ABSTRACT
Background: Lymphedema is a chronic, progressive clinical condition that evolves with intense fibrosis, the most advanced stage of which is stage III (lymphostatic fibrosclerosis). Aim: The aim of the present study was to show the possibility to reconstruct the dermal layers with the intensive treatment of fibrosis using the Godoy method. Case description: A 55-year-old patient with an eight-year history of edema of the lower limb of the leg had constant episodes of erysipelas, despite regular treatments. The edema progressed continually, associated with a change in the color of the skin and the formation of a crust. Intensive treatment (eight hours per day for three weeks) was proposed with the Godoy method. The ultrasound was performed and results revealed substantial improvement in the skin, with the onset of the reconstruction of the dermal layers. Conclusion: It is possible to reconstruct the layers of the skin in fibrotic conditions caused by lymphedema.
Subject(s)
Dermis , Fibrosis , Lymphedema , Skin Diseases , Humans , Middle Aged , Chronic Disease , Fibrosis/diagnostic imaging , Fibrosis/etiology , Fibrosis/pathology , Fibrosis/therapy , Lymphedema/complications , Lymphedema/diagnostic imaging , Lymphedema/pathology , Lymphedema/therapy , Skin/diagnostic imaging , Skin/pathology , Skin Diseases/complications , Skin Diseases/diagnostic imaging , Skin Diseases/pathology , Skin Diseases/therapy , Dermis/diagnostic imaging , Dermis/pathology , Ultrasonography/methodsABSTRACT
ABSTRACT A 27-year-old healthy man with a history of bilateral photorefractive keratectomy (PRK) enhancement after femtosecond laser in situ keratomileusis (LASIK) presented with decreased uncorrected distance visual acuity (UDVA) of 20/125 in the right eye (OD) and 20/300 in the left eye (OS) six months after PRK. Examination revealed bilateral dense subepithelial opacities. Both eyes (OU) were treated with superficial keratectomy combined with phototherapeutic keratectomy (PTK) and adjunctive application of mitomycin C 0.02%. At three months follow up UDVA was 20/30 OD and 20/25 OS. Superficial keratectomy combined with PTK seems to be a safe and efficient technique for treatment of dense subepithelial scar formation following PRK enhancement after LASIK.
RESUMO Um homem saudável de 27 anos de idade com história de aprimoramento com ceratectomia fotorrefrativa (PRK) bilateral, após Ceratomileuse Assistida por Excimer Laser In Situ (LASIK) com laser de femtossegundos, apresentou diminuição da acuidade visual à distância não corrigida (AVNC) de 20/125 no olho direito (OD) e 20/300 no olho esquerdo (OE) seis meses após PRK. O exame revelou opacidades subepiteliais densas bilaterais. Ambos os olhos (AO) foram tratados com queratectomia superficial combinada com ceratectomia fototerapêutica (PTK) e aplicação adjuvante de mitomicina C a 0,02%. Aos três meses de acompanhamento, o AVNC foi de 20/30 OD e 20/25 OE. A ceratectomia superficial combinada com PTK parece ser uma técnica segura e eficiente para o tratamento da formação densa de cicatrizes subepiteliais após o aprimoramento com PRK pós-LASIK.
Subject(s)
Humans , Male , Adult , Fibrosis/therapy , Photorefractive Keratectomy/adverse effects , Wound Healing , Fibrosis/etiology , Visual Acuity , Mitomycin/administration & dosage , Photorefractive Keratectomy/methods , Corneal Opacity/diagnosis , Corneal Opacity/etiology , Corneal Topography , Keratomileusis, Laser In Situ , Debridement , Corneal Surgery, Laser , Slit Lamp Microscopy , Myopia/surgeryABSTRACT
Schistosomiasis is a parasitic disease that affects about 166 million people around the world. It is estimated that 5%-10% of individuals with schistosomiasis develop severe forms of the disease, which are characterized by pulmonary hypertension, ascites, periportal fibrosis, and other significant complications. The chronic phase of the disease is associated with a Th2 type immune response, but evidence also suggests there are roles for Th1 and Th17 in the development of severe disease. The aim of this study was to evaluate the CD4+ T lymphocyte profile of patients with different degrees of periportal fibrosis secondary to schistosomiasis. These individuals had been treated for schistosomiasis, but since they live in a S. mansoni endemic area, they are at risk of reinfection. They were evaluated in relation to the degree of periportal fibrosis and classified into three groups: without fibrosis or with incipient fibrosis (WF/IFNE), n=12, possible periportal fibrosis/periportal fibrosis, n=13, and advanced periportal fibrosis/advanced periportal fibrosis with portal hypertension, n=4. We observed in the group without fibrosis a balance between the low expression of Th2 cytokines and high expression of T reg cells. As has already been described in the literature, we found an increase of the Th2 cytokines IL-4, IL-5, and IL-13 in the group with periportal fibrosis. In addition, this group showed higher expression of IL-17 and IL-10 but lower IL-10/IL-13 ratio than patients in the WF/IFNE group. Cells from individuals who present any level of fibrosis expressed more TGF-ß compared to the WF/IFNE group and a positive correlation with left lobe enlargement and portal vein wall thickness. There was a negative correlation between IL-17 and the thickness of the portal vein wall, but more studies are necessary in order to explore the possible protective role of this cytokine. Despite the fibrosis group having presented a higher expression of pro-fibrotic molecules compared to WF/IFNE patients, it seems there is a regulation through IL-10 and T reg cells that is able to maintain the low morbidity of this group.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Fibrosis/etiology , Fibrosis/metabolism , Schistosoma/immunology , Schistosomiasis/complications , Schistosomiasis/parasitology , Animals , Biomarkers , Cytokines/metabolism , Disease Susceptibility , Female , Fibrosis/pathology , Humans , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismABSTRACT
PURPOSE: Weekly irradiation in breast cancer in elderly patients is a treatment option, whose tolerance may be influenced by the fractionation used. The objective of this study is to compare the tolerance and long-term side effects of two different fractionations. MATERIALS AND METHODS: 47 elderly patients were recruited after conservative or radical treatment that also received irradiation with a dose per fraction of 6.25 Gy or 5 Gy for one session per week, 6 sessions in total. The long-term tolerance results are compared by assessing toxicity using CTCAE version 5.0 scales for dermatitis, telangectasia, fibrosis and pain of the irradiated breast. In addition, objective parameters of skin status (erythema, hyperpigmentation, elasticity and hydration) by a multi-probe MultiSkin Test-Center system were obtained and compared between groups. RESULTS: After an average follow-up of 5 years, all patients were free of disease and with complete local control. A total of 20 patients with 6.25 Gy fractionation and 27 patients with 5 Gy fractionation have been included. Patients treated with lower fractionation had a lower incidence of dermatitis, telangectasia, fibrosis, or local pain. The decrease in elasticity measured by the multi-probe system was smaller with the fractionation of 5 Gy. No differences were observed in the other objective parameters. CONCLUSION: Weekly irradiation with 5 Gy fractionation is better tolerated than with higher fractionation.
Subject(s)
Breast Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Dermatitis/epidemiology , Dermatitis/etiology , Female , Fibrosis/epidemiology , Fibrosis/etiology , Humans , Margins of Excision , Pain/epidemiology , Pain/etiology , Radiation Injuries/epidemiology , Radiation Tolerance , Radiotherapy Dosage , Telangiectasis/epidemiology , Telangiectasis/etiology , Time FactorsABSTRACT
Abstract Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.
Resumo Introdução: A fibrose renal é o desfecho de um processo iniciado no transplante, com reperfusão, isquemia e inflamação precoce, que progride ao longo do tempo com fenômenos imunológicos e não imunológicos. A identificação de marcadores morfológicos e a intervenção precoce poderiam melhorar a função e a sobrevida do enxerto. Objetivo: Avaliar a correlação entre intensidade e especificidade de anticorpos anti-HLA pré-transplante alterações histológicas do enxerto renal, de forma a identificar fatores de risco ou marcadores de disfunção precoces do aloenxerto. Métodos: O presente estudo incluiu uma coorte retrospectiva de receptores de transplante renal sensibilizados com anticorpos anti-HLA no pré-transplante submetidos a biópsia de enxerto nos primeiros dois anos após o transplante. Os grupos foram divididos em função da especificidade dos anticorpos anti-HLA: sem anticorpos doador-específicos (não-DSA, n = 29) e com anticorpos doador-específicos (DSA+, n = 16). Alterações histológicas do enxerto renal, função renal e proteinúria foram analisados. Resultados: Os dois grupos tinham características gerais semelhantes, exceto pela dose mais elevada de timoglobulina administrada nos indivíduos do grupo DSA+ (p < 0,05). O grupo não-DSA teve escores mais elevados de glomeruloesclerose, inflamação intersticial (i) e fibrose intersticial (ci) (p < 0,05), além de maior incidência de rejeição celular aguda (RCA). Não foi observada diferença estatística na incidência de rejeição mediada por anticorpos, função renal ou proteinúria durante o seguimento. Discussão e Conclusões: A diferença nos escores de inflamação e fibrose intersticial pode estar associada à maior incidência de RCA e nefropatia por poliomavírus no grupo não-DSA. Devemos considerar ainda o efeito protetor das doses mais elevadas de timoglobulina na redução da lesão por isquemia-reperfusão no grupo DSA+. O curto período de seguimento pode ter sido insuficiente para detectar alterações de longo prazo no tecido do aloenxerto, função renal e proteinúria.
Subject(s)
Humans , Male , Female , Middle Aged , Kidney Transplantation/adverse effects , Transplant Recipients , Graft Rejection/immunology , HLA Antigens/immunology , Kidney/immunology , Antibodies/blood , Proteinuria/diagnosis , Time Factors , Biopsy , Fibrosis/etiology , Reperfusion Injury/prevention & control , Retrospective Studies , Immunosuppression Therapy/methods , Treatment Outcome , Disease Progression , Preoperative Period , Graft Rejection/pathology , Kidney/blood supply , Antibody SpecificityABSTRACT
En las últimas décadas, los cambios en el estilo de vida pro-vocaron un incremento en la prevalencia del síndrome meta-bólico y que la enfermedad por hígado graso no alcohólico (nonalcoholic fatty liver disease, NAFLD sus siglas en inglés) se convierta en la enfermedad hepática crónica más fre-cuente en todo el mundo. Los componentes del síndrome metabólico no son sólo altamente prevalentes en pacientes con hígado graso no alcohólico, sino que a la vez aumentan el riesgo de desarrollarlo. Esta relación bidireccional ha sido claramente establecida. Asimismo se considera que NAFLD podría ser el componente hepático del síndrome metabólico. Aunque NAFLD se considera principalmente una enfermedad benigna, puede progresar a fibrosis hepática grave y carcino-ma hepatocelular (CHC), incluso se encontraría este último en hígados no cirróticos. El objetivo de esta revisión es determinar los procesos fisio-patológicos comunes a estas entidades, cuáles son las estra-tegias diagnósticas recomendadas y cuáles las intervenciones terapéuticas actualmente aprobadas.
Subject(s)
Humans , Male , Female , Carcinoma, Hepatocellular/etiology , Metabolic Syndrome/etiology , Non-alcoholic Fatty Liver Disease/complications , Liver Neoplasms/etiology , Fibrosis/etiology , Fibrosis/physiopathology , Fibrosis/therapy , Risk Factors , Carcinoma, Hepatocellular/physiopathology , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/diagnostic imaging , Metabolic Syndrome/diagnosis , Metabolic Syndrome/physiopathology , Metabolic Syndrome/therapy , Diabetes Mellitus/etiology , Diabetes Mellitus/physiopathology , Diabetes Mellitus/therapy , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/physiopathology , Non-alcoholic Fatty Liver Disease/therapy , Liver Neoplasms/physiopathology , Liver Neoplasms/therapy , Liver Neoplasms/diagnostic imagingABSTRACT
PURPOSE OF REVIEW: The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features. RECENT FINDINGS: Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.
Subject(s)
Diabetes Mellitus/genetics , Pancreas, Exocrine/pathology , Pancreatitis, Chronic/genetics , Trypsin/genetics , Acute Disease , Carcinoma, Pancreatic Ductal/etiology , Chymotrypsin/genetics , Diabetes Complications/complications , Diabetes Mellitus/diagnosis , Diabetes Mellitus/physiopathology , Diabetes Mellitus/therapy , Exocrine Pancreatic Insufficiency/genetics , Exocrine Pancreatic Insufficiency/physiopathology , Exocrine Pancreatic Insufficiency/therapy , Fibrosis/etiology , Humans , Pancreas, Exocrine/physiopathology , Pancreatic Neoplasms/etiology , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/physiopathology , Recurrence , Risk Factors , Trypsin Inhibitor, Kazal Pancreatic/geneticsABSTRACT
Maternal endotoxemia has been shown to increase renal collagen deposition in the offspring. Renal fibrosis is a hallmark of progressive chronic kidney disease. It was investigated whether maternal reactive oxygen species (ROS) leads to renal fibrosis or exacerbates unilateral ureteral obstruction (UUO)-induced renal fibrosis in the offspring of dams treated with lipopolysaccharide (LPS). Furthermore, it was studied the role of matrix metalloproteinases (MMPs) in these changes. Adults Wistar rats were obtained from dams submitted to LPS administration through the third part of gestation. To evaluate the role of maternal ROS, part of the dams received α-tocopherol simultaneously with LPS. Part of the offspring in each group was submitted to UUO at adulthood when sub-groups were treated with NADPH oxidase inhibitor, apocynin. Maternal LPS administration increased proteinuria, systolic arterial pressure and renal collagen deposition in adult offspring. LPS offspring rats also presented higher MMP-2 activity in parallel to a decreased renal cortical TIMP-2 content. These changes were correlated to increased amounts of TGF-ß1 and NOX2. Maternal α-tocopherol treatment prevented collagen deposition and reduced arterial pressure in adult offspring. α-Tocopherol also inhibited maternal endotoxemia-induced changes in TGF-ß1/NOX2/MMP-2 signaling. UUO led to increased collagen deposition in the contralateral kidneys of LPS offspring, which was correlated to increased NADPH oxidase activity and prevented by NADPH oxidase inhibition. In summary, maternal endotoxemia led to alterations in the TGF-ß1/NOX2/MMP-2 signaling pathway in renal tissue concomitant with collagen deposition, therefore contributing to hypertension in adult offspring.
Subject(s)
Collagen/metabolism , Endotoxemia/complications , Kidney Diseases/etiology , Kidney/metabolism , Prenatal Exposure Delayed Effects/metabolism , Signal Transduction/physiology , Animals , Endotoxemia/chemically induced , Extracellular Matrix/metabolism , Female , Fibrosis/etiology , Fibrosis/metabolism , Lipopolysaccharides , Male , Matrix Metalloproteinase 2/metabolism , NADPH Oxidase 2/metabolism , Pregnancy , Rats, Wistar , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta1/metabolism , Ureteral Obstruction/complications , Ureteral Obstruction/metabolism , alpha-Tocopherol/pharmacologyABSTRACT
BACKGROUND & AIMS: Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. METHODS: Mice with HSC-selective deletion of NRP (ColCre/Nrp1loxP) or synectin (ColCre/synectinloxP) vs. paired Nrp1loxP or synectinloxP mice were fed a control diet or the chronic/binge alcohol feeding model. Several markers of steatosis and inflammation were evaluated. RESULTS: ColCre/Nrp1loxP mice showed less fibrosis, as expected, but also less inflammation and steatosis, with lower hepatic triglyceride content. Similar results were observed in the synectin model. Hepatocytes treated with supernatant of HSCs from ColCre/Nrp1loxP mice compared to supernatant from Nrp1loxP mice were protected against ethanol-induced lipid droplet formation. An adipokine and inflammatory protein array from the supernatant of HSCs with NRP-1 knockdown showed a significant reduction in Igfbp3 (a major insulin-like growth factor-binding protein with multiple metabolic functions) and an increase in SerpinA12 (a serine-protease inhibitor) secretion compared to wild-type HSCs. Recombinant Igfbp3 induced lipid droplets, triglyceride accumulation, and lipogenic genes in hepatocytes in vitro, while SerpinA12 was protective against ethanol-induced steatosis. Finally, Igfbp3 was increased, and SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. CONCLUSION: Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. LAY SUMMARY: Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Fatty Liver, Alcoholic , Hepatic Stellate Cells/metabolism , Insulin-Like Growth Factor Binding Protein 3/metabolism , Neuropilin-1/metabolism , Serpins/metabolism , Animals , Disease Models, Animal , Fatty Liver, Alcoholic/complications , Fatty Liver, Alcoholic/metabolism , Fatty Liver, Alcoholic/pathology , Fibrosis/etiology , Fibrosis/immunology , Inflammation/metabolism , Mice , Serine Proteinase Inhibitors/metabolism , Signal TransductionABSTRACT
INTRODUCTION: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. OBJECTIVE: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. METHODS: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. RESULTS: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. DISCUSSION AND CONCLUSIONS: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.
Subject(s)
Antibodies/blood , Graft Rejection/immunology , HLA Antigens/immunology , Kidney Transplantation/adverse effects , Kidney/immunology , Transplant Recipients , Antibody Specificity , Biopsy , Disease Progression , Female , Fibrosis/etiology , Graft Rejection/pathology , Humans , Immunosuppression Therapy/methods , Kidney/blood supply , Kidney/pathology , Male , Middle Aged , Preoperative Period , Proteinuria/diagnosis , Reperfusion Injury/prevention & control , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Chicken fat and fructose are added into food-processing to reduce costs and enhance acceptability; however, these additives turn food into unhealthy and hypercaloric meals. Herein we have hypothesized that chronic feeding with chicken fat and fructose, together or by separate, can cause pulmonary redox and inflammatory changes. These changes are particularly related to neutrophils and myeloperoxidase, with consequent changes in the organ histophysiology. To test this hypothesis, we fed mice for 16 weeks with either control food (low-fat diet, LFD) or control food supplemented with 22% chicken fat and with or without 10% fructose in the drinking water. At the end of the feeding regimen, we measured redox and inflammatory changes in the lung with particular emphasis on neutrophil accumulation/activation and molecular-histological markers of fibrosis. Our results suggest that a diet supplemented with chicken fat and fructose causes additive effects on pulmonary oxidative stress, inflammation, and a pro-fibrotic status. Neutrophilic inflammation may play a critical role in pulmonary pathology associated with metabolic syndrome.
Subject(s)
Diet, High-Fat/adverse effects , Fibrosis/etiology , Neutrophils/pathology , Pneumonia/etiology , Animals , Inflammation/etiology , Lung/metabolism , Mice , Oxidation-Reduction , Oxidative Stress , Pneumonia/metabolism , Pneumonia/pathologyABSTRACT
IL-9 is a pleiotropic cytokine, recently recognized as belonging to Th9 cells that are involved in various pathologies. We aimed to evaluate the role of IL-9 in the course of hepatic and renal fibrosis. Female C57BL/6 mice were treated subcutaneously with IL-9 10 ng/mouse and 20 ng/mouse for 40 days, alternating every 5 days each application, the negative control of which was treated with PBS and positive control with CCL4. IL-9 demonstrated fibrogenic activity, leading to increased collagen I and III deposition in both liver and kidney, as well as triggering lobular hepatitis. In addition, IL-9 induced an inflammatory response with recruitment of lymphocytes, neutrophils, and macrophages to both organs. The inflammation was present in the region of the portal and parenchymal zone in the liver and in the cortical and medullary zone in the kidney. IL-9 deregulated liver and kidney antioxidant activities. Our results showed that IL-9 was able to promote hepatorenal dysfunction. Moreover, IL-9 poses as a promising target for therapeutic interventions.
Subject(s)
Fibrosis/etiology , Interleukin-9/adverse effects , Kidney/pathology , Liver/pathology , Animals , Collagen/metabolism , Female , Inflammation/chemically induced , Inflammation/pathology , Kidney/physiology , Liver/physiology , Mice , Mice, Inbred C57BLSubject(s)
Asbestos/adverse effects , Immunoglobulin G4-Related Disease/complications , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Pleura/pathology , Pleural Diseases/etiology , Retroperitoneal Fibrosis/etiology , Aged , Fibrosis/etiology , Humans , Male , Sclerosis/etiology , SternumABSTRACT
Abstract Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed.We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery. (AU)
Subject(s)
Animals , Vocal Cords/pathology , Fascia Lata/transplantation , Fibroblast Growth Factors/pharmacology , Rabbits , Fibrosis/etiology , Laryngeal Diseases/congenital , Inflammation/chemically induced , Neovascularization, Pathologic/etiologyABSTRACT
ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.
Subject(s)
Animals , Male , Rats , Pyrazines/therapeutic use , Ureteral Obstruction/complications , NF-E2-Related Factor 2/therapeutic use , Kidney Diseases/drug therapy , Thiones , Thiophenes , Ureteral Obstruction/pathology , Ureteral Obstruction/drug therapy , Fibrosis/etiology , Fibrosis/drug therapy , Immunohistochemistry , Cadherins/blood , Rats, Wistar , Disease Models, Animal , Transforming Growth Factor beta1/blood , Hydroxyproline/blood , Kidney Diseases/etiology , Kidney Diseases/pathology , Nitric Oxide/bloodABSTRACT
PURPOSE: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®. METHODS: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index. RESULTS: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000). CONCLUSION: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.
Subject(s)
Abdominal Wall/pathology , Collagen/adverse effects , Polyesters/adverse effects , Polyglactin 910/adverse effects , Polypropylenes/adverse effects , Surgical Mesh/adverse effects , Abdominal Wall/surgery , Animals , Collagen/administration & dosage , Fibrosis/etiology , Fibrosis/pathology , Materials Testing , Models, Animal , Polyesters/administration & dosage , Polyglactin 910/administration & dosage , Polypropylenes/administration & dosage , Time Factors , Tissue Adhesions/etiology , Tissue Adhesions/pathologyABSTRACT
Abstract Purpose: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®. Methods: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index. Results: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000). Conclusion: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.
Subject(s)
Animals , Polyesters/adverse effects , Polyglactin 910/adverse effects , Polypropylenes/adverse effects , Surgical Mesh/adverse effects , Collagen/adverse effects , Abdominal Wall/pathology , Polyesters/administration & dosage , Polyglactin 910/administration & dosage , Polypropylenes/administration & dosage , Time Factors , Fibrosis/etiology , Fibrosis/pathology , Materials Testing , Tissue Adhesions/etiology , Tissue Adhesions/pathology , Collagen/administration & dosage , Models, Animal , Abdominal Wall/surgeryABSTRACT
INTRODUCTION: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. MATERIALS AND METHODS: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-ß1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. RESULTS: TGF-ß1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. CONCLUSIONS: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.
Subject(s)
Kidney Diseases/drug therapy , NF-E2-Related Factor 2/therapeutic use , Pyrazines/therapeutic use , Ureteral Obstruction/complications , Animals , Cadherins/blood , Disease Models, Animal , Fibrosis/drug therapy , Fibrosis/etiology , Hydroxyproline/blood , Immunohistochemistry , Kidney Diseases/etiology , Kidney Diseases/pathology , Male , Nitric Oxide/blood , Rats , Rats, Wistar , Thiones , Thiophenes , Transforming Growth Factor beta1/blood , Ureteral Obstruction/drug therapy , Ureteral Obstruction/pathologyABSTRACT
Fundamento: O transplante hepático (TH) é cirurgia de grande porte indicada para tratamento de portadores de cirrose avançada e está associado a diversos riscos. Por esta razão, faz-se necessário estratificar o risco no período pré- transplante através da avaliação da função miocárdica e pesquisa de doença coronariana. Objetivo: Demonstrar a aplicabilidade da ressonância miocárdica cardíaca (RMC) na avaliação morfofuncional cardíaca, bem como seu uso na avaliação da isquemia miocárdica no pré-transplante. Método: Realizou-se estudo retrospectivo e descritivo, sendo avaliados dados de pacientes cirróticos encaminhados ao ambulatório de TH no período de Janeiro/2014 a Julho/2016 que se submeteram a RMC para avaliação cardíaca e como teste provocativo de isquemia miocárdica. Resultados: Foram encaminhados 135 pacientes; destes, 39 realizaram RMC. A idade média foi de 60 anos (50 a 71). Cerca de 87% (n = 34) eram do sexo masculino. Prevaleceu etiologia etanólica 56% (n = 22). A maioria era de pacientes CHILD C, MELD ≥ 18, (n = 26). A RMC evidenciou isquemia miocárdica em 03 pacientes (7,6%). A cineangiocoronariografia foi realizada nestes pacientes e a presença de doença arterial coronariana grave (obstrução > 70%) foi confirmada em todos, com consequente revascularização miocárdica. Em um seguimento de até 2 anos e 7 meses, a sobrevida dos transplantados foi de 87%, sem intercorrências cardiológicas. Conclusões: A realização da RMC na avaliação de cirróticos no pré-transplante mostrou-se estratégia segura ao evidenciar a presença de alterações morfofuncionais da cardiomiopatia do cirrótico e a presença de isquemia miocárdica. Entretanto, novos estudos devem ser realizados para padronização de métodos e critérios para avaliação cardiovascular em cirróticos
Background: Liver transplantation (LT) is a huge surgery performed to treat patients with advanced liver cirrhosis and is associated with several risks. For this reason, is necessary to stratify the risk in the pre-transplantation period through the evaluation of myocardial function and ischemia Objective: To demonstrate the applicability of cardiac magnetic resonance (CMR) in cardiac morphologic and functional evaluation, as well use in the evaluation of myocardial ischemia in pre-transplantation. Methods: Retrospective, descriptive study. Data from patients with cirrhosis referred to the liver transplant outpatient clinic from January 2014 to July 2016 were analyzed they underwent CMR for cardiac evaluation and as provocative test of myocardial ischemia. Results: 135 patients were referred of these, 39 performed CMR. The mean age was 60 (50 to 71). About 87% (n = 34) were males. Alcoholic etiology prevailed 56% (n = 22). Most were of CHILD C patients with MELD ≥ 18, (n = 26). CMR showed myocardial ischemia in 03 patients (7,6%). Coronary angiography was performed and presence of severe coronary artery disease (obstruction > 70%) was confirmed, with consequent myocardial revascularization. At a follow-up of 2 years and 7 months, the survival of transplanted patients was 87%, without cardiologic complications. Conclusions: The realization of CMR in the evaluation of cirrhotic patients in the pre-transplantation proved to be a safe strategy by showing presence of morphologic and functional changes of the cirrhotic cardiomyopathy and the presence of myocardial ischemia. However, more studies should be performed to standardize methods and criteria for cardiovascular evaluation in cirrhotic patients before the liver transplantation
Subject(s)
Humans , Male , Female , Middle Aged , Fibrosis/etiology , Liver Transplantation/methods , Magnetic Resonance Spectroscopy/methods , Myocardial Revascularization/methods , Patient Selection/ethics , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Coronary Artery Disease/etiology , Coronary Artery Disease/physiopathology , Diagnostic Imaging/methods , Echocardiography/methods , Heart Ventricles , Liver/physiopathology , Myocardial Ischemia/complications , Myocardial Ischemia/diagnosis , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: Here, we present the first reported case of intraoperative optical coherence tomography (OCT)-assisted Descemet membrane stripping automated endothelial keratoplasty (DSAEK) in a patient with anterior segment fibrous ingrowth. METHODS: A 61-year-old woman with corneal edema and chronic angle-closure glaucoma secondary to fibrous ingrowth after 2 glaucoma shunt device implantations underwent dissection and removal of anterior chamber fibrous ingrowth and DSAEK. The surgical techniques using intraoperative OCT and outcome are described. RESULTS: Intraoperative OCT provided a clear dissection plane of the fibrous membranes in the anterior chamber and view of their relation to the iris and corneal endothelium, despite an opacified cornea. The placement of the donor lenticule and absence of interface fluid were also verified intraoperatively. The postoperative course was uncomplicated with satisfactory outcome. CONCLUSIONS: We conclude that intraoperative OCT is a useful tool during DSAEK surgery, particularly in complicated cases such as anterior segment fibrous ingrowth and significant corneal edema.