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)

In a phase I trial, 28 patients with advanced solid tumors were given PCNU daily for 5 days by iv infusion over 20 minutes at 6-week intervals. The total dose for each course ranged from 25 to 150 mg/m2 in six escalation steps. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater than or equal to 82.5 mg/m2. Leukopenia occurred only at higher doses. Nausea was uncommon, and vomiting did not occur. There were no adverse drug-related effects on renal or hepatic function. No antitumor activity was observed. A dose range of 100-125 mg/m2 iv for each 5-day course (20-25 mg/m2/day) is recommended for phase II studies.
 ...
PMID:Phase I trial of PCNU. 631 29

The effect of chrysotile asbestos exposure on bone marrow and immune parameters was examined in mice at 2, 12, and 26 weeks following a 3-day inhalation exposure. Ultrastructural examination revealed that the fibers were deposited primarily at alveolar duct bifurcations within the centriacinar region of the lung. Histological pulmonary changes were minimal, but by 26 weeks early asbestosis characterized by clusters of macrophages and minimal fibrosis were present in the centriacinar region of the lung. Lymphoproliferative responses, antibody levels, and number of plaque forming cells were not significantly altered in exposed mice. Pulmonary macrophages, but not peritoneal macrophages, showed evidence of activation in the chrysotile-exposed mice at 26 weeks following exposure. The most striking change was the depression of the number of bone marrow pluripotent stem cells (CFU-S) and marrow granulocyte macrophage progenitors (CFU-GM) which were lower at all three postexposure examinations. It is felt that the depression of bone marrow progenitors in asbestos-exposed mice may have relevance to the leukopenia reported in workers with occupational history of asbestos exposure.
 ...
PMID:Bone marrow alterations induced in mice with inhalation of chrysotile asbestos. 632 13

Fifteen patients with inoperable non oat cell lung carcinoma, who had already been treated with telecobalt therapy in the mediastinum-hilar region, were treated with continuing therapy with misonidazole (MISO) and cyclophosphamide (Cy). MISO was administered in single doses of 1000 mg/m2 and 500 mg/m2, orally. Cy was administered in single doses of 500 mg/m2 and 250 mg/m2, i.v. This treatment was given every 4 weeks. All patients (15/15) suffered from hyporexia, nausea and vomiting within 48 hours from administration; furthermore, 2 patients had hemoragic cystitis, 2 had peripheral neurotoxicity, 3 had fever, and 2 had serious nervous depression. Leukopenia occurred in all patients immediately after drug administration, although it was not present in any patient by the time of the next administration. This clinical trial was concluded in December 1981. The follow-up at 18 months shows 7/15 cases of relapse (3 patients dead and 1 patient alive with recurrence, 2 patients dead and 1 patient alive with metastasis without recurrence). Eight of 15 patients are alive with progression of disease from 8 to 18 months.
 ...
PMID:Clinical trials with cyclophosphamide and misonidazole combination for maintaining treatment after radiation therapy of lung carcinoma. 648 Apr 56

We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.
 ...
PMID:[Toxicity of hydroxyquinoline derivatives]. 678 25

One of the serious toxicities of cyclophosphamide chemotherapy is urotoxicity. In addition to causing leukopenia, high-dose cyclophosphamide caused both depression of hepatic microsomal enzyme activities and extensive urinary bladder damage, suggesting that a common biochemical mechanism may be responsible for both of these effects. Administration of 180 or 200 mg cyclophosphamide per kg to Wistar rats caused 41 to 67% decrease in aryl hydrocarbon hydroxylase activity, a 21 to 54% decrease in aminopyrine demethylase activity, and a 34 to 40% decrease in cytochrome P-450 content. This dose of cyclophosphamide also caused hematuria as well as necrosis and edema in the urinary bladder. Administration of N-acetylcysteine or sodium-2-mercaptoethane sulfonate (mesnum) with cyclophosphamide, while not protecting against leukopenia, protected against the enzymatic inactivation and urotoxicity. The biochemical basis of these observations is discussed. The results suggest that a common metabolite of cyclophosphamide, most probably acrolein, is responsible for both of these undesirable effects of cyclophosphamide therapy. Use of combinations including cyclophosphamide and an appropriate thiol may increase the therapeutic index of this drug.
 ...
PMID:Protective role of thiols in cyclophosphamide-induced urotoxicity and depression of hepatic drug metabolism. 680 12

Aminoacid solutions were given to cholecystectomy patients for a period of 48 h starting 24 h after the operation. Infusion of the aminoacid component of parenteral nutrition regimens, without calorie source, frequently led to an acute fall in the serum folate concentration. The degree of depression varied with different commercial aminoacid solutions. (Aminoplex 14 = c.60%, Vamin = 30%, Aminosol = c.0%). The folate depression by Vamin infusion was unaffected by supplementation with L-methione but was alleviated by the addition of glycine. As a consequence of surgical operation itself, folate values fell by 37% during the 24 h following cholecystectomy. This seems likely to increase the risk of haematological toxicity (i.e. acute leukopenia and thrombocytopenia) in patients given folate-free parenteral nutrition after a surgical operation.
 ...
PMID:Aminoacid infusion induced depression of serum folate after cholecystectomy. 681 Apr 50

Cytotoxic drugs provoke teratogenic and mutagenic effects in animals and humans. Particularly at risk is the developing fetus, which in the first trimester of pregnancy undergoes rapid cell division and organogenesis. Systemic antineoplastic chemotherapy given to a pregnant women at this time may involve fetal risk of abortion, death, stunting, malformation, and systemic toxicity. Other adverse effects may include hematopoietic depression, infection secondary to leukopenia or immunosuppression, hemorrhagic phenomena, and hormonal alterations such as adrenal insufficiency. Although chemotherapy should be withheld during the first trimester unless the health and life of the mother are compromised, a review of the literature reveals that fetal malformation is not inevitable. Furthermore, the risk of fetal malformation following chemotherapy in the second and third trimester is minimal. However, investigators caution that fetal damage, including genetic impairment resulting from chemotherapy throughout pregnancy, may ot appear until much later in life. Most investigators agree that women who have recently recovered from or are being treated for a malignancy should not breast-feed their infants.
 ...
PMID:Fetal and neonatal effects of cytotoxic agents. 703 41

Bovine viral diarrhea virus infection of cattle interfered with normal blood clearance mechanisms, as evidenced by the detection of an endogenous bacteremia in up to 85% of infected calves during the first 5 days after infection. The occurrence of detectable bacteremia correlated with the period of leukopenia and depression of lymphocyte responses to mitogens. Noninoculated control animals, reinoculated immune calves, or calves inoculated with infectious bovine rhinotracheitis virus yielded consistently negative cultures. Bacillus spp were isolated in almost all calves. Similar organisms were isolated from the blood of normal calves when medium containing sodium poly-anetholesulfonate was used for culture. It was concluded that bovine viral diarrhea virus infection depressed the normal defense mechanisms, presumably humoral factors or phagocytic function, resulting in uninhibited blood circulation of bacteria during infection.
 ...
PMID:Detection of bacteremia in cattle inoculated with bovine viral diarrhea virus. 725 71

In 3 experiments, 45 castrated male weanling pigs (4 to 6 weeks old) were used to determine the hematologic alterations induced by adriamycin (ADR) given IV at 0.64, 1.6, or 3.2 mg/kg of body weight/week. The effect of selenium-vitamin E (Se-E) supplements on ADR toxicosis was evaluated. Mortality, decreased survival time, growth depression, leukopenia, and anemia were dose related in ADR-treated pigs. At 0.64 mg of ADR/kg/week for 16 weeks, important clinical or hematologic alterations did not develop. At 1.6 mg of ADR/kg/week for 13 weeks, mortality was 100%, mean survival time ws 65.7 days (min-max, 49 to 92 days), and moderate growth depression and marked leukopenia and anemia were present from weeks 7 to 13. At 3.2 mg of ADR/kg/week for 4 weeks, mortality was 100% and mean survival time was 22.0 days (min-max, 18 to 26 days); marked growth depression, leukopenia, and mild anemia developed (week 4). Cytologic study of smears of bone marrow from pigs that died of ADR toxicosis (3.2 mg/kg/week) revealed marked hypoplasia and evidence of decreased production and increased destruction of erythroid and myeloid cells. Beneficial effect of Se-E supplementation against ADR toxicosis was seen only in the pigs given 1.6 mg/kg/week, where prolonged survival and delayed onset of leukopenia and anemia was observed.
 ...
PMID:Effect of selenium-vitamin E on hematologic alterations of adriamycin toxicosis in young pigs. 727 Oct 34

The contribution of cellular and humoral factors of normal blood to resistance to endotoxin was evaluated by selectively transfusing them into beagle dogs prior to IV challenge with a lethal (2.75 mg/kg) dose of Salmonella typhi endotoxin. Supplementation of normal host defenses with 250 ml of plasma containing a heatlabile (56 degrees C for one hour) factor protected the dogs from lethal effects of the toxin. A similar volume of heparinized saline or a lesser volume of plasma (100 ml) was ineffective. The presence of 1 X 10(9) platelets and 7 X 10(10) leukocytes from leukapheresed foxhounds in some transfusion preparations did not affect survival. Protection by treatment with plasma was accompanied by severe tissue injury and loss of circulating platelets and leukocytes. Granulocyte concentrates also afforded protection and decreased tissue injury, as indicated by SGPT and taurine levels. Survivor and nonsurvivor animals experienced an early hyperglycemia as well as elevation of serum glutamic pyruvic transaminase and taurine levels. Thrombocytopenia was great in all experimental groups but was less marked in dogs transfused with cells. Leukopenia was comparable in all groups until six hours after challenge, at which time numbers of circulating leukocytes began a significant return toward normal levels in the cell-transfused group. Impairment of macrophage function was indicated by the depression of the release of colony-stimulating factor in survivor and nonsurvivor animals. Thus, normal plasma alone can protect dogs from endotoxin, but not without a significant amount of injury to the host.
 ...
PMID:Protection of dogs from lethal consequences of endotoxemia with plasma or leukocyte transfusions. 731 23


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