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1.
J Periodontal Res ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171518

RESUMEN

AIMS: Periodontitis and cardiovascular diseases (CVD) are highly prevalent non-communicable diseases, sharing an inflammatory pathogenesis and common risk factors. The objective of the present research is to assess the association between periodontitis and cardiovascular disease risk in a representative sample of the Spanish-employed population. METHODS: Cross-sectional data were obtained between 2008 and 2011 in the Workers' Oral Health (WORALTH) epidemiological study. Periodontal examinations were based on the evaluation of clinical attachment loss (CAL) and community periodontal index (CPI). Participants also underwent a medical check-up and answered a comprehensive health questionnaire. With this information, participants were categorized into three levels of CVD risk using the systemic coronary risk estimation (SCORE) algorithm for low-risk European countries. Crude and adjusted odds ratios (ORs) were determined with multiple logistic regression models for the association between periodontal status and CVD risk. RESULTS: Data from 4224 individuals were analyzed. The overall prevalence of high CVD risk (SCORE ≥ 5%) was 5.1%. The prevalence of SCORE ≥ 5% was 3.4%, 9.4%, and 15.2% for CAL 0-3 mm, 4-5 mm, and ≥6 mm, respectively (p < .001), and 6.2%, 6.5%, and 14.6% for CPI ≤2, 3, and 4, respectively (p < .001). Individuals with CPI = 4 presented an OR of 1.50 (95% confidence interval, CI [1.04; 2.17]) for high SCORE values, after adjusting for confounders (age, sex, and smoking habit). CONCLUSIONS: Periodontitis, defined by the presence of deep periodontal pockets (≥6 mm), was significantly associated with high CVD risk (SCORE ≥ 5%) in a representative sample of the employed population in Spain.

2.
Medicine (Baltimore) ; 103(28): e38943, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996114

RESUMEN

Over time, several studies have been conducted to demonstrate the functions of the neurotransmitter 5-hydroxytryptamine (5-HT), better known as serotonin. This neurotransmitter is associated with the modulation of various social and physiological behaviors, and its dysregulation has consequences at the behavioral level, leading to various neurophysiological disorders. Disorders such as anxiety, depression, schizophrenia, epilepsy, sexual disorders, and eating disorders, have been closely linked to variations in 5-HT concentrations and modifications in brain structures, including the raphe nuclei (RN), prefrontal cortex, basal ganglia, hippocampus, and hypothalamus, among others. The involvement of ß-arrestin proteins has been implicated in the modulation of the serotonergic receptor response, as well as the activation of different signaling pathways related to the serotonergic system, this is particularly relevant in depressive disorders. This review will cover the implications of alterations in 5-HT receptor expression in depressive disorders in one hand and how ß-arrestin proteins modulate the response mediated by these receptors in the other hand.


Asunto(s)
Receptores de Serotonina , beta-Arrestinas , Humanos , beta-Arrestinas/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Transducción de Señal/fisiología , Trastorno Depresivo/metabolismo , Trastorno Depresivo/fisiopatología , Encéfalo/metabolismo , Depresión/metabolismo
3.
Healthcare (Basel) ; 12(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38998858

RESUMEN

The aim of this study is to evaluate the relationship between clinical severity and functionality, occupational performance, and health-related quality of life in patients hospitalized with pulmonary embolism. Pulmonary embolism patients were grouped by clinical severity using the Pulmonary Embolism Severity Index. Those scoring ≥160 were in the high-severity group (HSG); those scoring < 160 in the low-moderate group (LMSG). The main variables were functionality assessed by the World Health Organization Disability Assessment Schedule (WHODAS), self-perception of occupational performance assessed by the Canadian Occupational Performance Measure (COPM), pain and fatigue assessed by a Visual Analogue Scale (VAS), and health-related quality of life assessed by the EuroQol-5Dimensions (EQ-5D). Patients were evaluated at hospital admission and at 1-month and 3-month follow-up. At admission, there were significant differences between groups in the WHODAS and health-related quality of life in favor of the LMSG. At 1-month and at 3-month follow-up, there were significant differences between the LMSG and HSG in WHODAS, COMP, NRS pain, fatigue and EQ-5D scores in favor of the LMSG. An association exists between clinical severity and mid-term functionality, self-perception of occupational performance, pain, fatigue, and health-related quality of life in PE patients.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39011816

RESUMEN

OBJECTIVE: The aim of this investigation was to evaluate the effect on clinical and radiological outcomes of the one-abutment, one-time protocol (test) versus placing the definitive abutment on the day of functional loading after having disconnected and connected three times the healing abutment during the prosthetic phase (control). MATERIALS AND METHODS: Forty patients with 80 implants were randomly allocated to either the test or the control group. Changes in the radiographic marginal bone levels (MBLs), clinical outcomes, prosthetic-related outcomes, and patient-reported outcomes measures (PROMs) were assessed and compared 6 and 12 months after functional loading. RESULTS: Thirty-seven patients with 74 implants were followed at 12 months. A statistically significant bone remodeling was observed in both groups following implant placement. MBLs were significantly greater in the control group at the 6- (-0.13 mm vs. -0.61 mm) and 12-month visits (-0.01 mm vs. -0.53 mm). Bone loss was significantly greater in the control group from surgery to 6 and 12 months and from loading to 6 and 12 months. The abutment height was significantly greater in the test group, however, there were no significant differences in the restorative angle. Similarly, there were no statistically significant differences between groups for the measured clinical variables (probing depth, plaque, and bleeding index) and PROMs. CONCLUSIONS: Disconnecting and reconnecting the healing abutment was associated with significantly higher bone loss after 12 months, as compared to the placement of the definitive abutment at implant installation.

5.
Front Endocrinol (Lausanne) ; 15: 1413810, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952395

RESUMEN

Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time. Design and patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235). Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered. Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.


Asunto(s)
Quistes del Sistema Nervioso Central , Humanos , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/patología , Femenino , Masculino , España/epidemiología , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Resultado del Tratamiento , Anciano , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Progresión de la Enfermedad , Estudios de Seguimiento , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Niño
6.
Healthcare (Basel) ; 12(14)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39057508

RESUMEN

BACKGROUND: The early stages of the COVID-19 pandemic overwhelmed general hospitals in Spain. In response, a dedicated hospital for COVID-19 care, the Hospital de Emergencias Enfermera Isabel Zendal (HEEIZ), was established. This study aimed to compare clinical outcomes of COVID-19 patients treated at the specialized HEEIZ with those at conventional general hospitals (CGHs) in Madrid, Spain. METHODS: The study was a prospective, observational cohort study including COVID-19 patients admitted to the HEEIZ and 14 CGHs (December 2020 to August 2021). Patients were assigned based on hospital preference. Clinical data were collected and analyzed using multivariate regression to assess primary and secondary outcomes, including hospital mortality, need of invasive mechanical ventilation (IMV), and pharmacological treatments. RESULTS: The HEEIZ cohort (n = 2997) was younger and had lower Charlson comorbidity scores than the CGH cohort (n = 1526). Adjusted HEEIZ hospital mortality was not significantly higher compared with CGHs (OR: 1.274; 95% CI: 0.781-2.079; p = 0.332). CONCLUSIONS: During the study period, patients admitted to the HEEIZ showed no significant differences in clinical outcomes, compared with patients admitted at CGHs. These results might support the use of specialized centers in managing pandemic surges, allowing CGHs to handle other needs.

7.
Int J Infect Dis ; 146: 107163, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38969329

RESUMEN

OBJECTIVES: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19. METHODS: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated. RESULTS: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (P = 0.009, P = 0.030 and P = 0.001, respectively). The 90-day overall survival was lower (P = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia. CONCLUSION: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Neoplasias Hematológicas , ARN Viral , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/inmunología , Masculino , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/inmunología , Anciano , Persona de Mediana Edad , ARN Viral/sangre , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Interferón gamma/sangre , Interferón-alfa/uso terapéutico , Anciano de 80 o más Años , Adulto , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación
8.
Nat Aging ; 4(8): 1102-1120, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38849535

RESUMEN

The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity.


Asunto(s)
Inflamación , Longevidad , Diana Mecanicista del Complejo 1 de la Rapamicina , Células Mieloides , Transducción de Señal , Animales , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Inflamación/patología , Inflamación/metabolismo , Células Mieloides/metabolismo , Células Mieloides/patología , Nutrientes/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
9.
J Nutr Health Aging ; 28(7): 100289, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38865737

RESUMEN

OBJECTIVES: Innovative precision dietary procedures are required to promote healthy aging. This study aimed to evaluate the effects of a personalised strategy based on the inclusion of individualised foods and digital tools on overall health status and quality of life within a follow-up of 3 months in older adults with overweight or obesity. METHODS: 127 men and women aged between 50 and 80 years with overweight/obesity participated in the study-between January 2020 and September 2020 at the Center for Nutrition Research-University of Navarra and IMDEA-ALIMENTACIÓN-and were randomly assigned to a usual-care group (standard recommendations) or precision group (precision nutrition strategy based on the inclusion of individualised foods and a mobile application). Anthropometry, body fat percentage, biochemical parameters, diet, and quality of life (SF-36 Health Survey) were assessed at baseline and after 3 months. RESULTS: Both strategies were found to improve overall metabolic health; however, the precision approach demonstrated significantly better outcomes. The precision strategy reduced body weight at 3 months (-4.3 kg; p < 0.001) with significant improvements in body fat percentage, blood pressure and general metabolic health (glycated haemoglobin; alanine aminotransferase; aspartate aminotransferase; hepatic steatosis index) in comparison with the standard recommendations. The precision approach significantly enhanced the quality of life (SF-36) of individuals, with additional improvements in emotional well-being (p = 0.024) and vitality (p = 0.008). Adherence to the Mediterranean diet was significantly associated with a higher quality of life and vitality. CONCLUSION: These results support the benefit of precision nutrition approaches for promoting healthy aging and emotional well-being, enhancing the quality of life in aging populations, during the COVID-19 pandemic.


Asunto(s)
Obesidad , Calidad de Vida , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Obesidad/psicología , Obesidad/dietoterapia , Obesidad/terapia , Sobrepeso/terapia , Sobrepeso/dietoterapia , Envejecimiento Saludable , Estado de Salud , COVID-19 , Estado Nutricional , Medicina de Precisión/métodos , Envejecimiento/fisiología , Dieta
10.
Front Bioeng Biotechnol ; 12: 1256190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576446

RESUMEN

Background: Altered lipid metabolism in cancer is associated to dissemination and prognosis. Bioactive compounds naturally occurring in Achillea millefolium L. (yarrow) have been reported to exert antitumour activities. Food biotechnology may provide on-demand mixtures of bioactive compounds with complementary activities in cancer treatment. Methods: Supercritical-antisolvent-precipitation (SAS) has been applied to fractionate the bioactive compounds from an Ultrasound-Assisted-Extraction yarrow extract resulting in two extracts with distinct polarity, yarrow-precipitate-(PP) and yarrow-separator-(Sep). Total phenolic content and relevant essential oils have been characterized. Antioxidant, anti-inflammatory and antiproliferative activities have been compared. Moreover, the effect on the inhibition of colorectal cancer cells' bioenergetics has been evaluated. Results: Yarrow-PP exerted the highest antioxidant activity, even higher than the complete UAE-yarrow extract, meanwhile yarrow-Sep showed the highest anti-inflammatory activity, even higher than the complete UAE-yarrow extract. Interestingly, yarrow-Sep inhibited key lipid metabolic targets in CRC cells extensively shown to be implicated in cancer dissemination and prognosis -SREBF1, FASN, ABCA1 and HMGCR- and epithelial to mesenchymal targets-CDH1, ATP1B1, CDH2 and Vimentin-augmenting cell adhesion. Conclusions: In summary, SAS technology has been applied to provide a novel combination of bioactive compounds, yarrow-Sep, which merits further research to be proposed as a potential complementary nutraceutical in the treatment of CRC.

11.
Clin Oral Implants Res ; 35(6): 609-620, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38506392

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the long-term (5 years) clinical efficacy of the one-abutment one-time protocol (test) versus the standard of care by placing the definitive abutment on the day of the prosthetic delivery (control). MATERIALS AND METHODS: In this study, 39 subjects with 60 implants were randomly allocated to either the test or the control group. Changes in the radiographic interproximal bone levels (DIB), modified sulcus bleeding index, probing depth, modified plaque index, papilla fill (Jemt score), incidence of peri-implantitis and peri-implant mucositis as well as patient-reported outcomes measures (PROMs) were collected and compared at 1, 3 and 5 years. RESULTS: At 5 years, the control group showed a greater, although not statistically significant, change in mean DIB values (0.97 mm vs. 0.53 mm). Regarding the other clinical parameters evaluated, no statistically significant differences were observed between groups at any time point. At 5 years, 51% of the implants presented peri-implant mucositis (25.5% in the control and 23.5% in the test), and only one implant in the test group developed peri-implantitis. CONCLUSIONS: The connection and disconnection of healing abutments during the healing period was not associated with higher long-term bone loss. Clinical outcomes and PROMs were similar between groups.


Asunto(s)
Pilares Dentales , Periimplantitis , Humanos , Femenino , Masculino , Persona de Mediana Edad , Pilares Dentales/efectos adversos , Periimplantitis/diagnóstico por imagen , Resultado del Tratamiento , Índice Periodontal , Implantación Dental Endoósea/métodos , Implantación Dental Endoósea/efectos adversos , Pérdida de Hueso Alveolar/diagnóstico por imagen , Adulto , Anciano , Medición de Resultados Informados por el Paciente , Implantes Dentales/efectos adversos , Índice de Placa Dental
12.
Eur J Gen Pract ; 30(1): 2320120, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38511739

RESUMEN

BACKGROUND: Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing. OBJECTIVES: To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD). METHODS: The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors. CONCLUSION: Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.


Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19.Periodontal treatment for optimal outcomes improves diabetes outcomes and surrogate measures of cardiovascular risk.Closer collaboration between oral health care professionals and family doctors is important in the early case detection and management of non-communicable diseases.Information on the reported associations should be made available to family doctors, oral health professionals, healthcare funders, patients, and the general population.


Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Humanos , Europa (Continente) , COVID-19/complicaciones , COVID-19/epidemiología , Diabetes Mellitus/terapia , Diabetes Mellitus/epidemiología , Enfermedades Periodontales/terapia , Periodontitis/terapia , Periodontitis/epidemiología , Consenso
13.
Molecules ; 29(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38542833

RESUMEN

A group of functionalized fluorene derivatives that are structurally similar to the cellular prion protein ligand N,N'-(methylenedi-4,1-phenylene)bis [2-(1-pyrrolidinyl)acetamide] (GN8) have been synthesized. These compounds show remarkable native fluorescence due to the fluorene ring. The substituents introduced at positions 2 and 7 of the fluorene moiety are sufficiently flexible to accommodate the beta-conformational folding that develops in amyloidogenic proteins. Changes in the native fluorescence of these fluorene derivatives provide evidence of transformations in the amyloidogenic aggregation processes of insulin. The increase observed in the fluorescence intensity of the sensors in the presence of native insulin or amyloid aggregates suggest their potential use as fluorescence probes for detecting abnormal conformations; therefore, the compounds can be proposed for use as "turn-on" fluorescence sensors. Protein-sensor dissociation constants are in the 5-10 µM range and an intermolecular charge transfer process between the protein and the sensors can be successfully exploited for the sensitive detection of abnormal insulin conformations. The values obtained for the Stern-Volmer quenching constant for compound 4 as a consequence of the sensor-protein interaction are comparable to those obtained for the reference compound GN8. Fluorene derivatives showed good performance in scavenging reactive oxygen species (ROS), and they show antioxidant capacity according to the FRAP and DPPH assays.


Asunto(s)
Amiloide , Insulina , Amiloide/química , Proteínas Amiloidogénicas , Fluorometría , Fluorenos/química
14.
Biology (Basel) ; 13(2)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38392342

RESUMEN

Environmental enrichment improves captive animal welfare by reducing stress-related behaviors. Previous studies in a captive colony of stumptail macaques (Macaca arctoides) reported a reduction of aggression, coprophilia, and stereotypic behaviors after an occupational enrichment program; however, the effect on stress hormones such as glucocorticoids has not been investigated yet. The goal of this study was to compare the effect of sex, age, and social rank on changes in fecal glucocorticoid metabolites (fGCM) after applying two kinds of enrichments (occupational vs. musical) in a captive colony of stumptail macaques. We collected 234 fecal samples from 25 stumptail macaques under the following conditions: (1) basal (no enrichment), (2) three weeks of occupational enrichment, and (3) three weeks of relaxing/classical music. The Generalized Estimated Equation Model showed an increase in fGCM levels after the occupational enrichment only in adult subjects (p = 0.003 compared to basal). The fGCM levels reached by the adults after the occupational enrichment was higher than that of juveniles (p = 0.002) and subadults (p = 0.02). Occupational and musical enrichment decreased fGCM levels only in middle-ranking individuals (p < 0.001 and p = 0.013, respectively). No sex differences were found. In conclusion, there were age and rank differences in individuals' physiological reactivity to the effects of environmental enrichment which need to be considered when planning enrichment programs.

16.
Cell Rep ; 43(2): 113705, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38307025

RESUMEN

Nerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in the humoral response is not well defined. Here, we study the effect of Ngfr loss on lymph node organization and function, demonstrating that Ngfr depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment. In accordance with this effect, stromal cells are altered in Ngfr-/- mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr-/- mice, with lost polarization together with impaired high-affinity antibody production and an increase in circulating autoantibodies. We observe higher levels of autoantibodies in Bcl2 Tg/Ngfr-/- mice, concomitant with a higher incidence of autoimmunity and lower overall survival. Our work shows that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance.


Asunto(s)
Receptor de Factor de Crecimiento Nervioso , Receptores de Factor de Crecimiento Nervioso , Animales , Ratones , Autoanticuerpos , Células Dendríticas Foliculares , Centro Germinal
17.
Carbohydr Polym ; 328: 121743, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38220353

RESUMEN

Sustainable composite foams based on rice starch and cellulosic long fibers were successfully fabricated using microwave irradiation. They were presented as a promising method to recycle some of the textile industry waste. A deep study of the processability and functionality of the composites revealed the performance improvement of starch with the addition of long cellulosic fibers, especially with 6 wt% of Arbocel®, in terms of foamability, water, and mechanical resistance features. Moreover, sodium bicarbonate, which acted as a blowing and pulping agent, led to a lower density and better fiber distribution that resulted in an improvement of the foams' functionalities. The range of the study is new in the domain of long fiber foam composites in terms of the foaming capability, and mechanical, thermal, and water resistance properties. Furthermore, all foams showed excellent biodegradability properties against a fungus commonly found in the environment; for example, values around 60 % weight loss after 33 days. Finally, the assessment of the CO2 emission during the process underlines the environmental benefits of the method employed.


Asunto(s)
Microondas , Almidón , Almidón/metabolismo , Textiles , Biodegradación Ambiental , Agua
18.
J Clin Oncol ; 42(7): 842-851, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-37922438

RESUMEN

PURPOSE: Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA), a cell surface antigen overexpressed in PC, provides a validated target. This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for 225Ac-J591, anti-PSMA monoclonal antibody J591 radiolabeled with the alpha emitter actinium-225. METHODS: Following investigational new drug-enabling preclinical studies, we enrolled patients with progressive mCRPC that was refractory to or who refused standard treatment options (including androgen receptor pathway inhibitor and had received or been deemed ineligible for taxane chemotherapy). No selection for PSMA was performed. Patients received a single dose of 225Ac-J591 at one of seven dose-escalation levels followed by expansion at the highest dose. Primary end point of dose-escalation cohort was determination of dose-limiting toxicity (DLT) and RP2D. RESULTS: Radiochemistry and animal studies were favorable. Thirty-two patients received 225Ac-J591 in an accelerated dose-escalation design (22 in dose escalation, 10 in expansion). One patient (1 of 22; 4.5%) experienced DLT in cohort 6 (80 KBq/kg) but none in cohort 7; MTD was not reached, and RP2D was the highest dose level (93.3 KBq/kg). The majority of high-grade adverse events (AEs) were hematologic with an apparent relationship with administered radioactivity. Nonhematologic AEs were generally of low grade. Prostate-specific antigen (PSA) declines and circulating tumor cell (CTC) control were observed: 46.9% had at least 50% PSA decline at any time (34.4% confirmed PSA response), and protocol-defined CTC count response occurred in 13 of 22 (59.1%). CONCLUSION: To our knowledge, this is the first-in-human phase I dose-escalation trial of a single dose of 225Ac-J591 in 32 patients with pretreated progressive mCRPC demonstrated safety and preliminary efficacy signals. Further investigation is underway.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Animales , Humanos , Masculino , Antagonistas de Receptores Androgénicos/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Antígenos de Superficie , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Resultado del Tratamiento
19.
Biomaterials ; 304: 122409, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38052135

RESUMEN

There is increasing interest in modulating the redox homeostasis of tumors since high levels of reactive oxygen species (ROS) make them more vulnerable to changes in these species. Nanomedicine offers promise in this context as such applications may provoke biological responses that induce ROS production. Indeed, iron oxide nanoparticles (IONPs) can induce ROS accumulation through the so-called Fenton reaction of iron, further augmenting the ROS in tumors and overloading the antioxidant system beyond its capacity, thereby driving oxidative stress to a level that is incompatible with cell survival. Here, three different coatings for IONPs were compared to assess their intrinsic capacity to induce ROS production in cells. Of these coatings, dimercaptosuccinic acid-coated IONPs (DMSA-NPs) provoked the strongest ROS production, which was associated with the ability to reprogram the metabolism of cancer cells. This latter phenomenon involved shutting-down oxidative phosphorylation (OXPHOS), shifting mitochondrial morphology towards a more elongated phenotype, reducing the total mitochondrial mass and ultimately, blocking cell proliferation by inducing G0/G1 cell cycle arrest. Consequently, the data obtained highlights the importance of studying the chemical properties of IONPs, presenting DMSA-NPs as a novel tool to induce oxidative stress in cancer cells and alter their cell fate.


Asunto(s)
Compuestos Férricos , Neoplasias , Humanos , Especies Reactivas de Oxígeno/metabolismo , Compuestos Férricos/química , Estrés Oxidativo , División Celular , Succímero , Nanopartículas Magnéticas de Óxido de Hierro
20.
Repert. med. cir ; 33(2): 158-162, 2024. tab
Artículo en Español | LILACS, COLNAL | ID: biblio-1561036

RESUMEN

Objetivo: caracterizar clínica y epidemiológicamente a los pacientes con enfermedad pulmonar obstructiva crónica. Métodos: estudio descriptivo retrospectivo trasversal, que incluyó pacientes adultos con diagnóstico de enfermedad pulmonar obstructiva crónica en un hospital universitario de Medellín. Material y métodos: la fuente de información fue secundaria a través de historias clínicas, el análisis se realizó en el programa Jamovi, empleando un análisis univariado. Resultados y discusión: se incluyeron 552 pacientes, la edad mediana fue 76 años con predominio del sexo femenino (56.7%). Respecto a la exposición a sustancias tóxicas respiratorias importantes en el desarrollo de la enfermedad, 24.1% consumían cigarrillo y 23% exposición a biomasa. Al momento del ingreso hospitalario 17.9% fueron clasificados con disnea grado IV; 74.1% recibió beta-agonistas de corta acción y antimuscarínicos de corta acción 60%; 11.6% requirió ingreso a las unidades de cuidados intensivos o especiales y 7.8% fallecieron durante la hospitalización. Conclusiones: se evidencia subdiagnóstico espirométrico de la enfermedad que puede estar relacionado con las limitaciones económicas, tecnológicas y de recurso humano capacitado, lo cual afecta el adecuado diagnóstico y manejo de la enfermedad, así como impacta la calidad de vida de los pacientes.


Objective: clinical and epidemiological characterization of patients with chronic obstructive pulmonary disease (COPD). Methods: a retrospective, cross-sectional, descriptive study, which included adult patients with a diagnosis of COPD in a university hospital in Medellín. Data sources were secondary, based on medical records. The Jamovi program was used to perform a univariate analysis. Results and discussion: 552 patients were included. Median age was 76 years with a female predominance (56.7%). Regarding exposure to major respiratory toxic substances implicated in the development of the disease, 24.1% were tobacco smokers and 23% were exposed to biomass smoke. At the time of hospital admission,17.9% were classified as having grade 4 dyspnea; 74.1% received short acting beta-agonists and 60% short-acting antimuscarinics,11.6% required intensive care unit or special care unit admission, and 7.8% died in hospital. Conclusions: under-diagnosis of COPD by spirometry may be related to economic, technological, and trained human resource limitations, which affect adequate diagnosis and management of the disease, as well as patient ́s quality of life.


Asunto(s)
Humanos
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