The objective of this study was to investigate the effect of a novel Zinc phthalocyanine (ZnPcH(1)) based photodynamic therapy (PDT) on acute monocytic leukemia cell lines SHI-1 and its mechanism, so as to provide theory basis for bone marrow purging in vitro for patients with leukemia. The killing effect of ZnPcH(1)-PDT on SHI-1 cells were assessed by MTT method; the SHI-1 cell death patterns were analyzed by AO/EB fluorescence staining, TdT-mediated dUTP nick end labeling (TUNEL), DNA ploidy analysis, and Annexin V-FITC/PI double staining.Cell mixture was established by integrating SHI-1 cells with normal bone marrow MNC (by 1:100-1:10 000). Purging effect of ZnPcH(1)-PDT against SHI-1 mixed into normal MNC was assessed by analyzing the expression of fusion gene MLL/AF6 mRNA using nested RT-PCR. The results showed that ZnPcH(1)-PDT could effectively inhibit SHI-1 cell proliferation in dose-dependent manner, and ZnPcH(1)-PDT could induce cell apoptosis in time-dependent manner. 0.5 µmol/L ZnPcH(1)-PDT could completely photoinactivated kill SHI-1 cells in the simulated remission bone marrow. It concluded that ZnPcH(1)-PDT may be a effective and convenient promising purging technique for leukemia.
Apoptosis ; drug effects ; Bone Marrow Purging ; methods ; Cell Death ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Indoles ; pharmacology ; therapeutic use ; Leukemia, Monocytic, Acute ; drug therapy ; pathology ; Organometallic Compounds ; pharmacology ; therapeutic use ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; therapeutic use

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 5 x 10(3) metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was started and continued for 12 days. Thalidomide was orally administrated 30 mg/kg/day and glucantime was administrated intraperitoneally (200 mg/kg/day). It was shown that the combined therapy is more effective than single therapies with each one of the drugs since the foot pad swelling in the group of mice received thalidomide and glucantime was significantly decreased (0.9 +/- 0.2 mm) compared to mice treated with either glucantime, thalidomide, or carrier alone (1.2 +/- 0.25, 1.4 +/- 0.3, and 1.7 +/- 0.27 mm, respectively). Cytokine study showed that the effect of thalidomide was not dependent on IL-12; however, it up-regulated IFN-gamma and down-regulated IL-10 production. Conclusively, thalidomide seems promising as a conjunctive therapy with antimony in murine model of visceral leishmaniasis.
Time Factors ; Thalidomide/pharmacology/*therapeutic use ; Organometallic Compounds/pharmacology/*therapeutic use ; Mice, Inbred BALB C ; Mice ; Meglumine/pharmacology/*therapeutic use ; Leishmaniasis, Visceral/*drug therapy/immunology ; Leishmania major/*drug effects ; Interleukin-12/analysis/biosynthesis ; Interleukin-10/analysis/biosynthesis ; Interferon Type II/analysis/biosynthesis/drug effects ; Immunosuppressive Agents/pharmacology/*therapeutic use ; Female ; Drug Therapy, Combination ; Disease Progression ; Disease Models, Animal ; Cells, Cultured ; Antiprotozoal Agents/pharmacology/*therapeutic use ; Animals

OBJECTIVETo investigate the effect of organic gallium and gallium chloride on bone metabolism and their therapeutic effect against tretinoin-induced osteoporosis in rats.

METHODSRat models of osteoporosis was established with intragastric administration of tretinoin at the daily dose of 85 mg/kg for 15 days and randomized into control, organic gallium and gallium chloride groups. After administration of the corresponding treatments (none for the control group) for 4 weeks, the changes of the indices for osteoporosis were evaluated through biochemical and pathological approaches.

RESULTSTretinoin induced obvious changes in bone structure and contents of bone calcium and other elements, causing also significantly increased tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (AKP), which suggested the development of osteoporosis. Administration of organic gallium and gallium chloride treatments increased the bone density, bone cortex thickness and the percentage of bone trabecula, and Ga, Ca, P contents in the femur and teeth, but lowered the activity of TRAP and AKP, suggesting decreased bone conversion rate. Compared with gallium chloride, organic gallium required smaller dose with better safety to produce better therapeutic effect.

CONCLUSIONOrganic gallium can be safe and effective for treatment of tretinoin-induced osteoporosis in rats.

Animals ; Cell Line, Tumor ; Female ; Femur ; drug effects ; metabolism ; pathology ; Gallium ; chemistry ; pharmacology ; therapeutic use ; Hemodynamics ; drug effects ; Organometallic Compounds ; chemistry ; pharmacology ; therapeutic use ; Osteoporosis ; chemically induced ; drug therapy ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Tooth ; drug effects ; metabolism ; Trace Elements ; metabolism ; Tretinoin ; pharmacology