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1.
Epilepsia ; 65(7): 1899-1906, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38624097

RESUMO

In the case of suspicion of nonconvulsive status epilepticus (NCSE), reactivity on electroencephalograms (EEGs) can provide valuable diagnostic information. Reactivity refers to responses to auditory or somatosensory stimulation, with changes in amplitude and frequency of background activity. Because of self-perpetuating processes and the failure of self-terminating mechanisms, status epilepticus is unlikely to cease when patients spontaneously move, and it cannot typically be stopped by external stimulation (i.e., auditory and tactile stimuli). The defining EEG characteristic of absence status epilepticus is the presence of bilateral, synchronous, symmetric, rhythmic paroxysmal activity that shows little or no reactivity to sensory stimulation. On the other hand, in metabolic/toxic or multifactorial encephalopathies, triphasic waves (TWs) are influenced by the level of vigilance. TWs may be transiently abolished when patients increase their level of alertness from a drowsy/lethargic state to a state of wakefulness. This reactivity is only observed when patients can be aroused by a somatosensory or auditory stimulus. This reactivity tends to disappear with increasing severity of the disease and in comatose patients. In patients without preexisting developmental and epileptic encephalopathy, this pattern of stimulus-induced wakefulness with transient improvement of the EEG is a major criterion in determining that the EEG patterns are not ictal. This criterion of reactivity on EEGs, beyond the classical clinical/EEG criteria of NCSE (Salzburg criteria), should now be systematically added.


Assuntos
Nível de Alerta , Eletroencefalografia , Estado Epiléptico , Humanos , Eletroencefalografia/métodos , Nível de Alerta/fisiologia , Estado Epiléptico/fisiopatologia , Estado Epiléptico/diagnóstico , Estimulação Acústica/métodos , Diagnóstico Diferencial
2.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473877

RESUMO

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n = 51) and BPH patients (n = 48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using a quantitative real-time polymerase chain reaction (qRT-PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a downregulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility for distinguishing of mCRPC from BPH.


Assuntos
MicroRNAs , Hiperplasia Prostática , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Soro/metabolismo , Citratos , Lactatos , Acetatos
3.
Pract Neurol ; 24(1): 2-10, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38050141

RESUMO

Electroencephalography (EEG) is a useful adjunct to clinical neurological examination, particularly as it may detect subtle or subclinical disturbance of cerebral function and it allows monitoring of cerebral activity over time. Continuous EEG combined with quantitative analysis and machine learning may help identify changes in real time, before the emergence of clinical signs and response to interventions. EEG is rarely pathognomonic in encephalopathy/encephalitis but when interpreted correctly and within the clinical context, certain phenotypes may indicate a specific pathophysiology (eg, lateralised periodic discharges in HSV-1, generalised periodic discharges in sporadic Creutzfeldt-Jakob disease, and extreme delta brushes in anti-n-methyl-D-aspartate receptor autoimmune encephalitis). EEG is included in some specialist guidelines for disease assessment, monitoring and prognostication (ie, hepatic, cancer immunotherapy, viral, prion, autoimmune encephalitis and hypoxic ischaemic encephalopathy). EEG is invaluable for confirming or excluding non-convulsive seizures or status epilepticus, particularly in critically ill patients, and in understanding new concepts such as epileptic encephalopathy and the ictal-interictal continuum.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalopatias , Estado Epiléptico , Humanos , Eletroencefalografia , Convulsões/tratamento farmacológico , Estado Epiléptico/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico
4.
Epilepsia ; 64(9): 2351-2360, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37350392

RESUMO

OBJECTIVE: The Salzburg criteria for nonconvulsive status epilepticus (NCSE) and the American Clinical Neurophysiology Society (ACNS) Standardized Critical Care EEG Terminology 2021 include a diagnostic trial with intravenous (IV) antiseizure medications (ASMs) to assess electroencephalographic (EEG) and clinical response as a diagnostic criterion for definite NCSE and possible NCSE. However, how to perform this diagnostic test and assessing the EEG and clinical responses have not been operationally defined. METHODS: We performed a Delphi process involving six experts to standardize the diagnostic administration of IV ASM and propose operational criteria for EEG and clinical response. RESULTS: Either benzodiazepines (BZDs) or non-BZD ASMs can be used as first choice for a diagnostic IV ASM trial. However, non-BZDs should be considered in patients who already have impaired alertness or are at risk of respiratory depression. Levetiracetam, valproate, lacosamide, brivaracetam, or (if the only feasible drug) fosphenytoin or phenobarbital were deemed appropriate for a diagnostic IV trial. The starting dose should be approximately two thirds to three quarters of the full loading dose recommended for treatment of status epilepticus, with an additional smaller dose if needed. ASMs should be administered during EEG recording under supervision. A monitoring time of at least 15 min is recommended. If there is no response, a second trial with another non-BDZ or BDZs may be considered. A positive EEG response is defined as the resolution of the ictal-interictal continuum pattern for at least three times the longest previously observed spontaneous interval of resolution (if any), but minimum of one continuous minute. For a clinical response, physicians should use a standardized examination before and after IV ASM administration. We suggest a definite time-locked improvement in a focal deficit or at least one-step improvement on a new dedicated one-domain 10-level NCSE response scale. SIGNIFICANCE: The proposed standardized approach of a diagnostic IV ASM trial further refines the ACNS and Salzburg diagnostic criteria for NCSE.


Assuntos
Estado Epiléptico , Humanos , Administração Intravenosa , Benzodiazepinas/uso terapêutico , Eletroencefalografia , Fenobarbital/uso terapêutico , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico , Ensaios Clínicos como Assunto
5.
Int J Mol Sci ; 24(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38139131

RESUMO

The study of an organism's response to cerebral ischemia at different levels is essential to understanding the mechanism of the injury and protection. A great interest is devoted to finding the links between quantitative metabolic changes and post-ischemic damage. This work aims to summarize the outcomes of the most studied metabolites in brain tissue-lactate, glutamine, GABA (4-aminobutyric acid), glutamate, and NAA (N-acetyl aspartate)-regarding their biological function in physiological conditions and their role after cerebral ischemia/reperfusion. We focused on ischemic damage and post-ischemic recovery in both experimental-including our results-as well as clinical studies. We discuss the role of blood glucose in view of the diverse impact of hyperglycemia, whether experimentally induced, caused by insulin resistance, or developed as a stress response to the cerebral ischemic event. Additionally, based on our and other studies, we analyze and critically discuss post-ischemic alterations in energy metabolites and the elevation of blood ketone bodies observed in the studies on rodents. To complete the schema, we discuss alterations in blood plasma circulating amino acids after cerebral ischemia. So far, no fundamental brain or blood metabolite(s) has been recognized as a relevant biological marker with the feasibility to determine the post-ischemic outcome or extent of ischemic damage. However, studies from our group on rats subjected to protective ischemic preconditioning showed that these animals did not develop post-ischemic hyperglycemia and manifested a decreased metabolic infringement and faster metabolomic recovery. The metabolomic approach is an additional tool for understanding damaging and/or restorative processes within the affected brain region reflected in the blood to uncover the response of the whole organism via interorgan metabolic communications to the stressful cerebral ischemic challenge.


Assuntos
Isquemia Encefálica , Hiperglicemia , Ratos , Animais , Isquemia Encefálica/metabolismo , Infarto Cerebral , Encéfalo/metabolismo , Ácido Láctico/metabolismo , Ácido gama-Aminobutírico/metabolismo , Hiperglicemia/metabolismo
6.
Mol Cell Biochem ; 477(5): 1621-1628, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35220548

RESUMO

Increased concentration of plasma homocysteine (Hcy) is an independent risk factor of cardiovascular disease, yet the mechanism by which hyperhomocysteinemia (HHcy) causes cardiac dysfunction is largely unknown. The aim of present study was to investigate the contribution of sarcoplasmic reticulum to impaired cardiac contractile function in HHCy. HHcy-induced by subcutaneous injection of Hcy (0.45 µmol/g of body weight) twice a day for a period of 2 weeks resulted in significant decrease in developed left ventricular pressure and maximum rate of ventricular relaxation. Our results show that abundances of SR Ca2+-handling proteins, Ca2+-ATPase (SERCA2), calsequestrin and histidine-rich calcium-binding protein are significantly reduced while the content of phospholamban is unchanged. Moreover, we found that increased PLN:SERCA2 ratio results in the inhibition of SERCA2 activity at low free Ca2+ concentrations. We further discovered that HHcy is not associated with increased oxidative stress in SR. Taken together, these findings suggest that disturbances in SR Ca2+ handling, caused by altered protein contents but not oxidative damage, may contribute to impaired cardiac contractility in HHcy.


Assuntos
Hiper-Homocisteinemia , Retículo Sarcoplasmático , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Calsequestrina/metabolismo , Coração/fisiologia , Hiper-Homocisteinemia/induzido quimicamente , Contração Miocárdica , Miocárdio/metabolismo , Ratos , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático
7.
Arch Gynecol Obstet ; 306(3): 707-715, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34782924

RESUMO

PURPOSE: Subtypes of depression have been under studied in women during the peripartum period and the year after childbirth and delivery. Due to heterogeneity of depression, researchers have attempted to identify phenotypes of maternal and postpartum depression based on key symptoms that may represent underlying genes and biological etiology (Leuchter et al. Dialog Clinic Neurosci 16(4):525, 2014). METHODS: The current study collected self-report data from 587 women and utilized exploratory and confirmatory factor analyses (CFA) to identify subtypes of depression symptoms across two measures. RESULTS: Findings of the study showed that: (1) using the Beck Depression Inventory (BDI-II) and the Postpartum Depression Screening Scale (PDSS), a five-factor solution best fit the data in our sample of mothers with infants aged 4-14 months. The factors included: anxiety/thought disorder; cognitive depression; suicide; somatic/neurovegetative; and sleep [χ2 (454, N = 587) = 1102.61, p < 0.001, comparative fit index (CFI) = 0.93, Tucker Lewis index (TLI) = 0.92, root mean square error of approximation (RMSEA) = 0.05]; and (2) the following factors significantly positively predicted interview-based diagnosis of depression: cognitive symptoms of depression and sleep [χ2 (482, N = 587) = 1170.40, p < 0.001, TLI = 0.91, CFI = 0.93, RMSEA = 0.05]. CONCLUSIONS: Future research could assess the clinical benefits of screening for maternal mood disorders.


Assuntos
Depressão Pós-Parto , Mães , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/psicologia , Análise Fatorial , Feminino , Humanos , Mães/psicologia , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Autorrelato , Inquéritos e Questionários
8.
Crit Care Med ; 49(12): e1241-e1251, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259657

RESUMO

OBJECTIVES: To identify early predictors of postictal delirium in adult patients after termination of status epilepticus. DESIGN: Retrospective study. SETTING: ICUs at a Swiss tertiary academic medical center. PATIENTS: Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018. INTERVENTIONS: None. METHODS: Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation). MEASUREMENTS AND MAIN RESULTS: Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1-3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53-7.33). CONCLUSIONS: Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2-3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.


Assuntos
Delírio/diagnóstico , Estado Epiléptico/complicações , Idoso , Benzodiazepinas/administração & dosagem , Estudos de Coortes , Delírio/epidemiologia , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Convulsões/complicações , Convulsões/epidemiologia , Índice de Gravidade de Doença , Estado Epiléptico/epidemiologia
9.
Acta Derm Venereol ; 101(6): adv00480, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33734423

RESUMO

The use of sunscreens is recommended to limit the impact of sun exposure on the skin. The objective of this study was to examine the relationship between sunscreen sales and melanoma in 4 different countries with diverse sunscreen regulations. Data from publicly avail-able databases were examined for Sweden, England, Australia, and the USA from 1999 to 2018. The association between incidence of melanoma and sunscreen sales was estimated using a generalized estimating equation, and modelling was used to predict melanoma cases. Incidence of melanoma was positively associated with sunscreen sales in England, Australia, and the USA, and negatively associated with sunscreen sales in Sweden. Growth rates in melanoma cases of 0.42%, 16.7%, 19.1% and 12.2% were predicted for Sweden, England, Australia, and the USA, respectively. The differences observed between England, Australia, and the USA, on the one hand, and Sweden, on the other hand, are consistent with the adoption of strong regulations requiring the use of ultraviolet A blocking agents in sunscreens.


Assuntos
Neoplasias Cutâneas , Protetores Solares , Austrália , Inglaterra , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Protetores Solares/uso terapêutico , Suécia , Raios Ultravioleta
10.
Neoplasma ; 68(1): 154-164, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32977723

RESUMO

Oncoproteomic technologies offer a complementary approach to the understanding of cancer proteins' function and the translation of molecular knowledge into clinical practice. Our aim was to compare the proteomic profiles of prostate tumors versus benign prostatic hyperplasia (BPH) tissues in order to identify modulated proteins as the potential biomarkers for prostate cancer. Proteins extracted from twenty prostate cancer tissue specimens and ten BPH tissues were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF mass spectrometry. Western blot and quantitative real-time PCR (RT-PCR) were performed to confirm the different amounts of protein biomarkers revealed by 2DE combined with MALDI mass spectrometry. We found 42 spots whose expression in the prostate was altered more than 1.5-fold compared with BPH tissue (p<0.05). These spots represented ten different proteins that were identified by a database search after mass spectrometry: they comprised proteins involved in the regulation of actin dynamics, the cytoskeleton, and cell motility (ACTG2, ACTA2, TPM1, DES, VIM, FLNA, and TAGLN), heat shock protein-27 (Hsp27), and proteins with other functions (TR and RANBP3). Subsequent western blot and RT-PCR assays for DES, VIM, TAGLN, and Hsp27 in prostate tumor tissues and BPH tissues confirmed the observations obtained by proteomic analysis. The cytoskeletal and cytoskeleton-associated proteins identified by this approach might be useful molecular targets for prostate cancer diagnostics and may contribute to novel therapies for prostate cancer.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Actinas/metabolismo , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Humanos , Masculino , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
11.
Sensors (Basel) ; 21(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34450969

RESUMO

Ultraviolet (UV) exposure significantly contributes to non-melanoma skin cancer. In the context of health, UV exposure is the product of time and the UV Index (UVI), a weighted sum of the irradiance I(λ) over all wavelengths from λ = 250 to 400 nm. In our analysis of the United States Environmental Protection Agency's UV-Net database of over 400,000 spectral irradiance measurements taken over several years, we found that the UVI is well estimated by 77 I310. To further understand this result, we applied an optical atmospheric model to generate terrestrial irradiance spectra and found that it applies across a wide range of conditions. An accurate UVI radiometer can be built from a photodiode covered by a bandpass filter centered at 310 nm.


Assuntos
Raios Ultravioleta , Estados Unidos
12.
Semin Neurol ; 40(6): 647-651, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33176371

RESUMO

Status epilepticus (SE) is the state of continuous or repetitive seizures, which can occur with or without convulsions. Evolving definitions of SE take into account the concept that neuronal injury may occur at different times in different types of SE.SE that does not respond to initial treatment may become refractory or even super-refractory. Nonconvulsive SE is increasingly recognized in comatose patients in critical care units, with the growing use of continuous electroencephalogram monitoring. SE is a neurologic emergency that carries a high risk of mortality and morbidity.


Assuntos
Anticonvulsivantes/uso terapêutico , Estado Epiléptico , Humanos , Estado Epiléptico/classificação , Estado Epiléptico/diagnóstico , Estado Epiléptico/epidemiologia , Estado Epiléptico/fisiopatologia
13.
J Intensive Care Med ; 35(11): 1235-1240, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31084284

RESUMO

OBJECTIVE: Research on continuous electro-encephalographic monitoring (cEEG) in the intensive care unit (ICU) has previously focused on neuroscience ICUs. This study determines cEEG utilization within a sample of specialty ICUs world-wide. METHODS: A cross-sectional electronic survey of attending level physicians across various intensive care settings. Twenty-five questions developed from consensus statements on the use of cEEG in the critically ill sent as an electronic survey. RESULTS: Of all, 9344 were queried and 417 (4.5%) responses were analyzed with 309 (74%) from the United States and 74 (18%) internationally. Intensive care units were: medical (10%), surgical (6%), neurologic/neurosurgical (12%), cardiac (4%), trauma (3%), pediatrics (29%), burn (<1%), multidisciplinary (30%), and other (5%). Intensive care units were: academic (65%), community (18%), public (3%), military (1%), and other (13%). Specialized cEEG teams were available in 71% of ICUs. Rapid 24/7 access and cEEG interpretation was available in 32% of ICUs. Interpretation changed clinical management frequently (28%) and sometimes (45%). CONCLUSIONS: Despite guideline recommendations for cEEG use, there is a discordance between availability, night coverage, and immediate interpretation. Only 27% have institutional protocols for indications and duration of cEEG monitoring. Furthermore, cEEG may be underutilized in nonneurologic ICUs as well as ICUs in smaller nonacademic affiliated hospitals and those outside of the United States.


Assuntos
Eletroencefalografia , Unidades de Terapia Intensiva , Criança , Cuidados Críticos , Estudos Transversais , Humanos , Monitorização Fisiológica
14.
Dev Psychobiol ; 62(4): 496-504, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31755553

RESUMO

Polymorphisms in the oxytocin receptor gene, OXTR_rs53576, have been linked to differences in maternal sensitivity and depressive symptoms. Although some studies suggest the A allele confers risk for mood disorders, individuals homozygous for the G allele may exhibit greater sensitivity to both positive and negative social experiences, including in the mother-infant dyad. Given the bi-directional nature of mother-infant influences on maternal mood, we tested the association between both mothers' and infants' OXTR_rs53576 genotype and maternal depression, as assessed through a self-report inventory. Although Beck Depression Inventory (BDI-II) scores were significantly higher for GG in comparison to AG/AA mothers, and for mothers of GG in comparison to AG/AA infants, an ANCOVA revealed that after sociodemographic risk factors had been controlled, infants', but not mothers', OXTR genotype predicted maternal depression scores, with no significant interaction between the two. The effect of infant OXTR on maternal depression was not explained by maternal reports of difficult infant temperament. We propose that GG infants have an enhanced capacity for processing both positive and negative socially meaningful contextual information, first amplifying and then differentially perpetuating negative affectivity in mothers who exhibit depressive characteristics.


Assuntos
Depressão Pós-Parto/genética , Relações Mãe-Filho , Receptores de Ocitocina/genética , Temperamento/fisiologia , Adulto , Feminino , Humanos , Lactente , Masculino
15.
Int J Mol Sci ; 21(20)2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33080955

RESUMO

Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. In this review, we discuss the current knowledge concerning the effects of HHcy on mitochondrial homeostasis, including energy metabolism, mitochondrial apoptotic pathway, and mitochondrial dynamics. The recent studies suggest that the interaction between Hcy and mitochondria is complex, and reactive oxygen species (ROS) are possible mediators of Hcy effects. We focus on mechanisms contributing to HHcy-associated oxidative stress, such as sources of ROS generation and alterations in antioxidant defense resulting from altered gene expression and post-translational modifications of proteins. Moreover, we discuss some recent findings suggesting that HHcy may have beneficial effects on mitochondrial ROS homeostasis and antioxidant defense. A better understanding of complex mechanisms through which Hcy affects mitochondrial functions could contribute to the development of more specific therapeutic strategies targeted at HHcy-associated disorders.


Assuntos
Encéfalo/irrigação sanguínea , Sistema Cardiovascular/metabolismo , Homocisteína/metabolismo , Mitocôndrias/metabolismo , Animais , Metabolismo Energético , Homocisteína/química , Humanos , Estresse Oxidativo
16.
Crit Care Med ; 47(8): 1106-1115, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31135501

RESUMO

OBJECTIVES: Recommendations regarding nutrition during status epilepticus are lacking, and it is unclear whether restriction of calorie intake would result in beneficial effects or potential harm. We thus aimed to investigate associations between daily calorie intake and outcome in adult status epilepticus patients deriving from a 5-year cohort with a systematic and prospective collection of nutritional data. DESIGN: Retrospective observational study. SETTING: Medical ICUs at a tertiary academic medical care center. PATIENTS: Consecutive patients with status epilepticus treated at the ICUs from 2012 to 2016 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients with status epilepticus were monitored regarding nutrition support provided according to the guidelines. Relative risks of no return to baseline were estimated by Poisson regression with robust error variance and adjusted for potential confounders. Of 203 patients, 86 (42%) had return to baseline. Metabolic characteristics of patients with and without return to baseline did not differ. Patients without return to baseline received more calories and proteins per status epilepticus day, and increasing nutritional support was associated with ventilator-associated pneumonia (relative risk, 1.19; 95% CI, 1.09-1.28). Multivariable regression analysis revealed significant increases in relative risks for no return to baseline with every percent of days with nutrition (relative risk, 1.35; 95% CI, 1.05-1.74), with every 100 kcal (relative risk, 1.01; 95% CI, 1.002-1.01), and gram of protein intake (relative risk, 1.01; 95% CI, 1.001-1.01) per status epilepticus day, independent of potential confounders (including fatal etiology, duration and severity of status epilepticus, Charlson comorbidity index, and treatment with anesthetics). CONCLUSIONS: Our results indicate that increased calorie intake during status epilepticus is independently associated with unfavorable outcome. These findings require further validation and investigations into potential mediators, such as induction of ketogenesis, immunomodulating effects, and/or reduction of ICU-associated complications, such as infections.


Assuntos
Ingestão de Energia , Pneumonia Associada à Ventilação Mecânica/fisiopatologia , Índice de Gravidade de Doença , Estado Epiléptico/terapia , Adulto , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Associada à Ventilação Mecânica/etiologia , Estudos Retrospectivos , Estado Epiléptico/complicações , Estado Epiléptico/fisiopatologia
17.
Epilepsia ; 60(1): 42-52, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30565664

RESUMO

OBJECTIVES: Early identification of patients who are at risk of prolonged status epilepticus (SE) and patients with high chances of full recovery despite prolonged SE may urge clinicians to intensify treatment rather than to withdraw care. We aimed to develop prediction models based on readily available clinical parameters to predict prolonged SE at seizure onset and to identify patients with high chances for full recovery. METHODS: From 2005 to 2016, all adult SE patients treated at the University Hospital Basel, a Swiss medical care center, were included. Multivariable Poisson regression was performed to identify predictors of prolonged SE (defined as SE for >12, >24, and >48 hours) and return to baseline from prolonged SE. The area under the receiver-operating characteristic curves (AUROC) for prediction models was calculated. RESULTS: Of 467 patients, the median age was 66.7 years and mortality was 12%. Relative risk (RR) for death was 1.06 (P < 0.0001) with every SE day. In multivariable analysis, nonconvulsive SE with coma, SE severity score ≥3, and acute brain lesions at SE onset independently predicted prolonged SE with an AUROC of 0.68 for >12, 0.67 for >24, and 0.72 for >48 hours of SE. Absence of nonconvulsive SE with coma and a decreasing Charlson comorbidity index were independent predictors for return to baseline in prolonged SE with an AUROC of 0.82 and 0.76 following cross-validation. Both associations remained significant despite adjustments for determinants of adverse outcome, such as anesthetics and vasopressors (nonconvulsive SE with coma RR = 0.24, 95% confidence interval [CI] 0.07-0.86; comorbidity index RR = 0.87, 95% CI 0.76-0.99). SIGNIFICANCE: Although our data indicate that identification of prolonged SE at seizure onset is unreliable, timely recognition of patients with high chances of good outcome despite prolonged SE is promising on the basis of comorbidities, type of SE, and level of consciousness. Further external validation of this prediction model is needed.


Assuntos
Recuperação de Função Fisiológica/fisiologia , Estado Epiléptico/diagnóstico , Estado Epiléptico/fisiopatologia , Idoso , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Diagnóstico Precoce , Eletroencefalografia/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Epiléptico/tratamento farmacológico , Suíça/epidemiologia , Fatores de Tempo
18.
Epilepsia ; 60(2): 189-200, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30585317

RESUMO

OBJECTIVE: To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction. METHODS: The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed. RESULTS: Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77-0.93 and OR = 1.34, 95% CI = 1.05-1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06-1.25). SIGNIFICANCE: Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.


Assuntos
APACHE , Escala de Coma de Glasgow , Escore Fisiológico Agudo Simplificado , Estado Epiléptico/terapia , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Estado Epiléptico/diagnóstico , Estado Epiléptico/fisiopatologia
19.
Gen Physiol Biophys ; 38(4): 305-314, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31219427

RESUMO

Blood biomarkers are usually present in low concentration and can be masked by the high-abundance proteins, of which albumin is the predominant one. The purpose of this study was to compare four different albumin removal methods compatible with in-gel based proteomics, applicable for plasma, without requiring specific techniques and high financial input. Plasma underwent albumin depletion with ultrafiltration device Amicon Ultra, commercial ProteoPrep Blue Albumin and IgG Depletion Kit, acetonitrile precipitation method and precipitation with acetonitrile-methanol protocol. All samples were evaluated by 1-D and 2-D gel electrophoresis with subsequent mass spectrometry protein identification. Two of the tested methods (ProteoPrep BlueKit and acetonitrile-methanol precipitation) maintained sufficient protein content for further in-gel analyses. Their 2-D protein profiles were distinctively separated and overlapped with protein profile of crude plasma. Protein spot count showed significant increase in protein spots, compared to crude plasma, only with acetonitrile-methanol precipitation method. Precipitation with acetonitrile-methanol method significantly increased number of protein spots on 2-D protein profile and improved score of mass spectrometry identification. However, albumin was still present and found in number of protein spots.


Assuntos
Albuminas/isolamento & purificação , Proteínas Sanguíneas/análise , Plasma/química , Proteômica/métodos , Eletroforese em Gel Bidimensional , Humanos
20.
Crit Care Med ; 46(1): 138-145, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29099419

RESUMO

OBJECTIVES: Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. DATA SOURCES: We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. STUDY SELECTION: All identified studies were screened for eligibility by two independent reviewers. DATA EXTRACTION: Key data were extracted using standardized data collection forms. DATA SYNTHESIS: Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. CONCLUSIONS: Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.


Assuntos
Emergências , Estado Epiléptico/complicações , Estado Epiléptico/terapia , Doença Aguda , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Cuidados Críticos/métodos , Humanos , Estado Epiléptico/etiologia
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