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1.
Eur J Neurol ; 26(7): 992-999, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30714278

RESUMEN

BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.


Asunto(s)
Síndrome de Isaacs/complicaciones , Miastenia Gravis/complicaciones , Timoma/complicaciones , Neoplasias del Timo/complicaciones , Adulto , Autoanticuerpos/sangre , Electromiografía , Femenino , Humanos , Masculino , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Miastenia Gravis/sangre , Recurrencia Local de Neoplasia , Netrina-1/inmunología , Estudios Retrospectivos , Timoma/sangre , Neoplasias del Timo/sangre
2.
Neurochem Res ; 41(8): 2017-28, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27084771

RESUMEN

Statins have been shown to promote neuroprotection in a wide range of neurological disorders. However, the mechanisms involved in such effects of statins are not fully understood. Quinolinic acid (QA) is a neurotoxin that induces seizures when infused in vivo and promotes glutamatergic excitotoxicity in the central nervous system. The aim of this study was to evaluate the putative glutamatergic mechanisms and the intracellular signaling pathways involved in the atorvastatin neuroprotective effects against QA toxicity. Atorvastatin (10 mg/kg) treatment for 7 days prevented the QA-induced decrease in glutamate uptake, but had no effect on increased glutamate release induced by QA. Moreover, atorvastatin treatment increased the phosphorylation of ERK1 and prevented the decrease in Akt phosphorylation induced by QA. Neither atorvastatin treatment nor QA infusion altered glutamine synthetase activity or the levels of phosphorylation of p38(MAPK) or JNK1/2 during the evaluation. Inhibition of MEK/ERK signaling pathway, but not PI3K/Akt signaling, abolished the neuroprotective effect of atorvastatin against QA-induced decrease in glutamate uptake. Our data suggest that atorvastatin protective effects against QA toxicity are related to modulation of glutamate transporters via MAPK/ERK signaling pathway.


Asunto(s)
Sistema de Transporte de Aminoácidos X-AG/antagonistas & inhibidores , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Atorvastatina/farmacología , Ácido Glutámico/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ácido Quinolínico/toxicidad , Animales , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones
3.
J Neurol Sci ; 461: 123047, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38759248

RESUMEN

BACKGROUND: Myasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies, especially in terms of tolerance to acetylcholinesterase inhibitors (AChEI). However, AChEI are often used as first line symptomatic treatment in MuSK-MG, despite reports that they are poorly tolerated, seldom effective or even deleterious. METHODS: We analyzed demographic, clinical and therapeutic responses and side-effects in the large cohort of 202 MuSK-MG patients cared for at the MG Clinic of Azienda Ospedaliero-Universitaria Pisana. RESULTS: 165 patients had received AChEI at first evaluation. Only 7/165 patients (4.2%) reported an initial clinical benefit. Conversely, 76.9% of patients reported at least one side effect, most commonly neuromuscular hyperexcitability (68.4%), gastrointestinal (53.9%) and neurovegetative (35.8%) disturbances. 56 (33.9%) patients reported a concomitant worsening of muscle weakness and twelve patients (7.3%) suffered a cholinergic crisis. According to these patients, the severity of cholinergic side effects was greater at higher doses of AChEI, but side effects occurred regardless of the dose administered and ceased once the drug was discontinued. CONCLUSIONS: This is the largest population of MuSK-MG patients reported for perceived responsiveness and tolerance to AChEI treatment. Our obervations strongly suggest avoiding this treatment in MuSK-MG.


Asunto(s)
Autoanticuerpos , Inhibidores de la Colinesterasa , Miastenia Gravis , Proteínas Tirosina Quinasas Receptoras , Receptores Colinérgicos , Humanos , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inmunología , Inhibidores de la Colinesterasa/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Receptores Colinérgicos/inmunología , Adulto , Proteínas Tirosina Quinasas Receptoras/inmunología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Anciano , Autoanticuerpos/sangre , Adulto Joven , Adolescente , Anciano de 80 o más Años , Resultado del Tratamiento , Estudios de Cohortes
4.
Minerva Chir ; 68(2): 163-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23612229

RESUMEN

AIM: The standard to treat liver tumors is a resection. When the future liver remnant (FLRV) is below 30% (healthy livers) or 40% (cirrhotic livers or previous chemotherapy), surgery carries the risk of severe complications. Portal vein embolization (PVE) gained a worldwide diffusion as a tool to augment the FLRV. Cell therapies are recent players at the frontiers of medicine. This study presents a clinical experience to evaluate the synergistic effect of combined PVE and autologous CD133+ cells coadministration. METHODS: Sixteen patients have been enrolled in the study up today. Inclusion criteria were: primary or metastatic liver malignancy with a FLRV<30% or 40%. A baseline volumetric CT-scan was obtained. CD34+ were mobilized to the blood stream by G-CSF administration and collected by immunomagnetic separation. Simultaneously with PVE, cells were administered to the non occluded liver segments. Follow-up CT scans were taken at 30th post treatment day. RESULTS: The patients (N.=6) showed an increased volume gain (Mann-Whitney test P<0.001, two sided) compared to a set of cases whose treatment was PVE only (N.=10). DISCUSSION: The use of autologous stem cells as an augmenter of liver regeneration has a clinical potential to improve the resectability of liver tumors.


Asunto(s)
Antígenos CD/análisis , Embolización Terapéutica , Glicoproteínas/análisis , Neoplasias Hepáticas/cirugía , Regeneración Hepática , Péptidos/análisis , Trasplante de Células Madre de Sangre Periférica/métodos , Vena Porta , Antígeno AC133 , Antígenos CD34/análisis , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética , Leucaféresis , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/terapia , Tamaño de los Órganos , Tomografía Computarizada Espiral , Trasplante Autólogo
5.
Neurol Sci ; 33(5): 1133-6, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22249401

RESUMEN

The objective of this study was to determine the relationship between sleepiness and migraine in the intercritical period and to evaluate the time course of critical drowsiness during the attacks. One hundred patients fulfilling IHCD 2nd (2004) criteria for migraine without aura were compared to 100 healthy subjects. Habitual excessive daily sleepiness, evaluated by means of Epworth Sleepiness Scale, was not more frequent in patients with episodic migraine than in controls (12% migraineurs vs. 8% controls, NS). The analysis of critical sleepiness by means of Stanford Sleepiness Scale (SSS) revealed a beginning of sleepiness increase before the attack onset, starting 12 h before, a peak of SSS values at the migraine attack onset and then a gradual decrease to reach baseline values only 12-24 h later. Moreover, patients responding to symptomatic drugs showed a greater and faster decrease of critical sleepiness in comparison with non-responder migraineurs; this finding allows excluding the role of medications in promoting critical somnolence and together with critical drowsiness time-course supports the hypothesis that vigilance impairment could be related to migraine pathogenesis.


Asunto(s)
Nivel de Alerta/fisiología , Trastornos de Somnolencia Excesiva/etiología , Trastornos Migrañosos/complicaciones , Fases del Sueño/fisiología , Adulto , Trastornos de Somnolencia Excesiva/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/fisiopatología , Adulto Joven
6.
G Ital Med Lav Ergon ; 34(3 Suppl): 378-80, 2012.
Artículo en Italiano | MEDLINE | ID: mdl-23405667

RESUMEN

A Questionnaire on sleep and vigilance disorders has been developed by the Italian Association of Sleep Medicine to help the occupational health physicians in screening for sleep disorders. Aim of this study was to compare the Questionnaire with standardized questionnaires for sleepiness and sleep apnea and with a polysomnographic evaluation. Four hundred sixty-three (463#) commercial bus drivers (454M, 9F; mean age +/- S.D. 41.6 +/- 8.1 yrs; mean body mass index 26.2 +/- 3.6 kg/m2) underwent clinical evaluation that included the Italian Association of Sleep Medicine Questionnaire on sleep and vigilance disorders and two standardized questionnaires (Berlin Questionnaire and Epworth Sleepiness Scale). According to the Italian Association of Sleep Medicine Questionnaire on sleep and vigilance disorders 40 subjects presented an high risk for sleep disturbance and in 28 subject the questionnaires were concordant. Preliminary results (16 patients) showed an high rate of concordance between questionnaire and PSG. These data strongly suggest that sleep disorders and symptoms, that are frequent in a population of professional bus drivers, should be better evaluated during occupational health visit.


Asunto(s)
Conducción de Automóvil , Salud Laboral , Polisomnografía , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Femenino , Humanos , Masculino
7.
Acta Neurol Scand ; 122(6): 389-97, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20175759

RESUMEN

OBJECTIVES: Disturbed sleep is common in elderly people and has been related to comorbidities. The aim of this study was to evaluate the prevalence of sleep problems and their relationship with chronic disease in an elderly population. MATERIALS AND METHODS: The whole population of subjects aged more than 65 years, in the municipality of Vecchiano, Pisa was considered as eligible and underwent a clinical interview and a questionnaire about insomnia, sleepiness, snoring and sleep apnea. A model of logistic regression was applied to the data. RESULTS: The participation rate was 60.3% (1427 subjects). Insomnia was observed in 44.2% of our population, while sleepiness in 31.3%, snoring in 47.2% and sleep apnea in 9.0%. The most common diseases associated with sleep symptoms were depression, cognitive decline and diabetes. CONCLUSIONS: Our results confirm that sleep problems are very common in elderly subjects and closely related to medical and psychiatric illnesses.


Asunto(s)
Evaluación Geriátrica , Trastornos del Sueño-Vigilia/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Italia/epidemiología , Modelos Logísticos , Masculino , Prevalencia , Factores Sexuales , Encuestas y Cuestionarios
8.
Braz J Med Biol Res ; 53(12): e10347, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33146284

RESUMEN

Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (ß=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.


Asunto(s)
Cognición , Glaucoma , Anciano , Brasil , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Pruebas Neuropsicológicas , Autoinforme
9.
Maturitas ; 129: 30-39, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31547910

RESUMEN

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.


Asunto(s)
Antidepresivos/uso terapéutico , Terapia de Reemplazo de Hormonas , Menopausia , Trastornos del Sueño-Vigilia/terapia , Terapia Cognitivo-Conductual , Presión de las Vías Aéreas Positiva Contínua , Depresión , Ejercicio Físico , Femenino , Humanos , Mirtazapina/uso terapéutico , Calidad de Vida , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéutico , Sueño , Apnea Obstructiva del Sueño/terapia , Trastornos del Inicio y del Mantenimiento del Sueño/terapia
11.
Eur J Surg Oncol ; 43(8): 1463-1471, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28528189

RESUMEN

BACKGROUND: Several studies demonstrated that intraoperative near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) identifies (sub)capsular colorectal liver metastases (CRLM) missed by other techniques. It is unclear if this results in any survival benefit. This study evaluates long-term follow-up after NIRF-guided resection of CRLM using ICG. METHODS: First, patients undergoing resection of CRLM with or without NIRF imaging were analyzed retrospectively. Perioperative details, liver-specific recurrence-free interval and overall survival were compared. Second, the prognosis of patients in whom additional metastases were identified solely by NIRF was studied. RESULTS: Eighty-six patients underwent resection with NIRF imaging and 87 without. In significantly more patients of the NIRF imaging cohort additional metastases were identified during surgery (25% vs. 13%, p = 0.04). Tumors identified solely by NIRF imaging were significantly smaller compared to additional metastases identified also by inspection, palpation or intraoperative ultrasound (3.2 ± 1.8 mm vs. 7.4 ± 2.6 mm, p < 0.001). Liver-specific recurrence-free survival at 4 years was 47% with NIRF imaging and 39% without (hazard ratio at multivariate analysis 0.73, 95% CI 0.42-1.28, p = 0.28). Overall survival at 4 years was 62% and 59%, respectively (p = 0.79). No liver recurrences occurred within 3 years follow-up in 52% of patients in whom additional metastases were resected based on only NIRF imaging. CONCLUSIONS: This study suggests that NIRF imaging identifies significantly more and smaller tumors during resection of CRLM, preventing recurrences in a subset of patients. Given its safety profile and low expense, routine use can be considered until tumor targeting fluorescent tracers are clinically available.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Cirugía Asistida por Computador/métodos , Femenino , Colorantes Fluorescentes , Estudios de Seguimiento , Humanos , Verde de Indocianina , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
12.
Brain Res Bull ; 71(1-3): 69-75, 2006 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-17113930

RESUMEN

Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, and on the subsequent disappearance of alpha activity on the posterior regions after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult, because of little or hardly detectable alpha activity on the posterior regions ('alpha rare'). The aim of this study was to evaluate the Olfactory Stop Reaction (OSR) by means of frequency band power calculation and subsequent topographical mapping in patients with post-traumatic anosmia, who presented 'alpha rare' EEG. Twenty-five consecutive patients, affected by anosmia caused by head trauma, were submitted to an EEG recording with olfactory stimulation. After signal processing and analysis, an Olfactory Stop Reaction was detected in 17 out of 25 patients; moreover, in these patients we detected a significant decrease in alpha band power in the occipital regions and an increase in theta band power on midline frontal and central regions after olfactory stimulation. In the remaining eight patients, no significant variation in band power was observed. In conclusion, an objective evaluation of the olfactory function with this method of automatic EEG signal analysis allows the limits given by psychophysical methods and traditional EEG to be overcome and attempts to fulfil the requirements for standardization of olfactory function evalution.


Asunto(s)
Lesiones Encefálicas/diagnóstico , Corteza Cerebral/fisiopatología , Electroencefalografía/métodos , Trastornos del Olfato/diagnóstico , Vías Olfatorias/fisiopatología , Adulto , Anciano , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/fisiopatología , Mapeo Encefálico/métodos , Corteza Cerebral/anatomía & histología , Potenciales Evocados/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/etiología , Trastornos del Olfato/fisiopatología , Vías Olfatorias/lesiones , Valor Predictivo de las Pruebas , Procesamiento de Señales Asistido por Computador , Olfato/fisiología
13.
Minerva Chir ; 61(2): 85-94, 2006 Apr.
Artículo en Italiano | MEDLINE | ID: mdl-16871139

RESUMEN

AIM: Organ transplantation is the most effective treatment for several degenerative end-stage diseases. While the mainstream immunosuppression can achieve satisfactory results, the therapy has either side effects and flaws. The golden target to reach should be a stable tolerance with the transplanted organ accepted without a long term drug administration. Recent studies demonstrated a tolerogenic effect of spleen cells. Aim of this study is to evaluate a model of combined spleen and whole organ transplantation in a significant preclinical setting in swine. METHODS: Twenty-five outbred Landrace/Large-White swine underwent combined spleen/kidney transplantation (SKTx). The experiments were stratified into 3 groups per randomization. Group 1 (N=7) received kidney transplantation (KTx) alone with no immunosuppressive treatment. Group 2 (N=9) had a combined KTx and whole graft spleen Tx. Group 3 (N=9) had KTx and spleen cells (DST), injected through the portal vein. Renal lab tests were collected to evaluate the onset of rejection. Survivals were evaluated as well. The end-point of the study was at onset of kidney failure or at the limit of 60 postoperative day (POD) in non-rejecting animals. Tissue samples were collected to evaluate grade and severity of rejection. RESULTS: Controls died from kidney failure within 10(th) POD. Group 2 and 3, had a delayed renal graft rejection and an overall prolonged graft survival. Whole graft and spleen cells injection share this effect, while spleen administration through the portal route proved a superior effect, which is significant compared to controls (Kaplan Meier survival analysis P<0.05). CONCLUSIONS: These results, from a non immunosuppressed setting, suggest that spleen plays a key role as an immunomodulatory organ.


Asunto(s)
Terapia de Inmunosupresión/métodos , Trasplante de Riñón , Bazo/trasplante , Animales , Femenino , Trasplante de Riñón/patología , Masculino , Bazo/patología , Porcinos
14.
Minerva Chir ; 61(5): 393-402, 2006 Oct.
Artículo en Italiano | MEDLINE | ID: mdl-17159747

RESUMEN

AIM: The liver as a solid graft has a known immunological privilege. Its tolerogenic property has been demonstrated in rodents. In humans the onset of chronic rejection and the severity of such complication is less frequent after liver transplantation compared to other organs. The underlying events whose effect is graft acceptance instead of rejection should be further investigated. Their control could open new ways to decrease the need for long-term immunosuppression after transplantation of other organs. Aim of this study is to evaluate a model of liver transplantation in swine as a preliminary step for immunological studies. METHODS: Ten outbred Landrace/Large White mismatched swine underwent to liver transplantation with a simple passive portocaval jugular bypass. The onset of rejection was monitored daily by liver function test. After death or sacrifice the liver parenchyma was studied to evaluate tissue damage and inflammatory infiltrate. RESULTS: The postoperative liver function showed a critical period for organ rejection about postoperative day 5. The animals that survived longer were sacrificed with a normal biochemical hepatic function. However, histology consistently showed a pattern of mild rejection in a still preserved architecture. CONCLUSIONS: The evidence of a prolonged liver function in a rejecting model of liver transplantation makes this model suitable for studies of tolerance induction.


Asunto(s)
Rechazo de Injerto/fisiopatología , Trasplante de Hígado , Tolerancia al Trasplante , Animales , Prueba de Histocompatibilidad , Pruebas de Función Hepática , Modelos Animales , Derivación Portocava Quirúrgica , Porcinos , Trasplante Homólogo
15.
Minerva Chir ; 60(6): 487-96, 2005 Dec.
Artículo en Italiano | MEDLINE | ID: mdl-16402003

RESUMEN

AIM: Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats. METHODS: Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts. RESULTS: In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2. CONCLUSIONS: Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.


Asunto(s)
Aorta/inmunología , Antígeno B7-1/inmunología , Vasos Sanguíneos/efectos de los fármacos , Antígenos CD28/inmunología , Rechazo de Injerto/prevención & control , Inmunoconjugados/farmacología , Animales , Aorta/patología , Aorta/trasplante , Aorta/ultraestructura , Modelos Animales de Enfermedad , Supervivencia de Injerto , Ratas , Ratas Endogámicas Lew , Ratas Wistar , Bazo/citología , Bazo/inmunología , Trasplante Homólogo
16.
Braz. j. med. biol. res ; 53(12): e10347, 2020. tab, graf
Artículo en Inglés | LILACS, Coleciona SUS (Brasil) | ID: biblio-1132512

RESUMEN

Recent evidence suggests that glaucoma and Alzheimer's disease are neurodegenerative diseases sharing common pathophysiological and etiological features, although findings are inconclusive. We sought to investigate whether self-reported glaucoma patients without dementia present poorer cognitive performance, an issue that has been less investigated. We employed cross-sectional data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) and included participants ≥50 years of age without a known diagnosis of dementia and a self-reported glaucoma diagnosis. We excluded those with previous stroke, other eye conditions, and using drugs that could impair cognition. We evaluated cognition using delayed word recall, phonemic verbal fluency, and trail making (version B) tests. We used multinomial linear regression models to investigate associations between self-reported glaucoma with cognition, adjusted by several sociodemographic and clinical variables. Out of 4,331 participants, 139 reported glaucoma. Fully-adjusted models showed that self-reported glaucoma patients presented poorer performance in the verbal fluency test (β=-0.39, 95%CI=-0.64 to -0.14, P=0.002), but not in the other cognitive assessments. Thus, our results support the hypothesis that self-reported glaucoma is associated with poor cognitive performance; however, longitudinal data are necessary to corroborate our findings.


Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Anciano , Glaucoma , Cognición , Brasil , Estudios Transversales , Estudios Longitudinales , Autoinforme , Pruebas Neuropsicológicas
17.
Transplantation ; 65(1): 32-6, 1998 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-9448140

RESUMEN

BACKGROUND: Treatment of fetal pancreas (FP) isografts with insulin-like growth factor-I greatly improves the rate of conversion to euglycemia in diabetic rats. Complete knowledge of other factors that may facilitate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers. ALR has trophic effects on regenerating liver. We studied the effects of in situ administration of this agent on FP isografts in rats. METHODS: Streptozotocin-diabetic Lewis rats (blood glucose > 300 mg/dl) received 16 FP isografts transplanted intramuscularly. ALR was delivered from day 1 through day 14, in doses of 40 or 400 ng/kg/d. Animals were followed for 3 months with serial weights and blood glucose monitoring. These animals were compared with those treated with vehicle alone. RESULTS: Of the group treated with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) were euglycemic (P=0.0003). Of the group treated with ALR at 400 ng/kg/day for 14 days, 88% (seven of eight) were euglycemic (P=0.0007). Of the group treated with vehicle alone, none of the six were euglycemic. Euglycemia is defined here as glucose < 200 mg/dl for 3 days. Pathology of the intramuscular transplant site showed patches of islet tissue embedded in fat. These patches demonstrated insulin immunoreactivity. CONCLUSIONS: Diabetes was reversed in a significantly greater proportion of FP + ALR-treated recipients than those animals treated with vehicle alone. Local delivery of growth factors may be used as an adjunct to FP transplantation to improve the rate of success. This in situ model may be useful to further evaluate other soluble factors.


Asunto(s)
Sustancias de Crecimiento/farmacología , Trasplante de Islotes Pancreáticos , Regeneración Hepática , Páncreas/embriología , Proteínas , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/terapia , Factor I del Crecimiento Similar a la Insulina/farmacología , Páncreas/patología , Ratas , Ratas Endogámicas Lew
18.
Transplantation ; 64(2): 185-90, 1997 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-9256171

RESUMEN

BACKGROUND: Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS: We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.


Asunto(s)
Ciclosporina/toxicidad , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Trasplante de Riñón/inmunología , Trasplante de Riñón/fisiología , Animales , Sinergismo Farmacológico , Rechazo de Injerto/prevención & control , Factor I del Crecimiento Similar a la Insulina/farmacología , Enfermedades Renales/inducido químicamente , Fragmentos de Péptidos/farmacología , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Trasplante Homólogo/inmunología
19.
Chemphyschem ; 1(4): 224-7, 2000 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-23696326

RESUMEN

A fourth generation POPAM dendrimer functionalized at the periphery with 32 dansyl groups (circles in the picture) can host up to six eosin dye molecules (black ovals) in two different sites (triangle, square). Efficient energy transfer processes from the dansyl to eosin molecules occur. The picture shows some characteristic wavelengths and lifetimes of these transitions; excitation, emission, and energy transfer processes are represented by dotted, dashed, and full arrows, respectively.

20.
Chemphyschem ; 2(12): 769-73, 2001 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-23686931

RESUMEN

An interior of 18 amide groups and a periphery functionalized with 24 dansyl groups forms a light-harvesting dendrimer which features intense absorption bands in the near-UV spectral region and a strong fluorescence band in the visible region. Upon encapsulation of Nd(3+) ions, the fluorescence of the dansyl groups is quenched and an intense sensitized near-infrared emission of Nd(3+) is observed. The associated energy transfer is shown in the cartoon.

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