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Kidney function may be impaired during pregnancy due to various reasons, and the physiological changes of pregnancy may unmask or worsen pre-existing kidney disease. Herein, we report a pregnant patient presenting with nephrotic-range proteinuria. She later developed acute kidney injury and pre-eclampsia. However, hemolytic anemia and thrombocytopenia persisted after delivery, and she was diagnosed with atypical hemolytic uremic syndrome (aHUS). Although hematological abnormalities resolved with eculizumab treatment, her renal functions did not improve. Kidney biopsy showed crescentic glomerulonephritis without thrombotic microangiopathy features. Concurrently, she was evaluated for hearing impairment, and a diagnosis of Alport syndrome was confirmed with genetic testing. Kidney function may worsen in patients with Alport syndrome during pregnancy. However, crescentic glomerulonephritis (GN) is a rare finding in Alport disease. Pauci-immune crescentic GN has been shown to be related to dysregulated activation of the alternative complement pathway, which is also the underlying pathophysiological mechanism in aHUS.
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BACKGROUND: Antiphospholipid syndrome (APS), particularly the catastrophic antiphospholipid syndrome (CAPS), is one of the rare causes of thrombotic microangiopathy (TMA). CAPS is the most severe form of APS, especially when accompanied by complement dysregulation, causes progressive microvascular thrombosis and failure in multiple organs. In this report, a case of CAPS with TMA accompanied by a genetic defect in the complement system is presented. CASE: A 13-year-old girl was admitted to the hospital with oliguric acute kidney injury, nephrotic range proteinuria, Coombs positive hemolysis, refractory thrombocytopenia, a low serum complement C3 level and anti-nuclear antibody (ANA) positivity. The kidney biopsy was consistent with TMA. She was first diagnosed with primary APS with clinical and pathological findings and double antibody positivity. As initial treatments, plasmapheresis (PE) was performed and eculizumab was also administered following pulsesteroid and intravenous immunoglobulin treatments. Her renal functions recovered and she was followed up with mycophenolate mofetil, hydroxychloroquine, low dose prednisolone and low molecular weight heparin treatments. The patient presented with severe chest pain, vomiting and acute deterioration of renal functions a few months after the diagnosis of TMA. A CAPS attack was considered due to radiological findings consistent with multiple organ thrombosis and intravenous cyclophosphamide (CYC) was given subsequent to PE. After pulse CYC and PE treatments, her renal functions recovered, she is still being followed for stage-3 chronic kidney disease. Complement factor H-related protein I gene deletion was detected in the genetic study. CONCLUSIONS: The clinical course of complement mediated CAPS tends to be worse. Complement system dysregulation should be investigated in all CAPS patients, and eculizumab treatment should be kept in mind if detected.
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Síndrome Antifosfolípido , Trombosis , Microangiopatías Trombóticas , Femenino , Humanos , Adolescente , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/genética , Microangiopatías Trombóticas/complicaciones , Microangiopatías Trombóticas/tratamiento farmacológico , Trombosis/etiología , Genes Reguladores , MutaciónRESUMEN
AIM: To understand the characterization of the ossification process both in the synostotic suture, and the adjacent parietal bone. MATERIAL AND METHODS: The surgical procedure for the 28 patients diagnosed with sagittal synostosis consisted of removing the synostotic bone as a whole, if possible, "Barrel-Stave" relaxation osteotomies, and strip osteotomies to the parietal and temporal bones perpendicular to the synostotic suture. The synostotic (group I) and parietal (group II) bone segments are obtained during osteotomies. Atomic absorption spectrometry was used to determine the amount of calcium in both groups, which is an indicator of ossification. Scanning electron microscopy and immunohistochemistry were employed to assess trabecular bone formation, osteoblastic density, and osteopontin, which is one of the in vivo indicators of new bone formation. RESULTS: Histopathologically, trabecular bone formation scores did not indicate any significant difference between the groups. However, the osteoblastic density and calcium accumulation in group I were higher than those in group II, and the difference was significant. Osteopontin staining scores in cells showing membranous and cytoplasmic staining with osteopontin antibodies significantly increased in group II. CONCLUSION: In this study, we found reduced differentiation of osteoblasts despite their increase in number. Moreover, the osteoblastic maturation rate was low in synostotic sutures, bone resorption becomes slower than new bone formation, and the remodeling rate is low in sagittal synostosis.
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Craneosinostosis , Osteopontina , Humanos , Niño , Lactante , Suturas Craneales/patología , Hueso Parietal/cirugía , Calcio , Craneosinostosis/cirugía , Craneosinostosis/patología , SuturasRESUMEN
PURPOSE: To determine expression differences of urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p and concentration differences of urinary BLCA-4, NMP22, APE1/Ref1, CRK, VIM between bladder cancer, follow-up patients, and control samples, to evaluate diagnostic importance of these differences and establish a diagnostic panel for bladder cancer. METHODS: Urine samples of 59 bladder cancer patients, 34 healthy controls, and 12 follow-up patients without recurrence were enrolled to this study. Real-time PCR and ELISA were performed to determine urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p expressions and urinary BLCA-4, NMP22, APE1/Ref1, CRK, VIM, creatinine concentrations. Logistic regression analyses were performed to determine the diagnostic panel, the sensitivity, and specificity of the panel assessed by the ROC curve analysis. p values < 0.05 were considered statistically significant. RESULTS: In bladder cancer risk groups, mir-139, -136, -19 and 210 expressions or positivity were found to be different and concentrations of urinary Ape1/Ref1, BLCA4, CRK, and VIM increased by twofold on average compared to healthy controls. Logistic regression and ROC analyses revealed that panel could differentiate bladder cancer patients from healthy controls with 80% sensitivity and 88% specificity (AUC = 0.899), low-risk patients from controls with 93% sensitivity and 95.5% specificity (AUC = 0.976). Despite the low number of samples, our findings suggest that urine exosomal miR-19b1-5p, 136-3p, 139-5p expression, and urinary APE1/Ref1, BLCA-4, CRK concentrations are promising candidates in terms of bladder cancer diagnosis. CONCLUSIONS: Although our panel has great sensitivity for early detection of BC, it needs to be validated in larger populations.
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Biomarcadores de Tumor/orina , MicroARNs/orina , Proteínas Nucleares/orina , Urinálisis/métodos , Neoplasias de la Vejiga Urinaria , Diagnóstico Diferencial , Exosomas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/orinaRESUMEN
INTRODUCTION: Inflammatory myofibroblastic tumor is a rare disease which is typically seen in children and young adults. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in over-expression of anaplastic lymphoma kinase gene. Herein, we present two anaplastic lymphoma kinase-positive cases with long-term remission with crizotinib. We do not know how long these therapies need to be continued. CASE REPORTS: We present two cases of inflammatory myofibroblastic tumor treated with anaplastic lymphoma kinase inhibitor therapies: an 8-year-old Turkish boy and a 21-year-old Caucasian man. MANAGEMENT AND OUTCOME: Two cases, both with good tumor control under crizotinib, but one who progressed on drug holiday, responded again to the same drug, and had a very short period of response after restarting crizotinib. CONCLUSION: A molecular-targeted drug (anaplastic lymphoma kinase inhibitor) was found to be extremely effective as selective therapy for inflammatory myofibroblastic tumor with anaplastic lymphoma kinase translocation. Here, we want to emphasize the continuation of this treatment after achieving a good response until progression or a major side effect.
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Quinasa de Linfoma Anaplásico/genética , Antineoplásicos/administración & dosificación , Crizotinib/administración & dosificación , Neoplasias de Tejido Muscular/tratamiento farmacológico , Neoplasias de Tejido Muscular/genética , Translocación Genética/genética , Niño , Humanos , Masculino , Miositis/diagnóstico por imagen , Miositis/tratamiento farmacológico , Miositis/genética , Neoplasias de Tejido Muscular/diagnóstico por imagen , Inhibidores de Proteínas Quinasas/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Gökçe I, Altuntas Ü, Filinte D, Alpay H. Polyarteritis nodosa in case of familial Mediterranean fever. Turk J Pediatr 2018; 60: 326-330. Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied by peritonitis, pleuritis, and arthritis. Protracted febrile myalgia syndrome (PFMS) is a rare form of vasculitic disease which is an uncommon dramatic manifestation of FMF, characterized by severe crippling myalgia and high fever. Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis affecting medium or small arteries. It is rarely observed in children, but its incidence increases in the presence of FMF. In this article we described a 14-year-old child diagnosed with FMF associated with PAN. Physicians should be aware of this possible association.
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Fiebre Mediterránea Familiar/complicaciones , Poliarteritis Nudosa/complicaciones , Adolescente , Azatioprina/uso terapéutico , Colchicina/uso terapéutico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Masculino , Poliarteritis Nudosa/tratamiento farmacológico , Prednisolona/uso terapéutico , Piel/patología , Moduladores de Tubulina/uso terapéuticoRESUMEN
OBJECTIVE: The present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model. METHODS: Thirty female Sprague-Dawley underwent experimental pharyngoesophagotomy and were grouped depending on the material used for pharyngocutaneous fistula closure: group I, which received primary sutures alone, group II, which received bacterial cellulose alone; and group III, which received both. After 7 days, the rats were sacrificed. Pharyngocutaneous fistula development was assessed, the gross wound was inspected, and histological examination was conducted. RESULTS: Pharyngocutaneous fistulae developed in 12 rats (41%) in all: 6 from group I (21%), 4 from group II (14%) and 2 from group III (7%). CONCLUSION: Fibroblast density and inflammatory cell infiltration were significantly greater in group III than group I. We concluded that bacterial cellulose may be useful for pharyngocutaneous fistula closure.
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Celulosa/uso terapéutico , Fístula Cutánea/terapia , Fibroblastos/patología , Enfermedades Faríngeas/terapia , Técnicas de Sutura , Animales , Fístula Cutánea/patología , Femenino , Laringectomía , Enfermedades Faríngeas/patología , Complicaciones Posoperatorias/terapia , Ratas , Ratas Sprague-DawleyRESUMEN
The most important problem in fat transplantation is the unpredictable rates of resorption. Deferoxamine (DFO) is an iron-chelating agent with many useful functions including stimulating angiogenesis and antioxidant nature. The purpose of the study is to evaluate the effects of DFO on fat graft viability in rat model. A total of 24 Wistar rats were divided into three groups and 0.5 g of the left inguinal fat pad was extracted. In control group, fat grafts were implanted to the parascapular area without performing any procedure. In sham group, they were implanted in 0.2 mL saline solution followed by serial saline injections for 1 month. In the study group, fat grafts were implanted in 0.2 mL saline solution and 300 mg DFO followed by serial DFO injections for 1 month. At the postoperative second month, fat grafts were taken back and sent for histopathologic examination. The weight measurements of biopsy specimens in the study group demonstrated significantly higher than in the other two groups. Inflammation and fibrosis rates were also found to be significantly higher in the study group compared with the other groups; however, no significant difference in the apoptosis rates was detected between the groups. Fat grafts enriched with DFO showed significant increase in fatty tissue content in the study group compared with the control and sham groups. DFO increases the fat graft survival in rats and it may be a useful addition in autologous fat grafting procedures to increase fat graft viability and obtain maximal long-term durability.
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Tejido Adiposo/trasplante , Deferoxamina/uso terapéutico , Supervivencia de Injerto/efectos de los fármacos , Sideróforos/uso terapéutico , Animales , Femenino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Botulinum toxin type-A (Bot-A) is a commonly used drug for both cosmetic and therapeutic purposes. The effects of Bot-A on skin and muscle flaps and the related mechanisms have been described previously. In this study, we used a rat transverse rectus abdominis musculocutaneous (TRAM) flap model to examine the effects of Bot-A on the skin island, which is perfused by the rectus abdominis muscle according to the angiosome concept. METHODS: Forty female rats were divided into five groups, including control and sham groups. In the control group, a TRAM flap was raised and sutured back after inserting a silicone sheath underneath the flap. In the sham group, the flap was raised 1 month after injecting saline into the muscle. In the chemical delay group, the flap was raised 1 month after injecting 10 IU of Bot-A. In the surgical delay group, the flap was raised 2 weeks after ligating the cranial epigastric artery. In the surgical and chemical delay group, a Bot-A injection was performed initially, a cranial epigastric artery was ligated after 2 weeks, and a TRAM flap was raised after the first month. In all groups, laser Doppler examination, photographic documentation, and analysis of the flap survival rates were performed. In the histopathological evaluation, the diameter measurements of the caudal epigastric vessels, vascular density measurements using CD31 stain, and apoptotic rate estimation using the Tunnel method were performed. RESULTS: The necrosis ratios, arterial cross-sectional diameters, and microvascular density measurements were significantly superior compared to those of control and sham groups; however, there was no significant difference between the delay groups. There was also no difference in the laser Doppler measurements between the groups and the zones of the TRAM flaps. CONCLUSION: An injection of Bot-A increases muscular circulation and flap survival of TRAM flaps in rats.
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Toxinas Botulínicas Tipo A/farmacología , Supervivencia de Injerto/efectos de los fármacos , Mamoplastia , Colgajo Miocutáneo/irrigación sanguínea , Animales , Arterias Epigástricas/diagnóstico por imagen , Femenino , Inyecciones , Flujometría por Láser-Doppler/métodos , Mamoplastia/efectos adversos , Mamoplastia/métodos , Modelos Anatómicos , Fármacos Neuromusculares/farmacología , Ratas , Recto del Abdomen/trasplante , Resultado del TratamientoRESUMEN
BACKGROUND: Postoperative atrial fibrillation (POAF) may develop after coronary artery bypass grafting (CABG). The aim of the study was to explore the relationship between preoperative left atrial function and atrial fibrosis and POAF after CABG. METHODS: Forty-eight consecutive patients undergoing CABG (mean age: 61.6±8.9 years, 39 male) were included. All patients were in sinus rhythm during surgery. Patients were followed by continuous electrocardiography monitoring and daily electrocardiogram. Left atrial function was assessed by both conventional and speckle tracking echocardiography. Atrial fibrosis was determined by samples taken from right atrium. RESULTS: Postoperative atrial fibrillation was detected in 13 patients. Female sex and number of bypassed vessels were significantly higher and cardiopulmonary bypass time was significantly longer in patients with POAF. Left atrial volume index (LAVI) was significantly higher while left atrial reservoir strain was significantly lower in POAF patients. The percentage of patients with severe fibrosis was higher in the POAF group. Regression analysis revealed fibrosis and LAVI as independent predictors of POAF. Left atrial volume index ≥36mL/m(2) predicted POAF with a sensitivity of 84.6% and specificity of 68.6% in our cohort. CONCLUSION: Patients who developed POAF after CABG had more fibrosis, increased LAVI and lower left atrial reservoir strain. Preoperative echocardiography might be helpful in discriminating these patients.
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Fibrilación Atrial , Puente de Arteria Coronaria/efectos adversos , Ecocardiografía , Complicaciones Posoperatorias/diagnóstico por imagen , Anciano , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/etiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Purpose The most important problem in fat transplantation is the durability, which is closely associated with the applied technique. This study includes the comparison of different centrifugation speeds on the survival of autogenous fat grafts in rats. Materials and methods Forty-nine Sprague-Dawley rats were divided into seven groups and the left inguinal fat pad was extracted and re-implanted under the scalp after performing appropriate preparation processes. In the first group the fatty tissue was re-implanted in en-bloc fashion and in the second group it was re-implanted after trimming. After trimming, centrifugation with a G-force of 111.8 (1000 rpm) was performed in the third group, 447.2 (2000 rpm) in the fourth group, 1006.2 (3000 rpm) in the fifth group, 1788.8 (4000 rpm) in the sixth group, and 2795 (5000 rpm) in the seventh group for 4 minutes. The fat grafts were taken after 3 months and histopathological and statistical evaluations were performed. Results The rate of viable fat grafts was significantly higher in the 4th and 5th groups comparing to the first three groups. Total weight and volume amounts of the 4th and 5th groups were also significantly higher comparing to the first three groups. Conclusion Maximal long-term durability and fat cell viability results were obtained in the groups with 2000 rpm or 447.2 G-force/4 minutes and 3000 rpm or 1006.2 G-force/4 minutes centrifugation speed, indicating that 4 minutes centrifugation with an average G-force of 698.75 or 2500 rpm provides the best results for the survival of autogenous fat grafts.
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Grasa Abdominal/trasplante , Centrifugación , Supervivencia Tisular , Animales , Recuento de Células , Supervivencia Celular , Ratas Sprague-Dawley , Manejo de EspecímenesRESUMEN
OBJECTIVES: In recent studies, collagen organization was blamed for the formation of capsular contracture which is still a challenging problem after silicone implant-based breast operations. In this study, effects of different concentrations of collagenase enzyme derived from Clostridium histolyticum on the capsular tissue formation around the silicone implants were investigated. The injectable form of collagenase has a routine clinical use in the treatment of both Dupuytren's and Peyronie's diseases. MATERIALS AND METHODS: Thirty-two Wistar albino rats were randomized into four groups. A 2 × 1 × 0.3-cm-sized silicone block was inserted inside a dorsal subcutaneous pocket in all groups. After 2 months of insertion, capsule thicknesses around the implants were detected under ultrasonography. This was followed by injection of isotonic saline, 150, 300, and 600 IU in Gr-1, 2, 3, and 4, respectively. All the animals were sacrificed at the end of the first week for histologic sampling to determine fibroblast proliferation, vessel density of the tissue, necrosis, edema, inflammation, and capsule thickness. All the data were statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests and compared for significance of the results. RESULTS: There was no significant difference in terms of capsule thinning between the 300 and 600 IU groups but in both groups thinning was significantly higher than the sham group. In the 150 IU group there was no significant thinning as compared to the sham group (p > 0.05). However, complications such as skin necrosis, infection, and seroma formation were seen only in the 600 IU injection group. The optimal safe and effective dose of the enzyme was accepted as 300 IU. The 300 IU injection provided up to 89 % thinning in the capsule tissue. There was thinning of the collagen bundles parallel to capsule thickness. In the 600 IU group, micro-pores were encountered at the thinnest points. CONCLUSION: However, the late results and recurrence rates of capsular contracture were not included in this study; collagenase seemed effective for the reduction of capsular tissue around the implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Implantes de Mama/efectos adversos , Colagenasas/administración & dosificación , Contractura Capsular en Implantes/tratamiento farmacológico , Contractura Capsular en Implantes/etiología , Geles de Silicona/efectos adversos , Animales , Femenino , Inyecciones Intralesiones , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
OBJECTIVE: The marginal, basal and subchorial regions of the placenta are considered to be more hypoxic than other regions. Therefore, it is not recommended to determine the increase in syncytiotrophoblast knots, based on the major morphological change in placental hypoxia, from the samples taken from these regions. However, the normal count of knots at various regions of placenta is not investigated. MATERIAL AND METHOD: In this study we have sampled morphologically and clinically normal placenta with eccentric cord insertion from various sites, either close to cord entrance or away from it (marginal, non-marginal basal, non-marginal subchorial, and nonmarginal midparanchymal). The number of knots was calculated on a total of at least 100 villi for each placental sample. The normal amount of knots in different regions and comparison between them were investigated. Twenty-eight placentas with eccentric cord insertion were sampled in the same manner. Hot spots from the above mentioned regions were counted in a total of 100 villi. RESULTS: No significant difference was found between the dual comparison of the mean percentages of different regions (p: 0.148). The variety of hypoxia in different regions of the placenta could not be demonstrated in this study. CONCLUSION: It is found that there is no difference in perfusion that can be morphologically demonstrated with increase in syncytiotrophoblast knot, between different regions of placenta.
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Placenta/irrigación sanguínea , Placenta/citología , Trofoblastos/citología , Recuento de Células , Hipoxia de la Célula , Femenino , Humanos , Circulación Placentaria , EmbarazoRESUMEN
We describe the case of a 60-year-old woman who presented with pulmonary artery sarcoma, a very rare tumor of the cardiovascular system. Her tumor was initially misdiagnosed as chronic pulmonary thromboembolism, and she underwent pulmonary endarterectomy. Early diagnosis of primary pulmonary artery sarcoma is crucial. That alternative should always be considered before settling on a diagnosis of pulmonary embolism. Suspicion should be aroused by the failure of anticoagulant treatment to alleviate pulmonary perfusion abnormalities and systemic symptoms. Surgical resection of the tumor-preferably by pulmonary endarterectomy, followed by reconstruction as needed-is currently the most promising treatment for pulmonary artery sarcoma.
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Arteria Pulmonar , Embolia Pulmonar/diagnóstico , Sarcoma/diagnóstico , Neoplasias Vasculares/diagnóstico , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Sarcoma/cirugía , Neoplasias Vasculares/cirugíaRESUMEN
New strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1% aerosolized OVA. 5×10(5) ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice.
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Asma/terapia , Células Madre Embrionarias/fisiología , Células Caliciformes/patología , Pulmón/inmunología , Células Madre Pluripotentes/fisiología , Trasplante de Células Madre , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Enfermedad Aguda , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Asma/inmunología , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Madre Embrionarias/trasplante , Eosinófilos/inmunología , Humanos , Hiperplasia , Inmunoglobulina E/sangre , Terapia de Inmunosupresión , Pulmón/patología , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos BALB C , MicroARNs/genética , Células Madre Pluripotentes/trasplante , Neumonía , Trasplante HomólogoRESUMEN
New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (P<0.001). Intravenous administration of mCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (P<0.001). We showed that GFP-labeled MSCs were located in the lungs of OVA group 2weeks after intravenous induction. mCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA+MSC group) (P<0.037). Our studies revealed that mCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma.
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Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Asma , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Alérgenos , Animales , Asma/inmunología , Asma/patología , Asma/terapia , Diferenciación Celular , Modelos Animales de Enfermedad , Fémur/citología , Pulmón/inmunología , Pulmón/patología , Linfocitos/inmunología , Ratones Endogámicos BALB C , Ovalbúmina , Neumonía/inmunología , Neumonía/patología , Neumonía/terapia , Linfocitos T Reguladores/inmunología , Tibia/citologíaRESUMEN
CONTEXT: Solid pseudopapillary tumor of the pancreas is a rare neoplasm, predominantly observed in young women and with greatest incidence in the second and third decade. Although large at the time of diagnosis, it has clinically good behavior. The occurrence of infiltrating varieties of solid pseudopapillary tumors is very rare. CASE REPORT: We report the case of a 48-year-old man with a giant mass in the pancreas, incidentally discovered during an abdominal ultrasonography. The mass was later investigated using multidetector computed tomography and magnetic resonance imaging. The lobulated lesion had cystic-necrotic appearances which lead the radiologists to suggest the possibility of either a gastrointestinal stromal tumor or a pancreatic cancer. The patient was operated. Operative signs showed that the tumor invaded the splenic hilum and mesentery of transverse colon. En-block resection of pancreas, spleen and transverse colon was performed as the mass was thought to be a locally advanced pancreas tumor. Pathological diagnosis reported a solid pseudopapillary tumor. CONCLUSION: Although solid pseudopapillary tumor is considered a rare tumor, with a very rare rate of locally infiltrating variety, and rarely presents in males, it must be kept in mind while making the differential diagnosis of cystic pancreatic lesions to begin appropriate clinical management.
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Carcinoma Papilar/diagnóstico , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Carcinoma Papilar/cirugía , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Páncreas/cirugía , Neoplasias Pancreáticas/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is characterized by neovascularization, increased inflammation, and interstitial fibrosis of the peritoneum. We investigated the effects of imatinib on the peritoneal membrane in an experimental EPS model. METHODS: We separated 24 non-uremic Wistar rats into four groups: the control group which was injected with 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks, the CG group which was injected with chlorhexidine gluconate (CG) IP daily for 3 weeks, the resting group which was injected with CG IP between weeks 0-3 followed by a peritoneal rest period between weeks 3-6, and the CG + Imatinib mesylate group (CG + IMA) which received CG through weeks 0-3 followed by 50 mg/kg imatinib mesylate through weeks 3-6. At the end of the study, we performed a 1-h-peritoneal equilibration test and examined the peritoneal function and transforming growth factor-ß1 (TGF-ß1) in dialysate. Morphologic changes were evaluated by microscopy and immunohistochemistry. RESULTS: An increased ultrafiltration, dialysate/plasma-creatinine-ratio, end-to-initial-dialysate-glucose-ratio, decreased active mesothelial cell ratio and inflammation, and a slightly decreased TGF-ß1 of dialysate were found in the CG + IMA group compared to CG alone. Furthermore, the CG + IMA group had a lower concentration of active mesothelial cells than did the resting group. Ultrafiltration was improved in CG + IMA group compared to resting group, however, significant decrease in peritoneal thickness and inflammation were not found compared to those in resting group. Furthermore, there was no significant difference in fibrosis or TGF-ß1-positivity on immunohistochemistry between the groups. CONCLUSIONS: Tyrosine kinase inhibition with imatinib may lead to a decrease in mesothelial cell activity and an increase in ultrafiltration. However, peritoneal fibrosis was unchanged by imatinib in EPS model.