AIMTo evaluate the effect of tamoxifen citrate on male reproductive system of rat.

METHODSGroups of male rats were gavaged with tamoxifen at doses of 200 mg x kg(-1) x d(-1), 400 mg x kg(-1) x d(-1) or 800 mg x kg(-1) x d(-1) in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5 microm thickness, stained with HE and analyzed microscopically.

RESULTSThere was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15.

CONCLUSIONTamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility.

Animals ; Antineoplastic Agents, Hormonal ; toxicity ; Dose-Response Relationship, Drug ; Giant Cells ; drug effects ; ultrastructure ; In Vitro Techniques ; Male ; Rats ; Rats, Wistar ; Seminiferous Tubules ; cytology ; drug effects ; Tamoxifen ; toxicity ; Testis ; cytology ; drug effects

Host immune response has been considered as an important disease-modifying factor of periodontitis, however, which immune cell(s) or factor(s) are involved in the destruction of periodontium remains unclear. Previously, we reported that osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8(+)T cells. We present new data that B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis. Purified murine B cells were activated with anti-IgD mAb, IL-4, and anti-CD40 mAb, in the absence (B(Th2)) or presence of Th1 cytokines, either IL-2 (B(IL-2)) or IFN-gamma (B(IFN-gamma)). Each activated B cell population was co-cultured with RAW264.7 cells in the presence of soluble receptor activator of NF-kappaB ligand (sRANKL), and the effect on osteoclastic differentiation was evaluated. While B(Th2)increased osteoclastogenesis, B(IL-2)and B(IFN-gamma)suppressed it profoundly. To verify the mediating molecule(s), we analyzed cytokine profiles of the activated B cells. Compared to B(Th2), B(IL-2)expressed increased amount of IFN-gamma and B(IFN-gamma)expressed decreased amounts of IL-4, IL-5, and IL-10. IFN-gamma was a key negative regulator of osteoclastic differentiation, and mediated the inhibition by B(IL-2). These results suggest that Th1 cytokines may have new important roles in resistance to periodontitis, acting directly on osteoclasts or indirectly through B cells.
Animals ; B-Lymphocytes/cytology/*drug effects/immunology ; Base Sequence ; Cell Differentiation/*drug effects ; Cytokines/*pharmacology ; Female ; Giant Cells/cytology/drug effects ; Interferon Type II/immunology/metabolism ; Lymphocyte Activation/*drug effects ; Mice ; Molecular Sequence Data ; Osteoclasts/*cytology/*drug effects ; Phenotype ; Support, Non-U.S. Gov't ; Th1 Cells/*immunology ; Tumor Necrosis Factor/pharmacology

AIMTo survey the uptake behavior and subcellular distribution of antisense oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) and infer its mechanism in MGC cell lines.

METHODSMGC cells were incubated at certain concentration of AS-ODN-SMP or AS-ODN for 8 h at 4 degrees C or 37 degrees C. Then the fluorescence oligodeoxynucleotide- labeled cells were counted by flow cytometer and the intracellular fluorescence intensity was determined after incubated with chloroquine for 2 h.

RESULTSCellular uptake of oligodeoxynucleotides was significantly increased following application of AS-ODN-SMP and total intracellular fluorescence intensity was enhanced by 683 folds with the vehicle concentration of 20 microg x mL(-1). AS-ODN-SMP entranced to cells profoundly with temperature-dependent manner. Rare cells took on fluorescence when incubated at 4 degrees C, while 37 degrees C they were significantly increased. But the intracellular fluorescence intensity appeared same level in present or absent of chloroquine.

CONCLUSIONWith the help of polyacrylate submicroparticles, oligonucleotides efficiently entranced the cells via endocytosis and could successfully escape the degradation in lysosome.

Animals ; Cell Line ; Drug Carriers ; Drug Delivery Systems ; Endocytosis ; drug effects ; Giant Cells ; cytology ; Lysosomes ; metabolism ; Nanoparticles ; Oligodeoxyribonucleotides, Antisense ; administration & dosage ; pharmacokinetics ; Particle Size ; Polymethacrylic Acids ; chemistry ; pharmacology ; Temperature