Reduction of lymphocytes

FU (12.5 mg/kg twice daily) plus chitosan (150, 375 and 750 mg/kg twice daily) inhibited the tumor growth as well as 5-FU alone. Chitosan (150 and 750 mg/kg twice daily) blocked the reduction of blood leukocyte number caused by 5-FU administration, and it prevented the injury of the small intestinal mucosa membrane and delayed the onset of diarrhea induced by 5-FU Fig. (1), Fig. (2) and Fig. (3) . Furthermore, chitosan (750 mg/kg twice daily) prevented the reduction of spleen weight induced by 5-FU in sarcoma 180-bearing mice Fig. (4) , and the reduction of lymphocyte, CD8+ and NK1.1.+ T cell numbers induced by 5-FU Fig. (5) . 

As shown in Fig. (27) , 4-hydroxyderricin (25 or 50 mg/kg, twice daily) inhibited metastasis to the lung in tumor-removed mice and the increase of lung weight that occurred in tumor-removed mice. In this study, we found that the number of lymphocytes, CD4" T, CDS T and NK cells in the spleen of LLC-removed mice were reduced compared to those of normal mice. 4-Hydroxyderricin (50 mg/kg x 2/day) inhibited the reduction of lymphocyte, CD4 and CDS" T cells and NK cell number in tumor-removed mice. On the other hand, the numbers of lymphocytes, CD4 T, CD8 T and NK cells were further reduced by the intraperitoneal administered doxorubicin compared to LLC-removed mice Table (18) . 

Although doxorubicin has a potent antitumor effect, it causes severe adverse effects such as decrease of body weight and immune system (the reduction of lymphocyte, CD4 T, CD8T and NK cell number) and death. Conversely, 4-hydroxyderricin did not cause any apparent adverse reactions. 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Miller Scott (1985) reported marked reduction in thymus weight in rats fed dioctyltin dichloride for 8 or 12 weeks at a level of 75 mg/kg diet. Numbers of lymphocytes together with T cell subpopulations were reduced in treated rats, but no difference was seen in antibody response to sheep red blood cells in vivo. No evidence was foimd of in vitro cytocidal effects of dioctyltin dichloride on blood lymphocytes. Evans et al. (1986) dosed pregnant and non-pregnant rats for 3 weeks at 75 mg/kg diet and reported severe thymic atrophy and extensive vacuolation of reticuloendothelial cells in pregnant animals only. 

Successful treatment in the older CLL patient depends on the reduction of malignant lymphocytes. Treatment often begins when a patient becomes symptomatic. A desirable response to therapy includes a reduction in lymphocytes, decrease in stage of the disease, and resolution of symptoms. Since CLL is not a curable disease, palliation of symptoms is a reasonable goal in older patients, and aggressive therapies are reserved for younger patients with high-risk CLL. 

A statistically significant reduction of 16% in the percentage of lymphocytes in whole blood was reported in rats receiving 1,000 mg/kg/day MIL-H-5606 for 26 days (Mattie et al. 1993). 

Mineral Oil Hydraulic Fluids. No information on hematological effects in humans after inhalation, oral, or dermal exposure to mineral oil hydraulic fluids is available. In another animal study, a statistically significant reduction of 16% was reported in the percentage of lymphocytes in whole blood in rats receiving 1,000 mg/kg/day MIL-H-5606 by gavage for 26 days (Mattie et al. 1993). 

Moderate but prolonged exposure of rats to TBT and TPhT acetate at subchronic levels (< 20 mg/kg OTC) brought about histopathologic lesions in lungs, liver, intestines and kidneys besides reduction in lymphocyte count at higher concentrations37. 

The thiazoloimidazopyridine derivatives 451 were tested for their effect on human immunodeficiency virus (HIV)-induced cytopathogenicity in a human T4-lymphocyte cell line and showed a reproducible anti-HIV activity that caused a 50% or greater reduction of viral cytophatic effect <1994FA345>. Finally, imidazo[2,1 -/dthiazolone 489 was found to have an antitumor activity and proved to be effective against brain tumor cell lines <2002JHC1133>. 

Hematologic/Lymphatic Anemia hemolytic anemia thrombocytopenia thrombocytopenic purpura eosinophilia leukopenia granulocytopenia neutropenia bone marrow depression agranulocytosis reduction of hemoglobin or hematocrit prolongation of bleeding and prothrombin time decrease in WBC and lymphocyte counts increase in lymphocytes, monocytes, basophils, and platelets. Hypersensitivity Adverse reactions (estimated incidence, 1% to 10%) are more likely to occur in individuals with previously demonstrated hypersensitivity. In penicillin-sensitive individuals with a history of allergy, asthma, or hay fever, the reactions may be immediate and severe. 

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