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2.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39062874

RESUMEN

To analyze the mechanism of copper accumulation in the marine alga Ulva compressa, it was cultivated with 10 µM of copper, with 10 µM of copper and increasing concentrations of a sulfide donor (NaHS) for 0 to 7 days, and with 10 µM of copper and a concentration of the sulfide acceptor (hypotaurine) for 5 days. The level of intracellular copper was determined as well as the level of glutathione (GSH) and phytochelatins (PCs) and the expression of metallothioneins (UcMTs). The level of intracellular copper in the algae treated with copper increased at day 1, slightly increased until day 5 and remained unchanged until day 7. The level of copper in the algae cultivated with copper and 100 or 200 µM of NaHS continuously increased until day 7 and the copper level was higher in the algae cultivated with 200 µM of NaHS compared to 100 µM of NaHS. In contrast, the level of intracellular copper decreased in the algae treated with copper and hypotaurine. The level of intracellular copper did not correlate with the level of GSH or with the expression of UcMTs, and PCs were not detected in response to copper, or copper and NaHS. Algae treated with copper and with copper and 200 µM of NaHS for 5 days were visualized by TEM and the elemental composition of electrondense particles was analyzed by EDXS. The algae treated with copper showed electrondense particles containing copper and sulfur, but not nitrogen, and they were mainly located in the chloroplast, but also in the cytoplasm. The algae treated with copper and NaHS showed a higher level of electrondense particles containing copper and sulfur, but not nitrogen, and they were located in the chloroplast, and in the cytoplasm. Thus, copper is accumulated as copper sulfide insoluble particles, and not bound to GSH, PCs or UcMTs, in the marine alga U. compressa.


Asunto(s)
Cobre , Glutatión , Metalotioneína , Fitoquelatinas , Sulfuros , Ulva , Cobre/metabolismo , Ulva/metabolismo , Ulva/efectos de los fármacos , Fitoquelatinas/metabolismo , Glutatión/metabolismo , Metalotioneína/metabolismo , Sulfuros/metabolismo , Taurina/análogos & derivados
4.
RECIIS (Online) ; 18(2)abr.-jun. 2024.
Artículo en Portugués | LILACS, ColecionaSUS | ID: biblio-1561671

RESUMEN

Este artigo, por meio de aproximação genealógica, buscou investigar o que chamaremos de pistas genealó-gicas do equipamento Consultório na Rua em município de médio porte no Sul do Brasil. Para o percurso da pesquisa, junto a uma vivência em um Consultório na Rua, nesse município do país, foram realizados entrevistas e levantamentos de documentos. Na investigação foi possível encontrar pistas que apontam para uma produção de criminalização e assimilação histórica dos viventes da rua pelo Estado brasileiro, de maneira que esses pontos precisam ser discutidos e problematizados para que tais regimes de verdade não sejam norteadores das políticas públicas para tais pessoas.


This article, employing a genealogical approach, aimed to examine the genealogical traces of the Street Clinic equipment in a medium-sized city in Brazil's southern region. In order to follow the path of the research, along with an experience in a Street Clinic in a Brazilian city, interviews and document surveys were conducted. In the investigation, it was possible to find elements of the production of criminalization and historical assimilation by the Brazilian State that need to be discussed and problematized so that such regimes of truth are not guiding the production of health care for people experiencing homelessness.


Este artículo, a través de un abordaje genealógico, buscó investigar pistas genealógicas del Consultorio en la Calle en una ciudad de tamaño medio en el sur de Brasil. Para el transcurso de la investigación, junto con una experiencia en un Consultorio en la Calle en un municipio de tamaño medio en el sur de Brasil, se efectuaron entrevistas y encuestas documentales. En la investigación, fue posible encontrar pistas que apuntan a una producción de criminalización y asimilación histórica de las personas en situación de calle por parte del Estado brasileño, por lo que estos puntos necesitan ser discutidos y problematizados para que tales regímenes de verdad no guíen políticas públicas para dicha población.


Asunto(s)
Atención Primaria de Salud , Apoyo Social , Personas con Mala Vivienda , Servicios de Salud Comunitaria , Política de Salud , Clase Social , Sistema Único de Salud , Colaboración Intersectorial , Conducta Criminal , Aculturación
5.
Expert Opin Biol Ther ; 24(7): 647-653, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38698351

RESUMEN

BACKGROUND: The rise of biologic agents has been a major breakthrough in treating immune-mediated inflammatory diseases (IMIDs). However, their high cost underscores the need for strategies to optimize treatment efficiency. Biosimilars offer cost-effective alternatives to biologics. This study aimed to assess biosimilar drug availability's impact on biologic therapy access for IMIDs. RESEARCH DESIGN AND METHODS: A retrospective observational study in 15 Spanish hospitals analyzed IMID patients (arthropathies, inflammatory bowel disease and psoriasis) initiating biologic therapy with originator or biosimilar drugs (infliximab, etanercept, adalimumab). Time to availability and initiation of biologic therapy were assessed. RESULTS: 267 patients were included, with 58.4% starting on biosimilars. The mean time to availability of the biologic drugs in the hospitals was 15.9 ± 6.7 months, (20.0 ± 12.4 for originator and 11.8 ± 5.2 for biosimilars). Mean time to biologic treatment was 7.7 ± 9.0 years (8.6 ± 8.9 for originators and 7.0 ± 9.0 for biosimilars). Showing statistically significant differences among conditions. CONCLUSION: The emergence of biosimilar drugs has enhanced market competition and accelerated their adoption into hospitals' therapeutic regimens over original reference drugs. This has significantly improved access to biologic therapy for patients with IMIDs, evidenced by a notable 1.6-year reduction in access time for biosimilar drugs.


Asunto(s)
Biosimilares Farmacéuticos , Humanos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/economía , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Terapia Biológica , Accesibilidad a los Servicios de Salud , España , Enfermedades del Sistema Inmune/tratamiento farmacológico , Anciano , Infliximab/uso terapéutico , Infliximab/economía
6.
Farm Hosp ; 48(4): T171-T175, 2024.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38806363

RESUMEN

OBJETIVES: The main objective was to compare the persistence between dolutegravir/lamivudine (DTG/3TC) and bictegravir/emtricitabine/tenofovir-alafenamide (BIC/FTC/TAF) and to analyze reasons for discontinuation. METHODS: We conducted a retrospective, non-interventional, descriptive, and longitudinal study. All human immunodeficiency virus (HIV) patients over 18 years treated with DTG/3TC or BIC/FTC/TAF in our center were included. Persistence after first year was compared using the χ2 test. Kaplan-Meier survival analysis was performed. RESULTS: Three hundred fifty-eight patients were included. 99.5% versus 90.99% of patients were persistent after the first year for DTG/3TC and BIC/FTC/TAF respectively (p=.001). Persistence with DGT/3TC was 1237 days (IC95% 1216-1258) and persistence with BIC/FTC/TAF was 986 days [(IC95% 950-1021); p<.001]. The difference was remained after adjusting for covariates with the cox regression model [HR=8.2 (IC95% 1.03-64.9), p=.047]. The main reasons for discontinuation for BIC/FTC/TAF were toxicity/tolerability. CONCLUSION: In our study, patients have a high persistence. Patients on DTG/3TC treatment are more persistent compared to BIC/FTC/TAF, although BIC/FTC/TAF have worse baseline characteristics. The main reason for discontinuation of BIC/FTC/TAF is tolerability/toxicity.


Asunto(s)
Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Lamivudine , Oxazinas , Piperazinas , Piridonas , Tenofovir , Humanos , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Piridonas/uso terapéutico , Femenino , Lamivudine/uso terapéutico , Piperazinas/uso terapéutico , Oxazinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Adulto , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Emtricitabina/uso terapéutico , Tenofovir/uso terapéutico , Alanina/uso terapéutico , Alanina/análogos & derivados , Estudios Longitudinales , Combinación de Medicamentos , Amidas/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Adenina/análogos & derivados , Adenina/uso terapéutico
7.
J Pediatr Nurs ; 77: e132-e138, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38594165

RESUMEN

PURPOSE: The objective was analysed the patterns use of healthcare services of this population and the influence of their clinical and sociodemographic characteristics. DESIGN AND METHODS: A six-year longitudinal follow-up study was performed to evaluate the annual healthcare resources use and clinical data among children with complex chronic diseases in Spain between 2015 and 2021. The sample trends in healthcare usage and the associated factors were analysed using ANCOVA and multivariable linear regression models. RESULTS: Patients had high attendance during the follow-up period, with >15 episodes year. This trend decreased over time, especially in children with oncological diseases compared with other diseases (F (16.75; 825.4) = 32.457; p < 0.001). A multivariable model showed that children with a greater number of comorbidities (ß = 0.17), shorter survival time (ß = -0.23), who had contact with the palliative care unit (ß = 0.16), and whose mothers had a higher professional occupation (ß = 0.14), had a greater use of the healthcare system. CONCLUSIONS: Children with a higher number of comorbidities and the use of medical devices made a greater frequentation of health services, showing a trend of decreasing use over time. Socioeconomic factors such as mothers' occupational status determine healthcare frequentation. These results suggest the existence of persistent gaps in care coordination sustained over time. PRACTICAL IMPLICATIONS: Systematized and coordinated models of care for this population should consider the presence of inequalities in health care use.


Asunto(s)
Aceptación de la Atención de Salud , Humanos , Femenino , Masculino , Niño , Estudios Longitudinales , Enfermedad Crónica , España , Estudios de Seguimiento , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Preescolar , Factores Socioeconómicos
8.
Farm Hosp ; 48(4): 171-175, 2024.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38448360

RESUMEN

OBJETIVES: The main objective was to compare the persistence between dolutegravir/lamivudine (DTG/3TC) and bictegravir/emtricitabine/tenofovir-alafenamide (BIC/FTC/TAF) and to analyze reasons for discontinuation. METHODS: We conducted a retrospective, non-interventional, descriptive and longitudinal study. All human immunodeficiency virus (HIV) patients over 18 years treated with DTG/3TC or BIC/FTC/TAF in our center were included. Persistence after first year was compared using the χ2 test. Kaplan-Meier survival analysis was performed. RESULTS: Three hundred fifty-eight patients were included. 99.5% versus 90.99% of patients were persistent after the first year for DTG/3TC and BIC/FTC/TAF respectively (p = 0.001). Persistence with DGT/3TC was 1,237 days (IC95% 1,216-1,258) and persistence with BIC/FTC/TAF was 986 days ([IC95% 950-1,021]; p < 0.001). The difference was remained after adjusting for covariates with the cox regression model (HR= 8.2 [IC95% 1.03-64.9], p = 0.047). The main reasons for discontinuation for BIC/FTC/TAF were toxicity/tolerability. CONCLUSION: In our study patients had a high persistence. Patients on DTG/3TC treatment were more persistent compared to BIC/FTC/TAF, although BIC/FTC/TAF have worse baseline characteristics. The main reason for discontinuation of BIC/FTC/TAF was tolerability/toxicity.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Lamivudine , Oxazinas , Piperazinas , Piridonas , Humanos , Estudios Retrospectivos , Infecciones por VIH/tratamiento farmacológico , Masculino , Femenino , Piridonas/uso terapéutico , Lamivudine/uso terapéutico , Oxazinas/uso terapéutico , Adulto , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Piperazinas/uso terapéutico , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Tenofovir/uso terapéutico , Emtricitabina/uso terapéutico , Estudios Longitudinales , Alanina/uso terapéutico , Alanina/análogos & derivados , Amidas/uso terapéutico , Combinación de Medicamentos
9.
Int Orthop ; 48(5): 1285-1294, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38478022

RESUMEN

PURPOSE: Prevalence of axillary (AN) and/or suprascapular (SSN) neuropathy in rotator cuff tear arthropathy (RCTA) is unknown. We aimed to prospectively evaluate for preoperative neurodiagnostic abnormalities in order to determine their prevalence, location, and influence on reverse shoulder arthroplasty (RSA) outcomes. METHODS: Patients who underwent RSA for RCTA were prospectively included. An electromyography and nerve conduction study were performed pre and post-surgery. Clinical situation: VAS, Relative Constant-Murley Score (rCMS) and ROM over a minimum of two years follow-up. RESULTS: Forty patients met the inclusion criteria; mean follow-up was 28.4 months (SD 4.4). Injuries in RCTA were present in 83.9% (77.4% in AN and 45.2% in SSN). There were no differences on preoperative VAS, ROM, and rCMS between patients with and without preoperative nerve injuries. Four acute postoperative neurological injuries were registered under chronic preoperative injuries. Six months after RSA, 69% of preoperative neuropathies had improved (82.14% chronic injuries and 77.7% disuse injuries). No differences in improvement between disuse and chronic injuries were found, but patients with preoperative neuropathy that had not improved at the postoperative electromyographic study at six months, scored worse on the VAS (1.44 vs 2.66; p .14) and rCMS (91.6 vs 89.04; p .27). CONCLUSIONS: The frequency of axillary and suprascapular neuropathies in RCTA is much higher than expected. Most of these injuries improve after surgery, with almost complete neurophysiological recovery and little functional impact on RSA. However, those patients with preoperative neuropathies and absence of neurophysiological improvement six months after surgery have lower functional results.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Lesiones del Manguito de los Rotadores , Artropatía por Desgarro del Manguito de los Rotadores , Articulación del Hombro , Humanos , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/complicaciones , Lesiones del Manguito de los Rotadores/diagnóstico , Lesiones del Manguito de los Rotadores/cirugía , Estudios Prospectivos , Hombro/cirugía , Articulación del Hombro/cirugía , Articulación del Hombro/inervación , Artroplastía de Reemplazo de Hombro/efectos adversos , Artroplastía de Reemplazo de Hombro/métodos , Resultado del Tratamiento , Estudios Retrospectivos , Rango del Movimiento Articular
10.
Obes Surg ; 34(4): 1316-1323, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38429485

RESUMEN

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative nausea and vomiting (PONV). We aimed to compare the effects of aprepitant on the incidence of PONV after LSG. METHODS: In this double-blind, randomized controlled trial, the case group received the standard care regimen for PONV (dexamethasone 10 mg, ondansetron 4 mg, and metoclopramide 10 mg) plus prophylactic oral aprepitant 80 mg 1 h preoperatively. The control group received standard care plus a placebo. Comparative analyses using the Rhodes index were performed at 0, 6, 12, and 24 h postoperatively. RESULTS: A total of 400 patients (201 in the aprepitant group and 199 in the placebo group) underwent LSG. The groups were homogeneous. The aprepitant group experienced less PONV: early, 69 (34.3%) vs. 103 (51.7%), p ≤ 0.001; 6 h, 67 (33.3%) vs. 131 (65.8%), p ≤ 0.001; 12 h, 41 (20.4%) vs. 115 (57.8%), p ≤ 0.001; and 24 h, 22 (10.9%) vs. 67 (33.7%), p ≤ 0.001. Fewer patients in the aprepitant group vomited: early, 3 (1.5%) vs. 5 (2.5%), p = 0.020; 6 h, 6 (3%) vs. 18 (9%), p = 0.020; 12 h, 2 (1%) vs. 17 (8.5%), p = 0.006; and 24 h, 1 (0.5%) vs. 6 (3%), p = 0.040. Patients in the aprepitant group required less additional PONV medication: early, 61 (30.3%) vs. 86 (43.2), p = 0.008; 6 h, 7 (3.5%) vs. 34 (17%), p = 0.001; 12 h, 6 (3%) vs. 31 (15.6%), p ≤ 0.001; and 24 h, 5 (2.5%) vs. 11 (5.5%), p ≤ 0.001. CONCLUSIONS: Prophylactic aprepitant improved PONV between 0 h (early) and 24 h postoperatively in patients undergoing LSG.


Asunto(s)
Antieméticos , Laparoscopía , Obesidad Mórbida , Humanos , Aprepitant , Antieméticos/uso terapéutico , Náusea y Vómito Posoperatorios/tratamiento farmacológico , Obesidad Mórbida/cirugía , Gastrectomía , Método Doble Ciego
11.
Front Med (Lausanne) ; 11: 1321692, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455478

RESUMEN

Obesity has become increasingly prevalent in the intensive care unit, presenting a significant challenge for healthcare systems and professionals, including rehabilitation teams. Caring for critically ill patients with obesity involves addressing complex issues. Despite the well-established and safe practice of early mobilization during critical illness, in rehabilitation matters, the diverse clinical disturbances and scenarios within the obese patient population necessitate a comprehensive understanding. This includes recognizing the importance of metabolic support, both non-invasive and invasive ventilatory support, and their weaning processes as essential prerequisites. Physiotherapists, working collaboratively with a multidisciplinary team, play a crucial role in ensuring proper assessment and functional rehabilitation in the critical care setting. This review aims to provide critical insights into the key management and rehabilitation principles for obese patients in the intensive care unit.

12.
Acute Crit Care ; 39(1): 47-60, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38303585

RESUMEN

During the coronavirus disease 2019 (COVID-19) pandemic, clinical staff learned how to manage patients enduring extended stays in an intensive care unit (ICU). COVID-19 patients requiring critical care in an ICU face a high risk of experiencing prolonged intensive care (PIC). The use of invasive mechanical ventilation in individuals with severe acute respiratory distress syndrome can cause numerous complications that influence both short-term and long-term morbidity and mortality. Those risks underscore the importance of proactively addressing functional complications. Mitigating secondary complications unrelated to the primary pathology of admission is imperative in minimizing the risk of PIC. Therefore, incorporating strategies to do that into daily ICU practice for both COVID-19 patients and those critically ill from other conditions is significantly important.

13.
Int J Mol Sci ; 25(3)2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38339195

RESUMEN

The consensus molecular subtypes (CMSs) classification of colorectal cancer (CRC) is a system for patient stratification that can be potentially applied to therapeutic decisions. Hakai (CBLL1) is an E3 ubiquitin-ligase that induces the ubiquitination and degradation of E-cadherin, inducing epithelial-to-mesenchymal transition (EMT), tumour progression and metastasis. Using bioinformatic methods, we have analysed CBLL1 expression on a large integrated cohort of primary tumour samples from CRC patients. The cohort included survival data and was divided into consensus molecular subtypes. Colon cancer tumourspheres were used to analyse the expression of stem cancer cells markers via RT-PCR and Western blotting. We show that CBLL1 gene expression is specifically associated with canonical subtype CMS2. WNT target genes LGR5 and c-MYC show a similar association with CMS2 as CBLL1. These mRNA levels are highly upregulated in cancer tumourspheres, while CBLL1 silencing shows a clear reduction in tumoursphere size and in stem cell biomarkers. Importantly, CMS2 patients with high CBLL1 expression displayed worse overall survival (OS), which is similar to that associated with CMS4 tumours. Our findings reveal CBLL1 as a specific biomarker for CMS2 and the potential of using CMS2 with high CBLL1 expression to stratify patients with poor OS.


Asunto(s)
Neoplasias Colorrectales , Humanos , Biomarcadores , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Genes myc , Análisis de Supervivencia , Ubiquitina-Proteína Ligasas/metabolismo
15.
Brain ; 147(5): 1871-1886, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38128553

RESUMEN

Multiple sclerosis is a chronic inflammatory disease in which disability results from the disruption of myelin and axons. During the initial stages of the disease, injured myelin is replaced by mature myelinating oligodendrocytes that differentiate from oligodendrocyte precursor cells. However, myelin repair fails in secondary and chronic progressive stages of the disease and with ageing, as the environment becomes progressively more hostile. This may be attributable to inhibitory molecules in the multiple sclerosis environment including activation of the p38MAPK family of kinases. We explored oligodendrocyte precursor cell differentiation and myelin repair using animals with conditional ablation of p38MAPKγ from oligodendrocyte precursors. We found that p38γMAPK ablation accelerated oligodendrocyte precursor cell differentiation and myelination. This resulted in an increase in both the total number of oligodendrocytes and the migration of progenitors ex vivo and faster remyelination in the cuprizone model of demyelination/remyelination. Consistent with its role as an inhibitor of myelination, p38γMAPK was significantly downregulated as oligodendrocyte precursor cells matured into oligodendrocytes. Notably, p38γMAPK was enriched in multiple sclerosis lesions from patients. Oligodendrocyte progenitors expressed high levels of p38γMAPK in areas of failed remyelination but did not express detectable levels of p38γMAPK in areas where remyelination was apparent. Our data suggest that p38γ could be targeted to improve myelin repair in multiple sclerosis.


Asunto(s)
Esclerosis Múltiple , Vaina de Mielina , Oligodendroglía , Remielinización , Animales , Remielinización/fisiología , Esclerosis Múltiple/patología , Esclerosis Múltiple/metabolismo , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Ratones , Oligodendroglía/metabolismo , Oligodendroglía/patología , Humanos , Proteína Quinasa 12 Activada por Mitógenos/metabolismo , Proteína Quinasa 12 Activada por Mitógenos/genética , Diferenciación Celular/fisiología , Cuprizona/toxicidad , Ratones Endogámicos C57BL , Masculino , Femenino , Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/metabolismo , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/patología , Ratones Transgénicos
16.
Trop Anim Health Prod ; 56(1): 28, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38151553

RESUMEN

The objective was to assess the in vitro rumen fermentation characteristics, methane production, and biohydrogenation of unsaturated fatty acids of diets with two protected fat (PF) sources from soybean or linseed oil, two levels of PF (0 and 6%) and two forage sources (canola silage (CS) or alfalfa hay (AH)) in a factorial 2x2x2 completely randomised design. Only fatty acids content at final incubation was affected (P<0.05) by triple interaction, where C18:2 was highest with AH plus 6% soybean PF (4.41mg/g DM), while C18:3 was with CS plus 6% linseed oil protected (1.98mg/g DM). C18:2 cis-9 trans-11 had high concentration (308 mg/g DM; P<0.05) with AH plus 6% PF regardless PF type, and C18:1 trans-11 was higher with 6% PF than without PF (13.41 vs 7.89 mg/g DM). Cumulative methane production was not affected by treatments (0.9973 ± 0.1549 mmol/g DM; P>0.05). Gas production and in vitro NDF digestibility were lower with 6% PF of linseed than soybean (160.88 vs 150.97 ml; and 69.28vs 62.89 %, respectively P<0.05). With linseed PF the NH3-N concentration was highest in CS than AH (41.27 vs 27.95 mg/dL; P<0.05) but IVDMD had the opposite result (78.54 vs 85.04). In conclusion, although methane production was not affected and in vitro digestibility and gas production were reduced with linseed PF, the concentration of C18:3 and C18:1 trans-11 was increased, which could improve the lipid profile of milk. The negative effects on digestibility were less with AH than of CS regardless of PF type and level.


Asunto(s)
Lino , Aceite de Linaza , Femenino , Animales , Aceite de Linaza/metabolismo , Lactancia , Rumen/metabolismo , Dieta/veterinaria , Ácidos Grasos Insaturados , Ácidos Grasos/metabolismo , Leche , Ensilaje/análisis , Metano/metabolismo , Fermentación , Zea mays
17.
Rev. cuba. med ; 62(4)dic. 2023.
Artículo en Español | CUMED, LILACS | ID: biblio-1550894

RESUMEN

Introducción: El neumoencéfalo (sinonimia: aerocele o neumatocele intracerebral), se define como la presencia de gas dentro de cualquiera de los compartimentos intracraneales (intraventricular, intraparenquimatosa, subaracnoidea, subdural y epidural). Objetivo: Describir los hallazgos clínicos, estudios complementarios, conducta terapéutica y evolución de un caso con neumoencéfalo como complicación de bloqueo regional epidural por radiculopatía lumbosacra. Presentación de caso: Se presentó un paciente masculino de 57 años de edad que comenzó con un cuadro súbito de desorientación, excitabilidad psicomotriz y convulsiones tónico-clónicas, a partir de una inyección epidural de metilprednisolona como método analgésico. Conclusiones: El caso presentado exhibió manifestaciones neurológicas inespecíficas, la aparición súbita posterior al proceder invasivo hizo sospechar en un evento neurológico agudo o fenómeno tromboembólico. Los estudios complementarios como la tomografía axial computarizada craneal simple, permitió su diagnóstico para tener una conducta consecuente. El manejo conservador del neumoencéfalo como complicación del uso de anestesia epidural, constituyó una conducta terapéutica eficaz y repercutió en la satisfactoria evolución del paciente(AU)


Introduction: Pneumocephalus (synonym: aerocele or intracerebral pneumatocele), is defined as the presence of gas within any of the intracranial compartments (intraventricular, intraparenchymal, subarachnoid, subdural and epidural). Objective: To describe the clinical findings, complementary studies, therapeutic conduct and evolution of a case with pneumocephalus as a complication of regional epidural block due to lumbosacral radiculopathy Case presentation: A 57-year-old male patient was presented who began with a sudden episode of disorientation, psychomotor excitability and tonic-clonic seizures, following an epidural injection of methylprednisolone as an analgesic method. Conclusions: The case presented exhibited non-specific neurological manifestations, the sudden appearance after the invasive procedure raised suspicion of an acute neurological event or thromboembolic phenomenon. Complementary studies such as simple cranial computed axial tomography, allowed its diagnosis to have a consistent conduct. The conservative management of pneumocephalus as a complication of the use of epidural anesthesia constituted an effective therapeutic approach and had an impact on the patient's satisfactory evolution(AU)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Radiculopatía/complicaciones , Metilprednisolona/uso terapéutico , Neumoencefalografía/métodos , Tomografía Computarizada Espiral/métodos , Anestesia Epidural/métodos
18.
J Immunol ; 211(12): 1767-1782, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37947442

RESUMEN

Understanding the mechanisms underlying the acquisition and maintenance of effector function during T cell differentiation is important to unraveling how these processes can be dysregulated in the context of disease and manipulated for therapeutic intervention. In this study, we report the identification of a previously unappreciated regulator of murine T cell differentiation through the evaluation of a previously unreported activity of the kinase inhibitor, BioE-1197. Specifically, we demonstrate that liver kinase B1 (LKB1)-mediated activation of salt-inducible kinases epigenetically regulates cytokine recall potential in effector CD8+ and Th1 cells. Evaluation of this phenotype revealed that salt-inducible kinase-mediated phosphorylation-dependent stabilization of histone deacetylase 7 (HDAC7) occurred during late-stage effector differentiation. HDAC7 stabilization increased nuclear HDAC7 levels, which correlated with total and cytokine loci-specific reductions in the activating transcription mark histone 3 lysine 27 acetylation (H3K27Ac). Accordingly, HDAC7 stabilization diminished transcriptional induction of cytokine genes upon restimulation. Inhibition of this pathway during differentiation produced effector T cells epigenetically poised for enhanced cytokine recall. This work identifies a previously unrecognized target for enhancing effector T cell functionality.


Asunto(s)
Citocinas , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas , Animales , Ratones , Diferenciación Celular , Citocinas/metabolismo , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo
19.
Nat Commun ; 14(1): 5759, 2023 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-37717054

RESUMEN

The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5' strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site-a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate sites of MRN-dependent processing by identifying sites of CtIP association and by sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated most efficiently when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that both complexes bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.


Asunto(s)
Núcleo Celular , Roturas del ADN de Doble Cadena , Animales , Proteolisis , Reparación del ADN , Proteína Quinasa Activada por ADN/genética , Mamíferos
20.
Int J Mol Sci ; 24(15)2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37569774

RESUMEN

The evidence sustaining the regenerative properties of mesenchymal stem cells' (MSCs) secretome has prompted a paradigm change, where MSCs have shifted from being considered direct contributors to tissue regeneration toward being seen as cell factories for producing biotech medicines. We have previously designed a method to prime MSCs towards osteogenic differentiation by silencing the Wnt/ß-Catenin inhibitor Sfpr1. This approach produces a significant increase in bone formation in osteoporotic mice. In this current work, we set to investigate the contribution of the secretome from the MSCs where Sfrp1 has been silenced, to the positive effect seen on bone regeneration in vivo. The conditioned media (CM) of the murine MSCs line C3H10T1/2, where Sfrp1 has been transiently silenced (CM-Sfrp1), was found to induce, in vitro, an increase in the osteogenic differentiation of this same cell line, as well as a decrease of the expression of the Wnt inhibitor Dkk1 in murine osteocytes ex vivo. A reduction in the RANKL/OPG ratio was also detected ex vivo, suggesting a negative effect of CM-Sfrp1 on osteoclastogenesis. Moreover, this CM significantly increases the mineralization of human primary MSCs isolated from osteoportotic patients in vitro. Proteomic analysis identified enrichment of proteins involved in osteogenesis within the soluble and vesicular fractions of this secretome. Altogether, we demonstrate the pro-osteogenic potential of the secretome of MSCs primmed in this fashion, suggesting that this is a valid approach to enhance the osteo-regenerative properties of MSCs' secretome.


Asunto(s)
Osteogénesis , Proteómica , Humanos , Animales , Ratones , Osteogénesis/genética , Secretoma , Péptidos y Proteínas de Señalización Intracelular/farmacología , Diferenciación Celular/genética
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