Subject(s)
Autoantibodies/blood , Glomerular Basement Membrane , Immunoglobulin G/blood , Immunoglobulin lambda-Chains/blood , Kidney Diseases , Paraproteinemias , Aged , Female , Glomerular Basement Membrane/metabolism , Glomerular Basement Membrane/pathology , Humans , Kidney Diseases/blood , Kidney Diseases/diagnosis , Kidney Diseases/pathology , Kidney Diseases/therapy , Paraproteinemias/blood , Paraproteinemias/diagnosis , Paraproteinemias/pathology , Paraproteinemias/therapyABSTRACT
Systemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas(lpr) lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyte-infiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220(+) CD4(-) CD8(-) T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRL-Fas(lpr) lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.
Subject(s)
Carbon Monoxide/pharmacology , Lupus Nephritis/therapy , Lymphocyte Activation/drug effects , Animals , Antibodies, Antinuclear/blood , Antigen-Antibody Complex/immunology , Autoantibodies/biosynthesis , Autoantibodies/immunology , Carbon Monoxide/therapeutic use , Cytokines/biosynthesis , Disease Models, Animal , Disease Progression , Female , Kidney Glomerulus/cytology , Kidney Glomerulus/immunology , Kidney Glomerulus/injuries , Leukocyte Common Antigens/metabolism , Lung/cytology , Lung/immunology , Mice , Mice, Inbred MRL lpr , Neutrophil Infiltration/immunology , Proteinuria/metabolism , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunologySubject(s)
Fibrosarcoma/complications , Fibrosarcoma/diagnosis , Gastrointestinal Stromal Tumors/diagnosis , Renal Insufficiency/metabolism , Water-Electrolyte Imbalance/complications , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Alkylating/toxicity , Biopsy , Creatinine/blood , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Diagnosis, Differential , Disease Progression , Docetaxel , Drug Administration Schedule , Fibrosarcoma/drug therapy , Fibrosarcoma/pathology , Follow-Up Studies , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Humans , Ifosfamide/toxicity , Inflammation/pathology , Kidney/surgery , Kidney Glomerulus/cytology , Kidney Glomerulus/ultrastructure , Kidney Tubules/pathology , Male , Middle Aged , Taxoids/therapeutic use , Treatment Outcome , Water-Electrolyte Imbalance/blood , GemcitabineABSTRACT
Sexual impotence has been reported to increase sixfold after sequential renal transplantations. This study examined the effects of age, diabetes mellitus, systemic hypertension, uremia, arteriosclerosis, penile blood flow, and patency of hypogastric arteries on impotence. Sixty-one male transplant patients were followed up from six to 108 months. An age of greater than 40 years was the only factor deleterious to potency (P = .006). Interruption of both hypogastric arteries is not necessarily related to impotence. Post-transplantation male impotence is perhaps best treated by penile prosthesis insertion. A hemodynamic classification is proposed.
