Activities of daily living in patients with chronic obstructive pulmonary disease with depressive symptoms / Atividades de vida diária em pacientes com doença pulmonar obstrutiva crônica com sintomas depressivos / Actividades de la vida diaria en pacientes con enfermedad pulmonar obstructiva crónica y síntomas depresivos

ABSTRACT This cross-sectional study assessed the activities of daily living (ADL) and risk factors for developing depressive symptoms in patients with chronic obstructive pulmonary disease (COPD) and was carried out at the pulmonology outpatient clinic of the Hospital Universitário Oswaldo Cruz. Two hundred two (202) patients with COPD participated in the study. We evaluated the sociodemographic and anthropometric data, the ADL by means of Pulmonary Functional Status and Dyspnea Questionnaire - Modified version (PFSDQ-M), and the presence of depressive symptoms using the Beck Depression Inventory (BDI). All domains (dyspnea, fatigue and activity changes) of PFSDQ are compromised in patients with depressive symptoms. The prevalence of depressive symptoms was 38.6%. The chance of developing these symptoms was higher for those who used more than one bronchodilator (OR: 2.82, CI 95%: 1.47-5.38, p=0.002), presented dyslipidemias (OR: 2.74, CI95%: 1.24-6.07, p=0.012), had a heart disease (OR: 2.82, CI 95%: 1.18-6.74, p=0.020), presented expectoration (OR: 2.44, CI 95%: 1.2-4.95, p=0.014) or did not have a partner (OR: 2.58, CI 95%: 1.36-4.9, p=0.004). COPD patients with depressive symptoms had all domains of ADL compromised compared to patients without these symptoms.

RESUMO O objetivo foi avaliar as atividades de vida diária (AVD) e fatores de risco para o desenvolvimento de sintomas depressivos nos pacientes com doença pulmonar obstrutiva crônica (DPOC). Estudo transversal realizado no ambulatório de Pneumologia do Hospital Universitário Oswaldo Cruz. Participaram do estudo 202 pacientes com DPOC. Foram avaliados os dados sociodemográficos e antropométricos; as AVD, através do Pulmonary Functional Status and Dyspnea Questionnaire - Modified version (PFSDQ-M); e a presença de sintomas depressivos por meio do inventário de depressão de Beck. Todos os domínios (dispneia, fadiga e mudanças de atividades) do PFSDQ-M se apresentaram comprometidos nos pacientes com sintomas depressivos. A prevalência de sintomas depressivos foi de 38,6%. As chances de desenvolvimento desses sintomas ocorreram para aqueles que utilizavam mais de um broncodilatador (OR: 2,82, IC95%: 1,47-5,38, p=0,002), que apresentavam dislipidemias (OR: 2,74, IC95%: 1,24-6,07, p=0,012), que possuíam cardiopatia (OR: 2,82, IC95%: 1,18-6,74, p=0,02); que apresentavam expectoração (OR: 2,44, IC95%: 1,2-4,95, p=0,014); e não tinham companheiros (OR: 2,58, IC95%: 1,36-4,9, p=0,004). Pacientes com DPOC com sintomas depressivos apresentaram todos os domínios das AVD comprometidos em relação aos pacientes sem esses sintomas.

RESUMEN El objetivo fue evaluar las actividades de la vida diaria (AVD) y los factores de riesgo para el desarrollo de síntomas depresivos en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Estudio transversal realizado en el ambulatorio de Neumología del Hospital Universitario Oswaldo Cruz. En el estudio, participaron 202 pacientes con EPOC. Se evaluaron los datos sociodemográficos y antropométricos, las AVD por medio de Pulmonary Functional Status and Dyspnea Questionnaire: Modified version (PFSDQ-M), y la presencia de síntomas depresivos por medio del Inventario de depresión de Beck. Todos los dominios (disnea, fatiga y cambios en las actividades) del PFSDQ-M estuvieron comprometidos en pacientes con síntomas depresivos. La prevalencia de síntomas depresivos fue del 38,6%. Las posibilidades para el desarrollo de estos síntomas ocurrieron para aquellos que utilizaban más de un broncodilatador (OR: 2,82, IC95%: 1,47-5,38, p=0,002), que tenían dislipidemias (OR: 2,74, IC95%: 1,24-6,07, p=0,012), que tenían enfermedad cardiaca (OR: 2,82, IC95%: 1,18-6,74, p=0,02), que tenían expectoración (OR: 2,44, IC95%: 1,2-4,95, p=0,014), y no tenían parejas (OR: 2,58, IC95%: 1,36-4,9, p=0,004). Los pacientes con EPOC y síntomas depresivos tuvieron todos los dominios de las AVD afectados en comparación con los pacientes sin estos síntomas.

Atividade de vida diária e sintomas depressivos em pacientes com doença pulmonar obstrutiva crônica / Daily life activity of patients with chronic obstructive pulmonary disease and with depressive symptoms

Objetivo: avaliar a presença de sintomas depressivos e as atividades de vida diária em pacientes com doença pulmonar obstrutiva crônica (DPOC). Métodos: Participaram 114 pacientes com DPOC classificados de acordo com Global Strategy for the Diagnosis, Manegement and Prevention in COPD nos estágios 2, 3 e 4. Foram avaliados a presença de sintomas depressivos (Inventário de Depressão de Beck) e as limitações nas atividades de vida diária (AVDs) (London Chest Activity of Daily Living Scale - LCADL). Resultados: A prevalência de sintomas depressivos foi 41,2%. Os pacientes com sintomas depressivos apresentaram comprometimento em todos os domínios do LCADL (Cuidado pessoal, p<0,001; Atividades domésticas, p=0,004; Atividade Física, p=0,002; Lazer, p<0,001 e Escore total, p<0,001). Conclusão: os pacientes com DPOC e com sintomas depressivos apresentaram limitações na capacidade de desempenhar as AVDs, sendo necessário não só o rastreamento desses sintomas como também a avaliação das AVDs na prática clínica.

Objective: To evaluate the presence of depressive symptoms and the activities of daily living in patients with chronic obstructive pulmonary disease (COPD). Methods: 114 patients with COPD were classified according to the Global Strategy for the Diagnosis, Management and Prevention in COPD in stages 2, 3 and 4. The presence of depressive symptoms (Beck Depression Inventory) and the patients' limitations in the activities of daily living (ADLs) (London Chest Activity of the Daily Living Scale - LCADL) were evaluated. Results: The prevalence of depressive symptoms was 41.2%. Patients with depressive symptoms showed impairment in all areas of the LCADL (Personal Care, p<0,001; Domestic Activities, p=0,004; Physical Activity, p=0,002; Leisure, p<0,001 and Total Score, p <0.001). Conclusion: Patients with both COPD and depressive symptoms had limited performance in their ADLs, requiring not only the screening for these symptoms but also the evaluation of ADLs in the clinical practice.

A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine.

Urged by the unmet medical needs in endometriosis treatment, often with undesirable side effects, and encouraged by N-acetylcysteine (NAC) efficacy in an animal model of endometriosis and by the virtual absence of toxicity of this natural compound, we performed an observational cohort study on ovarian endometriosis. NAC treatment or no treatment was offered to 92 consecutive Italian women referred to our university hospital with ultrasound confirmed diagnosis of ovarian endometriosis and scheduled to undergo laparoscopy 3 months later. According to patients acceptance or refusal, NAC-treated and untreated groups finally comprised 73 and 72 endometriomas, respectively. After 3 months, within NAC-treated patients cyst mean diameter was slightly reduced (-1.5 mm) versus a significant increase (+6.6 mm) in untreated patients (P = 0.001). Particularly, during NAC treatment, more cysts reduced and fewer cysts increased their size. Our results are better than those reported after hormonal treatments. Twenty-four NAC-treated patients-versus 1 within controls-cancelled scheduled laparoscopy due to cysts decrease/disappearance and/or relevant pain reduction (21 cases) or pregnancy (1 case). Eight pregnancies occurred in NAC-treated patients and 6 in untreated patients. We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy.

More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis.

N-acetyl-L-cysteine exerts a complex action on endometrial cells, involving regulation of gene expression and protein activity and location, all converging into a decreased proliferation and a switch toward a differentiating, less invasive, and less inflammatory phenotype. Also considering the lack of undesired side effects, including unaffected fertility potential, this suggests a beneficial use of NAC in endometriosis clinical treatment.

Thiol redox transitions in cell signaling: a lesson from N-acetylcysteine.

The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

Estradiol binding prevents ApoB-100 misfolding in electronegative LDL(-).

Seeking for a modified lipoprotein present in plasma that could account for the atherogenic effect of high cholesterol, several years ago electronegative LDL(-) was identified. The peculiar feature of LDL(-) is an apoprotein misfolding that triggers the formation of aggregates, perfectly fitting in size the subendothelial droplets observed in early phases of atherogenesis. Apoprotein misfolding was therefore proposed as a possible atherogenic modification. LDL(-) can be spontaneously produced in vitro by plasma incubation through phospholipid hydrolysis catalyzed by the activity of endogenous phospholipases. As a consequence, apoprotein is misfolded. 17beta-Estradiol (E2), a specific ligand to apoB-100, was used to unravel the relationship between negative charge of the lipoprotein and apoprotein structural/conformational shift. Although E2 addition to plasma does not prevent LDL(-) generation nor phospholipase activity, it deeply stabilizes apoB-100 structure, thus preventing its structural and conformational shift. Apoprotein stabilization extends to lipids. Indeed, while a loosening of lipid packing is observed together with apoprotein misfolding, conversely, when E2 stabilizes apoprotein, lipid structure is preserved. Finally, even in the presence of LDL(-), the E2-stabilized LDL is resistant to aggregation, unambiguously demonstrating that misfolding, but not negative charge, primes aggregation. In conclusion, electronegative charge and misfolding are independent and distinct features of LDL(-), and apoprotein misfolding rather than the increase in the negative charge emerges both as a valid biomarker and as an appealing pharmacological and nutritional target.

Generation in human plasma of misfolded, aggregation-prone electronegative low density lipoprotein.

Human plasma contains small amounts of a low density lipoprotein in which apoprotein is misfolded. Originally identified and isolated by means of anion-exchange chromatography, this component was subsequently described as electronegative low density lipoprotein (LDL)(-), with increased concentrations associated with elevated cardiovascular disease risk. It has been recognized recently as the trigger of LDL amyloidogenesis, which produces aggregates similar to subendothelial droplets observed in vivo in early atherogenesis. Although LDL(-) has been produced in vitro through various manipulations, the mechanisms involved in its generation in vivo remain obscure. By using a more physiological model, we demonstrate spontaneous, sustained and noticeable production of LDL(-) during incubation of unprocessed human plasma at 37 degrees C. In addition to a higher fraction of amyloidogenic LDL(-), LDL purified from incubated plasma contains an increased level of lysophospholipids and free fatty acids; analysis of LDL lipids packing shows their loosening. As a result, during plasma incubation, lipid destabilization and protein misfolding take place, and aggregation-prone particles are generated. All these phenomena can be prevented by inhibiting calcium-dependent secretory phospholipases A2. Our plasma incubation model, without removal of reaction products, effectively shows a lipid-protein interplay in LDL, where lipid destabilization after lipolysis threatens the apoprotein's structure, which misfolds and becomes aggregation-prone.

N-acetyl-l-cysteine fosters inactivation and transfer to endolysosomes of c-Src.

The non-receptor-protein tyrosine kinase c-Src is overexpressed and activated in a large number of human cancers, in which it is associated with tumor development and progression. Canonical regulation takes place by means of an alternative phosphorylation of tyrosine residues -- Tyr419 for activation and Tyr530 for inactivation. An independent redox regulation mechanism, involving cysteine residues, has also been proposed, in which oxidation activates the enzyme. Here we present a kinetic analysis of the effect of N-acetyl-l-cysteine (NAC) on c-Src, demonstrating that reduction reverts the oxidation-driven activation. In cancer cells, we show that NAC treatment produces an increase in specifically labeled reduced thiols of c-Src cysteines, thus confirming a redox transition. In addition to a decrease in Tyr419 phosphorylation, this leads to a massive shift of c-Src from plasma membranes -- where its active form is located -- to endolysosomal compartments. With the objective of deciphering the complex issue of c-Src regulation and of devising new strategies to revert its activation in cancers, redox regulation thus emerges as a promising area for study.