Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protective effects of Asparagus racemosus (AR) and Tinospora cordifolia (TC) against myelosuppression induced by single doses of cyclophosphamide (CP) have been previously reported. Presented here are the results of a comparative study between AR, TC, glucan and lithium carbonate against the myelosuppressive effects of single and multiple doses of cyclophosphamide in mice. Cyclophosphamide was administered as a single dose 200 mg/kg subcutaneously to one group of mice, while a second group received 3 doses of 30 mg/kg intraperitoneally. Both groups received AR, TC and lithium orally for 15 days before CP. Glucan was administered intravenously in 3 doses, before cyclophosphamide in the first group and together with cyclophosphamide in the second group. In both groups peripheral and differential WBC counts were done before and after drug treatment and serially after cyclophosphamide injection. All four drugs produced leucocytosis with neutrophilia. When compared to control group, all 4 drugs prevented, to varying degrees, leucopenia produced by cyclophosphamide. We conclude, therefore, that both indigenous plants, AR and TC, are potent immunostimulants, with effects comparable to lithium and glucan. They need further evaluation in patients receiving cytotoxic drugs.
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PMID:Comparative study of immunomodulating activity of Indian medicinal plants, lithium carbonate and glucan. 323 38

Suppression of hematopoiesis is far too often the main consequence of antineoplastic therapy, such that the developing degree of myelosuppression and/or thrombocytopenia are usually the rate-limiting steps to adjuvant therapy. This communication reports the results of studies designed to investigate the capability of lithium to accelerate in vivo hematopoietic recovery following exposure to vinblastine sulfate (VB). Male mice (144 BC3F1) received VB (4 mg/kg/b.w.) i.v. Twenty-four h following VB, 72 mice received 35 micrograms m/animal, ultra-pure lithium carbonate (Li2CO3) i.p. Another 72 mice received either VB or phosphate buffered saline as controls. Beginning 24 h later and continuing on days 2, 5, 7, 9, 12, 21 and 28, three mice from each group were randomly sacrificed and their hematological parameters analyzed. Bone marrow and splenic granulocyte-macrophage progenitor cells (CFU-gm) and megakaryocyte progenitor cells (CFU-meg) content were evaluated. Lithium was unable to prevent the onset of either neutropenia or thrombocytopenia; however, lithium was successful in restoring normal white blood cell and platelet values earlier than the VB control group, thus significantly reducing the period of drug-induced neutropenia and thrombocytopenia. This lithium-enhanced hematopoiesis was measured by an accelerated recovery in both marrow and splenic CFU-gm and CFU-meg compared to controls. These data demonstrate the efficacy of lithium to accelerate hematopoietic recovery following exposure to cytotoxic antineoplastic drugs.
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PMID:Lithium and hematopoietic toxicity. II. Acceleration in vivo of murine hematopoietic progenitor cells (CFU-gm and CFU-meg) following treatment with vinblastine sulfate. 357 50

Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis-platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P less than 0.01, less than 0.01, less than 0.05 respectively) and the interval between treatments was shorter (P less than 0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy-induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug-induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapy-induced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.
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PMID:The effect of lithium carbonate on chemotherapy-induced neutropenia and thrombocytopenia. 642 95

A group of 51 patients treated surgically for ovarian carcinoma was randomly subdivided to test the efficacy of lithium carbonate in the prevention of leucopenia during systemic chemotherapy. In 26 patients receiving sequential lithium carbonate the side effect of myelosuppression was mitigated and the leucocyte count during treatment, which determines the dosage of the cytostatic drugs, was significantly higher in this group. It was, thus, possible to reduce the number of cytostatic courses of treatment in the lithium group in comparison with the treatment courses in the 25 control patients. Lithium therapy had to be discontinued due to side effects in seven patients, which were then excluded from the trial.
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PMID:[Lithium carbonate--a preventive agent against leukopenia during cytostatic therapy]. 644 51

Lithium is an agent capable of influencing many aspects of blood cell production, in particular, the formation of granulocytes. Because of this property, lithium has been demonstrated to be an effective agent whenever granulocyte production is either faulty or inadequate. The anti-viral drug zidovudine (AZT) has used been extensively in the treatment of acquired immune deficiency syndrome (AIDS). However, its effectiveness is limited because of the myelosuppression and bone marrow toxicity associated with its use. We have previously demonstrated that lithium, when combined with AZT in vitro with normal bone marrow cells or when administered in vivo to mice receiving dose-escalation AZT, reduced the myelosuppression and marrow toxicity of AZT significantly. We report here further studies designed to evaluate the extent of lithium's capacity to modulate AZT toxicity by investigating the ability of lithium to influence blood cell production when administered to normal mice during an initial exposure to AZT. C57BL6 were administered dose-escalation AZT (1.0 mg/ml and 2.5 mg/ml) for a period of 4-weeks in the presence or absence of lithium carbonate (1 mM). This was followed by an additional 4-week period during which mice received only AZT. Animals were analyzed on a weekly basis for their peripheral blood indices. Animals receiving dose-escalation AZT demonstrated anemia, thrombocytopenia, and neutropenia which was dose-related. During the period when animals received combination lithium/AZT, there was significantly less anemia, thrombocytopenia, and neutropenia as compared to the AZT controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lithium and anti-viral drug toxicity: II. Further studies on the ability of lithium to modulate the hematopoietic toxicity associated with the anti-viral drug zidovudine (AZT). 758 37

The drug zidovudine (AZT), a synthetic thymidine analogue, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, and overall bone marrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoiesis such as the induction of neutrophilia, thrombopoiesis, and protection against suppression of hematopoietic progenitor stem cells following exposure to anti-cancer drugs and/or radiation at doses commonly used in the treatment of malignant disease. We report here the result of studies designed to evaluate the effectiveness of lithium in reversing zidovudine-induced haematopoietic suppression when administered to normal mice in vivo in the presence of dose-escalation zidovudine. Lithium carbonate (Li2CO3) reversed zidovudine toxicity as measured by increases in peripheral WBC, platelets, and CFU-GM and CFU-Meg haematopoietic progenitors; however lithium was insufficient in reversing the reduction of erythropoiesis associated with zidovudine use in vivo. These results further confirm the effective use of lithium to reverse the development of myelosuppression and thrombocytopenia associated with the anti-viral drug zidovudine, but is less effective in ameliorating the induction of anaemia.
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PMID:Modulation of the haematopoietic toxicity associated with zidovudine in vivo with lithium carbonate. 845 Feb 94

Ion-trapping theory predicts that alkalinization of tumor extracellular pH will enhance the anti-tumor activity of weak-base chemotherapeutics. We have previously demonstrated that chronic and acute treatment of tumor-bearing mice with sodium bicarbonate results in tumor-specific alkalinization of extracellular pH. Furthermore, bicarbonate pretreatment enhances the anti-tumor activity of doxorubicin and mitoxantrone in two different mouse tumor models. Previous work has indicated subtle, yet significant differences between the pH sensitivities of the biodistribution and anti-tumor efficacies of doxorubicin and mitoxantrone in vitro. The present study demonstrates that systemic alkalinization selectively enhances tumor uptake of radiolabeled mitoxantrone, but not doxorubicin. Results using these two drugs are quantitatively and qualitatively very different, and can be explained on the basis of differences in the octanol-water partition coefficients of their charged forms. These results suggest that inducing metabolic alkalosis in patients would have a positive effect on response to mitoxantrone therapy. However, the therapeutic index would not increase if sodium bicarbonate also caused increased retention of mitoxantrone in susceptible normal tissues in the host. The major dose-limiting organ systems for mitoxantrone are heart, liver, bone marrow, spleen and blood cells. Bicarbonate was found to have no significant effect on the distribution of mitoxantrone to any of these tissues except for spleen. However, neither spleen weights nor lymphocyte counts were adversely affected by NaHCO(3) pretreatment, indicating that this co-therapy does not enhance myelosuppression due to mitoxantrone therapy. These findings suggest that metabolic alkalosis would produce a net gain in mitoxantrone therapeutic index.
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PMID:Tumor acidity, ion trapping and chemotherapeutics. II. pH-dependent partition coefficients predict importance of ion trapping on pharmacokinetics of weakly basic chemotherapeutic agents. 1450 1

A lyophilized kit formulation for the efficient labelling of lipiodol with generator-produced rhenium-188 is described. The preliminary preparation of the lipophilic complex bis-(diethyldithiocarbamato)nitrido rhenium-188 (188ReN-DEDC) was carried out using a two-vial kit containing S-methyl-N-methyl-dithiocarbazate, SnCl2 and sodium oxalate in the first vial, and diethyldithiocarbamate and a carbonate buffer in the second vial. After mixing of the reaction solution with lipiodol, the complex 188ReN-DEDC was quantitatively extracted and retained by this hydrophobic substance, thus allowing the stable incorporation of the beta-emitting radionuclide. The radiochemical purity of the complex 188ReN-DEDC was 97+/-2%. The activity extracted into the lipiodol phase was 96+/-3% of the initial activity, indicating that the complex 188ReN-DEDC was almost quantitatively removed from the aqueous reaction solution. In vitro stability studies in human plasma, at 37 degrees C, demonstrated the release of less than 15% of the activity within three half-lives. The biodistribution of Re-lipiodol in non-tumour-bearing Wistar rats at 6, 24, 48 and 72 h after intraportal venous injection showed one-third of total activity in the liver at 6 h, declining to 2% retention at 72 h. Bowel uptake at 6 and 24 h declined to low levels at 48 and 72 h. Renal activity peaked at 1.7%, diminishing to 0.6% over 48 h. Rat whole body gamma imaging showed gut activity in addition to hepatic uptake at 6 and 24 h, but only liver was evident from 48 to 72 h. Kidneys were not demonstrable at any imaging time point. In nine patients, activity was localized in the tumours immediately following intrahepatic arterial injection. Computed tomography/single-photon emission computed tomography (CT/SPECT) imaging at 1 and 24 h confirmed the retention of 188Re-lipiodol in the hepatoma, with minimal gut uptake and no lung activity over 24 h. These patients were subsequently treated with activities of 2.5-5 GBq of 188Re-lipiodol fractions without adverse effects. Six patients followed for up to 2 years in the pilot study achieved stable disease and there was objective partial response in one patient. Repeated treatments were performed on two to three occasions in three patients without evident toxicity. An additional patient given 6 GBq of 188Re-lipiodol demonstrated myelosuppression, which recovered with granulocyte colony-stimulating factor (GCSF) and platelet support. It is concluded that 188Re-lipiodol, prepared using our novel kit formulation, is stable in vivo and provides safe and effective therapy of unresectable hepatocellular carcinoma when given via the hepatic artery, either alone or in combination with transarterial chemoembolization.
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PMID:A kit formulation for the preparation of 188Re-lipiodol: preclinical studies and preliminary therapeutic evaluation in patients with unresectable hepatocellular carcinoma. 1520 96