DPP-4 Inhibition Leads to Decreased Pancreatic Inflammatory Profile and Increased Frequency of Regulatory T Cells in Experimental Type 1 Diabetes.

Sitagliptin is a dipeptidyl peptidase-4 inhibitor (iDPP-4), which has been used for type 2 diabetes treatment. Recently, iDPP-4 has been described as a promising treatment of type 1 diabetes (T1D) but is still necessary to evaluate immune effects of sitagliptin. C57BL/6 mice were induced by multiple low doses of streptozotocin. Diabetes incidence, insulin, glucagon, glucagon-like peptide-1 (GLP-1) serum levels, and inflammatory cytokine levels were quantified in pancreas homogenate after 30 and 90 days of treatment. In addition, frequencies of inflammatory and regulatory T cell subsets were determined in the spleen and in the pancreatic lymph nodes. iDPP-4 decreased blood glucose level while increased GLP-1 and insulin levels. After long-term treatment, treated diabetic mice presented decreased frequency of CD4+CD26+ T cells and increased percentage of CD4+CD25hiFoxp3+ T cells in the spleen. Besides, pancreatic lymph nodes from diabetic mice treated with iDPP-4 presented lower percentage of CD11b+ cells and decreased levels of inflammatory cytokines in the pancreas. Treatment of type 1 diabetic mice with iDPP-4 improved metabolic control, decreased inflammatory profile in the pancreatic microenvironment, and increased systemic regulatory T cell frequency. Therefore, we suggest the long-term use of sitagliptin as a feasible and effective therapy for T1D.

Multipotent mesenchymal stromal cells from patients with newly diagnosed type 1 diabetes mellitus exhibit preserved in vitro and in vivo immunomodulatory properties.

BACKGROUND: Type 1 diabetes mellitus (T1D) is characterized by autoimmune responses resulting in destruction of insulin-producing pancreatic beta cells. Multipotent mesenchymal stromal cells (MSCs) exhibit immunomodulatory potential, migratory capacity to injured areas and may contribute to tissue regeneration by the secretion of bioactive factors. Therefore, MSCs are considered as a promising approach to treat patients with different autoimmune diseases (AID), including T1D patients. Phenotypical and functional alterations have been reported in MSCs derived from patients with different AID. However, little is known about the properties of MSCs derived from patients with T1D. Since autoimmunity and the diabetic microenvironment may affect the biology of MSCs, it becomes important to investigate whether these cells are suitable for autologous transplantation. Thus, the aim of the present study was to evaluate the in vitro properties and the in vivo therapeutic efficacy of MSCs isolated from bone marrow of newly diagnosed T1D patients (T1D-MSCs) and to compare them with MSCs from healthy individuals (C-MSCs). METHODS: T1D-MSCs and C-MSCs were isolated and cultured until third passage. Then, morphology, cell diameter, expression of surface markers, differentiation potential, global microarray analyses and immunosuppressive capacity were in vitro analyzed. T1D-MSCs and C-MSCs therapeutic potential were evaluated using a murine experimental model of streptozotocin (STZ)-induced diabetes. RESULTS: T1D-MSCs and C-MSCs presented similar morphology, immunophenotype, differentiation potential, gene expression of immunomodulatory molecules and in vitro immunosuppressive capacity. When administered into diabetic mice, both T1D-MSCs and C-MSCs were able to reverse hyperglycemia, improve beta cell function and modulate pancreatic cytokine levels. CONCLUSIONS: Thus, bone marrow MSCs isolated from T1D patients recently after diagnosis are not phenotypically or functionally impaired by harmful inflammatory and metabolic diabetic conditions. Our results provide support for the use of autologous MSCs for treatment of newly diagnosed T1D patients.

Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model.

Major skin burns are difficult to treat. Patients often require special care and long-term hospitalization. Besides specific complications associated with the wounds themselves, there may be impairment of the immune system and of other organs. Mesenchymal stromal cells (MSCs) are a recent therapeutic alternative to treat burns, mainly aiming to accelerate the healing process. Several MSC properties favor their use as therapeutic approach, as they promote angiogenesis, stimulate regeneration, and enhance the immunoregulatory function. Moreover, since patients with extensive burns require urgent treatment and because the expansion of autologous MSCs is a time-consuming process, in this present study we chose to evaluate the therapeutic potential of xenogeneic MSCs in the treatment of severe burns in rats. MSCs were isolated from mouse bone marrow, expanded in vitro, and intradermally injected in the periphery of burn wounds. MSC-treated rats presented higher survival rates (76.19%) than control animals treated with PBS (60.86%, p < 0.05). In addition, 60 days after the thermal injury, the MSC-treated group showed larger proportion of healed areas within the burn wounds (90.81 ± 5.05%) than the PBS-treated group (76.11 ± 3.46%, p = 0.03). We also observed that CD4(+) and CD8(+) T cells in spleens and in damaged skin, as well as the percentage of neutrophils in the burned area, were modulated by MSC treatment. Plasma cytokine (TGF-ß, IL-10, IL-6, and CINC-1) levels were also altered in the MSC-treated rats, when compared to controls. Number of injected GFP(+) MSCs progressively decreased over time, and 60 days after injection, few MSCs were still detected in the skin of treated animals. This study demonstrates the therapeutic effectiveness of intradermal application of MSCs in a rat model of deep burns, providing basis for future regenerative therapies in patients suffering from deep burn injuries.

Metabolic and pancreatic effects of bone marrow mesenchymal stem cells transplantation in mice fed high-fat diet.

The purpose of this study was to investigate the effects of multiple infusions of allogeneic MSCs on glucose homeostasis and morphometry of pancreatic islets in high- fat diet (HFD) fed mice. Swiss mice were fed standard diet (C group) or HFD (HFD group). After 8 weeks, animals of HFD group received sterile phosphate-buffered saline infusions (HFD-PBS) or four infusions of MSCs one week apart (HFD-MSCs). Fasting glycemia (FG) was determined weekly and glucose (GTT) and insulin (ITT) tolerance tests were performed 4, 8, 12, and 16 weeks after the infusions of MSCs. The MSCs transplanted mice were classified as responder (FG < 180 mg/dL, 72.2% of transplanted mice) or non-responder (FG > 180mg/dL, 28.8%) Seven weeks after MSCs infusions, FG decreased in HFD-MSCs responder mice compared with the HFD-PBS group. Sixteen weeks post MSCs infusions, GTT and ITT areas under the curve (AUC) decreased in HFD-MSCs responder mice compared to HFD-PBS group. Serum insulin concentration was higher in HFD-PBS group than in control animals and was not different compared with the other groups. The relative volume of α-cells was significantly smaller in HFD-PBS group than in C group and significantly higher in HFD-MSCs-NR than in HFD-PBS and HFD-MSCs-R groups. Cell apoptosis in the islets was higher in HFD-PBS group than in C group, and lower in HFD-MSCs responder mice than in HFD-PBS group and non-responder animals. The results demonstrate the ability of multiple infusions of MSCs to promote prolonged decrease in hyperglycemia and apoptosis in pancreatic islets and increase in insulin sensitivity in HFD fed mice.

Therapeutic efficacy and biodistribution of allogeneic mesenchymal stem cells delivered by intrasplenic and intrapancreatic routes in streptozotocin-induced diabetic mice.

INTRODUCTION: Mesenchymal stromal/stem cells (MSCs) are multipotent cells that have the ability to express and secrete a wide range of immunomodulatory molecules, cytokines, growth factors and antiapoptotic proteins. MSCs modulate both innate and adaptive immune responses making them potential candidates for the treatment of patients with type 1 diabetes mellitus (T1D). However, one problem frequently associated with the systemic MSCs administration is the entrapment of the cells mainly in the lungs. In this sense, trying to avoid the lung barrier, the purpose of this study was to evaluate the long-term therapeutic efficacy and biodistribution of allogeneic adipose tissue-derived MSCs (ADMSCs) injected via two different delivery routes (intrasplenic/I.Sp and intrapancreatic/I.Pc) in a murine model of diabetes induced by streptozotocin (STZ). METHODS: Experimental diabetes was induced in C57BL/6 male mice by multiple low-doses of STZ. MSCs were isolated from adipose tissue (ADMSCs) of Balb/c mice. A single dose of 1x10(6) ADMSCs was microinjected into the spleen or into the pancreas of diabetic mice. Control group received injection of PBS by I.Sp or I.Pc delivery routes. Glycemia, peripheral glucose response, insulin-producing ß cell mass, regulatory T cell population, cytokine profile and cell biodistribution were evaluated after ADMSCs/PBS administration. RESULTS: ADMSCs injected by both delivery routes were able to decrease blood glucose levels and improve glucose tolerance in diabetic mice. ADMSCs injected by I.Sp route reverted hyperglycemia in 70% of diabetic treated mice, stimulating insulin production by pancreatic ß cells. Using the I.Pc delivery route, 42% of ADMSCs-treated mice responded to the therapy. Regulatory T cell population remained unchanged after ADMSCs administration but pancreatic TGF-ß levels were increased in ADMSCs/I.Sp-treated mice. ADMSCs administrated by I.Sp route were retained in the spleen and in the liver and ADMSCs injected by I.Pc route remained in the pancreas. However, ADMSCs injected by these delivery routes remained only few days in the recipients. CONCLUSION: Considering the potential role of MSCs in the treatment of several disorders, this study reports alternative delivery routes that circumvent cell entrapment into the lungs promoting beneficial therapeutic responses in ADMSCs-treated diabetic mice.

Influence of fludarabine on the pharmacokinetics of oral busulfan during pretransplant conditioning for hematopoietic stem cell transplantation.

This study evaluated the influence of fludarabine on the pharmacokinetics of busulfan administered orally to patients receiving a conditioning regimen for hematopoietic allogeneic stem cell transplantation (HSCT). Twenty-six patients treated with oral busulfan (1 mg/kg/6 h for 4 days) were divided into two groups according to the concomitant administration of fludarabine (n = 11; 30 mg/m(2) for 5 days) or subsequent administration of cyclophosphamide (n = 15; 60 mg/kg for 2 days). Serial blood samples were collected on Day 4 of busulfan administration. Plasma busulfan concentrations were determined by HPLC-UV and the pharmacokinetic parameters were calculated using the WinNonlin program. Patients concomitantly treated with fludarabine showed reduced apparent clearance of busulfan (110.5 mL/h/kg vs. 157.4 mL/h/kg) and higher AUC0-6 (area under the plasma concentrations vs. time curve) than patients subsequently treated with cyclophosphamide (7.9 µg h/mL vs. 5.7 µg h/mL). No association was observed between busulfan AUC0-6 and clinical evolution of the patients. Although plasma busulfan concentrations were higher in patients receiving concomitant fludarabine, myelosuppression-related toxicity was less frequent than in patients treated with busulfan and cyclophosphamide. The results suggest that patients treated with fludarabine should receive 30% lower busulfan doses during conditioning protocols for HSCT.

Dynamic changes of the Th17/Tc17 and regulatory T cell populations interfere in the experimental autoimmune diabetes pathogenesis.

A balance between proinflammatory (Th17 and Tc17) and anti-inflammatory (regulatory T cells) subsets of T cells is essential to maintain immunological tolerance and prevent the onset of several autoimmune diseases, including type 1 diabetes. However, the kinetics of these subsets and disease severity during the streptozotocin (STZ)-induced diabetes course has not been determined. Thus, susceptible C57BL/6 mice were administrated with multiple low doses of STZ and we evaluated the frequency/absolute number of these T cell subsets in the pancreatic lymph nodes (PLNs) and spleen and Th1, Th17, Treg cytokine production in the pancreatic tissue. At different time points of the disease progression (6, 11, 18 and 25 days after the last STZ administration), the histopathological alterations were also evaluated by H&E and immunohistochemistry staining. During the initial phase of diabetes development (day 6), we noted increased numbers of CD4(+) and CD8(+) T cells in spleen and PLNs. At the same time, the frequencies of Th17 and Tc17 cells in PLNs were also enhanced. In addition, the early augment of interferon gamma (IFN-γ), tumoral necrosis factor (TNF-α), IL-6 and IL-17 levels in pancreatic tissue correlated with pancreatic islet inflammation and mild ß-cell damage. Notably, the absolute number of Treg cells increased in PLNs during over time when compared to control group. Interestingly, increased IL-10 levels were associated with control of the inflammatory process during the late phase of the type 1 diabetes (day 25). In agreement, mice lacking the expression of IL-17 receptor (Il17r) showed impairment in STZ-induced diabetes progression, reduced peri-insulitis and beta cells preservation when compared with wild-type mice. Our findings suggest that dynamic changes of pathogenic Th17/Tc17 and regulatory T cell subsets numbers is associated with early strong inflammation in the pancreatic islets followed by late regulatory profile during the experimental STZ-induced diabetes course.

Reappraisal of total body irradiation followed by bone marrow transplantation as a therapy for inflammatory bowel disease.

The main current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated inflammation in the gut. Although these therapies have been successful, they are not curative and it is not possible to predict whether a beneficial response will occur or which patients will be refractory to the treatment. Total body irradiation (TBI) associated with chemotherapy is the first choice in the treatment of some hematological disorders and is an applicable option in the preparation of patients with hematologic diseases for hematopoietic stem cell transplantation. Then, in this study we investigated the association of TBI as immunosuppressive therapy and bone marrow cell (BMC) transplantation as a strategy to induce colitis recovery and immune reconstitution in the TNBS model of intestinal inflammation. TNBS mice treated with TBI associated with BMC transplantation presented elevated gain of weight and an overall better outcome of the disease when compared to those treated only with TBI. In addition, TBI associated or not with BMC reduced the frequency of inflammatory cells in the gut and restored the goblet cell counts. These results were accompanied by a down regulation in the production of inflammatory cytokines in the colon of mice treated with TBI alone or in association with BMC transplantation. The BMC infused were able to repopulate the ablated immune system and accumulate in the site of inflammation. However, although both treatments (TBI or TBI+BMC) were able to reduce gut inflammation, TBI alone was not enough to fully restore mice weight and these animals presented an extremely reduced survival rate when their immune system was not promptly reconstituted with BMC transplantation. Finally, these evidences suggest that the BMC transplantation is an efficient strategy to reduce the harmful effects of TBI in the colitis treatment, suggesting that radiotherapy may be an important immunosuppressive therapy in patients with IBD, by modulating the local inflammatory response.

Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer.

Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFNγ signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFNγ in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFNγ and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFNγ (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFNγ mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFNγ axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.

Toward personalized cell therapies: autologous menstrual blood cells for stroke.

Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered source of stem cells with potential relevance for the treatment of stroke. Migration to the infarct site, modulation of the inflammatory reaction, secretion of neurotrophic factors, and possible differentiation warrant these cells as therapeutic tools. We here propose the use of autologous menstrual blood cells in the restorative treatment of the subacute phase of stroke. We highlight the availability, proliferative capacity, pluripotency, and angiogenic features of these cells and explore their mechanistic pathways of repair. Practical aspects of clinical application of menstrual blood cells for stroke will be discussed, from cell harvesting and cryopreservation to administration to the patient.

Qualidade de vida e transplante de células-tronco hematopoéticas alogênico: um estudo longitudinal / Quality of life following allogeneic, hematopoietic stem cell transplantation: a longitudinal study

Este estudo teve como objetivo avaliar a qualidade de vida de pacientes submetidos ao transplante de células-tronco hematopoéticas alogênico, comparando as fases pré-transplante de células-tronco hematopoéticas, o momento do isolamento protetor na Enfermaria e o pós-transplante de células-tronco hematopoéticas imediato. A amostra foi composta por sete pacientes (quatro homens e três mulheres) submetidos ao transplante de células-tronco hematopoéticas no primeiro semestre de 2008. Na coleta de dados foi utilizado o Questionário Genérico de Avaliação de Qualidade de Vida (SF-36), aplicado individualmente em situação face a face. A comparação das médias obtidas nas fases pré-transplante de células-tronco hematopoéticas e Enfermaria evidenciou diferença estatisticamente significante nos domínios Capacidade Funcional (p=0,022) e Dor (p=0,036). Comparando-se as etapas da Enfermaria e do pós-transplante de células-tronco hematopoéticas, evidenciou-se diferença significativa no Estado Geral de Saúde (p=0,036). Não foram encontradas diferenças estatisticamente significantes entre as variáveis no pré e pós-transplante de células-tronco hematopoéticas. Desse modo, comparando-se as três etapas do transplante foi possível verificar que houve depreciação da qualidade de vida durante o isolamento protetor na Enfermaria, seguida de recuperação dos aspectos mensurados.(AU)

This research aimed to assess the quality of life of patients undergoing allogeneic, hematopoietic stem cell transplantation, comparing the pre-hematopoietic stem cell transplantation phase with the phase of protective isolation in the ward and theimmediate post-hematopoietic stem cell transplantation. The sample comprised seven patients (four men and three women) who were submitted to this procedure in the first half of 2008. For the data collection, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used and individually applied in face-to-face situations. The comparison between mean data collected in the pre-hematopoietic stem cell transplantation phase and in the ward revealed a statistically significant difference in Functional Capacity (p=0.022) and Pain (p=0.036). When comparing the ward and post-hematopoietic stem cell transplantation phases, a significant difference in General Health (p=0.036) was clearly shown. There was no statistically significant difference between the pre- and post-hematopoietic stem cell transplantation variables. Thus, when comparing the three transplantation phases, it was found that the quality of life diminished during protective confinement in the ward, followed by the recovery of the evaluated aspects.(AU)

Qualidade de vida e transplante de células-tronco hematopoéticas alogênico: um estudo longitudinal / Quality of life following allogeneic, hematopoietic stem cell transplantation: a longitudinal study

Este estudo teve como objetivo avaliar a qualidade de vida de pacientes submetidos ao transplante de células-tronco hematopoéticas alogênico, comparando as fases pré-transplante de células-tronco hematopoéticas, o momento do isolamento protetor na Enfermaria e o pós-transplante de células-tronco hematopoéticas imediato. A amostra foi composta por sete pacientes (quatro homens e três mulheres) submetidos ao transplante de células-tronco hematopoéticas no primeiro semestre de 2008. Na coleta de dados foi utilizado o Questionário Genérico de Avaliação de Qualidade de Vida (SF-36), aplicado individualmente em situação face a face. A comparação das médias obtidas nas fases pré-transplante de células-tronco hematopoéticas e Enfermaria evidenciou diferença estatisticamente significante nos domínios Capacidade Funcional (p=0,022) e Dor (p=0,036). Comparando-se as etapas da Enfermaria e do pós-transplante de células-tronco hematopoéticas, evidenciou-se diferença significativa no Estado Geral de Saúde (p=0,036). Não foram encontradas diferenças estatisticamente significantes entre as variáveis no pré e pós-transplante de células-tronco hematopoéticas. Desse modo, comparando-se as três etapas do transplante foi possível verificar que houve depreciação da qualidade de vida durante o isolamento protetor na Enfermaria, seguida de recuperação dos aspectos mensurados.

This research aimed to assess the quality of life of patients undergoing allogeneic, hematopoietic stem cell transplantation, comparing the pre-hematopoietic stem cell transplantation phase with the phase of protective isolation in the ward and theimmediate post-hematopoietic stem cell transplantation. The sample comprised seven patients (four men and three women) who were submitted to this procedure in the first half of 2008. For the data collection, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used and individually applied in face-to-face situations. The comparison between mean data collected in the pre-hematopoietic stem cell transplantation phase and in the ward revealed a statistically significant difference in Functional Capacity (p=0.022) and Pain (p=0.036). When comparing the ward and post-hematopoietic stem cell transplantation phases, a significant difference in General Health (p=0.036) was clearly shown. There was no statistically significant difference between the pre- and post-hematopoietic stem cell transplantation variables. Thus, when comparing the three transplantation phases, it was found that the quality of life diminished during protective confinement in the ward, followed by the recovery of the evaluated aspects.

CXCL12 rs1801157 polymorphism and expression in peripheral blood from breast cancer patients.

The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3'A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p=0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.

Stem cell-based therapies and immunomodulatory approaches in newly diagnosed type 1 diabetes.

Type 1 diabetes mellitus is an autoimmune disease against pancreatic ß cells. The autoimmune response begins months or years before the clinical presentation. At the time of hyperglycemic symptoms a small amount of ß cell mass still remains. The main therapeutic option to type 1 diabetes mellitus is daily insulin injections which is shown to promote tighter glucose control and to reduce much of diabetic chronic complications. Subgroup analysis of the Diabetes Control and Complication Trial (DCCT) showed another important aspect related to long term complications of diabetes, ie, patients with initially larger residual ß cell mass suffered less microvascular complications and less hypoglycemic events than those patients with small amounts of ß cells at diagnosis. In face of this, ß cell preservation has become another important target in the management of type 1 diabetes and its related complications. In this review, we summarize various immunomodulatory regimens ever used in humans, including stem cell-based strategies, aiming at blocking autoimmunity against pancreatic ß cells and at promoting ß cell preservation and/or possible ß cell regeneration in recent-onset type 1 diabetes.

Impact of autologous hematopoietic stem cell transplantation on the quality of life of type 1 diabetes mellitus patients / Impacto do transplante de células-tronco hematopoéticas sobre a qualidade de vida de pacientes com diabetes mellitus tipo 1

The present study aimed at assessing the health-related quality of life (HRQoL) of patients with type 1 diabetes mellitus (DM1) submitted to autologous hematopoietic stem cell transplantation (HSCT). This study is part of a pioneering research protocol which tests the applicability of autologous hematopoietic stem cell transplantation as a new therapeutic approach to DM1. The study was conducted on 14 patients admitted to the ward of the Bone Marrow Transplantation Unit of a university hospital during the period from October 2006 to December 2007. The patients were evaluated at admission and on the occasion of the ambulatory return visit 100 days after transplantation. They answered the SF-36 quality of life questionnaire and the data were analyzed according to literature recommendations. The results showed that 100 days after transplantation the value of the patients' quality of life was higher compared to the pre-HSCT value, with significant differences in the Physical Domains (Role Limitations due to Physical Problems) (p = .009), Vitality (p = .02) and Mental Health (p = .04), demonstrating significant appreciation of those domains after the procedure. The results indicate an improvement in HRQoL after HSCT. The SF-36 proved to be a useful instrument for the assessment of quality of life in patients with DM1 submitted to HSCT.(AU)

Este estudo teve como objetivo avaliar a qualidade de vida relacionada à saúde (QVRS) de pacientes com diabetes mellitus tipo 1 (DM1) submetidos ao Transplante de Células-Tronco Hematopoéticas (TCTH). O estudo é parte de um protocolo de pesquisa pioneiro no mundo, que testa a aplicabilidade do TCTH como nova abordagem terapêutica no DM1. Foram investigados 14 pacientes, que constituíram a população de pessoas internadas na enfermaria da Unidade de Transplante de Medula Óssea de um hospital universitário, no período de outubro de 2006 a dezembro de 2007. Os pacientes foram avaliados na admissão e no retorno ambulatorial 100 dias pós-transplante com o questionário de qualidade de vida SF-36. Os resultados mostraram que, 100 dias após o transplante, a qualidade de vida apresentou valores superiores ao pré-TCTH, com diferenças significantes nos Aspectos Físicos (p = 0,009), Vitalidade (p = 0,02) e Saúde Mental (p = 0,04), evidenciando significativa apreciação nesses domínios após o procedimento. Os resultados sugerem que houve melhora na QVRS pós-TCTH.(AU)

Motivo de retirada do cateter de Hickman em pacientes submetidos ao transplante de células-tronco hematopoéticas / Rationale for Hickman catheter removal in patients undergoing hematopoietic stem cell transplantation / Motivo del retiro del catéter de Hickman en pacientes sometidos al transplante de células-tronco hematopoéticas

OBJETIVO: Identificar os motivos da retirada do primeiro cateter de Hickman implantado em pacientes submetidos ao transplante de células-tronco hematopoéticas alogênico, os micro-organismos envolvidos na ocorrência de infecção e o tempo de permanência do cateter in situ. MÉTODOS: Estudo transversal retrospectivo. A amostra foi constituída por 57 prontuários de pacientes transplantados. Para a obtenção dos dados, elaborou-se um instrumento contendo variáveis relativas à identificação do paciente, tempo de permanência do cateter, motivo de retirada e micro-organismo isolado. RESULTADOS: Dentre os motivos de retirada do cateter, destacou-se como o mais frequente a infecção (49 por cento). O Stenotrophomonas maltophilia (25 por cento) foi o micro-organismo identificado com maior frequência. CONCLUSÕES: Diante da elevada incidência de complicações infecciosas que levam à retirada do cateter de Hickman, faz-se necessária uma padronização de cuidados relacionados a esse cateter, tanto para a equipe de saúde como ao paciente e seu cuidador.

OBJECTIVE: To identify rationale for removal of the first Hickman catheter implanted in patients undergoing allogeneic hematopoietic stem cell transplantation, the micro-organisms involved in the occurrence of infection, and the length of time the catheter was in situ. METHODS: A cross sectional, retrospective study was conducted. The sample consisted of 57 transplant recipients. To conduct chart review, an instrument was developed containing variables related to patient identification, time of catheter use, reason for withdrawal, and isolated micro-organisms. RESULTS: Among the reasons for catheter removal, frequent infection (49 percent) was the most common; the Stenotrophomonas maltophilia microorganism (25 percent) was the most frequently isolated. CONCLUSIONS: Due to the high incidence of infectious complications leading to Hickman catheter removal, it is essential to standardize catheter care for the health care team, patients and their caregivers.

OBJETIVO: Identificar los motivos del retiro del primer catéter de Hickman implantado en pacientes sometidos al transplante de células-tronco hematopoéticas alogénico, los microorganismos involucrados en la ocurrencia de infección y el tiempo de permanencia del catéter in situ. MÉTODOS: Estudio transversal retrospectivo. La muestra estuvo constituída por 57 historias clínicas de pacientes transplantados. Para la obtención de los datos, se elaboró un instrumento conteniendo variables relativas a la identificación del paciente, tiempo de permanencia del catéter, motivo del retiro y microorganismo aislado. RESULTADOS: Entre los motivos del retiro del catéter, se destacó como el más frecuente la infección (49 por ciento). El Stenotrophomonas maltophilia (25 por ciento) fue el microorganismo identificado con mayor frecuencia. CONCLUSIONES: Frente a la elevada incidencia de complicaciones infecciosas que llevan al retiro del catéter de Hickman, se hace necesaria una patronización de cuidados relacionados a ese catéter, tanto para el equipo de salud como para el paciente y su cuidador.

Impact of autologous hematopoietic stem cell transplantation on the quality of life of type 1 diabetes mellitus patients / Impacto do transplante de células-tronco hematopoéticas sobre a qualidade de vida de pacientes com diabetes mellitus tipo 1

The present study aimed at assessing the health-related quality of life (HRQoL) of patients with type 1 diabetes mellitus (DM1) submitted to autologous hematopoietic stem cell transplantation (HSCT). This study is part of a pioneering research protocol which tests the applicability of autologous hematopoietic stem cell transplantation as a new therapeutic approach to DM1. The study was conducted on 14 patients admitted to the ward of the Bone Marrow Transplantation Unit of a university hospital during the period from October 2006 to December 2007. The patients were evaluated at admission and on the occasion of the ambulatory return visit 100 days after transplantation. They answered the SF-36 quality of life questionnaire and the data were analyzed according to literature recommendations. The results showed that 100 days after transplantation the value of the patients' quality of life was higher compared to the pre-HSCT value, with significant differences in the Physical Domains (Role Limitations due to Physical Problems) (p = .009), Vitality (p = .02) and Mental Health (p = .04), demonstrating significant appreciation of those domains after the procedure. The results indicate an improvement in HRQoL after HSCT. The SF-36 proved to be a useful instrument for the assessment of quality of life in patients with DM1 submitted to HSCT.

Este estudo teve como objetivo avaliar a qualidade de vida relacionada à saúde (QVRS) de pacientes com diabetes mellitus tipo 1 (DM1) submetidos ao Transplante de Células-Tronco Hematopoéticas (TCTH). O estudo é parte de um protocolo de pesquisa pioneiro no mundo, que testa a aplicabilidade do TCTH como nova abordagem terapêutica no DM1. Foram investigados 14 pacientes, que constituíram a população de pessoas internadas na enfermaria da Unidade de Transplante de Medula Óssea de um hospital universitário, no período de outubro de 2006 a dezembro de 2007. Os pacientes foram avaliados na admissão e no retorno ambulatorial 100 dias pós-transplante com o questionário de qualidade de vida SF-36. Os resultados mostraram que, 100 dias após o transplante, a qualidade de vida apresentou valores superiores ao pré-TCTH, com diferenças significantes nos Aspectos Físicos (p = 0,009), Vitalidade (p = 0,02) e Saúde Mental (p = 0,04), evidenciando significativa apreciação nesses domínios após o procedimento. Os resultados sugerem que houve melhora na QVRS pós-TCTH.

Bone marrow donation from the perspective of sibling donors.

This study aimed to characterize the sociodemographic profile of sibling bone marrow donors and to describe how they perceive the donation. This was a descriptive, exploratory and longitudinal study. Participants were 20 related bone marrow donors, between 18 and 42 years of age (mean=30.5 years, sd=7.47). Interviews were held before and immediately after the donation. Sociodemographic data were subject to descriptive statistical analysis and qualitative data to categorical content analysis. In the interviews held before the donation, stressor events were the sibling's disease and treatment and the responsibility of being the donors. During the interviews after the donation, the following were mentioned: anxiety on the day before and on the day of the donation, pain the following day, and acknowledgement of the health team's support as a facilitator of the donation process. In view of the findings, it is important for the team to outline intervention strategies to meet to the donors' specific needs.