RESUMO
Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat's striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl2/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson's disease and other copper dysregulation states.
Assuntos
Cobre , Corpo Estriado , Dopamina , Líquido Extracelular , Ácido Homovanílico , Animais , Dopamina/metabolismo , Cobre/metabolismo , Ácido Homovanílico/metabolismo , Ratos , Masculino , Líquido Extracelular/metabolismo , Corpo Estriado/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Ratos Wistar , Serotonina/metabolismo , Norepinefrina/metabolismoRESUMO
AbstractThe purpose of this study is to evaluate the influence of several risk factors and, among them, the role of different types of antibiotics, in the development of the first recurrent episode of Clostridioides difficile (CD) infection. We performed a case control study from 2006 to 2016. We included patients admitted to the hospital with CD infection that received any antibiotic treatment during the year before the onset of the infection. First, we described the characteristics of CD infection in a Spanish third level hospital and then we compared first cases of CD infection that presented recurrence with those that did not. We included 110 cases, corresponding to 94 individuals. There were 14 first CD infection episodes that later presented recurrence (12.7%). Receiving more than 3 types of antibiotics during the year before the onset of symptoms was associated with higher risk of presenting a recurrent episode (OR = 4.69, 95% CI 1.01-21.78), as well as the past history of neoplasia (OR = 4.58, 95% CI 1.00-20.98). The number of previous hospital admissions was associated with the development of recurrences in the univariate study (p < 0.05). No differences were observed related to the type of antibiotic used immediately before the CD episode neither with the treatment received. The number of types of antibiotics used during the year before the first episode of CD infection or having a personal history of neoplasia was associated with 4 times higher risk of recurrent episodes. Type of antibiotic used did not show to influence recurrences.
Assuntos
Infecções por Clostridium/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Masculino , Recidiva , Fatores de Risco , Espanha/epidemiologiaRESUMO
In the 79 countries revised, two fundamental internal medicine (IM) training patterns were in evidence, first, only basic training needed, requiring a 3-4-year residency period for obtaining the diploma of internist; and advanced training needed, requiring 5-7 years of study. Second, evaluation of common IM training for sub-specialists revealed the following three patterns: dual training; core training and separate training.
Assuntos
Currículo , Medicina Interna/educação , Internato e Residência/organização & administração , Humanos , EspecializaçãoRESUMO
High lipoprotein(a) (Lp(a)) levels are associated with an increased risk of arterial hypertension (AHT) and atherosclerotic cardiovascular disease. However, little is known about the detailed profile of AHT based on Lp(a) levels. This observational study focused on elucidating the relationship between Lp(a) concentrations and specific indices obtained from 24-h ambulatory blood pressure (BP) monitoring in hypertensive patients over 18 years of age. We gathered and analyzed data on BP indices along with demographic, epidemiological, clinical, and laboratory variables from 227 hypertensive patients, median age 56 years, including 127 women (56%). After comparing hypertensive patients with Lp(a) levels above and below 125 nmol/L, we found that a 10 mmHg increase in nocturnal systolic BP and all pulse pressure indices (24-h, daytime, and night-time) was associated with an increased risk of high Lp(a) levels by more than 20% and 40%, respectively. Similarly, each 10% increase in the area under the function over time of nocturnal diastolic BP dipping was associated with more than a 30% decrease in the odds of belonging to the elevated Lp(a) levels category. Additionally, Lp(a) levels above 125 nmol/L were associated with higher 24-h, daytime, and night-time systolic BP and pulse pressure load. The relationship between Lp(a) and AHT appears to extend beyond conventional BP measurements, which may be relevant given the prognostic implications of nocturnal BP and pulse pressure indices.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão , Lipoproteína(a) , Humanos , Feminino , Lipoproteína(a)/sangue , Hipertensão/sangue , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Fatores de RiscoRESUMO
INTRODUCTION AND OBJECTIVES: Some studies have pointed to a relationship between Phenyketonuria (PKU) and an increased cardiovascular risk (CVR). This study aimed to evaluate the influence of metabolic control on classical CVR factors in adult patients with PKU. MATERIAL AND METHODS: It was a cross-sectional study conducted in patients older than 18 years with a diagnosis of classical PKU and under strict dietary control. Demographic, epidemiological and laboratory variables related to CVR were collected. The variables of metabolic control were some parameters related to phenylalanine (Phe) plasma levels. RESULTS: A total of 47 patients were included with a mean age of 36±10 years of which 30 (64%) were women. Multivariate analysis revealed that range Phe (B=-2.211, P=0.044, 95%CI: -4.354-(-0.068)) levels were within the model for triglyceride concentrations, while minimum (B=-2.803, P=0.051, 95%CI: -5.612-0.007) and range (B=-1.515, P=0.039, 95%CI: -2.945-(-0.084)) Phe levels were within the model for high-density lipoprotein cholesterol concentrations. Median Phe levels showed a stronger correlation with waist circumference (WC) (B=1.216, P=0.002, 95%CI: 0.462-1.969) than with body mass index (B=0.355, P=0.052, 95%CI: -0.004-0.714). CONCLUSIONS: High Phe levels and wide Phe fluctuations were related to weight gain, increased WC and lipid profile abnormalities. Systematic CVR assessments and comprehensive monitoring of Phe levels may be desirable to prevent or delay cardiovascular disease in PKU patients.
Assuntos
Fenilalanina , Fenilcetonúrias , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Circunferência da Cintura , Fenilcetonúrias/diagnóstico , Fenilcetonúrias/metabolismo , TriglicerídeosRESUMO
We aimed to evaluate the role of plasma phenylalanine (Phe) levels and its fluctuations in some neurocognitive domains and brain magnetic resonance imaging (MRI) findings in adult patients with phenylketonuria (PKU). It was an observational study that included patients older than 18 years with early-treated classical PKU. Plasma Phe levels were measured every other month throughout 2 years and predictor variables were the mean, maximum (max), minimum (min), range (min-max), and plasma Phe levels at the time of cognitive testing. Patients were evaluated for executive function, processing speed, visual attention, and fluid cognitive abilities using the Trail Making Test (TMT) and for the presence of brain MRI abnormalities. In all, 22 patients with a mean age of 34 years were included, of which 18 (81%) were women. Patients with higher range and maximum Phe levels had a poorer time-based performance on TMT form A and form B. Patients with brain MRI abnormalities had higher range, maximum, and mean Phe levels. Range of Phe levels showed a good performance for MRI abnormalities (area under the curve (AUC): 0.881, standard error (SE): 0.095, 95% CI: 0.695-0.999, p = 0.044) and for the poorest time-based performances on TMT form A (AUC: 0.822, SE: 0.092, 95% CI: 0.641-0.999, p = 0.024) and B (AUC: 0.816, SE: 0.094, 95% CI: 0.632-0.999, p = 0.021). Greater Phe variability may have a negative impact on some neurocognitive domains and could be related to the severity of brain structural damage in adult patients with PKU.
Assuntos
Fenilalanina , Fenilcetonúrias , Humanos , Adulto , Feminino , Masculino , Fenilalanina/uso terapêutico , Cognição , Função Executiva , Imageamento por Ressonância Magnética , Fenilcetonúrias/tratamento farmacológicoRESUMO
Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues and early coronary disease but with highly variable clinical expression. Herein, we describe a case study of a 59-year-old male patient with features typical of TD, in whom a likely pathogenic variant in the ABCA1 gene was identified by whole-exome sequencing (WES), identified for the first time as homozygous (NM_005502.4: c.4799A>G (p. His1600Arg)). In silico analysis including MutationTaster and DANN score were used to predict the pathogenicity of the variant and a protein model generated by SWISS-MODEL was built to determine how the homozygous variant detected in our patient may change the protein structure and impact on its function. This case study describes a homozygous variant of the ABCA1 gene, which is responsible for a severe form of TD and underlines the importance of using bioinformatics and genomics for linking genotype to phenotype and better understanding and accounting for the functional impact of genetic variations.
RESUMO
BACKGROUND AND AIMS: We aimed to evaluate the differences in some cardiovascular risk (CVR) factors between adult patients without and with phenylketonuria (PKU) and to explore the correlation between waist circumference (WC) and body mass index (BMI) with the previous variables. METHODS: This was an observational case-control study that included patients older than 18 years with a diagnosis of classic PKU. The controls were age- and sex-matched individuals. We collected demographic, epidemiological, clinical, and laboratory variables, including WC, BMI, and lipid profile parameters. RESULTS: A total of 72 patients (25 controls and 47 cases) were included with a mean age of 36 years, of which 45 (62%) were women. Adult PKU patients showed lower high-density lipoprotein cholesterol (HDL-c) and higher triglyceride (TG) levels than the control group. We found an association between WC and uric acid (B=0.024, P=0.013, 95%CI: 0.005-0.043), TG (B=0.768, P=0.024, 95%CI: 0.107-1.428), and HDL-c (B=-0.254, P=0.026, 95%CI: -0.477 to (-0.032)) levels in PKU patients. However, we did not find any trend between WC and uric acid, TG and HDL-c levels that reached statistical significance (P<0.05) in patients without PKU. CONCLUSIONS: Waist circumference rather than BMI may better represent the CVR in patients with PKU.
Assuntos
Doenças Cardiovasculares , Fenilcetonúrias , Humanos , Adulto , Feminino , Masculino , Circunferência da Cintura , Obesidade , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Ácido Úrico , Triglicerídeos , Índice de Massa Corporal , HDL-Colesterol , Fatores de Risco de Doenças Cardíacas , Fenilcetonúrias/complicações , Fenilcetonúrias/diagnósticoRESUMO
To date, no model has jointly encompassed clinical, inflammatory, and redox markers with the risk of a non-dipper blood pressure (BP) profile. We aimed to evaluate the correlation between these features and the main twenty-four-hour ambulatory blood pressure monitoring (24-h ABPM) indices, as well as to establish a multivariate model including inflammatory, redox, and clinical markers for the prediction of a non-dipper BP profile. This was an observational study that included hypertensive patients older than 18 years. We enrolled 247 hypertensive patients (56% women) with a median age of 56 years. The results showed that higher levels of fibrinogen, tissue polypeptide-specific antigen, beta-2-microglobulin, thiobarbituric acid reactive substances, and copper/zinc ratio were associated with a higher risk of a non-dipper BP profile. Nocturnal systolic BP dipping showed a negative correlation with beta-globulin, beta-2-microglobulin, and gamma-globulin levels, whereas nocturnal diastolic BP dipping was positively correlated with alpha-2-globulin levels, and negatively correlated with gamma-globulin and copper levels. We found a correlation between nocturnal pulse pressure and beta-2-microglobulin and vitamin E levels, whereas the day-to-night pulse pressure gradient was correlated with zinc levels. Twenty-four-hour ABPM indices could exhibit singular inflammatory and redox patterns with implications that are still poorly understood. Some inflammatory and redox markers could be associated with the risk of a non-dipper BP profile.
RESUMO
As in other fields, chronotherapy applied to arterial hypertension (AHT) may have implications on oxidative stress. We compared the levels of some redox markers between hypertensive patients with morning and bedtime use of renin-angiotensin-aldosterone system (RAAS) blockers. This was an observational study that included patients older than 18 years with a diagnosis of essential AHT. Blood pressure (BP) figures were measured using twenty-four-hour ambulatory BP monitoring (24-h ABPM). Lipid peroxidation and protein oxidation were assessed using the thiobarbituric acid reactive substances (TBARS) and reduced thiols assays. We recruited 70 patients with a median age of 54 years, of whom 38 (54%) were women. In hypertensive patients with bedtime use of RAAS blockers, reduced thiol levels showed a positive correlation with nocturnal diastolic BP decrease. TBARS levels were associated with bedtime use of RAAS blockers in dipper and non-dipper hypertensive patients. In non-dipper patients, bedtime use of RAAS blockers was also associated with a decrease in nocturnal diastolic BP. Chronotherapy applied to bedtime use of some BP-lowering drugs in hypertensive patients may be linked to a better redox profile.
RESUMO
BACKGROUND: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection. METHODS: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations. RESULTS: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations. CONCLUSIONS: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.
RESUMO
We aimed to explore the influence that the circadian blood pressure (BP) profile could exert on the correlation between some inflammatory markers and hypertension-mediated organ damage (HMOD). This was a cross-sectional study that included patients with primary arterial hypertension older than 18 years old. We included some parameters of 24 h ambulatory blood pressure monitoring collection and several inflammatory markers, as follows: platelet count (PTC), erythrocyte sedimentation rate (ESR), ultrasensitive C-reactive-protein, ferritin, fibrinogen, and uric acid. Myocardial hypertrophy, albuminuria, carotid intima-media thicknesses and ankle brachial index were assessed as HMOD presentations. Individuals were divided into two groups: patients with and without HMOD. We included 522 patients (47% women, mean age of 54 years). Multivariate logistic regression analysis showed that male patients older than 50 years old with uric acid levels above 7 mg/dL, ESR higher than 20 mm/h, fibrinogen greater than 320 mg/dL and PTC lower than 275 × 103/µL were associated with HMOD (p < 0.05). The circadian BP profile (dipper versus non-dipper pattern) did reach neither statistical significance nor influence the odds ratio of those inflammatory markers for HMOD. We found that differences in some inflammatory markers between patients with and without HMOD were not explained by a different circadian BP profile.
RESUMO
An impaired nocturnal decrease in diastolic blood pressure (DBP) increases the blood pressure (BP) load, which is a main factor in endothelial dysfunction, atherosclerosis, and arterial stiffness. We aimed to quantify some markers of oxidative stress in hypertensive patients, to compare their levels between individuals with dipper and non-dipper DBP profiles, and to assess their correlation with the nocturnal DBP (nDBP) dipping. It was an observational study that included patients older than 18 years with a diagnosis of essential hypertension who consented to participate. The collected variables were some indices of 24-h ambulatory blood pressure monitoring, demographic, epidemiological, clinical, and laboratory variables. Plasma thiobarbituric acid reactive substances (TBARS) and reduced thiols, together with serum vitamin E, vitamin A, copper (Cu), and zinc (Zn) levels were assessed as oxidative stress markers. We recruited 248 patients with a median age of 56 years (56% women). The percentage of nDBP dipping showed a weak positive correlation with reduced thiol, vitamin E, and vitamin A levels; and a weak negative correlation with Cu levels. We also found a negative correlation between nDBP dipping and the TBARS/Thiol, TBARS/Vitamin E, and TBARS/Vitamin A ratios. After multivariate analysis, we found that increased TBARS/Thiol ratio and serum Cu levels were associated with a higher risk of a non-dipper DBP profile. As in other situations of increased cardiovascular risk, an impaired nDBP decrease may coincide with abnormalities in redox status.
RESUMO
We aimed to evaluate the correlation of plasma levels of thiobarbituric acid reactive substances (TBARS) and reduced thiols with morbidity, mortality and immune response during and after SARS-CoV-2 infection. This was an observational study that included inpatients with SARS-CoV-2 infection older than 65 years. The individuals were followed up to the twelfth month post-discharge. Plasma levels of TBARS and reduced thiols were quantified as a measure of lipid and protein oxidation, respectively. Fatal and non-fatal events were evaluated during admission and at the third, sixth and twelfth month post-discharge. Differences in oxidative stress markers between the groups of interest, time to a negative RT-qPCR and time to significant anti-SARS-CoV-2 IgM titers were assessed. We included 61 patients (57% women) with a mean age of 83 years old. After multivariate analysis, we found differences in TBARS and reduced thiol levels between the comparison groups in fatal and non-fatal events during hospital admission. TBARS levels were also correlated with fatal events at the 6th and 12th months post-discharge. One year after hospital discharge, other predictors rather than oxidative stress markers were relevant in the models. The median time to reach significant anti-SARS-CoV-2 IgM titers was lower in patients with low levels of reduced thiols. Assessment of some parameters related to oxidative stress may help identify groups of patients with a higher risk of morbidity, mortality and delayed immune response during and after SARS-CoV-2 infection.
Assuntos
COVID-19 , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais , Biomarcadores , Feminino , Humanos , Imunoglobulina M , Lipídeos , Masculino , Estresse Oxidativo , Alta do Paciente , Prognóstico , SARS-CoV-2 , Compostos de Sulfidrila , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
The mechanisms underlying liver disease in patients with COVID-19 are not entirely known. The aim is to investigate, by means of novel statistical techniques, the changes over time in the relationship between inflammation markers and liver damage markers in relation to survival in COVID-19. The study included 221 consecutive patients admitted to the hospital during the first COVID-19 wave in Spain. Generalized additive mixed models were used to investigate the influence of time and inflammation markers on liver damage markers in relation to survival. Joint modeling regression was used to evaluate the temporal correlations between inflammation markers (serum C-reactive protein [CRP], interleukin-6, plasma D-dimer, and blood lymphocyte count) and liver damage markers, after adjusting for age, sex, and therapy. The patients who died showed a significant elevation in serum aspartate transaminase (AST) and alkaline phosphatase levels over time. Conversely, a decrease in serum AST levels was observed in the survivors, who showed a negative correlation between inflammation markers and liver damage markers (CRP with serum AST, alanine transaminase [ALT], and gamma-glutamyl transferase [GGT]; and D-dimer with AST and ALT) after a week of hospitalization. Conversely, most correlations were positive in the patients who died, except lymphocyte count, which was negatively correlated with AST, GGT, and alkaline phosphatase. These correlations were attenuated with age. The patients who died during COVID-19 infection displayed a significant elevation of liver damage markers, which is correlated with inflammation markers over time. These results are consistent with the role of systemic inflammation in liver damage during COVID-19.
Assuntos
COVID-19 , Hepatopatias , Aspartato Aminotransferases , Biomarcadores , COVID-19/complicações , Humanos , Inflamação/metabolismo , Fígado/metabolismo , Hepatopatias/etiologiaRESUMO
Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).
RESUMO
Bacille Calmette-Guérin (BCG) administration for superficial bladder cancer is a well-tolerated and very effective therapy. However, unpredictable systemic complications may occur on rare occasions. We present the case of a patient who attended for consultation because of fever, asthenia and weight loss following BCG immunotherapy. The clinical response to treatment and computed tomography scanning were key to diagnosis. LEARNING POINTS: It is essential to keep a high index of suspicion of possible, although uncommon, complications in patients treated with BCG immunotherapy.Response to treatment should always be evaluated to confirm diagnostic suspicion.