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

Arotinoids, which are analogs of retinoic acid (RA) and retinol (RO) with the carbon skeleton in a rigid conformation, have more favorable therapeutic indices relative to all-trans-RA and all-trans-RO. The purpose of this investigation was to obtain preliminary in vivo toxicity data on SMR-2(analog of RO) and SMR-6 (analog of RA), arotinoids with promising activity (ED50's of 20 X 10(-11) and 5 X 10(-11) M, respectively; ED50 of RA = 1 X 10(-11) M) for reversal of keratinization in tracheal organ culture. A preliminary toxicity study was conducted in male B6D2F1 mice with gavage of retinoids in corn oil (0.01, 0.05, and 0.1 mg/kg/day of SMR-2 or SMR-6; 1, 5, and 10 mg/kg/day of RA as reference control). Due to lack of toxicity, each dose level for SMR-2 and SMR-6 was increased by 4-fold on Day 29 of dosing. The study was terminated on Day 57. Hypervitaminosis A (weight loss, alopecia, skin scaling, and bone thinning) was induced in the mid- and high-dose SMR groups; weight-gain depression was predominant in the high-dose RA group. The SMR compounds were approximately 100-fold more toxic, based on weight loss, than RA. In the SMR dose groups with hypervitaminosis A, white blood cell counts were elevated 2- to 4-fold; and there were microscopic lesions in skin, testes, epididymis, bone, thymus, bone marrow, peripheral lymph nodes, spleen, stomach, adrenal, and pituitary. The leukocytosis was attributed to leukopoiesis in spleen and bone marrow, which may be due to either a direct effect and/or a secondary response to a subacute inflammatory reaction in skin. Only peripheral lymph node hyperplasia was observed in SMR-2 and RA low-dose groups. Enlarged thymus, lymph node hyperplasia, leukopoiesis in spleen and bone marrow, elevated alkaline phosphatase with bone hypertrophy, and testicular degeneration were observed in the mid-dose RA group. The results indicate that immune stimulation may be a primary early response to retinoids and that skin, leukopoietic tissues, reproductive organs, stomach, and bone are primary targets for retinoid toxicity.
 ...
PMID:Preliminary toxicity profile of arotinoids SMR-2 and SMR-6 in male B6D2F1 mice. 360 38

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.
 ...
PMID:Clinical and immunological evaluation of 20 patients with advanced colorectal cancer treated with high dose recombinant leukocyte interferon-alpha A (rIFN alpha A). 363 19

The synergistic hepatotoxicity of dietary disulfiram (DSF) with 1,2-dichloroethane (DCE) subchronically administered by inhalation at three concentration levels (150, 300, and 450 ppm) was studied. The criteria for hepatotoxicity were treatment-related increases in serum activities of sorbitol dehydrogenase, 5'-nucleotidase, and alkaline phosphatase, and in liver-to-body weight ratios. DSF alone did not elicit these responses while DCE at the highest concentration level increased liver-to-body weight ratios and the activity of 5'-nucleotidase. Exposure to DSF alone decreased cytochrome P450 levels, but in combination with DCE, the decrement of cytochrome P450 was additive in a DCE concentration-dependent manner. However, depression of cytochrome P450 by DCE alone was not concentration dependent. Although DSF and DSF/DCE combination increased the activity of glutathione S-transferases (GSTs), both DSF and DCE singly and in combination increased the tissue levels of reduced glutathione (GSH). Evidence is presented showing that the potentiation of the hepatotoxicity of DCE observed in the presence of DSF may be due to an inhibition of microsomal mixed-function oxidase-mediated metabolism of DCE and to a compensatory increase in DCE metabolism to reactive metabolites generated by GST-mediated conjugation of DCE with GSH.
 ...
PMID:Interaction between 1,2-dichloroethane and tetraethylthiuram disulfide (disulfiram). II. Hepatotoxic manifestations with possible mechanism of action. 378 26

The clinical, pathomorphological and serological features of acute canine leptospirosis are evaluated and the IgM- and IgG-specific ELISA for leptospirosis serology in dogs is assessed. The clinical syndrome of acute canine leptospirosis was characterized by depression, anorexia, vomiting and often haemorrhagic diarrhoea. In addition, jaundice, uraemia, elevated creatinine and alkaline phosphatase were observed in the majority of the dogs. In pups invagination of the intestines was a noteworthy finding. The clinical signs and the post-mortem findings were rather non-specific so that the clinical and post-mortem diagnosis had to be confirmed serologically. In acute clinical cases of canine leptospirosis a high anti-leptospiral IgM titre, ranging from 160 in pups to 10240 in adults, was always present, whereas the anti-leptospiral IgG titre and the agglutination titre usually were negative or low. Dogs died from leptospirosis in spite of a high anti-leptospiral IgM titre. Only two dogs having, at the first examination, a high IgM titre in conjunction with a high IgG titre survived an acute infection. The possible role of IgM and IgG in the pathogenesis of an acute leptospiral infection is discussed. Different serological patterns in reference dogs, which were not suffering from acute leptospirosis, are presented.
 ...
PMID:Clinical, pathological and serological features of spontaneous canine leptospirosis. An evaluation of the IgM- and IgG-specific ELISA. 379 34

The subacute toxic effects of cyclopiazonic acid (CPA; given orally) were characterized in the dog (CPA was purified from cultures of Aspergillus flavus). Four groups of dogs were given CPA in gelatin capsules for 90 days at the following dosage levels: 0.05, 0.25, 0.5, and 1.0 mg/kg of body weight; a 5th group was used as controls. All dogs administered the 0.5 and 1.0 mg of CPA/kg dosages and 1 dog given the 0.25 mg of CPA/kg dosage died or were humanely killed before the scheduled termination of the study. Clinical signs of intoxication appeared 2 to 44 days after dosing was started and consisted of anorexia and, in 1 to 2 days, vomiting, diarrhea, pyrexia, dehydration, weight loss, and CNS depression. Grossly, the entire alimentary tract had diffuse hyperemia with focal areas of hemorrhage and ulceration. Other lesions were renal infarcts, necrotizing epididymitis, and ulcerative dermatitis. Microscopic lesions included ulceration, necrosis, vasculitis, lymphoid necrosis, karyomegaly in several organs, and decreased mitotic activity in intestinal crypt epithelium. Ulcerative and necrotic lesions were usually associated with vascular lesions. Clinical pathologic changes were leukocytosis, neutrophilia, lymphopenia, monocytosis, and increased serum alkaline phosphatase activity.
 ...
PMID:Cyclopiazonic acid mycotoxicosis in the dog. 392 55

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.
 ...
PMID:Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs. 395 18

Rocky Mountain spotted fever (RMSF) or ehrlichiosis was diagnosed in dogs on the basis of specific immunofluorescent testing for each disease. Comparisons between clinical and laboratory findings were made between the 2 diseases. The incidence of RMSF tended to be more seasonal and it affected younger dogs. Purebred dogs appeared to be more susceptible to both diseases. In general, RMSF had a more rapid and severe course of clinical illness than did ehrlichiosis, but acute ehrlichiosis was difficult to differentiate from RMSF. Both diseases were characterized by fever, depression, lymphadenopathy, and signs of neurologic dysfunction; petechial hemorrhages or other signs of hemorrhagic diathesis were evident only in a small proportion of cases. Anemia, leukopenia, and thrombocytopenia were more common in dogs with ehrlichiosis, whereas those with RMSF more often had leukocytosis and thrombocytopenia. Hypoalbuminemia was found in dogs with both diseases, but those with ehrlichiosis usually had concurrent hyperglobulinemia. High serum alkaline phosphatase activity and serum cholesterol concentration, and low serum calcium concentration were more common in dogs with RMSF than with ehrlichiosis. Rising serum titers or positive direct immunofluorescence for Rickettsia rickettsii in skin biopsy specimens were used to confirm RMSF, whereas a single serum titer for Ehrlichia canis enabled detection of ehrlichiosis. In the absence of neurologic deficits and when dogs were treated with tetracycline, dogs with RMSF made a more rapid and consistent recovery than did dogs with ehrlichiosis.
 ...
PMID:Rocky Mountain spotted fever in dogs and its differentiation from canine ehrlichiosis. 397 6

Thirteen patients with painful Paget's disease of bone were treated as outpatients with low doses of synthetic salmon calcitonin 22.5-50 mug three times weekly. Treatment produced full remission of pain in a mean time of 5.5 weeks and a mean depression of serum alkaline phosphatase activity of 33%.The interval before symptomatic relief could not be predicted from the variables studied. The ultimate fall in serum alkaline phosphatase activity, however, could be predicted from the initial levels and from the early rate of decrease (P < 0.001). Biochemical resistance to treatment, which occurred in three cases, could be related to the dose and duration of treatment.Prolonged remissions of pain may occur which are not related to biochemical remission, to the dose of calcitonin, or to the duration of treatment. The side effects attributable to salmon calcitonin were transient nausea (in nine patients), transient flushing (in four), diarrhoea (in two), and rash (in one) though in only one patient did treatment have to be withdrawn prematurely because of these effects.
 ...
PMID:Treatment of Paget's disease of bone with synthetic salmon calcitonin. 447 16

The observation that patients with extensive small bowel resection have impaired hepatocellular function with reduced BSP clearance and fatty change in biopsies from the liver led to a systematic study of liver structure and function following proximal and distal small bowel resection in the rat. While anaesthesia and surgery impaired BSP clearance per se, small bowel resection further reduced BSP clearance with impairment of both uptake and excretion phases of BSP excretion. The increased BSP retention was more marked after distal than after proximal small bowel resection, but in both experimental groups the abnormalities of BSP excretion spontaneously returned to normal three to four weeks after surgery. Circulating liver enzymes were normal but serum alkaline phosphatase was significantly depressed, particularly after distal resection. Isoenzyme studies showed that the depression of serum AP was due to a reduced intestinal isoenzyme. While serum levels remained consistently depressed up to eight weeks after proximal resection, in parallel with mucosal regeneration, serum AP returned to normal two to four weeks after ileectomy. While these minor changes in hepatic structure and function would normally be of little clinical importance, the additional insult of hepatic dysfunction may well be important in malnourished patients after extensive small bowel resection.
 ...
PMID:Liver structure and function following small bowel resection. 471 9

There was a significant depression of the activities of intestinal lactase, invertase, and alkaline phosphatase in rats given drinking water containing 2.5 mg of colchicine per 100 ml. Activities of intestinal maltase, aspartate transcarbamylase, and dihydroorotase were not affected by the drug. Injection of colchicine (1 mg/kg) caused depression of intestinal invertase activity within 8 hr. Investigation of the effect of colchicine on the disaccharides in vitro demonstrated that invertase and maltase were not affected by concentrations up to 125 mg/100 ml. Intestinal lactase was inhibited by concentrations exceeding 5 mg/100 ml. Calculation of the concentration of colchicine present in the intestine, after a single injection, indicated that the in vivo effect of colchicine was not due to simple enzyme inhibition. Histological examination showed an increase in crypt cells but no decrease in the length of the villi. Cellular migration along the villi, as well as activity of uridine kinase in intestinal mucosa, was increased in colchicine-treated rats. It was concluded that colchicine did not depress intestinal invertase, lactase, and alkaline phosphatase by decreasing cellular renewal, but rather it exerted its effect directly on the differentiated cells of the villus.
 ...
PMID:Effect of colchicine on intestinal disaccharidases: correlation with biochemical aspects of cellular renewal. 541 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>