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This study aimed to compare the pre- and post-operative temporomandibular joint (TMJ) condylar position in dentofacial deformity (DFD) patients who had orthognathic surgeries using cone beam computed tomography (CBCT). A retrospective study evaluating the pre- and post-operative CBCT for 79 DFD patients (equivalent to 158 TMJs) (mean age = 26.62 ± 9.5 years) with a bilateral sagittal split osteotomy with or without Le Fort I surgeries (n = 29 Class II DFD, n = 50 Class III DFD) was performed. This included the compartmental measurement of TMJ spaces, in addition to the measurement of intercondylar distances and angles. Condylar position centricity was assessed using the Pullinger and Hollender formula. Clinical data were analysed for DFD class, the type of surgery and post-operative CBCT timing. Pre- and post-operative measurements were compared statistically using a paired t-test, Wilcoxon signed-rank test, and Stuart-Maxwell test. TMJ condyles tended to relocate post-operatively in a posterosuperior position with internal rotation in Class II DFD and a superior position with internal rotation in Class III DFD. However, the overall changes were within <0.5 mm translation and <4° rotation and the number of concentrically positioned condyles (according to the Pullinger and Hollender formula) did not change significantly. Orthognathic surgery is associated with minor post-operative translational and rotational condylar positional changes in Class II and III DFDs.
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Objective: In Germany, only a few standardized evaluation tools for assessing the usability of mobile Health apps exist so far. This study aimed to translate and validate the English patient version for standalone apps of the mHealth App Usability Questionnaire (MAUQ) into a German version. Methods: Following scientific guidelines for translation and cross-cultural adaptation, the patient version for standalone apps was forward and back-translated from English into German by an expert panel. In total, 53 participants who were recruited as part of the beta testing process of the recently developed mHealth app HerzFit, answered the questions of the German version of the MAUQ (GER-MAUQ) and the System Usability Scale. Subsequently, a descriptive as well as a psychometric analysis was performed to test validity and reliability. Results: After conducting three cognitive interviews, five items were modified. The values for Cronbach alpha for the entire questionnaire and the three subscales (0.966, 0.814, 0.910, and 0.909) indicate strong internal consistency. The correlation analysis revealed that the scores of the GER-MAUQ, the subscales and the SUS were strongly correlated with each other. The correlation coefficient of the SUS and the GER-MAUQ overall score was r = 0.854, P < 0.001 and the coefficients of the subscales and the SUS were r = 0.642, P < 0.001; r = 0.866, P < 0.001 and r = 0.643, P < 0.001. Conclusions: We have developed a novel German version of the MAUQ and demonstrated it as a reliable and valid measurement tool for assessing the usability of standalone mHealth apps from the patients' perspective. The GER-MAUQ allows a new form of standardized assessment of usability of mHealth apps for patients with cardiovascular disease in Germany. Further research with a larger sample and other samples is recommended.
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BACKGROUND: In Germany, there is no data available on the frequency of inpatient rehabilitation (IR) after elective endovascular (EVAR) and open (OAR) abdominal aortic aneurysm (AAA) repair. OBJECTIVE: To report for the first time on the outcome of patients 65 years and older and thus of retirement age with and without IR after AAA repair in a retrospective analysis of routine data from all eleven regional companies of the AOK health insurance fund (AOK-Gesundheit). METHODS: Anonymized data of 16,358 patients 65 years and older with intact abdominal aortic aneurysm treated with EVAR (nâ¯=â¯12,960) or OAR (nâ¯=â¯3,398) between 01/01/2010 and 12/31/2016 were analyzed. Patients with postoperative IR (nâ¯=â¯1,531) were compared to those without postoperative IR (nâ¯=â¯14,827) with respect to general patient characteristics, comorbidities, perioperative and postoperative outcomes, and survival. The average follow-up of patients with postoperative and without postoperative IR was 49.9 months and 51.8 months, respectively. RESULTS: 5.4% of EVAR patients, but 24.6% of OAR patients were referred to IR (pâ¯<â¯0.001). Patients with IR were sicker than those without IR. Parameters significantly influencing the use of IR included OAR vs EVAR (Odds Ratio [OR] 6.03), condition after cerebral infarction (OR 1.53), and women vs men (OR 1.49). Perioperative influencing parameters were cerebral infarction (OR 2.40), blood transfusions (OR 2.21) and complex critical care (OR 2.15). After nine years, the Kaplan-Meier estimated survival was 41.9% for patients with vs 43.4% for those without IR in the EVAR group (pâ¯=â¯0.178). For OAR, it was 50.2% for patients with IR vs 49.8% for patients without IR (pâ¯=â¯0.006). In multivariate regression analysis, postoperative IR had a significant effect on long-term survival in OAR but not in EVAR patients. CONCLUSION: There are no generally binding guidelines for the indication of IR after AAA repair. It should therefore be a requirement for the future that the fitness of each patient with elective AAA repair be determined with a score before and after the procedure in order to make indications for AHB more comparable. The score should be documented in the hospital discharge letter.
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Aneurisma de la Aorta Abdominal , Procedimientos Endovasculares , Masculino , Humanos , Femenino , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Pacientes Internos , Factores de Riesgo , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Tiempo , Alemania , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/etiología , Infarto Cerebral/etiología , Complicaciones Posoperatorias/epidemiologíaRESUMEN
PURPOSE: To identify prognostic factors for patients with neuroendocrine liver metastases (NELM) undergoing conventional transarterial chemoembolization (c-TACE), microwave ablation (MWA), or laser interstitial thermotherapy (LITT) and to determine the most effective therapy regarding volume reduction of NELM and survival. MATERIALS AND METHODS: Between 1996 and 2020, 130 patients (82 men, 48 women) were treated with c-TACE, and 40 patients were additionally treated with thermal ablation. Survival was retrospectively analyzed using the Kaplan-Meier-method. Additional analyses were performed depending on the therapeutic intention (curative, palliative, symptomatic). Prognostic factors were derived using Cox regression. To find predictive factors for volume reduction in response to c-TACE, a mixed-effects model was used. RESULTS: With c-TACE, an overall median volume reduction of 23.5â% was achieved. An average decrease in tumor volume was shown until the 6th c-TACE treatment, then the effect stopped. C-TACE interventions were most effective at the beginning of c-TACE therapy, and treatment breaks longer than 90 days negatively influenced the outcome. Significant prognostic factors for survival were number of liver lesions (pâ=â0.0001) and type of therapeutic intention (pâ<â0.0001). Minor complications and one major complication occurred in 20.3â% of LITT and only in 8.6â% of MWA interventions. Complete ablation was observed in 95.7â% (LITT) and 93.1â% (MWA) of interventions. CONCLUSION: New prognostic factors were found for survival and volume reduction. Efficacy of c-TACE decreases after the 6th intervention and treatment breaks longer than 90 days should be avoided. With thermal ablation, a high rate of complete ablation was achieved, and survival improved. KEY POINTS: · Number of liver lesions and therapeutic intention are prognostic factors for survival.. · Regarding volume reduction, C-TACE is most effective at the beginning of treatment and longer treatment breaks should be avoided.. · With MWA and LITT, a high rate of complete ablation was achieved. MWA trends toward fewer complications than LITT in the treatment of NELM (pâ=â0.07)..
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Hipertermia Inducida , Neoplasias Hepáticas , Tumores Neuroendocrinos , Masculino , Humanos , Femenino , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Tumores Neuroendocrinos/terapia , Quimioembolización Terapéutica/métodos , Hipertermia Inducida/métodos , Terapia Combinada , Resultado del TratamientoRESUMEN
BACKGROUND: Having cancer adversely effects the outcome of treatment for an unruptured abdominal aortic aneurysm (AAA). METHODS: A retrospective secondary analysis was performed on the basis of anonymized data from AOK, a German nationwide statutory healthinsurance carrier. Data were evaluated from all of the 20 683 patients who underwent either endovascular (EVAR, 15 792) or open surgical (OAR, 4891) treatment for an unruptured AAA in the years 2010-2016. It was determined in each case whether the patient had a known cancer at the time of the procedure to treat AAA. The analysis concerned patient characteristics, periprocedural complications, and survival after the procedure up to 31 December 2018. RESULTS: 18 222 patients were free of cancer. In accordance with the known 6:1 sex ratio of AAA, 85.3% of the cancer-free patients and 92.8% of those with cancer were men. At the time of their AAA procedure, 1398 had cancer of the intestine (n = 318), lung (n = 301), prostate (n = 380), or bladder or ureter (n = 399). One-year survival after the AAA procedure was 91.5% in cancer-free patients and 84%, 74.4%, 85.8%, and 85.5% in the patients with the respective types of cancer just mentioned. Having cancer was a significant risk factor for periprocedural mortality (OR 1.326, p = 0.041) and for long-term survival (HR 1.515; p < 0.001). CONCLUSION: Having cancer is a risk factor for periprocedural mortality and long-term survival in patients undergoing treatment for an unruptured AAA. This implies that the indications for surgery should be considered with care, particularly in patients with lung cancer, whose 5-year survival rate is only 37.2%.
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INTRODUCTION AND HYPOTHESIS: The use of synthetic mesh for prolapse and incontinence surgery is discussed controversially and in several countries is either no longer used or permissible. Previous approaches with autologous tissue did not show from a patient´s perspective convincing long-term results. As there have been repeatedly significant complications with synthetic mesh, a new approach is urgently needed. During orthopedics and trauma surgeries, tendons from the thigh have been used for decades to replace cruciate ligament. The procedure of tendon removal from the thigh is fast, easy to learn and morbidity is low. In addition, a long-term durability of the transplant ought to be expected. The objective of this investigation was to show our experience with a semitendinosus tendon instead of a mesh for genital prolapse repair. METHOD: After the first successful attempts using such tendons in cervicosacropexy and pectopexy in patients with genital prolapse, we initiated a national multicenter study in 2020. Five German hospitals participated in order to determine the feasibility of cervicosacropexy with tendon tissue instead of mesh. RESULT: Up until now, we have operated and observed 113 patients for at least 6 months and have seen stable results in terms of fixation of the apical compartment. The expected low morbidity at the donor site was also confirmed through subjective assessment of the patients (Knee and Osteoarthritis Outcome Score). Improvement of quality of life was confirmed after the procedure with the Short Form Health Survey 12, Version 2.0. The results of this multicenter study showed that the desired elevation of the apical compartment with tendon tissue can be achieved with low morbidity and without a synthetic mesh. CONCLUSION: Women with uterine prolapse can be treated minimally invasively and with very low morbidity by using the semitendinosus tendon. The involvement of multiple (five) medical centers confirms that the technique is easy to learn and be transferred to other clinical centers.
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OBJECTIVE: Endovascular aortic aneurysm repair (EVAR) has been established as a standard treatment option for intact abdominal aortic aneurysm (iAAA) and gained importance due to a lower perioperative mortality than open repair (OAR). However, whether this survival advantage can be maintained or if OAR is beneficial in terms of long-term complications and reinterventions remains questionable. DESIGN: In this retrospective cohort study data from patients undergoing elective EVAR or OAR for iAAAs in the years 2010-2016 was analyzed. The patients were followed through 2018. METHODS: In the propensity score matched cohorts the perioperative and long-term outcomes of the patients were assessed. We identified 20 683 patients undergoing elective iAAA repair (76.4% EVAR). The propensity matched cohorts included 4886 pairs of patients. RESULTS: The perioperative mortality was 1.9% for EVAR and 5.9% for OAR (P = <.001). The perioperative mortality was mainly influenced by patients age (Odds-Ratio (OR):1.073, confidence interval (CI):1.058-1.088, P ≤ .001) and OAR (OR:3.242, CI:2.552-4.119, P ≤ .001). The early survival benefit after endovascular repair persisted for approximately 3 years (estimated survival EVAR 82.3%, OAR 80.9%, P = .021). After that time the estimated survival curves were similar. After 9 years the estimated survival was 51.2% after EVAR as compared to 52.8% after OAR (P = .102). The operation method didn't influence long-term survival significantly (Hazard-Ratio (HR): 1.046, CI: .975-1.122, P = .211). The vascular reintervention rate was 17.4% in the EVAR cohort and 7.1% in the OAR cohort (P ≤ .001). CONCLUSION: EVAR has a significantly lower perioperative mortality than OAR, a survival benefit that lasts up to 3 years after intervention. Thereafter, no significant difference in survival was observed between EVAR and OAR. The decision between EVAR or OAR may depend on patient preference, surgeons' experience, and the institutions' ability to handle complications.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Procedimientos Endovasculares/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Tiempo , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Factores de Riesgo , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: This retrospective propensity score matched study presents the perioperative mortality and long-term survival up to 9 years after endovascular (EVAR) and open (OAR) repair of patients with ruptured abdominal aortic aneurysm (rAAA) in Germany using health insurance data. MATERIALS AND METHODS: 2170 patients treated between January 1st, 2010 and December 31st, 2016, for rAAA within 24 hours of hospital admission and receiving blood transfusions were enrolled in the study and tracked until December 31st, 2018. For better comparability of EVAR and OAR, a 1:1 propensity score matching with 624 pairs according to patient age, sex and comorbidities was carried out using the R program (Foundation for Statistical Computing, Vienna, Austria). RESULTS: In the unadjusted groups, 29.1% (631/2170) of the patients were treated with EVAR and 70.9% (1539/2170) with OAR. EVAR patients had a significantly higher overall rate of comorbidities. After adjustment, EVAR patients showed significantly better perioperative survival (EVAR 35.7%, OAR 51.0%, p = 0.000). Perioperative complications occurred in 80.4% of EVAR patients and 80.3% of OAR patients (p = 1.000). At the end of follow-up, Kaplan-Meier estimated that 15.2% of patients survived after EVAR vs. 19.5% after OAR (p = 0.027). In the multivariate Cox regression analysis, OAR, age ≥ 80 years, diabetes mellitus type 2 and renal failure stages 3 to 5 had a negative impact on overall survival. Patients treated on weekdays had a significantly lower perioperative mortality than patients treated during the weekend (perioperative mortality on weekdays 40.6% vs. 53.4% during the weekend; p = 0.000) and a better overall survival as estimated by Kaplan-Meier. CONCLUSION: Significantly better perioperative and overall survival was observed with EVAR than with OAR in patients with rAAA. The perioperative survival benefit of EVAR was also found in patients older than 80 years. Female gender had no significant influence on perioperative mortality and overall survival. Patients treated on weekends had a significantly poorer perioperative survival than patients treated on weekdays, and this lasted through the end of follow-up. The extent to which this was dependent on hospital structure was unclear.
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OBJECTIVES: The objective of this work was to evaluate the incremental value of MR angiography over plain radiographs and MRI for the differentiation of aneurysmal bone cysts (ABCs) from unicameral bone cysts (UBCs). METHODS: Thirty-six juvenile patients with histologically secured primary ABCs or UBCs were included in this retrospective study. Two radiologists assessed all obtained images in a blinded fashion using a catalog of previously suggested imaging findings. A second readout with supplementary MR angiography images was performed after 8 weeks to prevent observer recall bias. Diagnostic accuracy parameters were calculated for individual imaging findings, and overall diagnostic accuracy and diagnostic confidence were assessed for all readouts. Receiver operating characteristic (ROC) curve comparison was used to determine the incremental value of MR angiography. RESULTS: Of 16 imaging features, only abnormal vascularization in MR angiography provided sufficient diagnostic accuracy for the identification of ABCs. Other imaging features such as fluid-fluid levels and internal septations were insufficient for the differentiation of UBCs from ABCs. Availability of MR angiography images significantly increased diagnostic accuracy (94.4 vs 75.0% and 83.3 vs 69.4%, respectively, p < 0.05) and diagnostic confidence (4.5 vs 3.7, p < 0.05) of reading radiologists. CONCLUSION: The presence of arterial feeders in MR angiography can accurately discriminate primary ABCs from UBCs and increases the diagnostic accuracy and diagnostic confidence of reporting radiologists. ADVANCES IN KNOWLEDGE: Radiographic differentiation of cystic bone lesions such as ABCs and UBCs remains challenging. We demonstrate that MR angiography provides incremental value and suggest inclusion in standard examination protocols.
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Quistes Óseos , Humanos , Estudios Retrospectivos , Quistes Óseos/diagnóstico por imagen , Quistes Óseos/patología , Imagen por Resonancia Magnética/métodos , Radiografía , AngiografíaRESUMEN
Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital's databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Enfermedad Crítica/terapia , Estudios Retrospectivos , Prevalencia , COVID-19/complicaciones , COVID-19/diagnóstico por imagen , COVID-19/terapia , Neuroimagen , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiologíaRESUMEN
The failure of insulin-producing ß-cells is the underlying cause of hyperglycemia in diabetes mellitus. ß-cell decay has been linked to hypoxia, chronic inflammation, and oxidative stress. Thioredoxin (Trx) proteins are major actors in redox signaling and essential for signal transduction and the cellular stress response. We have analyzed the cytosolic, mitochondrial, and extracellular Trx system proteins in hypoxic and cytokine-induced stress using ß-cell culture, isolated pancreatic islets, and pancreatic islet transplantation modelling low oxygen supply. Protein levels of cytosolic Trx1 and Trx reductase (TrxR) 1 significantly decreased, while mitochondrial Trx2 and TrxR2 increased upon hypoxia and reoxygenation. Interestingly, Trx1 was secreted by ß-cells during hypoxia. Moreover, murine and human pancreatic islet grafts released Trx1 upon glucose stimulation. Survival of transplanted islets was substantially impaired by the TrxR inhibitor auranofin. Since a release was prominent upon hypoxia, putative paracrine effects of Trx1 on ß-cells were examined. In fact, exogenously added recombinant hTrx1 mitigated apoptosis and preserved glucose sensitivity in pancreatic islets subjected to hypoxia and inflammatory stimuli, dependent on its redox activity. Human subjects were studied, demonstrating a transient increase in extracellular Trx1 in serum after glucose challenge. This increase correlated with better pancreatic islet function. Moreover, hTrx1 inhibited the migration of primary murine macrophages. In conclusion, our study offers evidence for paracrine functions of extracellular Trx1 that improve the survival and function of pancreatic ß-cells.
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Reductasa de Tiorredoxina-Disulfuro , Tiorredoxinas , Animales , Auranofina , Humanos , Ratones , Oxidación-Reducción , Estrés Oxidativo , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMEN
Substitution of pancreatic islets is a potential therapy to treat diabetes and it depends on reconstitution of islet's capillary network. In this study, we addressed the question whether stabilization of Glucagon-Like-Peptide-1 (GLP-1) by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) increases ß-cell mass by modulating vascularization. Mouse or porcine donor islets were implanted under kidney capsule of diabetic mice treated with DPP-IV inhibitor sitagliptin. Grafts were analyzed for insulin production, ß-cell proliferation and vascularization. In addition, the effect of sitagliptin on sprouting and Vascular Endothelial Growth Factor (VEGF)-A expression was examined ex vivo. The cAMP response element-binding (CREB) and VEGF-A/ Vascular Endothelial Growth Factor Receptor (VEGFR)-2 signaling pathway leading to islet vascularization was explored. Sitagliptin increased mean insulin content of islet grafts and area of insulin-positive tissue as well as ß-cell proliferation. Interestingly, sitagliptin treatment also markedly increased endothelial cell proliferation, microvessel density and blood flow. Finally, GLP-1 (7-36) stimulated sprouting and VEGF expression, which was significantly enhanced by sitagliptin- mediated inhibition of DPP-IV. Our in vivo data demonstrate that sitagliptin treatment phosphorylated CREB and induced islet vascularization through VEGF-A/VEGFR-2 signaling pathway. This study paves a new pathway for improvement of islet transplantation in treating diabetes mellitus.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Islotes Pancreáticos/irrigación sanguínea , Islotes Pancreáticos/metabolismo , Neovascularización Fisiológica , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Glucemia , Proliferación Celular/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Péptido 1 Similar al Glucagón/sangre , Insulina/biosíntesis , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Trasplante de Islotes Pancreáticos , Ratones , Neovascularización Fisiológica/efectos de los fármacos , Pirazinas/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Fosfato de Sitagliptina , Porcinos , Serina-Treonina Quinasas TOR/metabolismo , Triazoles/farmacologíaRESUMEN
Islet transplantation provides an approach to compensate for loss of insulin-producing cells in patients with type 1 diabetes. However, the intraportal route of transplantation is associated with instant inflammatory reactions to the graft and subsequent islet destruction as well. Although matrix metalloprotease (MMP)-2 and -9 are involved in both remodeling of extracellular matrix and leukocyte migration, their influence on the outcome of islet transplantation has not been characterized. We observed comparable MMP-2 mRNA expressions in control and transplanted groups of mice, whereas MMP-9 mRNA and protein expression levels increased after islet transplantation. Immunostaining for CD11b (Mac-1)-expressing leukocytes (macrophage, neutrophils) and Ly6G (neutrophils) revealed substantially reduced inflammatory cell migration into islet-transplanted liver in MMP-9 knockout recipients. Moreover, gelatinase inhibition resulted in a significant increase in the insulin content of transplanted pancreatic islets and reduced macrophage and neutrophil influx compared with the control group. These results indicate that the increase of MMP-9 expression and activity after islet transplantation is directly related to enhanced leukocyte migration and that early islet graft survival can be improved by inhibiting MMP-9 (gelatinase B) activity.
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Supervivencia de Injerto/fisiología , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz , Animales , Antígeno CD11b/metabolismo , Captopril/farmacología , Movimiento Celular/efectos de los fármacos , Inflamación/prevención & control , Insulina/metabolismo , Hígado/cirugía , Macrófagos/fisiología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , PorcinosRESUMEN
Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential.