microbial phytase to a diet containing phytate on the availability of zinc. The rats were fed a semisynthetic diet based of egg white and cornstarch over a 3-week period. All diets were supplemented with 20 mg Zn/kg. Group I (control) was fed the basal diet free of phytic acid (PA) and phytase. By replacing cornstarch by Na-phytate (0.5% in group II and 1.0% group III), molar phytate: Zn ratios of 25 and 50:1 were obtained, respectively. In groups IV (0.5% PA) and V (1.0% PA) 1000 U of microbial phytase were added. A molar phytate:Zn ratio of 25 (group II) and 50:1 (group III) resulted in a dose-dependent depression of growth and feed efficiency ratio. These negative effects of the addition of PA could be completely counteracted by the supplementation of 1,000 U of phytase in group IV and partially so in group V. Similarly, the apparent absorption and retention of Zn, Zn-concentration in femur and testes and different Zn-status-parameters in plasma (Zn-concentration, percent unsaturated plasma-Zn binding capacity, activity of alkaline phosphatase) were improved by adding 1,000 U microbial phytase/kg diet. The present study shows that an addition of microbial phytase to phytate-rich diets considerably improves the availability of Zn in growing rats.
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PMID:[The effect of a supplement of microbial phytase on zinc availability]. 133 30

Clinical and epidemiologic examinations of 260 workers engaged in enzyme production revealed the structure of skin disease incidence: mycoses--31%, atopic dermatitis--19%, contact dermatitis--9%, allergic, dermatitis--5%. The majority of these skin diseases were associated with hyperphosphatemia and monoaminoxidase (MAO) depression. Changes of alkaline phosphatase and MAO activities, serum albumins and gamma-globulins may be considered as sensitive markers of disease.
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PMID:[Changes in the serum enzymo- and proteinograms of workers in enzyme production suffering from skin diseases (the validation of the diagnosis and of the therapeutic-preventive measures)]. 142 48

Glutathione (GSH) homeostasis and turnover were investigated in totally hepatectomized (HX) rats. A technique is described to remove the liver totally, with preservation of the hepatic portal and vena caval vasculature. Euglycemia could be maintained with hourly infusions of 50 mg 100 g-1 b.m. of glucose after bolus i.v. injection of glucose at the same dose. The efficiency of the animal model was demonstrated by examination of paraclinical blood parameters: progressive increases in total plasma bilirubin and alkaline phosphatase activity were noted after HX; the other parameters tested were predominantly in the normal range during the observation period of 6 hours. Histological examination revealed an acute but reversible impairment of intestine and kidneys. These results indicate that the surgical procedure and postoperative care were able to secure sufficient physiological conditions for the experiments over a longer period. 3 to 6 hours after HX we observed a decreased but stable plasma GSH level in anhepatic rats (about 50% of the control value). The GSH levels of brain and kidney were not changed. With increasing time period after HX the heart and lung GSH levels were depressed. A small depression of muscle GSH concentration was observed 4 and 6 hours after HX. A progressive increase in the concentration of oxidized glutathione was seen in brain and kidney. Our observations could be indicative for a high GSH export capacity of extrahepatic tissues contributing about 50% of the total GSH influx into circulation. Probably, the skeletal musculature is an important GSH origin for plasma.
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PMID:Glutathione homeostasis and turnover in the totally hepatectomized rat: evidence for a high glutathione export capacity of extrahepatic tissues. 144 65

During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.
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PMID:Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study. 153 21

Brown Hisex chicks were fed diets containing 2% and 5% Azadirachta indica leaf from their 7th to 35th day of age. Thereafter, the chicks were fed control diet for 2 weeks. A depression in body weight gain and efficiency of feed utilization was observed in chicks fed A. indica leaf when compared with the control. The main clinicopathological changes were increases in lactic dehydrogenase, glutamic oxaloacetic transaminase and alkaline phosphatase activities and uric acid and bilirubin concentrations and decreases in the total protein levels in serum. Changes in the values of erythrocyte count, haemoglobin concentration, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin were remarkable and associated with yellow discoloration on the legs and combs and hepatonephropathy. Tissue recovery was incomplete 2 weeks after removal from the experimental diets.
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PMID:On the toxicology of Azadirachta indica leaves. 804 48

6-Phosphofructo-2-kinase (PFK-2) was analyzed in four organs of the anoxia-tolerant marine gastropod mollusk Busycon canaliculatum. Whelk PFK-2 resembled the nonhepatic enzyme from mammals with highest activity occurring in gill (22 pmol.min-1.g-1). Hepatopancreas PFK-2 was purified over 8,000-fold to a final specific activity of 11 mU/mg protein (at 20 degrees C) and gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was a dimer with a native molecular mass of 142 kDa and a subunit molecular mass of 67 kDa. The purified enzyme showed negligible fructose-2,6-bisphosphatase (FBPase-2) activity, although the activity ratio of PFK-2 to FBPase-2 was 0.625 in crude extracts. In response to environmental anoxia, the activity of PFK-2 dropped in all organs to 34-56% of the corresponding aerobic value (half-time was 2 h in gill), and the Michaelis constant for fructose 6-phosphate increased by 50% (to 92 microM in gill). These changes paralleled decreases in organ fructose 2,6-bisphosphate concentration and pyruvate kinase activity and contribute to the overall glycolytic rate depression induced by anoxia in this facultative anaerobe. In vitro treatment of the anoxic form of hepatopancreas PFK-2 with alkaline phosphatase increased enzyme activity, suggesting that the aerobic and anoxic enzyme forms are interconverted by reversible protein phosphorylation. However, the protein kinase involved in this process is not yet known; incubation of aerobic PFK-2 with Mg-ATP plus adenosine 3',5'-cyclic monophosphate-dependent protein kinase or protein kinase C did not alter enzyme activity.
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PMID:Inactivation of 6-phosphofructo-2-kinase during anaerobiosis in the marine whelk Busycon canaliculatum. 164


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