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)

ASTA Z 7557 is a stabilized cytostatic metabolite of cyclophosphamide which forms crystals at room temperature and releases 4-OH-cyclophosphamide in aqueous solution. The LD50/30 in mice after push injection is 417 mg/kg, after fractionated administration (q 6 hours X 4) 794 mg/kg. Daily treatment times 5 gives a LD50/30 value of 200 mg/kg. Depression of nucleated bone marrow cells and of leukocytes in the peripheral blood is observed after treatment. Recovery is slow. This holds true for push and fractionated administration. ASTA Z 7557 is a powerful cytostatic drug for treatment of an Ehrlich ascites tumor, a Lewis lung and a mammary carcinoma. Of two human tumor xenografts a malignant amelanotic melanoma responded with slight growth delay, whereas a gastric cancer did not.
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PMID:Preclinical evaluation of toxicity and therapeutic efficacy of a stabilized cytostatic metabolite of cyclophosphamide (ASTA Z 7557, INN mafosfamide). 646 14

The present study examined the role of cell-mediated immunity (CMI) in the production of experimental autoimmune glomerulonephritis (EAG) in chickens deficient in humorally mediated immunity (HMI). Cyclophosphamide bursectomized (Bsx) and normal control chickens were used. Bsx chickens were used only if they had severe depression of HMI, which was evidenced by marked reduction in bursal weights (0.89 +/- 0.23 vs. 2.92 +/- 0.9 g), decreased serum IgG to less than or equal to 10% of normal, and total lack of HMI to immunization with sheep red blood cells. EAG was produced by immunizing chickens with bovine glomerular basement membrane (GBM) in complete Freund's adjuvant. CMI manifested by wattle thickness increments to PPD was not different, 3.89 +/- 0.45 mm for Bsx compared with 3.73 +/- 0.75 mm for controls. No circulating antibodies to GBM developed in 68% of Bsx chickens, and the anti-GBM titers were less than 1:312 in those Bsx chickens positive for antibody compared with greater than 2,000 for controls. GBM deposits of IgG by fluorescence were much decreased, 0.53 +/- 0.16 compared with 2.19 +/- 0.32 for controls, and were absent in 64% of Bsx chickens. Nonetheless, proliferative nephritis with crescents was present and was even more severe in Bsx chickens than in controls, with glomerular sizes of 20.8 +/- 0.6 U for Bsx-GBM, 19.8 +/- 1.2 for control-GBM, 14.9 +/- 1.5 for Bsx, and 13.6 +/- 0.8 for normal chickens. Nephritic eluates did not produce disease in normal chickens, while administration of sensitized cells with [H3]thymidine to naive birds was associated with increased mesangial grain counts by autoradiography. These findings suggest that CMI plays a major role in the pathogenesis of EAG in chickens in the absence of HMI. By implication, CMI may be crucial in the development of other types of glomerulonephritis as well.
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PMID:New avian model of experimental glomerulonephritis consistent with mediation by cellular immunity. Nonhumorally mediated glomerulonephritis in chickens. 658 68

Central nervous system regulation of endocrine functions is mediated by neurotransmitters, via hypothalamic hypophysiotropic factors which in turn control anterior pituitary functions. The evidence of serotonergic-endocrine interrelations with regard to adrenal, thyroid, gonadal and prolactin functions is fast accumulating. Our study extends the importance of those interrelations to some functions of the immune system. Multiple administration of 5-hydroxytryptamine(serotonin) or its precursor, 5-hydroxy-L-tryptophan(5-HTPH), produces marked depression of T cell dependent, humoral, hemolytic, primary immune response in mice. L-tryptophan, a more distant serotonin precursor, produces slight but significant depression of this immune response. Multiple treatment of mice infected with Friend Leukemia Virus (FLV) with serotonin or 5-HTPH alone or in combination with cyclophosphamide (Cytoxan) results in significant delay of the clinical progression of the infection. L-tryptophan produces a modest but significant improvement. Administration of serotonin or 5-HTPH causes a marked reduction of the thymus weight. It is reasonable to postulate that the described effects result from the thymus involution which affects the T cell compartment of the immune system. This is the consequence of hormonal imbalance caused by the alteration of the serotonin biosynthetic pathway in the brain. The adrenal cortex is not implicated in the mediation of this effect. Since many clinically used drugs affect the serotonin metabolism, the clinical consequences of the resulting alteration of the immunological responsiveness should be considered.
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PMID:Serotonin and its precursors as modulators of the immunological responsiveness in mice. 696 31

Immunocompetent cell functions were evaluated in spontaneously hypertensive rats (SHR). Hematological studies revealed decreased absolute numbers of lymphocytes and increases number of polynucleic cells in the peripheral blood of SHR. The SHR had a reduced number of immature T lymphocytes in their thymuses in comparison with an original strain of Wistar rats, as detected by the rosette formation test with guinea pig erythrocytes. The antibody response to sheep red blood cells (SRBC) of the 3-month-old SHR was profoundly depressed and was about one-teeth that of the Wistar rats. Cell cooperation experiments suggest that the T lymphocytes of the SHR were selectively impaired in antibody responses to SRBC in cooperation with B lymphocytes. B lymphocytes from the bone marrow of the SHR were not affected and produced normal numbers of plaque-forming units. Cyclophosphamide treatment, which selectively depletes suppressor T lymphocytes, did not enhance the delayed-type hypersensitivity response to SRBC in SHR. This may rule out the possibility of the involvement of the suppressor mechanism in the T cell depression of the SHR.
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PMID:Characterization of immunological depression in spontaneously hypertensive rats. 697 79

The cardiac effects of chemotherapeutic regimens using high doses of cyclophosphamide (180 mg/kg over four days) were assessed in 32 patients with hematologic malignant neoplasms. Left ventricular systolic function, determined by the fractional shortening on echocardiogram, declined substantially five to 16 days after the initiation of cyclophosphamide therapy. Although pericardial effusion on echocardiogram occurred in 33% of the patients studied, ECG voltage decreased five to 14 days after beginning cyclophosphamide therapy even in those patients without pericardial effusion. Congestive heart failure was noted in nine patients (28%) within three weeks of cyclophosphamide administration. Six of these patients (19%) died of myocardial failure. Pericardial tamponade occurred in six patients (19%), including five who died of myocardial failure. Histopathologic and electron microscopic findings showed endothelial injury and a hemorrhagic myopericarditis. Cyclophosphamide in this high dose is associated with a toxic, often fatal, pericardiomyopathy. Depression of ECG voltage and systolic left ventricular function, though common, do not necessarily predict clinical cardiac deterioration.
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PMID:Cardiotoxicity associated with high-dose cyclophosphamide therapy. 723 84

After radical mastectomy and postoperative radiotherapy 56 patients with loco-regional breast cancer and positive lymph nodes and/or tumor size over 2 cm in diameter were treated by a "mild" adjuvant chemotherapy: Cyclophosphamide 150 mg p.o./day + Methotrexate 7,5 mg on three consecutive days p.o./week. The study was started on July 1st 1975, duration of treatment was planned for two years/patient. At the time of evaluation (May 1st 1979) 21 pre- and 35 postmenopausal patients were under study. 7 patients (12,5%) recurred within 6-36 months after the beginning of chemotherapy. Two women died after 20 resp. 36 months. Median time of treatment was 19 months. Chemotherapy caused very mild toxicity and was well tolerated. Patients under adjuvant chemotherapy developed only a transitory depression of B- and T-cells as well as mitogen-induced lymphocyte stimulation whereas patients under polychemotherapy showed a marked depression of these immunological markers.
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PMID:[Adjuvant chemotherapy in breast neoplasms. Clinical and immunologic results]. 738 Mar 77

Adult male mice were stereotaxically implanted with permanent indwelling guide cannulae for bilateral injections into the nucleus accumbens (ACB). The effects on spontaneous locomotor activity of selective agonists for adenosine receptor subtypes were examined following bilateral injections into the ACB. Intra-ACB injections of CGS 21680, a potent and selective agonist at striatal adenosine A2a receptors, elicited pronounced, dose-related reductions in locomotor activity whereas similar bilateral dosages of CPA, a selective agonist at adenosine A1 receptors, did not significantly affect locomotor activity. The pronounced locomotor depression elicited by intra-ACB injections of CGS 21680 were completely blocked by I.P. pretreatment with DMPX, an adenosine receptor antagonist exhibiting selectivity for striatal A2 receptors, at a dosage which alone had no significant effect on locomotor activity. Adenosine A2a receptors in the nucleus accumbens may selectively modulate dopamine-mediated mesolimbic behavioral circuits involved in spontaneous locomotion.
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PMID:Role of adenosine A2a receptors in the nucleus accumbens. 807 88

5'-Ester derivatives of the potent adenosine agonists N6-[4-[[[[4-[[[(2-acetylaminoethyl)amino]carbonyl]methyl] anilino]carbonyl]methyl]phenyl]adenosine (N-AcADAC; 1) and N6-cyclopentyladenosine (CPA; 2) were prepared as prodrugs. Both alkyl esters or carbonates (designed to enter the brain by virtue of increased lipophilicity) and 1,4-dihydro-1-methyl-3-[(pyridinylcarbonyl)oxy]esters designed to concentrate in the brain by virtue of a redox delivery system were synthesized. In the 5'-blocked form, the adenosine agonists displayed highly diminished affinity for rat brain A1-adenosine receptors in binding assays. The dihydropyridine prodrug 29 was active in an assay of locomotor depression in mice, in which adenosine agonists are highly depressant. The behavior depression was not reversible by peripheral administration of a non-central nervous system active adenosine antagonist. In an assay of the peripheral action of adenosine (i.e., the inhibition of lipolysis in rats), the parent compounds were highly potent and the dihydropyridine prodrug was much less potent.
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PMID:Adenosine receptor prodrugs: synthesis and biological activity of derivatives of potent, A1-selective agonists. 813 9

Carboxymethylglucan (CMG) in two different degrees of substitution of carboxymethyl groups (0.56 and 0.89) was administered to cyclophosphamide (CY) treated (200 mg/kg) C57B1/6 mice in three doses (10, 50, and 100 mg/kg) 24 h after CY. The influence of CMG administration on the cell suppression caused by CY was observed in the subsequent days. The cellularity of spleen, bone marrow and peripheral blood was quantified on days 2, 5, 8, 11, 15, and 21 after CY treatment. CY treated mice developed a significant decrease in peripheral blood cell counts, and spleen and bone marrow cellularity during the initial 5 days, followed by recovery in the next 15 days, with an overshoot reaction in spleen cellularity and erythrocyte levels. The initial cellularity depression and the following recovery was modified by both carboxymethyl derivatives of glucan. Cyclophosphamide treated mice exhibited less pronounced immunosuppression and more rapid hematopoietic recovery when administered with CMG, although this reaction was only of a modest degree. The effects were not dose dependent and the differences between the two glucans were not significant.
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PMID:The effect of two glucan carboxymethyl derivatives with various substitution degrees on cyclophosphamide immunosuppression in mice. 834 50

The effects on locomotor activity (LA) of selective agonists for adenosine receptor subtypes were examined in mice following bilateral injections into the nucleus accumbens (ACB). The ACB is not only richly innervated by dopaminergic (DA) terminals but also exhibits the highest densities of adenosine A2a receptors in the brain. CGS 21680 (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosi ne), a potent and highly selective adenosine A2a receptor agonist, elicited pronounced, dose-related reductions in LA (ID50 dosage = 0.0031 nmol/mouse). NECA (5'-N-ethylcarboxamidoadenosine), a mixed adenosine receptor agonist which exhibits high selectivity and potency at striatal A2a receptors, similarly elicited dose-related reductions in LA (ID50 dosage = 0.0023 nmol/mouse). In contrast, intra-ACB injections of CPA (N6-cyclopentyladenosine), a highly selective agonist for adenosine A1 receptors, did not exert any significant effects on LA, even at 2.0 nmol/mouse, a dosage at which both CGS 21680 and NECA depressed LA by almost 90% compared to vehicle controls. Further, the pronounced locomotor depression elicited by intra-ACB injections of both CGS 21680 and NECA, at approximately the ID65 dosage, was significantly antagonized by IP pretreatment with DMPX, (3,7-dimethyl-1-propargylxanthine), an adenosine receptor antagonist with selectivity for A2 receptors in the striatum, at a dosage (0.15 micromol/mouse) [corrected] which alone had no significant effect on LA. These observations provide support for the notion that adenosine may selectively modulate DA-mediated mesolimbic behavioral circuits via agonist actions at a population of A2a receptors densely concentrated in the ventral striatum.
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PMID:Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression. 849 Jul 38


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