RESUMEN
Brain-derived neurotrophic factor (BDNF) and its high-affinity full-length (FL) receptor, TrkB-FL, play a central role in the nervous system by providing trophic support to neurons and regulating synaptic plasticity and memory. TrkB and BDNF signaling are impaired in Alzheimer's disease (AD), a neurodegenerative disease involving accumulation of amyloid-ß (Aß) peptide. We recently showed that Aß leads to a decrease of TrkB-FL receptor and to an increase of truncated TrkB receptors by an unknown mechanism. In the present study, we found that (1) Aß selectively increases mRNA levels for the truncated TrkB isoforms without affecting TrkB-FL mRNA levels, (2) Aß induces a calpain-mediated cleavage on TrkB-FL receptors, downstream of Shc-binding site, originating a new truncated TrkB receptor (TrkB-T') and an intracellular fragment (TrkB-ICD), which is also detected in postmortem human brain samples, (3) Aß impairs BDNF function in a calpain-dependent way, as assessed by the inability of BDNF to modulate neurotransmitter (GABA and glutamate) release from hippocampal nerve terminals, and long-term potentiation in hippocampal slices. It is concluded that Aß-induced calpain activation leads to TrkB cleavage and impairment of BDNF neuromodulatory actions.
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Péptidos beta-Amiloides/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Calpaína/farmacología , Lóbulo Frontal/efectos de los fármacos , Neuronas/efectos de los fármacos , Receptor trkB/metabolismo , Animales , Encéfalo/citología , Embrión de Mamíferos , Inhibidores Enzimáticos/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Ácido Glutámico/metabolismo , Humanos , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Receptor trkB/genética , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Adenosine, through A(2A) receptor (A(2A)R) activation, can act as a metamodulator, controlling the actions of other modulators, as brain-derived neurotrophic factor (BDNF). Most of the metamodulatory actions of adenosine in the hippocampus have been evaluated in excitatory synapses. However, adenosine and BDNF can also influence GABAergic transmission. We thus evaluated the role of A(2A)R on the modulatory effect of BDNF upon glutamate and GABA release from isolated hippocampal nerve terminals (synaptosomes). BDNF (30 ng/ml) enhanced K(+)-evoked [(3)H]glutamate release and inhibited the K(+)-evoked [(3)H]GABA release from synaptosomes. The effect of BDNF on both glutamate and GABA release requires tonic activation of adenosine A(2A)R since for both neurotransmitters, the BDNF action was blocked by the A(2A)R antagonist SCH 58261 (50 nM). In the presence of the A(2A)R agonist, CGS21680 (30 nM), the effect of BDNF on either glutamate or GABA release was, however, not potentiated. It is concluded that both the inhibitory actions of BDNF on GABA release as well as the facilitatory action of the neurotrophin on glutamate release are dependent on the activation of adenosine A(2A)R by endogenous adenosine. However, these actions could not be further enhanced by exogenous activation of A(2A)R.
Asunto(s)
Agonistas del Receptor de Adenosina A2/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ácido Glutámico/metabolismo , Hipocampo/metabolismo , Receptor de Adenosina A2A/efectos de los fármacos , Sinaptosomas/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacología , Antagonistas del Receptor de Adenosina A2/farmacología , Animales , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Fenetilaminas/farmacología , Potasio/farmacología , Pirimidinas/farmacología , Ratas , Ratas Wistar , Sinaptosomas/efectos de los fármacos , Triazoles/farmacologíaRESUMEN
OBJECTIVES: The recent approval of first-line tyrosine kinase inhibitor plus immuno-oncology agent combination therapy for the treatment of advanced renal cell carcinoma offers substantially improved response rates and survival compared with the previous standard of care. This expansion of treatment options has also led to a greater range and complexity of potential treatment-related adverse events related to overlapping toxicities. The aim of this article is to discuss the management of common treatment-emergent adverse events (AEs) associated with axitinib plus immuno-oncology therapy, highlight the specific roles of oncology nurses in managing these events, and provide AE management resources to aid oncology nurses in their care of patients with advanced renal cell carcinoma. DATA SOURCES: Author experience, journal articles, and treatment guidelines were used. CONCLUSION: The use of oncology nurses and nurse-led innovations to monitor and assess treatments can have a positive impact on the management of AEs in cancer patients by identifying those who are most at risk, providing regular assessment, appropriate patient education, and supporting the monitoring of patient safety. IMPLICATIONS FOR NURSING PRACTICE: Skilled oncology nurses should be a key part of a team that addresses the supportive care needs and management of AEs that are associated with novel cancer treatments. Early and ongoing communication between the patient and oncology nurses regarding the development of adverse events is a critical component of maximizing treatment outcomes and quality of life.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/inducido químicamente , Axitinib/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/inducido químicamente , Calidad de Vida , Inhibidores de Proteínas QuinasasRESUMEN
The European Oncology Nursing Society Nightingale Challenge was a professional development program delivered via seven one-hour webinars focusing on leadership, career development, and managing burnout. A total of 151 partici.
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Liderazgo , Enfermeras y Enfermeros , Humanos , Europa (Continente) , Oncología Médica , Enfermería OncológicaRESUMEN
Chemotherapy-induced nausea and vomiting (CINV) and radiotherapy-induced nausea and vomiting (RINV) strongly affect the quality of life of patients with cancer. Inadequate antiemetic control leads to the decline of patients' quality of life, increases rescue interventions, and may even compromise adherence to cancer treatment. Although there are international recommendations for controlling CINV and RINV, these recommendations focus mainly on pharmacological management, with scarce information on additional measures that patients may adopt. Moreover, the prophylaxis and management of CINV/RINV are not always applied. Thus, we identified the need to systematize the strategies for preventing and managing CINV/RINV and the associated risk factors to implement and promote effective prophylactic antiemetic regimens therapy in patients with cancer. This review sought to create a set of practical recommendations for managing and controlling CINV/RINV, according to the current international recommendations for antiemetic therapy and the main risk factors. Conclusively, we intended to produce a patient-centered guidance document for health care professionals focused on the awareness, monitoring, and treatment of CINV/RINV.
RESUMEN
Cancer pain is a common symptom in patients with cancer and can largely affect their quality of life. Pain management is important to minimize the impact of pain on daily activities. Cancer nurses are significantly involved in all steps of pain management and contribute to the success of therapy through their knowledge and expertise. While they generally play an important role in the screening, assessment, diagnosis, treatment and follow-up of patients and their (pain) symptoms, this varies from country to country in Europe. An important aspect is their role in educating patients and their families about what pain is, what impact it can have, how it can be treated pharmacologically or non-pharmacologically and what effects or problems can occur during treatment. While there is a great discrepancy between education and training opportunities for cancer nurses in different European countries, there is a continued need for education and training in pain management. Cancer is increasingly becoming a chronic disease, and the management of pain in cancer survivors will be crucial to maintain an adequate quality of life. With this, the crucial role of cancer nurses is becoming even more important.
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OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.
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Isquemia Encefálica , Angiopatía Amiloide Cerebral , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/epidemiología , Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/epidemiología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/epidemiologíaRESUMEN
The thalamocortical network appears to play a pivotal role in ictogenesis. We herein present three cases of non-convulsive status epilepticus (SE), in adult patients without previous history of epilepsy or seizures, precipitated by acute thalamic vascular and metabolic-induced lesions. In all cases the EEG showed patterns consistent with generalized SE confirmed either by a fast and complete clinical and EEG response to anti-seizure medication or definitive subtle motor signs consistent with SE. We argue that the subcortical disruption of thalamocortical networks due to the thalamic lesion predisposed to the occurrence of non-convulsive SE. In patients with thalamic disorders and unexplained mental status changes EEG evaluation should always be considered.
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Trastornos Mentales , Estado Epiléptico , Adulto , Electroencefalografía , Humanos , Convulsiones , Estado Epiléptico/etiología , Tálamo/diagnóstico por imagenRESUMEN
An epileptic seizure is one of the causes of so-called "transient neurological events" (TNEs). The differential diagnosis of a TNE relies mainly on history and physical examination. Laboratory markers are less frequently useful. After diagnosing an epileptic seizure, a distinction must be made between an acute symptomatic and an unprovoked seizure, since they have different treatments and prognosis. History, physical examination and other examinations (laboratory and imaging) are paramount in this distinction. After the diagnosis of a first unprovoked seizure, an EEG should be requested which may aid in establishing the diagnosis, evaluating the recurrence risk or ascertaining the self-limited nature of the seizure. 3T-MRI with an epilepsy protocol can be considered when CT has not clarified the aetiology. The decision to treat should be discussed with the patient/relatives, taking into account the risk of recurrence, the clinical characteristics (aetiology, seizure type, age, job, epileptic seizure schedule, comorbidities and polymedication), probability of AED side effects, and stigmatization. Nowadays, the chosen regimen is usually monotherapy with a second-generation AED that better suits the patient's characteristics, comorbidities and concurrent medication. Counselling should include first aid, precipitating factors, sport and physical exercise in order to avoid possible driving restrictions, the need for therapy compliance, and risk of recurrence and SUDEP.
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Epilepsia , Convulsiones , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Electroencefalografía , Epilepsia/tratamiento farmacológico , Epilepsia/terapia , Humanos , Imagen por Resonancia Magnética , Pronóstico , Recurrencia , Riesgo , Convulsiones/tratamiento farmacológico , Convulsiones/terapiaRESUMEN
Sighs are physiological phenomena and may occasionally occur during sleep in healthy young adults. Although inspiratory sighs are considered a diagnostic red flag for the parkinsonian form of multiple system atrophy (MSA), its frequency and characteristics are unclear. We aimed to define sigh frequency during sleep recordings in patients with MSA compared to Parkinson's disease (PD) patients, as well as evaluate possible associated breathing disorders or autonomic changes. We analyzed 9 polysomnography's from patients with MSA and 9 from matched PD patients. The proportion of MSA patients (both MSA-P and MSA-C) with sleep-related sighs was significantly higher than that of PD patients, and these occurred predominantly in stages N1 and N2. The median sigh index in sleep and wakefulness were also significantly higher in MSA, although with a significant inter-subject variability. Higher sigh indexes were not associated to other breathing disturbances or with longer disease duration. In MSA, 12% of sighs were associated with oxygen desaturation, while none of the events in PD patients presented with significant changes in oxygen saturation. Respiratory events followed 45% of sighs in MSA, predominantly central sleep apneas, and 29% of sighs in PD, predominantly hypopneas. Our data suggests that high sigh frequencies during sleep should also be considered a red flag for MSA, and future studies should aim to determine whether increased sighing frequency during sleep is specific for this disorder.