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1.
Nature ; 628(8006): 195-203, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38480879

RESUMEN

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.


Asunto(s)
Complejo I de Transporte de Electrón , Inflamación , Microglía , Enfermedades Neuroinflamatorias , Animales , Femenino , Humanos , Masculino , Ratones , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Modelos Animales de Enfermedad , Transporte de Electrón/efectos de los fármacos , Complejo I de Transporte de Electrón/antagonistas & inhibidores , Complejo I de Transporte de Electrón/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Multiómica , Células Mieloides/metabolismo , Células Mieloides/patología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Especies Reactivas de Oxígeno/metabolismo
2.
Ecotoxicol Environ Saf ; 229: 112969, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34922166

RESUMEN

Since the 1960s, invasive sea lamprey (Petromyzon marinus) populations in the Laurentian Great Lakes have been controlled by applying two chemicals, 3-trifluoromethyl-4-nitrophenol (TFM) and 2',5-dichloro-4'-nitrosalicylanilide (niclosamide, aka. Bayluscide®), to streams infested with larval sea lamprey. These "lampricide" applications primarily rely on TFM, and are often combined with 1-2% niclosamide, which increases treatment effectiveness. Niclosamide is also used alone to treat lentic habitats and in rivers with high discharge. However, little is known about niclosamide's possible adverse physiological effects on non-target organisms. Of particular concern is the lake sturgeon (Acipenser fulvescens), which is threatened throughout the Great Lakes basin where its habitat often overlaps with larval lamprey. Because niclosamide is believed to impair ATP production by uncoupling oxidative phosphorylation, we determined how it altered metabolic processes and acid-base balance in young-of-the-year (YOY) lake sturgeon exposed to their 9-h LC50 of niclosamide (0.11 mg L-1) for 9 h. Exposure to niclosamide led to decreased brain ATP and glucose reserves, and increased lactate, with no effect on brain glycogen. In contrast, substantial (60%) reductions in glycogen were observed in liver, suggesting that hepatic glycogen reserves were mobilized to meet the brain's glucose requirements when ATP supply was impaired during niclosamide exposure. Disturbances in carcass included reduced phosphocreatine (65-70%), 2- and 4-fold increases in pyruvate and lactate, and a slight metabolic acidosis, characterized by a 0.1 unit decrease in intracellular pH (pHi). Each of these disturbances were corrected within 24 h following depuration in clean (niclosamide-free) water. We conclude that if lake sturgeon survive exposure to niclosamide, they are able to rapidly replenish their energy stores (glycogen, ATP, phosphocreatine) and correct any corresponding metabolic disturbances within 24 h.


Asunto(s)
Niclosamida , Petromyzon , Animales , Metabolismo Energético , Peces , Lagos , Niclosamida/toxicidad
3.
Rheumatol Int ; 39(3): 533-539, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30415452

RESUMEN

Systemic lupus erythematosus (SLE), pathology with net feminine predominance, is one of the most complex autoimmune diseases and has major impact on patients' life. The aim is to identify patient and disease-related factors associated with self-perceived disease severity in female SLE patients. This cross-sectional study enrolled 73 women fulfilling the 2012 Systemic Lupus International Collaborating Clinic (SLICC) criteria. SLE disease activity was assessed by the Systemic Lupus Activity Measure (SLAM) score and overall damage by the SLICC/American College of Rheumatology (ACR) index. Patients' general characteristics, associated conditions as well as SLE specific clinical involvements and therapeutic principles were also noted. Fatigue was assessed by FACIT-fatigue scale. Self-perceived disease severity was assessed using numerical rating scales (1-10 NRSs), to evaluate the disease severity at inclusion (1-10 NRS now) and worst severity anytime during disease history (1-10 NRS worst ever). In regard to worst ever lupus severity, 54.8% of patients responded with 9 or 10, while none with 1 or 2 even if only 22.9% of the patients responded with 7 or more for disease severity at inclusion (1-10 NRS now). Women with higher 1-10 NRS now answers had also higher 1-10 NRS worst ever, SLAM, SLICC, and FACIT-fatigue scores. They associated more frequently anxiety/depression diagnosis, antiphospholipid syndrome, joint involvement as well as treatments with corticosteroids. Self-reported disease severity worst ever, anxiety/depression diagnosis, fatigue, and the daily dose of corticosteroids were independently associated with patients' perception on lupus severity at inclusion: OR (95% CI), 2.13 (1.15-3.94) p = 0.017, 6.67 (1.11-39.97) p = 0.038, 1.10 (1.02-1.19) p = 0.018, and 1.11 (1.02-1.21) p = 0.020, respectively. The vast majority of patients identified severe and very severe events during their disease history, results that raise awareness of burden concerning lupus occurrence in women's life. Self-perceived lupus severity is multifactorial, influenced also by factors less considered in the SLE management like fatigue and the depression/anxiety disorders, but also by the previous patient's experience.


Asunto(s)
Corticoesteroides/uso terapéutico , Síndrome Antifosfolípido/fisiopatología , Fatiga/fisiopatología , Lupus Eritematoso Sistémico/fisiopatología , Adulto , Síndrome Antifosfolípido/complicaciones , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/psicología , Estudios Transversales , Trastorno Depresivo/complicaciones , Trastorno Depresivo/psicología , Fatiga/etiología , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/psicología , Persona de Mediana Edad , Autoinforme , Índice de Severidad de la Enfermedad
5.
Aquat Toxicol ; 242: 106006, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34801746

RESUMEN

Since the 1960s, chemical control of larval sea lamprey has been achieved using the pesticides 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide (Bayluscide®). Much more potent, niclosamide is often used as an adjuvant for TFM, and on its own to treat lentic habitats, rivers with high discharge and currents, and for population surveys. Yet, little is known about its mode of action or physiological effects on sea lamprey. Like TFM, niclosamide is thought to impair mitochondrial ATP production by uncoupling oxidative phosphorylation. We therefore tested the hypothesis that niclosamide would result in metabolic perturbations and disturbances to acid-base balance in larval lamprey due to their need to balance ATP supply with ATP demands. When larval sea lamprey were exposed to the nominal 9-h niclosamide LC50 (0.11 mg L-1) over 9 h, it resulted in significant decreases in brain, phosphocreatine (35 %) and glycogen (50 %), accompanied by a 5-fold increase in lactate. In carcass, there were 25-30 % decreases in glycogen, corresponding increases in pyruvate and lactate, and a pronounced 0.5 unit decrease in intracellular pH. Calculation of the NAD+/NADH ratio in the carcass indicated that neither oxygen delivery nor the flux of reducing equivalents through the mitochondrial electron transport chain were impaired by niclosamide, supporting the hypothesis that niclosamide interferes with mitochondrial ATP production by uncoupling oxidative phosphorylation. Thus, greater reliance on glycogen, characterized by higher rates of glycolysis, temporarily mitigates the corresponding shortfall in ATP supply caused by niclosamide. Notably, all lamprey that survived niclosamide exposure readily restored ATP, phosphocreatine, glycogen and acid-base balance after recovery in niclosamide-free water. This resilience suggests that sea lamprey that survive or escape niclosamide treatment could compromise sea lamprey control efforts by subsequently completing their larval stage and developing into parasitic juvenile sea lamprey that could ultimately threaten Great Lake's fisheries populations.


Asunto(s)
Niclosamida , Plaguicidas , Petromyzon , Contaminantes Químicos del Agua , Equilibrio Ácido-Base , Animales , Larva , Niclosamida/toxicidad , Plaguicidas/toxicidad , Contaminantes Químicos del Agua/toxicidad
6.
BMC Musculoskelet Disord ; 12: 124, 2011 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-21635793

RESUMEN

BACKGROUND: Assessment of synovitis in rheumatoid arthritis (RA) is a major issue for a proper treatment administration; it has been proven that ultrasound (US) examination could be of valuable help and it is currently being investigated as a possible outcome measure for the disease. It is, though, of greatest importance to accurately establish the place of US scores among the already validated outcome measures, according to Outcome Measures for Rheumatoid Arthritis in Clinical Trials (OMERACT) filter. The present study is designed to compare the results of gray-scale ultrasound (GSUS) and Power Doppler ultrasound (PDUS) additive scores, separately calculated for volar and dorsal aspects of the hand, with physical examination, patient's evaluation of disease pain and global activity on Visual Analogic Scale (VAS) and traditional scores for disease activity assessment (DAS28, CDAI, SDAI, HAQ). The final aim is to prove the advantages of volar US evaluation in RA patients. METHODS: 42 RA patients have been clinically evaluated for pain and swelling of their hand joints, completed VAS and HAQ questionnaires and underwent both volar and dorsal sonography of the hands during the same day. The US examiner was blinded to clinical assessments and lab results. For each patient 20 joints were assessed by sonography (radiocarpal, intercarpal, metacarpophalangeal (MCP) 2-5, proximal interphalangeal (PIP) 2-5). Carpal joints were only evaluated from dorsal view, while MCPs and PIPs were evaluated both from dorsal and volar aspect resulting a total of 36 distinct evaluations for each patient. GSUS synovial hypertrophy was assessed both by quantitative measurement and semiquantitative scale (0-3 grades); Doppler signal (PDUS) was recorded on a semiquantitative scale (0-3 grades). The semiquantitative grades for both GSUS and PDUS evaluation of each joint were added and the sum was defined as the Echographic Score (ES) of each patient. Separately, we added the semiquantitative grades for volar and dorsal side, resulting in Volar ES (VES) and Dorsal ES (DES) of each patient. RESULTS: We found ESs correlated with other activity scores: DAS28, CDAI, SDAI, HAQ. Correlations with clinical indices as CDAI and SDAI were stronger for VES than for DES. US discovered more synovitis than clinical examination. CONCLUSION: VES is a suitable reflection of RA activity and volar US examination should accompany the dorsal one both in clinical practice and in clinical trials.


Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Articulaciones de la Mano/diagnóstico por imagen , Membrana Sinovial/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/patología , Femenino , Articulaciones de la Mano/patología , Humanos , Hipertrofia , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Examen Físico , Valor Predictivo de las Pruebas , Rumanía , Índice de Severidad de la Enfermedad , Membrana Sinovial/patología , Sinovitis/patología
7.
Conserv Physiol ; 9(1): coab069, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34512991

RESUMEN

The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is applied to rivers and streams draining into the Laurentian Great Lakes to control populations of invasive sea lamprey (Petromyzon marinus), which are ongoing threats to fisheries during the lamprey's hematophagous, parasitic juvenile life stage. While TFM targets larval sea lamprey during treatments, threatened populations of juvenile lake sturgeon (Acipenser fulvescens), particularly young-of-the-year (<100 mm in length), may be adversely affected by TFM when their habitats overlap with larval sea lamprey. Exposure to TFM causes marked reductions in tissue glycogen and high energy phosphagens in lamprey and rainbow trout (Oncorhynchus mykiss) by interfering with oxidative ATP production in the mitochondria. To test that environmentally relevant concentrations of TFM would similarly affect juvenile lake sturgeon, we exposed them to the larval sea lamprey minimum lethal concentration (9-h LC99.9), which mimicked concentrations of a typical lampricide application and quantified energy stores and metabolites in the carcass, liver and brain. Exposure to TFM reduced brain ATP, PCr and glycogen by 50-60%, while lactate increased by 45-50% at 6 and 9 h. A rapid and sustained depletion of liver glucose and glycogen of more than 50% was also observed, whereas the respective concentrations of ATP and glycogen were reduced by 60% and 80% after 9 h, along with higher lactate and a slight metabolic acidosis (~0.1 pH unit). We conclude that exposure to environmentally relevant concentrations of TFM causes metabolic disturbances in lake sturgeon that can lead to impaired physiological performance and, in some cases, mortality. Our observations support practices such as delaying TFM treatments to late summer/fall or using alternative TFM application strategies to mitigate non-target effects in waters where lake sturgeon are present. These actions would help to conserve this historically and culturally significant species in the Great Lakes.

8.
Clin Exp Rheumatol ; 28(6): 820-7, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21205460

RESUMEN

OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).


Asunto(s)
Artritis Reumatoide/fisiopatología , Cooperación Internacional , Índice de Severidad de la Enfermedad , Fumar/efectos adversos , Estudios Transversales , Bases de Datos como Asunto , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante
9.
Nanotechnology ; 20(37): 375501, 2009 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-19706940

RESUMEN

Carbon nanotube surfaces, activated and randomly decorated with metal nanoclusters, have been studied in uniquely combined theoretical and experimental approaches as prototypes for molecular recognition. The key concept is to shape metallic clusters that donate or accept a fractional charge upon adsorption of a target molecule, and modify the electron transport in the nanotube. The present work focuses on a simple system, carbon nanotubes with gold clusters. The nature of the gold-nanotube interaction is studied using first-principles techniques. The numerical simulations predict the binding and diffusion energies of gold atoms at the tube surface, including realistic atomic models for defects potentially present at the nanotube surface. The atomic structure of the gold nanoclusters and their effect on the intrinsic electronic quantum transport properties of the nanotube are also predicted. Experimentally, multi-wall CNTs are decorated with gold clusters using (1) vacuum evaporation, after activation with an RF oxygen plasma and (2) colloid solution injected into an RF atmospheric plasma; the hybrid systems are accurately characterized using XPS and TEM techniques. The response of gas sensors based on these nano(2)hybrids is quantified for the detection of toxic species like NO(2), CO, C(2)H(5)OH and C(2)H(4).


Asunto(s)
Gases/análisis , Gases/química , Oro/química , Nanopartículas del Metal/química , Nanotecnología/métodos , Nanotubos de Carbono/química , Nanopartículas del Metal/ultraestructura , Microscopía Electrónica de Transmisión , Nanotubos de Carbono/ultraestructura
11.
Semin Arthritis Rheum ; 48(2): 343-355, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29502800

RESUMEN

Reproduction capacity and long-term preserved hormonal function are important aspects with big impacts on patients' quality of life. Updated information on the interaction between drug therapy and reproductive function is essential when discussing family planning with patients. Currently, limited data is published regarding paternal exposure to different medications. Thus, it may be a challenge for the practitioner to choose the right therapy for a young male patient. Therefore we reviewed the literature, for effects of antirheumatic drugs on male gonadal function with a focus on spermatogenesis and offspring.


Asunto(s)
Antirreumáticos/farmacología , Exposición Paterna , Motilidad Espermática/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Humanos , Masculino
12.
Clin Rheumatol ; 36(7): 1511-1519, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28451872

RESUMEN

We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.


Asunto(s)
Artritis Reumatoide/psicología , Personalidad , Calidad de Vida/psicología , Espondilitis Anquilosante/psicología , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Determinación de la Personalidad , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/diagnóstico , Adulto Joven
13.
Rom J Intern Med ; 55(1): 44-52, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28103201

RESUMEN

BACKGROUND & AIMS: Considering the ability of anti-TNF alpha drugs to lower the burden intestinal inflammation in patients with inflammatory bowel disease (IBD), and the similarity between IBD and ankylosing spondylitis (AS) regarding inflammatory intestinal involvement, we aimed to investigate the impact of anti-TNF alpha biologic therapy on subclinical intestinal inflammation in AS patients. METHODS: Between January 2008 and December 2013, 38 AS patients and 23 controls were enrolled in the study and investigated with small bowel videocapsule endoscopy examination and ileocolonoscopy. Each tertile of the small bowel (proximal, mid and distal) was assessed by calculating the Lewis score based on the image stream. RESULTS: The Lewis scores were significantly higher in the AS group compared to controls (580.9 ± 818 vs. 81 ± 121, p<0.001). 16 patients (42.1%) were on anti-TNF alpha therapy (Adalimumab (n = 5), Infliximab (n = 5) or Etanercept (n = 6)).31.3% of them used NSAIDs simultaneously, compared with 77.3% of the other patients (p<0.01). Their Lewis scores were lower compared to the other patients for the entire small bowel (306 ± 164 vs. 790 ± 1038, p = 0.015), its proximal and distal tertiles (238 ± 154 vs. 560 ± 543, p = 0.021, and 140 ± 189 vs. 300 ± 220, p = 0.027, respectively). The Lewis score was also lower in patients receiving Adalimumab/Infliximab compared to those on Etanercept for the entire bowel and its distal tertile (262 ± 165 vs. 380 ± 148, p = 0.069 and 62 ± 101 vs. 273 ± 236, p = 0.060, respectively). CONCLUSION: Anti-TNF alpha therapy in patients with AS reduces the subclinical intestinal inflammation, but the magnitude seems to depend upon the class anti-TNF alpha agent used (Clinical Trials. gov NCT00768950).


Asunto(s)
Antirreumáticos/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal/patología , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/administración & dosificación , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Endoscopios en Cápsulas , Colonoscopía/métodos , Quimioterapia Combinada , Etanercept/administración & dosificación , Femenino , Hospitales Universitarios , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Infliximab/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico , Resultado del Tratamiento
14.
Int J Clin Pharmacol Res ; 25(1): 9-18, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15864873

RESUMEN

The aim of this study was to analyze the phenotype of circulating dendritic cells (DCc) in rheumatoid arthritis (RA) patients before and after treatment with infliximab (at 24 h and 6 months) and the correlation between these changes and the clinical response to treatment. Sixteen patients with RA were recruited and clinical status was determined using the Disease Activity Score 28 (DAS28). All patients had active disease (mean DAS28 = 5.96) and were suitable for treatment with infliximab. Samples of peripheral venous blood were obtained before administration of the first dose of infliximab and again at 24 h and 6 months after treatment. DCc populations were analyzed by flow cytometry. At 24 h, there were no differences in the clinical status of the patients. However, we found a decrease in CD11c+ and, to a lesser extent, CD123+ DCc percentages. The expression of CD83, the most important activation marker for DC, was also shown to be decreased 24 h after infliximab therapy. After 6 months of treatment, all patients showed significant clinical improvement (mean DAS28 = 3.64, p < 0.001) and expression of the activation marker on DCc remained low. In conclusion, this study supports the role of tumor necrosis factor (TNF)-alpha blockade in preventing the maturation of DCc and in reducing the expression of their activation markers. Although the clinical response to infliximab was not observed after 24 h, DCc activation was strongly reduced by anti-TNF-alpha therapy. After 6 months of treatment, current data show a less active phenotype of DCc associated with clinical improvement in all patients in the study.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Metotrexato/uso terapéutico , Adulto , Anticuerpos Monoclonales/administración & dosificación , Antígenos CD , Antirreumáticos/efectos adversos , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Antígeno CD11c/biosíntesis , Antígeno CD11c/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Quimioterapia Combinada , Femenino , Citometría de Flujo , Humanos , Inmunoglobulinas/biosíntesis , Inmunoglobulinas/inmunología , Infliximab , Masculino , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/inmunología , Metotrexato/administración & dosificación , Persona de Mediana Edad , Fenotipo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Antígeno CD83
15.
J Med Life ; 8 Spec Issue: 109-14, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26366227

RESUMEN

The appearance of osteoporosis in elders and the growth of the frequency which it is diagnosed with as we approach patients who are older and older, makes this health problem very important in the societies in which a high number of persons reach old age. These societies, usually belonging to economically advanced jurisdictions, are the first interested in the way health expenses can balance the benefits of the quality of life acquired in these groups of population. The evaluation of the quality of life has become a very important process, which still raises methodological problems to the researchers. The aim of this study was to analyze to what extent the factors involved in defining the quality of life by the patients modified according to the existence of osteoporosis as a defined but also as a perceived disease, as far as it is considered a serious or less serious affection by each patient. 210 female patients participated in the study. The statistical analysis was done by using SPSS 22.0 (IBM Corp. - U.S.A.). p < 0,05 was used as a limit for the statistical significance. Descriptive and analytical analyses were made by following Pearson correlation index in cases of normal distributions, the comparison between groups was made by using t-Student test, respectively chi square test in the cases which required its use. The current study highlights a direct relationship between the quality of life, as it is perceived by the patients, and the quality of the health status, which is more important than the relationship between the quality of life and the other objectives measured by WHOQOL scale. This study also shows that for the Romanian patient diagnosed with osteoporosis, who is enclosed in the age limits of this study, the health status represents the main driver of monitoring the quality of life.


Asunto(s)
Osteoporosis/economía , Osteoporosis/psicología , Percepción , Calidad de Vida/psicología , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Dieta , Femenino , Estado de Salud , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Factores Socioeconómicos , Encuestas y Cuestionarios
16.
J Med Life ; 8 Spec Issue: 119-23, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26361520

RESUMEN

Osteoporosis is a disease characterized by the reduction of the bone mass and the modification of the bone architecture, which leads to the risk of fracture of the fragile bones, this being the main clinical consequence of the disease. At the same time, osteoporosis is not only a problem by itself, but it is very important from the point of view of the consequences it may produce. Among its consequences, fractures should be mentioned especially in elders, their presence finally leading to an important decrease in the quality of life or even to death. Osteoporosis affects a high amount of persons, preponderantly elders, being considered a very important problem as the society we are talking about deals with the problem of aging. Socio-economical factors and their impact in the development of different pathologies have been seriously analyzed, especially by the western school of medicine. The aim of the current study is to evaluate the adherence to the treatment for osteoporosis of patients diagnosed with osteoporosis or in whom this diagnosis was taken into consideration by the physician, according to some characteristics identified as being the most relevant by a group of specialists. 210 patients were evaluated in this study during January 2011 and December 2013. This study highlighted the way patients with a real or presumptive diagnosis of osteoporosis adhere to the treatment for this disease according to the conditions considered relevant by a team of rheumatologists. It is important to notice that, still from the beginning, once the duration of the disease grows, patients become more and more conscious of the seriousness of the disease and more and more of them adhere to the treatment.


Asunto(s)
Conservadores de la Densidad Ósea/economía , Conservadores de la Densidad Ósea/uso terapéutico , Cumplimiento de la Medicación , Osteoporosis/tratamiento farmacológico , Osteoporosis/economía , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Factores Socioeconómicos
17.
Rom J Intern Med ; 53(4): 321-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26939208

RESUMEN

BACKGROUND: The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. AIM: To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. METHODS: 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE's criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS's criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive "criteria" APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-P2 glycoprotein I antibodies (aß2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aß2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/ without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aß2 GPI (IgG and IgM ) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the "non-criteria" APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. CONCLUSIONS: IgG aß2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the "non-criteria" APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the "non-criteria" APLAs with the antiDNA and complement C3 levels were also observed.


Asunto(s)
Síndrome Antifosfolípido/etiología , Lupus Eritematoso Sistémico/inmunología , Adulto , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Biophys Chem ; 64(1-3): 175-97, 1997 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-17029834

RESUMEN

We discuss a number of questions pertaining to the analysis of data to extract thermodynamic parameters for the reversible unfolding of proteins. Simulations are presented to illustrate problems in trying to test the validity of the two-state model, vis-a-vis a more complicated unfolding model. A conceptual and practical problem is how to consider the unfolded state and how to relate the observed signal to this state. We discuss the idea that the unfolded state can be described as a single macrostate, comprising a distribution of microstates having different degrees of solvent-accessible surface area. We also discuss the possibilities and thermodynamic consequences of having more than one unfolded state and of having a denaturant which both stabilizes and destabilizes the protein's native state.

19.
Photochem Photobiol ; 57(2): 367-70, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8451299

RESUMEN

Binding of sodium dodecyl sulfate (SDS) to bovine serum albumin (BSA) and human serum albumin (HSA) in aqueous solutions at room temperature induces significant changes in the phosphorescence lifetime of tryptophan (Trp) residues. A steep rise of the phosphorescence lifetime from 1.9 ms to 10.0 ms for BSA and from 1.9 ms to 5.5 ms for HSA is observed when the total SDS concentration increases from 0.0 mM to 0.22 mM at 1 mg/mL protein concentration. As the total SDS concentration is further increased to 2.2 mM, a slower increase in the phosphorescence lifetime is observed, from 10.0 ms to 19.5 ms for BSA and from 5.5 ms to 7.2 ms for HSA. It appears that the phosphorescence lifetime modifications are mainly due to an increase of protein matrix rigidity around Trp residues. The observed differences (between HSA and BSA) allow us to distinguish the contribution of the two Trp residues to the BSA phosphorescence.


Asunto(s)
Albúmina Sérica Bovina/metabolismo , Albúmina Sérica/metabolismo , Dodecil Sulfato de Sodio/metabolismo , Humanos , Luminiscencia , Espectrofotometría
20.
Ann Otolaryngol Chir Cervicofac ; 92(1-2): 73-8, 1975.
Artículo en Francés | MEDLINE | ID: mdl-1217803

RESUMEN

The authors carried out comparative research into the topography and the histopathological nature of pharyngo-laryngeal cancers in Zaire and in countries in other continents. They found that in all countries, cancers of the larynx seem mainly located on the vocal cords, but that pharyngeal cancers, and more especially those in rhino-pharyngeal sites which are seen more often in Asiatic than in European countries, occur very frequently in Zaire. From the histopathological point of view, they show that contrary to the high frequency of differentiated spinocellular epitheliomas often described in European countries, most pharyngo-laryngeal cancers which they observed were usually undifferentiated epitheliomas.


Asunto(s)
Neoplasias Laríngeas/patología , Neoplasias Faríngeas/patología , Humanos
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