RESUMO
BACKGROUND: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. PURPOSE: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. PATIENTS AND METHODS: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. RESULTS: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. CONCLUSION: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.
Assuntos
Circulação Cerebrovascular/fisiologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Endotélio Vascular/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Circulação Cerebrovascular/efeitos dos fármacos , Transtorno Depressivo Maior/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fluxo Sanguíneo Regional/efeitos dos fármacos , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.
Assuntos
Antineoplásicos , Tumores Neuroendócrinos , Antineoplásicos/uso terapêutico , Diarreia , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Somatostatina/uso terapêuticoRESUMO
OBJECTIVES: Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. METHODS AND RESULTS: Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro-B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg(-1) min(-1) vs 23.0 ± 7.2 mL kg(-1) min(-1); P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with (18)FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). CONCLUSIONS: In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life.
Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Isquemia Miocárdica , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cintilografia , Resultado do TratamentoRESUMO
Secure attachment, developed through consistent relationships with attachment figures in childhood, is a crucial factor in fostering healthy interpersonal relationships and a positive self-perception. Part of the positive parenting approach and the theory of affect is taken as a basis to assess how perceived security, as an indicator of secure attachment, predicts adult self-concept through the mediating effects of resilience and positive self-esteem. A quantitative, cross-sectional, and nonprobabilistic study was conducted with 383 participants. We unveiled significant positive associations between perceived security, self-concept, resilience, and positive self-esteem. Path analysis demonstrated that resilience and positive self-esteem sequentially mediate the relationship between perceived security during childhood and adult self-concept. Findings suggest that the ability to cope with adversity and personal acceptance underlie the impact of perceived security on self-concept. It is recommended to promote family intervention programs framed within positive parenting that focus on fostering secure attachment given its influence on adult life. It is also deemed essential to incorporate the promotion of resilience and self-esteem into programs aimed at youths, and adult role models can enhance their self-perception and resilience in the face of potential effects stemming from insecure parenting practices.
RESUMO
Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.
Assuntos
Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile/epidemiologia , Cromogranina A/sangue , Feminino , Humanos , Ácido Hidroxi-Indolacético/sangue , Incidência , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/mortalidade , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/mortalidade , Serotonina/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
The Basque population inhabits the Franco-Cantabrian region in southwest Europe where Palaeolithic human groups took refuge during the Last Glacial Maximum. Basques have been an isolated population, largely considered as one of the most ancient European populations and it is possible that they maintained some pre-Neolithic genetic characteristics. This work shows the results of mitochondrial DNA analysis of seven ancient human remains from the Cave of Santimamiñe in the Basque Country dated from Mesolithic to the Late Roman period. In addition, we compared these data with those obtained from a modern sample of Basque population, 158 individuals that nowadays inhabits next to the cave. The results support the hypothesis that Iberians might have been less affected by the Neolithic mitochondrial lineages carried from the Near East than populations of Central Europe and revealed the unexpected presence of prehistoric maternal lineages such as U5a2a and U3a in the Basque region. Comparison between ancient and current population samples upholds the hypothesis of continuity of the maternal lineages in the area of the Franco-Cantabrian region.
Assuntos
DNA Antigo/química , Evolução Molecular , Genoma Mitocondrial , Linhagem , Haplótipos , Migração Humana , Humanos , Espanha , População Branca/genéticaRESUMO
The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).
Assuntos
Antivenenos/uso terapêutico , Bothrops , Venenos de Crotalídeos/sangue , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Adulto , Idoso , Animais , Antivenenos/sangue , Antivenenos/química , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Caprilatos/farmacologia , Fracionamento Químico/métodos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrinogênio/metabolismo , Humanos , Imunoglobulina G , Masculino , Camundongos , Pessoa de Meia-Idade , Propiolactona/farmacologia , Recidiva , Mordeduras de Serpentes/sangue , Resultado do Tratamento , Tempo de Coagulação do Sangue TotalRESUMO
El arte se debate precisamente entre responder al papel
asignado por la modernidad como campo de la estética,
y de escapar de ese lugar e interrogar la re-presentación
para abrir el horizonte de sentido, pero esta vez introduciendo
lo singular como su única garantía de tratar lo
real. Lo cual dista del ámbito de la investigación. El arte,
en consecuencia, está expuesto al peligro de sucumbir a
la demanda de la realidad en el capitalismo de la modernidad
tardía. La pertinencia de tratar lo singular en su
propia lógica, es decir sin la pretensión de compararlo
con lo universal, mediante la creación artística y la elaboración
simbólica, permite tramitar lo incomprensible, lo
real, lo insoportable dándole una forma y una materia,
lo cual implica contrarrestar los efectos del retorno de lo
real puesto en el acto atroz
Assuntos
PsicanáliseRESUMO
El arte se debate precisamente entre responder al papel asignado por la modernidad como campo de la estética, y de escapar de ese lugar e interrogar la re-presentación para abrir el horizonte de sentido, pero esta vez introduciendo lo singular como su única garantía de tratar lo real. Lo cual dista del ámbito de la investigación. El arte, en consecuencia, está expuesto al peligro de sucumbir a la demanda de la realidad en el capitalismo de la modernidad tardía. La pertinencia de tratar lo singular en su propia lógica, es decir sin la pretensión de compararlo con lo universal, mediante la creación artística y la elaboración simbólica, permite tramitar lo incomprensible, lo real, lo insoportable dándole una forma y una materia, lo cual implica contrarrestar los efectos del retorno de lo real puesto en el acto atroz
Art is debating precisely between responding to the role assigned by modernity as a field of aesthetics and escaping from that place and questioning the re-presentation to open the horizon of meaning, but this time introducing the singular as its only guarantee of trying the real. Which is far from the scope of the investigation. Consequently, art is exposed to the danger of succumbing to the demand of reality in late modern capitalism. The relevance of treating the singular in its own logic, that is, without the pretense of comparing it with the universal, through artistic creation and symbolic elaboration, allows us to process the incomprehensible, the real, the unbearable, giving it a form and a matter, which it implies counteracting the effects of the return of the real put into the heinous act
Assuntos
Humanos , Mudança Social , ArteRESUMO
Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.
Assuntos
Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Antineoplásicos/uso terapêutico , Somatostatina/uso terapêutico , DiarreiaRESUMO
Radionuclide isotopic ventriculography with phase analysis was performed in 30 patients with stable heart failure (HF), determining left ventricular (LV) and interventricular contraction synchrony at baseline and after 6 months of treatment with maximal tolerated doses of carvedilol. Patients with HF had significant ventricular dyssynchrony compared with a normal population. The 50th percentile of patients with the greatest dyssynchrony at baseline showed significant improvement in ventricular synchrony after receiving carvedilol, and this was correlated positively with a reduction in end-diastolic LV volumes.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Carbazóis/administração & dosagem , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Propanolaminas/administração & dosagem , Remodelação Ventricular/efeitos dos fármacos , Carvedilol , Doença Crônica , Relação Dose-Resposta a Droga , Esquema de Medicação , Eletrocardiografia , Feminino , Insuficiência Cardíaca/mortalidade , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.
Assuntos
Antídotos/uso terapêutico , Bothrops , Venenos de Crotalídeos/toxicidade , Hemorragia/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Zingiberaceae , Animais , Rim/efeitos dos fármacos , Rim/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Miocárdio/patologia , Fitoterapia , Mordeduras de Serpentes/tratamento farmacológicoRESUMO
An L-amino acid oxidase (LAAO) from Crotalus durissus cumanensis venom (CdcLAAO) was purified to homogeneity using a combination of size-exclusion and ion exchange chromatographies. CdcLAAO is a monomeric protein exhibiting an apparent molecular mass of 55 kDa and a calculated pI of 8. Its complete 498-amino-acid sequence was deduced through cDNA and protein sequencing. The enzyme oxidized L-Leu with K(m) and a V(Max) of 9.23 µM and 0.46 µM/min respectively, and exhibited Kcat and a Kcat/K(m) of 1.8 s(-1) and 195 mM(-1)s(-1). CdcLAAO inhibited in a dose-dependent manner the growth of Staphylococcus aureus and Acinetobacter baumannii. The inhibitory effect was more significant on S. aureus, with a Minimal Inhibitory Concentration (MIC) of 8 µg/mL and Minimal Bactericidal Concentration (MBC) of 16 µg/mL, than against A. baumannii, with a MIC of 16 µg/mL and MBC of 32 µg/mL. However, against Escherichia coli CdcLAAO did not show inhibitory capacity at the concentrations tested (2-128 µg/mL). CdcLAAO did not exhibit cytotoxic activity on the mouse myoblast cell line C(2)C(12) and on peripheral blood mononuclear cell (PBMC).
Assuntos
Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Venenos de Crotalídeos/enzimologia , Crotalus/metabolismo , L-Aminoácido Oxidase/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Acinetobacter/crescimento & desenvolvimento , Acinetobacter/ultraestrutura , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Clonagem Molecular , Venenos de Crotalídeos/genética , DNA Complementar/metabolismo , Humanos , L-Aminoácido Oxidase/química , L-Aminoácido Oxidase/genética , L-Aminoácido Oxidase/isolamento & purificação , Leucócitos Mononucleares/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Mioblastos/efeitos dos fármacos , Oxirredução , Estrutura Terciária de Proteína , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/ultraestruturaRESUMO
INTRODUCTION: Traditional medicine is an invaluable source of research into new medicines as a supplement for the treatment of snakebite, considered as a serious public health problem worldwide. The extracts of the medicinal plant, Renealmia alpina, have been used traditionally by indigenous people of Chocó (Colombia) against Bothrops asper snakebite, a snake responsible for the majority of snakebite accidents in Colombia. OBJECTIVE: The ability of extracts of R. alpinia leaves was tested for its ability to neutralize the hemorrhagic, coagulant and proteolytic effects of the snakebite venom of B. asper. MATERIALS AND METHODS: The acute toxicity tests and analgesic activity of R. alpina were evaluated in vivo. In addition, tests were undertaken in in vitro conditions to demonstrate inhibition of coagulant, haemolytic and proteolytic activity of the B. asper venom. Results. Renealmia alpinia extracts had no toxic effects in experimental animals and also provided analgesic and antiophidian effects and protection against the lethal effects of the venom of B. asper. CONCLUSION: Renealmia. alpinia was an effective therapeutic alternative in association with antivenom treatment in the event of a B. asper snakebite accident. It was demonstrated to protect against the lethal effects and provided analgesic properties as well.
Assuntos
Bothrops , Venenos de Crotalídeos/antagonistas & inibidores , Fitoterapia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Mordeduras de Serpentes/tratamento farmacológico , Zingiberaceae , Acetatos , Analgésicos/uso terapêutico , Analgésicos/toxicidade , Animais , Coagulação Sanguínea/efeitos dos fármacos , Venenos de Crotalídeos/toxicidade , Avaliação Pré-Clínica de Medicamentos , Etanol , Feminino , Hemólise/efeitos dos fármacos , Hexanos , Masculino , Metanol , Cloreto de Metileno , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Proteólise/efeitos dos fármacos , SolventesRESUMO
Snake venoms are complex mixtures of proteins among which both basic and acidic phospholipases A(2) (PLA(2)s) can be found. Basic PLA(2)s are usually responsible for major toxic effects induced by snake venoms, while acidic PLA(2)s tend to have a lower toxicity. A novel PLA(2), here named PnPLA(2), was purified from the venom of Porthidium nasutum by means of RP-HPLC on a C18 column. PnPLA(2) is an acidic protein with a pI of 4.6, which migrates as a single band under both non-reducing and reducing conditions in SDS-PAGE. PnPLA(2) had a molecular mass of 15,802.6 Da, determined by ESI-MS. Three tryptic peptides of this protein were characterized by HPLC-nESI-MS/MS, and N-terminal sequencing by direct Edman degradation showing homology to other acidic PLA(2)s from viperid venoms. PnPLA(2) displayed indirect hemolytic activity in agarose erythrocyte-egg yolk gels and bactericidal activity against Staphylococcus aureus in a dose-dependent manner, with a MIC and MBC of 32 µg/mL. In addition, PnPLA(2) showed a potent inhibitory effect on platelet aggregation with doses up to 40 µg/mL. This acidic PLA(2), in contrast to basic enzymes isolated from other viperid snake venoms, was not cytotoxic to murine skeletal muscle myoblasts C(2)C(12). This is the first report on a bactericidal protein of Porthidium nasutum venom.
Assuntos
Antibacterianos/isolamento & purificação , Venenos de Crotalídeos/química , Fosfolipases A2/genética , Fosfolipases A2/isolamento & purificação , Viperidae , Animais , Antibacterianos/análise , Antibacterianos/toxicidade , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Venenos de Crotalídeos/toxicidade , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Espectrometria de Massas , Camundongos , Dados de Sequência Molecular , Mioblastos/efeitos dos fármacos , Fosfolipases A2/toxicidade , Análise de Sequência de DNA , Homologia de Sequência , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Ventricular dyssynchrony is a common finding in patients with heart failure (HF), especially in the presence of conduction delays. The loss of ventricular synchrony leads to progressive impairment of contractile function, which may be explained in part by segmental abnormalities of myocardial metabolism. However, the association of these metabolic disarrangements with parameters of ventricular dyssynchrony and electrocardiography (ECG) findings has not yet been studied. METHODS: Our aim was to determine the correlation between the presence of left bundle branch block (LBBB) with left ventricular (LV) mechanical synchrony assessed by multiple-gated acquisition scan (MUGA) and with patterns of 18-fluorodeoxyglucose (18FDG) uptake in patients with non-ischemic heart failure. Twenty-two patients with non-ischemic cardiomyopathy, LV ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) Functional Class II or III symptoms under standard medical therapy were included, along with 10 healthy controls matched for age and gender. A 12-lead ECG was obtained to measure the length of the QRS. Mechanical LV synchrony was assessed by MUGA using phase analysis. All patients and controls underwent positron emission tomography with 18FDG to determine the distribution of myocardial glucose uptake. The standard deviation of peak (18)FDG uptake was used as an index of metabolic heterogeneity. Student's t-test and Pearson's correlation were used for statistical analysis. RESULTS: The mean age of the patients with HF was 54 ± 12 years and 72% were male. The length of the QRS was 129 ± 31 milliseconds and LBBB was present in 9 patients. Patients with HF had decreased LV 18FDG uptake compared with controls (7.56 ± 3.36 vs. 11.63 ± 4.55 standard uptake value; p = 0.03). The length of the QRS interval correlated significantly with glucose uptake heterogeneity (r = 0.62; p = 0.002) and mechanical dyssynchrony (r = 0.63; p = 0.006). HF patients with LBBB showed marked glucose uptake heterogeneity compared with HF patients without LBBB (41.4 ± 10 vs 34.7 ± 4.9 ml/100 g/min, respectively; p = 0.01). CONCLUSIONS: Patients with non-ischemic heart failure exhibit a global decrease in myocardial glucose uptake. Within this group, subjects who also have LBBB exhibit a marked heterogeneity in segmental glucose uptake, which directly correlates with QRS duration.
Assuntos
Bloqueio de Ramo/metabolismo , Bloqueio de Ramo/fisiopatologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Fluordesoxiglucose F18/metabolismo , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Volume Sistólico/fisiologiaRESUMO
The efficacy and safety of two polyvalent horse-derived antivenoms in Bothrops asper envenomings were tested in a randomized, double-blind, clinical trial performed in Colombia. Both antivenoms were manufactured from the same pool of hyperimmune plasma. Antivenom A was made of F(ab')2 fragments, generated by pepsin digestion and caprylic acid precipitation, whereas antivenom B consisted of whole IgG molecules produced by caprylic acid precipitation followed by ion-exchange chromatography. Besides the different nature of the active substance, antivenom B had higher protein concentration, slightly higher turbidity and aggregate content. No significant differences were observed in the efficacy of antivenoms. Both halted local and systemic bleeding (P = 0.40) within 6-12 h of treatment in 100% of the cases, and restored blood coagulation (P = 0.87) within 6-24 h in 84.7% of patients, and within 48 h in all of them, in agreement with restoration of plasma fibrinogen concentration. Venom concentrations in serum dropped significantly (P < 0.001), to very low levels, 1 h after antivenom infusion. Nevertheless, eight patients (11.1%), four for each antivenom, presented recurrence of venom antigenaemia at different times, from 6 to 96 h, with clinical significance (recurrent coagulopathy) only in one group B patient (2.9%). Serum creatine kinase (CK) activity was increased, as a consequence of local myonecrosis. There was no significant difference (P = 0.51) in the incidence of early adverse reactions to antivenom administration (28.9% for patients of group A and 20.6% for patients of group B), most of the reactions being mild, mainly cutaneous. The most frequent complications were cellulitis (16.7%), abscess formation (5.6%), acute renal failure (8.3%), and compartmental syndrome (5.6%). In conclusion, IgG and F(ab')2 antivenoms, prepared by caprylic acid fractionation, presented similar efficacy and safety profiles for the treatment of B. asper envenomings in Colombia.
Assuntos
Antivenenos/uso terapêutico , Bothrops/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Animais , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Caprilatos/farmacologia , Fracionamento Químico/métodos , Cromatografia por Troca Iônica/métodos , Colômbia , Venenos de Crotalídeos/metabolismo , Método Duplo-Cego , Avaliação de Medicamentos , Feminino , Fibrinogênio/análise , Hemorragia/tratamento farmacológico , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoglobulina G/uso terapêutico , Incidência , Masculino , Pepsina A/metabolismo , Resultado do TratamentoRESUMO
Si se trata de un encuentro, este
es posible en el campo del tratamiento
de lo real, allí donde tanto
Lacan como Heidegger introducen
un límite al campo abierto por
Descartes, sostenido en la lógica
de la consciencia y la razón y, de
una manera mucho más radical, en
la lógica del objeto, por parte de la
ciencia y la técnica moderna. Tanto
las elaboraciones de Heidegger a
propósito del olvido del ser en la
modernidad, como las de Lacan
en relación con la forclusión del
sujeto por parte de la ciencia, se
orientan a introducir, mediante
lo singular, una hendidura en la
noción de verdad de la época. El
artículo tratará, a manera de introducción,
las elaboraciones sobre la
verdad en Heidegger y en Lacan, de
cara a la consumación del ideario
cartesiano
Assuntos
PsicanáliseRESUMO
Adolescence is a developmental period that implies a series of rapid changes that might complicate the role of parents. This study evaluates changes in parental monitoring and the strategies to solve family conflicts reported by parents who participated in the "Living Adolescence in Family" program in local social services and school centers. In addition, the study analyses the moderating role of family and facilitator variables that may affect the final results. The participants were 697 parents attending the social services (438 in the intervention group and 259 in the control group) and 1283 parents from school centers (880 in the intervention group and 403 in the control group). The results showed that families from local social services decreased the amount of control and improved monitoring in education and leisure spheres as well as self-disclosure whereas the families coming from school centers improved supervision in leisure and in self-disclosure. In addition, both groups of families improved their strategies for solving family conflicts, increasing the use of integrative strategies and decreasing the use of dominant strategies. There were differences across contexts: the results of the program in the social services context differed according to the participant and professional profiles whereas program results were more homogeneous in the school context. In sum, the program appears to be an efficient work tool, both for the professionals who work with at-risk families with adolescents and for the teachers who make use of the program for families with children at risk of early school dropout
La adolescencia es un período de desarrollo que implica una serie de cambios rápidos que podrían complicar el papel de los padres. Este estudio evalúa los cambios en la supervisión parental y en las estrategias de resolución de conflictos familiares reportados por los padres que participan en el programa 'Vivir la adolescencia en familia' en los servicios sociales locales y en los centros escolares. Además, el estudio analiza el papel moderador de la familia y las variables de los facilitadores que pueden afectar a los resultados finales. Los participantes fueron 697 padres que asistieron a los servicios sociales (438 en el grupo de intervención y 259 en el grupo control) y 1283 padres de los centros escolares (880 en el grupo de intervención y 403 en el grupo de control). Los resultados mostraron que las familias de los servicios sociales locales disminuyeron el control y mejoraron en supervisión educativa y en las esferas de ocio, así como en la apertura, mientras que las familias procedentes de centros escolares mejoraron la supervisión en el ocio y en la apertura. Además, ambos grupos de familias mejoraron las estrategias de resolución de conflictos familiares, aumentando el uso de estrategias integradoras y disminuyendo el uso de estrategias dominantes. Como signo de distinción, los resultados del programa en el contexto de los servicios sociales diferían según los participantes y los perfiles profesionales, mientras que los resultados del programa fueron más homogéneos en el contexto escolar. En resumen, el programa parece ser una herramienta de trabajo eficiente, tanto para los profesionales que trabajan con las familias con hijos adolescentes en situación de riesgo como para los profesores que han realizado el programa para familias con niños en riesgo de abandono escolar temprano
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Planejamento em Saúde/organização & administração , Planejamento em Saúde/normas , Serviço Social/métodos , Serviço Social/organização & administração , Conflito Familiar/psicologia , Comportamento do Adolescente/psicologia , Psicologia do Adolescente/métodos , Família/psicologia , Poder Familiar/psicologia , Conflito Psicológico , Desenvolvimento do Adolescente/fisiologia , Relações Pais-Filho , Pais/psicologia , Planejamento/métodosRESUMO
It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.