ABSTRACT
AIMS: Several alternative cellular approaches using biomaterials to host insulin-producing cells derived from stem cells have been developed to overcome the limitations of type 1 diabetes treatment (exogenous insulin injection). However, none seem to fulfill all requirements needed to induce pancreatic cells successful colonization of the scaffolds. Here, we report a polymeric platform adherent to the native mice pancreas filled with human adipose stem cells (hASCs) that was able to induce growth of pancreatic parenchyma. MAIN METHODS: Synthetic polyether-polyurethane discs were placed adjacent to pancreas of normoglycemic and streptozotocin-induced diabetic mice. At day 4 post implantation, 1×106 hASCs were injected intra-implant in groups of normoglycemic and diabetic mice. Immunohistochemistry analysis of the implants was performed to identify insulin positive cells in the newly formed tissue. In addition, metabolic, inflammatory and angiogenic parameters were carried out in those mice. KEY FINDINGS: This study provides evidence of the ability of a biohybrid device to induce the growth of differentiated pancreas parenchyma in both normoglycemic and streptozotocin-induced diabetic mice as detected by histological analysis. Glucose metabolism and body weight of hyperglycemic mice bearing hASCs implants improved. SIGNIFICANCE: The synthetic porous scaffold bearing hASC cells placed adjacent to the native animal pancreas exhibits the potential to be exploited in future cell-based type 1 diabetes therapies.
Subject(s)
Adipose Tissue/metabolism , Diabetes Mellitus, Experimental , Extracellular Matrix/chemistry , Insulin-Secreting Cells/metabolism , Polyurethanes/chemistry , Regeneration , Stem Cell Transplantation , Stem Cells/metabolism , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/therapy , Heterografts , Humans , Insulin-Secreting Cells/pathology , Male , Mice , Stem Cells/pathologyABSTRACT
Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis, prevalent in Latin America, particularly in Brazil. Central nervous system (CNS) involvement occur in about 10% of cases. Thirteen patients with PCM involving CNS were studied considering clinical manifestation, neuroradiology and treatment modalities. Age ranged from 30 to 71 years-old (M=47.1+/-11.6 Me=46). There were eleven men and two women. The most frequent symptoms were motor deficits (53.8%), cognitive disturbance (53.8%), weight loss (46.1%), headaches (46.1%) and seizures (46.1%). The diagnosis was confirmed by the demonstration of P. brasiliensis. Granulomatous forms were present in all patients. Four (30.8%) of them had also meningeal involvement (mixed form). Computerized tomography (CT) scans were obtained in all cases and magnetic resonance imaging (MRI) was used in one case. Serology for HIV was done in ten patients (76.9%), and all the tests were negatives. Amphotericin B was used in twelve patients (92.3%), one of them by intraventricular infusion. In eight patients (61.5%), trimethopim and sulfamethoxazole were used, and, in two (15.4%), sulfadiazine and pirimetamine. Fluconazole, ketoconazole and itraconazole were each one used in a different patient as well. Six patients died (46.1%) and seven (53.9%) had satisfatory outcome. The follow-up period ranged from 2 to 74 (M=30.9) months. In conclusion, the CNS involvement in paracoccidioidomycosis is more frequent and more serious than thought before. The clinical manifestations, CT scans and MRI findings are not specific of paracoccidioidomycosis.
Subject(s)
Antifungal Agents/therapeutic use , Central Nervous System Fungal Infections/diagnosis , Paracoccidioides/isolation & purification , Paracoccidioidomycosis/diagnosis , Adult , Aged , Central Nervous System Fungal Infections/drug therapy , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Paracoccidioidomycosis/drug therapy , Tomography, X-Ray ComputedABSTRACT
A paracoccidioidomicose (PCM) é infecção granulomatosa sistêmica, causada pelo fungo Paracoccidioides brasiliensis, prevalente na América Latina, particularmente no Brasil. Acomete o sistema nervoso central (SNC) em 10 por cento dos casos. Foram estudados 13 pacientes com paracoccidioidomicose no SNC, entre 1991 e 2001, com ênfase para os aspectos clínicos, neuroradiológicos e terapêuticos. Onze pacientes eram do sexo masculino (84,6 por cento) e dois do feminino (15,4 por cento), com idade entre 30 e 71 anos (M= 47,1 ± 11,6 Me= 46). Os sintomas mais freqüentes foram déficits motores (53,8 por cento), alterações cognitivas (53,8 por cento), emagrecimento (46,1 por cento), cefaléia (46,1 por cento) e crises convulsivas (46,1 por cento). O diagnóstico foi confirmado pela detecção do P. brasiliensis no SNC. Todos os pacientes apresentavam a forma granulomatosa e quatro (30,8 por cento) tinham a forma meningoencefalítica associada. Todos foram estudados com tomografia computadorizada (TC) de crânio e um caso com ressonância magnética (RM) encefálica. Dez pacientes (76,9 por cento) realizaram sorologia para o HIV, todos com resultados negativos. A anfotericina B foi utilizada em 12 casos (92,3 por cento), em um deles por via intratecal. Em oito casos (61,5 por cento) o sulfametoxazol-trimetropim foi utilizado; em dois (15,4 por cento) a sulfadiazina e pirimetamina, e o fluconazol, cetoconazol e itraconazol, cada um deles em um paciente. Seis pacientes (46,1 por cento) morreram e sete evoluíram satisfatoriamente. O tempo de seguimento variou de 2 a 74 meses (M=30,9). Conclui-se que as manifestações clínicas assim como os exames de imagem na PCM do SNC são inespecíficos.
