RESUMO
Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.
Assuntos
Antiprotozoários/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Animais , Sistemas de Liberação de Medicamentos , Feminino , Inflamação/prevenção & controle , Interferon gama/imunologia , Interleucina-10/biossíntese , Leishmaniose Visceral/parasitologia , Lipossomos/uso terapêutico , Meglumina/química , Antimoniato de Meglumina , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/química , Carga Parasitária , Polietilenoglicóis/químicaRESUMO
This study compared the therapeutic potential of the chemotherapy using meglumine antimoniate encapsulated in a mixture of conventional and PEGylated liposomes (Nano Sbv) and immunotherapy with anti-canine IL-10 receptor-blocking monoclonal antibody (Anti IL-10R) on canine visceral leishmaniasis (CVL). Twenty mongrel dogs naturally infected by L. infantum, displaying clinical signs of visceral leishmaniasis were randomly divided in two groups. In the first one, nine dogs received six intravenous doses of a mixture of conventional and PEGylated liposomes containing meglumine antimoniate at 6.5 mg Sb/kg/dose. In the second one, eleven dogs received two intramuscular doses of 4 mg of anti-canine IL-10 receptor-blocking monoclonal antibody. The animals were evaluated before (T0) and 30, 90, and 180 days after treatments. Our major results demonstrated that both treatments were able to maintain hematological and biochemical parameters, increase circulating T lymphocytes subpopulations, increase the IFN-γ producing T-CD4 lymphocytes, restore the lymphoproliferative capacity and improve the clinical status. However, although these improvements were observed in the initial post-treatment times, they did not maintain until the end of the experimental follow-up. We believe that the use of booster doses or the association of chemotherapy and immunotherapy (immunochemotherapy) is promising to improve the effectiveness of treating CVL for improving the clinical signs and possibly reducing the parasite burden in dogs infected with Leishmania infantum.
Assuntos
Anticorpos Monoclonais/farmacologia , Doenças do Cão/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Lipossomos/química , Antimoniato de Meglumina/farmacologia , Polietilenoglicóis/química , Receptores de Interleucina-10/antagonistas & inibidores , Alopurinol/farmacologia , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Doenças do Cão/metabolismo , Cães , Fatores Imunológicos/metabolismo , Imunoterapia/métodos , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/metabolismo , Compostos Organometálicos/farmacologiaRESUMO
Complexes of gadolinium(III) with N-octanoyl-N-methylglucamine (L8) and N-decanoyl-N-methylglucamine (L10) with 1 : 2 stoichiometry were synthesized and characterized by elemental analysis, electrospray ionization-tandem mass spectrometry (ESI-MS), infrared (IR) spectroscopy, and molar conductivity measurements. The transverse (r 2) and longitudinal (r 1) relaxivity protons were measured at 20 MHz and compared with those of the commercial contrasts. These complexes were incorporated in liposomes, resulting in the increase of the vesicle zeta potential. Both the free and liposome-incorporated gadolinium complexes showed high relaxation effectiveness, compared to commercial contrast agent gadopentetate dimeglumine (Magnevist). The high relaxivity of these complexes was attributed to the molecular rotation that occurs more slowly, because of the elevated molecular weight and incorporation in liposomes. The results establish that these paramagnetic complexes are highly potent contrast agents, making them excellent candidates for various applications in molecular MR imaging.
RESUMO
Estudo descritivo e documental que objetivou analisar o perfil de diagnósticos de enfermagem em relação ao tempo depermanência e evolução clínica de pacientes internados na Unidade de Terapia Intensiva de um municípiode Minas Gerais.Foram analisados 240 prontuários, identificados 4.130 títulos de diagnósticos de enfermagem, média de18 títulosdiagnósticos por paciente. O título diagnóstico mais frequente foi risco de infecção (100%), seguido de risco de integridadeda pele prejudicada (95%), risco de desequilíbrio de volume de líquido (90%), risco de alteração da nutrição: menos do queo corpo necessita (89%) edéficitno autocuidado (84%). A média de permanência dos diagnósticos de enfermagem nospacientes foi de quatro dias, variando entre um e 42 dias. Foram identificadas diferenças significativas para nove (13,6%)diagnósticos de enfermagem identificados segundo aevolução clínica dos pacientes. Todos esses diagnósticos deenfermagem foram reais. O estabelecimento do perfilde diagnósticos de enfermagem contribui para se conhecer ademanda de cuidados de enfermagem, demonstrando preocupação com os aspectos de prevenção de problemasquedevem ser valorizados pela equipe.
A descriptive and documentary study that aimed to analyze the nursing diagnoses profile in relation tolength of stay andclinical progress of patients admitted to IntensiveCare Unit of a Minas Gerais city. 240 patients records were analyzed. Itwas identified 4130 nursing diagnoses labels, average of 18 diagnoses labels per patient. The most frequent diagnosis labelwas risk of infection (100%), followed by risk of impaired skin integrity (95%), risk of imbalance fluid volume (90%), risk ofaltered nutrition: less than body needs (89%) and self-care deficit (84%). The average length of stayof the nursingdiagnoses in patients was 4 days, ranging between 1and 42 days. Significant differences were identified in 9 (13.6%)nursing diagnoses according to patient clinical progress. All these nursing diagnoses were real. Knowing the profile ofnursing diagnoses contributes to meet the demand for nursing care, demonstrating concern about aspectsof problemsprevention that should be valued by staff.
Estudio descriptivo y documental tiene como objetivo analizar el perfil de los diagnósticos de enfermería en relación a lalongitud de la estancia y el resultado de los pacientes ingresados en la Unidad de Cuidados Intensivosde una ciudad enMinas Gerais. Se analizaron 240 historias clínicas.Se identificaron 4130 títulos diagnósticos de enfermería, un promedio de18 títulos de diagnósticos por paciente. El títulodiagnóstico más frecuente fue el riesgo de infección (100%), seguido porel riesgo de deterioro de la integridad de la piel(95%), el riesgo de desequilibrio de volumen de líquido (90%), el riesgo dealteración de la nutrición: menos de las necesidades del cuerpo (89%) y el déficit de autocuidado (84%). La estancia mediade los diagnósticos de enfermería en pacientes fuede 4 días, oscilando entre 1 y 42 días. Se identificaron diferenciassignificativas en 9 (13,6%) diagnósticos de enfermería de acuerdo con el progreso clínico de pacientes. Todos estosdiagnósticos de enfermería eran reales. El perfil de los diagnósticos de enfermería contribuye a satisfacer la demanda decuidados de enfermería, lo que demuestra la preocupación por los aspectos de la prevención de los problemas que debenser valorados por el personal.
Assuntos
Humanos , Cuidados de Enfermagem , Diagnóstico de Enfermagem , Unidades de Terapia IntensivaRESUMO
O controle de Infecção Hospitalar (IH) é um desafiopara a equipe cirúrgica, o que faz com que os profissionais da áreabusquem novas medidas para diminuir tal ocorrência.O estudo objetivou investigar a prevalência de IHem pacientescirúrgicos através de um estudo descritivo, retrospectivo, de abordagem quantitativa. Observou-se umataxa de infecçãohospitalar em pacientes cirúrgicos de 4,14%. Dos casos, 63,40% eram do sexo masculino; 65,90% foram encaminhados parao centro de terapia intensiva e 46,30% apresentavamalguma comorbidade. A maior ocorrência ocorreu nosÃtio cirúrgico(33,30%), seguida de pneumonia associada à ventilação mecânica (31,40%). Durante a internação, 31 (75,61%) pacientesutilizaram procedimentos invasivos e os antimicrobianos mais utilizados foram as cefalosporinas de 3ªgeração. Conclui-seque, para o controle eficaz da IH, é necessária a atuação efetiva da Comissão de Controle de InfecçãoHospitalar e osdados do estudo apontam para necessidade de intensificação de ações preventivas.
The control of Nosocomial Infection (IH) is a challenge for the surgical team, which makes the professionals look for newmeasures to reduce this occurrence. The study aimedto investigate the prevalence of IH in surgical patients using adescriptive, retrospective study, with quantitativeapproach. There was a surgical infection rate of 4.14%. Of these,63.40% were male, 65.90% were referred to the intensive care unit and 46.30% had a comorbidity. The highest occurrencewas at the surgical site (33.30%), followed by ventilator-associated pneumonia (31.40%). During hospitalization, 31(75.61%) patients used invasive procedures and themost used antimicrobials were the 3rd generation cephalosporins. It isconcluded that for effective control of IH effective action of the Hospital Infection Control Commission is required and thestudy data point to a need for increased preventionefforts.
El control de Infección Hospitalaria (IH) es un reto para el equipo quirúrgico, lo que hace que los profesionales busquennuevas medidas para reducir su incidencia. El objetivo del estudio fue investigar la incidencia de lainfección hospitalariaen los pacientes quirúrgicos mediante un estudio descriptivo, retrospectivo, con enfoque cuantitativo.Hubo una tasa deinfección quirúrgica del 4,14%. De los casos, 63,40% eran hombres, 65,90% fueron remitidos a la unidadde cuidadosintensivos y 46,30% presentaban alguna comorbilidad. La mayor incidencia se produjo en el sitio quirúrgico (33,30%),seguida de neumonÃa asociada al ventilador (31,40%). Durante la hospitalización, 31 (75,61%) pacientesse sometieron aprocedimientos invasivos y los antimicrobianos másusados fueron las cefalosporinas de tercera generación. Se concluyeque, para un control efectivo de la IH, se requiereuna acción eficaz de la Comisión de Control de Infecciones Hospitalaria,y los datos del estudio apuntan a la necesidad de aumento de los esfuerzos de prevención.