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Immunosuppressant Drugs (immunosuppressant + drug)

Distribution by Scientific Domains
Medical Sciences83%

Selected Abstracts

Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw,like disease in mice

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2010
Takashi Kikuiri
Abstract Patients on high-dose bisphosphonate and immunosuppressive therapy have an increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ); despite the disease severity, its pathophysiology remains unknown, and appropriate therapy is not established. Here we have developed a mouse model of BRONJ-like disease that recapitulates major clinical and radiographic manifestations of the human disease, including characteristic features of an open alveolar socket, exposed necrotic bone or sequestra, increased inflammatory infiltrates, osseous sclerosis, and radiopaque alveolar bone. We show that administration of zoledronate, a potent aminobisphosphonate, and dexamethasone, an immunosuppressant drug, causes BRONJ-like disease in mice in part by suppressing the adaptive regulatory T cells, Tregs, and activating the inflammatory T-helper-producing interleukin 17 cells, Th17. Most interestingly, we demonstrate that systemic infusion with mesenchymal stem cells (MSCs) prevents and cures BRONJ-like disease possibly via induction of peripheral tolerance, shown as an inhibition of Th17 and increase in Treg cells. The suppressed Tregs/Th17 ratio in zoledronate- and dexamethasone-treated mice is restored in mice undergoing salvage therapy with Tregs. These findings provide evidence of an immunity-based mechanism of BRONJ-like disease and support the rationale for in vivo immunomodulatory therapy using Tregs or MSCs to treat BRONJ. © 2010 American Society for Bone and Mineral Research [source]

FK506-binding protein localizations in human penile innervation

BJU INTERNATIONAL, Issue 5 2008
Gwen Lagoda
OBJECTIVE To determine if FK506-binding proteins (FKBPs) are localized to the autonomic nerve supply of the human penis because FK506 (an immunosuppressant drug) has been linked to enhanced nerve regeneration after nerve injury and neurodegenerative diseases by binding to FKBPs, a select group of immunophilins. MATERIALS AND METHODS Human lower genitourinary tract specimens were obtained and embedded in paraffin wax. The tissue was sectioned (10 µm) and processed for immunohistochemistry using antibodies for FKBPs 12, 38, 52, 65, 135 and neuronal nitric oxide synthase (nNOS). To confirm specificity of the antibody, we processed some tissue in the absence of primary antibody, with mouse or rabbit IgG, and with a blocking peptide for FKBP12. RESULTS In the pelvis, immunoreactivity for all the FKBPs and nNOS was localized to the periprostatic ganglia although FKBP12 was the only FKBP localized to nerve bundles in this location. In penile tissue, immunoreactivity for all five FKBPs and nNOS was localized to nerves, although immunoreactivity for FKBP38 was minimal. The FKBPs were also evident in epithelial, endothelial and smooth muscle cells of the prostate and penis. Negative controls did not produce staining. CONCLUSIONS Identification and localization of immunophilins to nerves coursing in prostate and penile tissue suggest a likely molecular basis to apply immunophilin ligand therapy to protect or regenerate cavernosal nerves. Our findings support the hypothesis that immunosuppressant drugs such as FK506, working via specific receptor mechanisms, are potentially useful to sustain erectile function in men after radical prostatectomy. [source]

Chagas' disease reactivation with skin symptoms in a patient with kidney transplant

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2007
Verónica Gallerano MD
Immunodepressed patients in the intermediate phase of Chagas' disease may undergo reactivation of the disease together with atypical symptoms. The case of an immunodepressed kidney transplant patient with reactivation of Chagas' disease with skin symptoms is reported. A 65-year-old man presented with infiltrated erythematous lesions on the anterior aspect of the right thigh of 2 weeks' duration. The lesions later extended to the abdomen, thorax, and lower limbs. In the histologic skin examination, amastigotes and Trypanosoma cruzi trypoamastigotes were observed. A fresh smear showed positive parasitemia. Using the Strout hemoconcentration method, multiple Trypanosoma cruzi trypoamastigotes with motility could be seen. Polymerase chain reaction was positive for Trypanosoma cruzi. An immunofluorescence test was positive (1 : 64) and there was hemoagglutination (1 : 32). Treatment was started with benznidazole, 7 mg/kg/day. The patient did not evolve favorably and died 20 days after hospitalization. Skin lesions may be a manifestation of the reactivation of Chagas' disease in immunosuppressed patients. All patients with positive Chagas' serology who require immunosuppressant drugs should receive specific treatment for Chagas' disease. [source]

Progress technology in microencapsulation methods for cell therapy

BIOTECHNOLOGY PROGRESS, Issue 4 2009
Jean-Michel Rabanel
Abstract Cell encapsulation in microcapsules allows the in situ delivery of secreted proteins to treat different pathological conditions. Spherical microcapsules offer optimal surface-to-volume ratio for protein and nutrient diffusion, and thus, cell viability. This technology permits cell survival along with protein secretion activity upon appropriate host stimuli without the deleterious effects of immunosuppressant drugs. Microcapsules can be classified in 3 categories: matrix-core/shell microcapsules, liquid-core/shell microcapsules, and cells-core/shell microcapsules (or conformal coating). Many preparation techniques using natural or synthetic polymers as well as inorganic compounds have been reported. Matrix-core/shell microcapsules in which cells are hydrogel-embedded, exemplified by alginates capsule, is by far the most studied method. Numerous refinement of the technique have been proposed over the years such as better material characterization and purification, improvements in microbead generation methods, and new microbeads coating techniques. Other approaches, based on liquid-core capsules showed improved protein production and increased cell survival. But aside those more traditional techniques, new techniques are emerging in response to shortcomings of existing methods. More recently, direct cell aggregate coating have been proposed to minimize membrane thickness and implants size. Microcapsule performances are largely dictated by the physicochemical properties of the materials and the preparation techniques employed. Despite numerous promising pre-clinical results, at the present time each methods proposed need further improvements before reaching the clinical phase. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]

FK506-binding protein localizations in human penile innervation

BJU INTERNATIONAL, Issue 5 2008
Gwen Lagoda
OBJECTIVE To determine if FK506-binding proteins (FKBPs) are localized to the autonomic nerve supply of the human penis because FK506 (an immunosuppressant drug) has been linked to enhanced nerve regeneration after nerve injury and neurodegenerative diseases by binding to FKBPs, a select group of immunophilins. MATERIALS AND METHODS Human lower genitourinary tract specimens were obtained and embedded in paraffin wax. The tissue was sectioned (10 µm) and processed for immunohistochemistry using antibodies for FKBPs 12, 38, 52, 65, 135 and neuronal nitric oxide synthase (nNOS). To confirm specificity of the antibody, we processed some tissue in the absence of primary antibody, with mouse or rabbit IgG, and with a blocking peptide for FKBP12. RESULTS In the pelvis, immunoreactivity for all the FKBPs and nNOS was localized to the periprostatic ganglia although FKBP12 was the only FKBP localized to nerve bundles in this location. In penile tissue, immunoreactivity for all five FKBPs and nNOS was localized to nerves, although immunoreactivity for FKBP38 was minimal. The FKBPs were also evident in epithelial, endothelial and smooth muscle cells of the prostate and penis. Negative controls did not produce staining. CONCLUSIONS Identification and localization of immunophilins to nerves coursing in prostate and penile tissue suggest a likely molecular basis to apply immunophilin ligand therapy to protect or regenerate cavernosal nerves. Our findings support the hypothesis that immunosuppressant drugs such as FK506, working via specific receptor mechanisms, are potentially useful to sustain erectile function in men after radical prostatectomy. [source]

The present role of corticosteroids in uveitis

ACTA OPHTHALMOLOGICA, Issue 2009
M KHAIRALLAH
Corticosteroids are the most widely used anti-inflammatory and immunosuppressant drugs in ophthalmology in general, and remain the mainstay of therapy for patients with uveitis. An infectious etiology for intraocular inflammation should be adequately excluded or appropriately covered with anti-infectious therapy before administration of corticosteroid therapy. Topical corticosteroids alone are usually effective in the management of anterior uveitis and have little activity against intermediate or posterior uveitis. Ocular adverse effects of topical steroid therapy mainly include ocular hypertension and cataract. The use of periocular steroid injections (subconjunctival, anterior or posterior subtenon, orbital floor) are important modalities in the management of anterior uveitis refractory to topical treatment and intermediate or posterior uveitis, particularly unilateral cases. Systemic corticosteroids remain the initial drug of choice for most patients with severe bilateral intermediate or posterior uveitis. Therapy is initiated with 1.0 to 2.0 mg/Kg of oral prednisone or prednisolone as a single morning dose, followed by a slow taper. Use of intravenous pulse steroid therapy is an important option in acute, severe, bilateral posterior segment inflammation. In several cases, the level of systemic steroid required to control the inflammation is too high and unacceptable. Immunosuppressive drugs as steroid-sparing agents are indicated is such cases. Intravitreal injection of triamcinolone acetonide and slow-release intraocular devices are therapeutic options that can be used in selected uveitis cases refractory to conventional therapy and biologic agents. [source]