ABSTRACT
Topical pimecrolimus is an alternative treatment of atopic dermatitis. However, rare cases of malignancy have been reported with their use. This study was performed to investigate the possible geno- or cytotoxic effect in mouse bone marrow caused by systemic absorption of pimecrolimus 1% cream. In order to determine this, induction of micronucleated erythrocytes (MNE) in mouse peripheral blood was determined after the cutaneous application of three different doses, daily for 5 consecutive days. No differences were found in frequencies of polychromatic erythrocytes, MNE, and micronucleated polychromatic erythrocytes in the different groups of study. In conclusion, under described conditions, no geno- or cytotoxic effects were detected after the cutaneous application of pimecrolimus.
Subject(s)
Erythrocytes/drug effects , Immunosuppressive Agents/toxicity , Micronuclei, Chromosome-Defective/chemically induced , Tacrolimus/analogs & derivatives , Administration, Cutaneous , Animals , Cell Survival/drug effects , Erythrocytes/pathology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/pharmacokinetics , Male , Mice , Mice, Inbred BALB C , Micronucleus Tests , Ointments , Skin/metabolism , Skin Absorption , Tacrolimus/administration & dosage , Tacrolimus/pharmacokinetics , Tacrolimus/toxicitySubject(s)
Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Doxorubicin/pharmacology , Leukemia, Myeloid, Acute/pathology , Pentoxifylline/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Drug Synergism , Humans , In Vitro Techniques , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/pathologyABSTRACT
The aim of this study was to determine how gossypol affects the viability and activity of polymorphonuclear leukocytes and monocytes in blood obtained from healthy donors. Loss of mitochondrial membrane potential (delta psi m) and apoptosis was maximized in human polymorphonuclear leukocytes and monocytes after incubation with gossypol. Pretreatment with a caspase-9 inhibitor or antioxidants (superoxide dismutase or Trolox) inhibited gossypol-induced loss of the delta psi m and apoptosis. Likewise, we observed participation of caspase -3, -7, and -10 in gossypol-induced apoptosis. Expression of the proapoptotic genes bax, bak, bad and p53/Tp53 increased in polymorphonuclear leukocytes exposed to gossypol. The expression of the anti-apoptotic genes bcl-(XL) and mcl-1 was reduced when polymorphonuclear leukocytes and monocytes were treated with gossypol. Gossypol treatment also inhibited yeast phagocytosis by these cells. We concluded that gossypol induces apoptosis in phagocytic cells and that this effect was dose-dependent. The findings in this report may be important to consider in light of possible gossypol use in clinical strategies for cancer treatment.
Subject(s)
Apoptosis/drug effects , Gossypol/administration & dosage , Mitochondria/drug effects , Monocytes/drug effects , Neutrophils/drug effects , Reactive Oxygen Species/metabolism , Adult , Antioxidants/metabolism , Caspases/metabolism , Chromans/metabolism , Cyclin D1/biosynthesis , Female , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Myeloid Cell Leukemia Sequence 1 Protein , Phagocytosis/drug effects , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Superoxide Dismutase/metabolism , Tumor Suppressor Protein p53/biosynthesis , Young Adult , bcl-2 Homologous Antagonist-Killer Protein/biosynthesis , bcl-2-Associated X Protein/biosynthesis , bcl-Associated Death Protein/biosynthesisABSTRACT
Introducción. Chlamydia trachomatis se considera el agente causal de tracoma, salpingitis, endometritis y podría estar involucrada en la ruptura prematura de membrana (PMR) y amenaza de parto prematuro (PDT). El objetivo de este trabajo fue determinar la presencia de antígenos de C. trachomatis y anticuerpos contra C. trachomatis en mujeres embarazadas con PMR, PDT (ambos grupos de etiología desconocida) y mujeres con embarazo normal (NP).Material y métodos. Se obtuvieron 50 muestras endocervicales por cada grupo de mujeres embarazadas, para la determinación de antígenos de C. trachomatis, por el método de inmunofluorescencia directa. Asimismo fueron tomados 5 ml de sangre venosa, para identificar la presencia de anticuerpos contra C. trachomatis por inmunofluorescencia indirecta. Resultados. Seis por ciento (3/50) de las pacientes con PMR presentaron antígenos de C. trachomatis y anticuerpos IgG anti-C. trachomatis. Dos por ciento (1/50) con PDT tuvieron antígenos de C. trachomatis y anticuerpos IgM anti-C. trachomatis. Seis por ciento (3/50) de las pacientes con NP mostraron antígenos de C. trachomatis, pero no anticuerpos anti-C. trachomatis. Sin embargo, en 10 por ciento (5/50), 10 por ciento (5/50) y 16 por ciento (8/50) con PMR, PDT o NP, respectivamente; solamente se encontraron anticuerpos IgG anti-C. trachomatis. Conclusión. El hallazgo tanto de antígenos como anticuerpos anti-C. trachomatis en los tres grupos estudiados, resalta la importancia de la oportuna identificación de la infección, para la aplicación del tratamiento adecuado, para prevenir las secuelas de la infección, tanto en las mujeres embarazadas como en sus productos.
