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1.
Am J Transplant ; 23(9): 1375-1387, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37146942

RESUMO

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.


Assuntos
Transplante de Órgãos , Farmacêuticos , Humanos , Seguimentos , Certificação
2.
mBio ; 11(1)2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911495

RESUMO

Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against Cryptococcus neoformans, an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients. However, the effect of CARD9 deficiency on the induction of protective immune responses against C. neoformans is unknown. Immunization with a C. neoformans mutant that overexpresses the transcription factor zinc finger 2, denoted LW10, results in protection against an otherwise lethal challenge with wild-type (WT) C. neoformans Our results showed that CARD9 is essential for the induction of vaccine-mediated immunity against C. neoformans infection. We observed significant decreases in interleukin-17 (IL-17) production and significant increases in Th2-type cytokine (IL-4, IL-5, and IL-13) production in CARD9-deficient mice after inoculation with strain LW10. While leukocyte infiltration to the lungs of CARD9-deficient mice was similar in LW10 and WT C. neoformans-infected mice, macrophages derived from CARD9-deficient mice inherently skewed toward an M2 activation phenotype, were unable to contain the growth of LW10, and failed to produce nitric oxide in response to infection with LW10 or stimulation with lipopolysaccharide. These results suggest that CARD9-mediated signaling is required for M1 macrophage activation and fungicidal activity necessary for the induction of vaccine-mediated immunity against C. neoformansIMPORTANCECryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus neoformans/imunologia , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/microbiologia , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Animais , Biomarcadores , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Criptococose/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Resistência à Doença/imunologia , Feminino , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Imunofenotipagem , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Pneumopatias Fúngicas/metabolismo , Masculino , Camundongos , Receptores de Reconhecimento de Padrão/metabolismo
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