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1.
Rheumatol Int ; 43(6): 1151-1159, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36786872

RESUMO

Biological agents are widely used for the management of systemic rheumatic diseases (SRDs) and their therapeutic implications have been expanded beyond inflammatory arthropathies to more complicated autoimmune disorders, such as systemic lupus erythematosus, vasculitis, and systemic sclerosis. The aim of this study was to investigate treatment satisfaction and overall experience of SRDs' patients receiving biologics as well as to explore patient's perspectives on the quality of services provided by rheumatology departments and to determine factors related to the level of satisfaction. We performed a synchronous correlation study. Patients with SRDs answered an anonymous questionnaire assessing their satisfaction and how treatment with biologics has affected their quality of life and functionality. Sample consisted by 244 patients (65.2% women), with mean age of 50.4 years, and the most common diagnosis was rheumatoid arthritis (37.3%). Sixty one percent of patients received intravenous therapy and 39% subcutaneously. Overall, 80.5% of the patients reported a positive/very positive effect of their treatment on their life. The average total patient satisfaction from the unit was 79.8%. The presence of mental disease was significantly associated with less positive impact of the treatment on patients' life, worse quality of life, and greater pain. In conclusion, patients with a broad spectrum of SRDs were generally satisfied and treatment with biologic regimens appeared to have a positive impact on several aspects of their life. The majority of patients were at least satisfied with all the characteristics of the unit staff and better quality of life was associated with greater satisfaction about the Unit and more positive affect of the treatment in patients' life.


Assuntos
Artrite Reumatoide , Produtos Biológicos , Doenças Reumáticas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Autorrelato , Satisfação do Paciente , Qualidade de Vida , Inquéritos e Questionários , Artrite Reumatoide/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Terapia Biológica , Produtos Biológicos/uso terapêutico , Satisfação Pessoal
2.
Medicina (Kaunas) ; 59(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37763781

RESUMO

The first few hours following thyroidectomy are the most crucial for pain management. Adequate postoperative pain control, reduction in opioid abuse and the possibility of implementing one-day operations are the considered parameters when developing the postoperative analgesic strategy. A study of the available literature was conducted, exploring the efficacy of (open) thyroidectomy wound infiltration. Seventeen full-text RCTs were extracted. Local anesthetics and non-steroidal anti-inflammatory drugs were infiltrated. Emphasis was given to postoperative pain scores and requirements for rescue analgesia with opioids. Most authors agree that local wound infiltration for thyroidectomized patients is effective in the management of postoperative pain parameters. In the era of multimodal analgesia, thyroidectomy wound infiltration could represent an essential adjunct contributing to lower VAS scores and reduced opioid requirements.

3.
Connect Tissue Res ; 63(6): 577-589, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35175165

RESUMO

PURPOSE OF THE STUDY: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA. MATERIALS AND METHODS: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis. RESULTS: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue. CONCLUSIONS: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.


Assuntos
Antirreumáticos , Artrite Experimental , Artrite Juvenil , Animais , Anticorpos Monoclonais Humanizados , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Juvenil/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Interleucina-23/uso terapêutico , Interleucina-6 , Masculino , Metotrexato/uso terapêutico , Ratos , Tendões/patologia , Fator de Necrose Tumoral alfa , Microtomografia por Raio-X
4.
Crit Care ; 25(1): 147, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863353

RESUMO

There is a large gender gap in critical care medicine with women underrepresented, particularly in positions of leadership. Yet gender diversity better reflects the current critical care community and has multiple beneficial effects at individual and societal levels. In this Viewpoint, we discuss some of the reasons for the persistent gender imbalance in critical care medicine, and suggest some possible strategies to help achieve greater equity and inclusion. An explicit and consistent focus on eliminating gender inequity is needed until gender diversity and inclusion become the norms in critical care medicine.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Equidade de Gênero , Médicas/provisão & distribuição , Cuidados Críticos/tendências , Feminino , Humanos , Médicas/tendências
5.
Inflammopharmacology ; 29(3): 661-672, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33982199

RESUMO

Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Inflamação/tratamento farmacológico , Infliximab/uso terapêutico , Tendões/efeitos dos fármacos , Animais , Antirreumáticos/farmacologia , Artrite Experimental/diagnóstico por imagem , Densidade Óssea/fisiologia , Inflamação/diagnóstico por imagem , Infliximab/farmacologia , Masculino , Ratos , Ratos Wistar , Tendões/diagnóstico por imagem , Microtomografia por Raio-X/métodos
6.
Calcif Tissue Int ; 107(2): 109-120, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32356018

RESUMO

CIA is a well-studied animal model of autoimmune arthritis. It resembles rheumatoid arthritis as far as histopathological changes and molecular pathogenesis are concerned. CIA is induced by immunization with collagen type II in susceptible strains. The purpose of this review is to assess the use of CIA animal model on bone metabolism and the potential therapeutic agents that could reverse this effect. A database search from their inception to 2019 was conducted to identify experimental animal studies pertinent to CIA model and bone examination. Studies including ovariectomy or without a direct comparison between control and CIA groups were excluded. Forty-eight articles were considered suitable for inclusion. Imaging techniques, biomechanical analysis, histopathological studies, and molecular biology techniques were employed. A decrease in bone mineral density in CII arthritic animals was established. Bone loss was either periarticular, generalized or both. Although trabecular bone loss was clear, the effect on cortical bone is yet to be determined. The proposed mechanism is an imbalance between bone formation and resorption as a result of osteoclast activation. The signal pathways implicated appear to be the RANKL/RANK/OPG and the Wnt pathway. Many therapeutic targets were investigated with promising results.


Assuntos
Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Osso e Ossos/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/induzido quimicamente , Colágeno , Modelos Animais de Doenças , Feminino , Osteoclastos , Transdução de Sinais
7.
Eur J Clin Pharmacol ; 76(2): 161-174, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31768574

RESUMO

PURPOSE: The aim of this systematic review was to evaluate current evidence on the efficacy and safety of levetiracetam as migraine prophylaxis in adult patients suffering from migraine attacks. METHODS: PubMed, Scopus, Cochrane Central Register of Controlled Trials, and International Web of Science were searched (last search in August 2018) for studies investigating levetiracetam for migraine prophylaxis in adults. Both randomized and non-randomized trials were eligible. Efficacy was the primary outcome, but tolerability was also investigated. The study is registered on PROSPERO, number CRD42018088900. RESULTS: Nine studies, enrolling 215 patients, were included. Levetiracetam decreased the frequency of attacks with headache in all studies, with a pooled mean difference of -3.02 (95% CI: -4.59 to -1.45; I2 = 0%), -4.65(-7 to -2.3; I2 = 0%), and -5.71 (-8.60 to -2.82; I2 = 0%) at 1, 3, and 6 months compared with baseline. Three randomized controlled trials were included, and levetiracetam was superior to placebo in two but was inferior to sodium valproate in reducing headache frequency. Similar results were found in the other indices of efficacy, and levetiracetam was generally well tolerated. CONCLUSION: Levetiracetam may be a relatively safe and efficacious treatment for the prophylaxis of migraine based on limited evidence, most from uncontrolled studies. Further evidence from randomized controlled trials is necessary.


Assuntos
Anticonvulsivantes/administração & dosagem , Levetiracetam/administração & dosagem , Transtornos de Enxaqueca/prevenção & controle , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Valproico/administração & dosagem
8.
Aging Clin Exp Res ; 32(9): 1821-1828, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31606859

RESUMO

BACKGROUND: Senior individuals are particularly vulnerable to influenza. Research suggests that protection against the virus and its transmission in this high-risk group of the population can be achieved by active immunization against the pathogen. AIMS: To explore and analyze the attitudes, knowledge and behavior of people over the age of 60 on influenza vaccination. POPULATION AND METHODS: This cross-sectional survey included people over the age of 60 who were eligible candidates for the influenza vaccine from 3 regions from Northern and 1 region from Southern Greece. A self-completed questionnaire based upon the Theory of Planned Behaviour, the Motivation for Vaccination (MoVac-flu) and the Vaccination Advocacy Scale (MovAd) was administered to the participants. Demographic characteristics and information about health status were also obtained. RESULTS: The final sample included 318 participants with mean age of 70.7 years. More than half of the participants (56.6%) had received a flu vaccine in 2018 while 50.8% received it annually in previous years. Behavioral (p < 0.001), normative (p < 0.001), and control beliefs (p < 0.001), promoted the uptake of the vaccine and the increased intention score (p < 0.001) was associated with increased probability of vaccination. Greater age (p = 0.001) and frequent visits to the doctors (p = 0.003) had a positive influence upon the uptake of the vaccine. CONCLUSIONS: Only a small proportion of those over the age of 60 had received the influenza vaccine. This finding is worrying, as it indicates the impact that a future outbreak of seasonal influenza could exert upon vulnerable groups. There is an urgent need for further, better and more evidence-based information from healthcare professionals to achieve greater vaccination coverage in the community.


Assuntos
Vacinas contra Influenza , Influenza Humana , Idoso , Estudos Transversais , Grécia/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Influenza Humana/prevenção & controle , Inquéritos e Questionários , Vacinação
9.
Pain Pract ; 20(5): 550-563, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32012446

RESUMO

OBJECTIVES: The aim of this systematic review and meta-analysis was to appraise clinical evidence of the impact of peritonsillar infiltration of tramadol, on postoperative pain control and the occurrence of adverse effects in children undergoing tonsillectomy. METHODS: A database search was conducted to identify randomized controlled trials (RCTs) pertinent to peritonsillar infiltration of tramadol compared to no treatment (placebo) or other analgesic regimens. The outcomes of interest were postoperative pain intensity, time to first analgesic demand, rescue analgesic consumption up to 24 hours after intervention, and the occurrence of adverse events. RESULTS: Twelve RCTs enrolling 972 pediatric patients were selected for qualitative analysis, among which eight were suitable for meta-analysis. Tramadol infiltration induced a significant reduction of pain intensity up to 24 hours post-tonsillectomy (mean difference [MD], -2.31; 95% confidence interval [CI], -3.49 to -1.12; P < 0.001; I2  = 97%) and time to first analgesic (MD 180.54; 95% CI, 56.91 to 304.18; P = 0.004; I2  = 99%), with no profound impact on postoperative nausea and vomiting (risk ratio [RR] 0.98; 95% CI, 0.73 to 1.32; P = 0.90; I2  = 0%) compared to the placebo group. The analgesic efficacy of tramadol infiltration was equivalent to the local or systematic use of ketamine or infiltration with local anesthetics. This effect was further enhanced when tramadol infiltration served as an adjunct to other analgesic interventions. No serious adverse events were reported. CONCLUSIONS: In children undergoing tonsillectomy, peritonsillar infiltration of tramadol is associated with a postoperative analgesic benefit when compared to placebo, with negligible adverse events. Yet, no definite conclusion can be drawn due to the low quality, considerable heterogeneity, and paucity of the available data.


Assuntos
Analgésicos Opioides/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Tonsilectomia/efeitos adversos , Tramadol/administração & dosagem , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Nutr Cancer ; 71(3): 491-507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30273051

RESUMO

Crocus sativus L., a dietary herb, has been used for various diseases including cancer. This is an in vitro study investigating the antineoplastic effect of the extract of the plant against C6 glioma rat cell line. The mechanism of cellular death and the synergistic effect of the extract with the alkylating agent temozolomide (TMZ) were investigated. Cellular viability was examined in various concentrations of the extract alone or in combination with TMZ. Apoptosis was determined with flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and autophagy by western blotting of the light chain 3 (LC3)-II. Cellular viability was reduced after exposure to the extract with half maximal inhibition concentration at 3 mg/ml. Flow cytometry and TUNEL assay suggested that the extract does not induce apoptosis. Moreover, their combination increased the ratio dead/apoptotic cells 10-fold (P < 0.001). LC3-II protein levels reduced after Crocus extract while this effect was reversed when the calpain inhibitor MDL28170 was added, suggesting a calpain-dependent death possibly through autophagy. We concluded that the extract of Crocus increases dead cell number after 48 h of exposure. Our results suggest that the cell undergoes calpain-dependent programmed cell death while co-exposure to Crocus extract and TMZ enhances the antineoplastic effect of the latter.


Assuntos
Calpaína/fisiologia , Morte Celular/efeitos dos fármacos , Crocus/química , Glioma/patologia , Extratos Vegetais/farmacologia , Temozolomida/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Calpaína/antagonistas & inibidores , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Sinergismo Farmacológico , Glioma/tratamento farmacológico , Marcação In Situ das Extremidades Cortadas , Ratos
11.
Eur J Clin Pharmacol ; 74(11): 1377-1389, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30008121

RESUMO

PURPOSE: This systematic review and meta-analysis appraise the clinical evidence on efficacy and safety of dexmedetomidine (DEX), as a sedative and analgesic adjunct in adult patients undergoing spine surgery. METHODS: A database search was conducted to identify randomized clinical trials (RCTs) pertinent to the perioperative use of DEX in spine surgery. Sedative and analgesic efficacy of DEX constituted the primary outcomes, whilst the incidence of hemodynamic changes, quality of recovery and occurrence of adverse events served as secondary ones. RESULTS: Fifteen studies enrolling a total of 913 patients were selected for qualitative analysis, among which eight RCTs incorporating a placebo comparison group were included in the meta-analysis. Most of the retrieved studies were of moderate to good quality and demonstrated an acceptable risk of bias. DEX-treated patients showed a significant reduction of both propofol [mean difference (MD), -214.47 mg; 95%CI, -253.16 to -175.78; P < 0.001] and morphine equivalents consumption both intraoperatively and postoperatively (MD, -2.69; 95% CI, -3.05 to -2.33; P < 0.001 and MD, -4.36 mg; 95%CI, -6.93 to -1.79; P < 0.001, respectively) compared to those assigned to placebo. Postoperative nausea and vomiting incidence were comparable between DEX and placebo groups, whilst other adverse events were not consistently reported. CONCLUSIONS: DEX emerges as an attractive alternative to standard sedative and analgesic modalities applied in spine surgery, by attaining a notable sedative and opioid-sparing effect, which goes with an enhanced safety profile. Yet, no definite conclusion can be drawn due to the considerable heterogeneity of available data. TRIAL REGISTRATION: PROSPERO CRD42015029537.


Assuntos
Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Coluna Vertebral/cirurgia , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Dexmedetomidina/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Assistência Perioperatória/métodos , Náusea e Vômito Pós-Operatórios , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Subst Use Misuse ; 53(1): 77-85, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-28777681

RESUMO

BACKGROUND: Non-medical use of prescription medications has risen to unprecedented levels over the past decade worldwide; however, studies assessing misuse across medical students are sparse. OBJECTIVES: The purpose of this study was to1) estimate the lifetime and the past-year prevalence of non-medical use of prescription medications among medical students in Greece 2) identify the motivation for use. METHODS: 591 medical students completed an anonymous, self-administered, web-based survey assessing lifetime and past-year prevalence of non-medical use of four classes of prescription drugs (opioid painkillers, tranquillizers, sleeping and stimulant medications). According to the motivation to use the responders were classified into three subtypes (selftreatment, recreational, and mixed). RESULTS: The prevalence of lifetime use was 10.7% for at least one of the four prescription drug classes and 9% of the respondents reported lifetime misuse of multiple categories of prescription drugs. The past-year prevalence was approximately 7.7% for at least one of the four prescription drug classes, while the majority misused the drugs "1-2 times per year". Senior students used tranquilizers more than junior students. Self-treatment and mixed subtypes of tranquillizers misuse was more prevalent among women than men while the self-treatment subtype was the most prevalent subtype in all the four drug classes. CONCLUSIONS: This is the first study investigating non-medical use of prescription medications among Greek medical students and indicates a high prevalence of misuse of some categories of prescription drugs, mostly for self-treatment purposes.


Assuntos
Motivação , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Estudantes de Medicina/psicologia , Adolescente , Adulto , Analgésicos Opioides , Estimulantes do Sistema Nervoso Central , Feminino , Grécia , Humanos , Hipnóticos e Sedativos , Masculino , Prevalência , Tranquilizantes , Adulto Jovem
13.
J Perianesth Nurs ; 33(2): 129-137, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29580592

RESUMO

PURPOSE: To assess the comparable applicability of four methods of endotracheal tube cuff (ETTc) inflation on the basis of optimal level of intracuff pressure and presence of intubation-related complications. DESIGN: Double-blind, randomized trial. METHODS: A total of 139 adult surgical patients scheduled to undergo nitrous oxide-free general anesthesia were assigned into one of four groups according to the method used for ETTc inflation. The cuff pressure and air volume applied in each method, and laryngotracheal complications were recorded. FINDINGS: The highest and lowest ETTc pressure and air volume values were recorded in palpation and minimum leak technique group, respectively. Laryngotracheal complaints were maximized in palpation and minimized in minimal occlusive volume and minimum leak techniques. CONCLUSIONS: The air-return back into the syringe method emerges as an attractive and simple-to-perform alternative regarding effective ETTc sealing and low incidence of intubation-related morbidity when a cuff manometer is not readily available. STUDY REGISTRATION: ACTRN12615000699561.


Assuntos
Anestesia Geral/instrumentação , Intubação Intratraqueal/instrumentação , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Laringe , Masculino , Pessoa de Meia-Idade , Palpação , Pressão , Traqueia
14.
Curr Opin Anaesthesiol ; 30(5): 534-539, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28692438

RESUMO

PURPOSE OF REVIEW: This review reports an update of the evidence on practices applied for the prevention and management of the most common complications after craniotomy surgery. RECENT FINDINGS: Latest guidelines support the combined thromboprophylaxis with the use of both mechanical and chemical modalities, preferably applied within 24 h after craniotomy. Nevertheless, a heightened risk of minor hemorrhagic events remains an issue of concern. Postoperative nausea and vomiting (PONV) and pain constitute the complications most commonly encountered during the first 24 h postcraniotomy. Recently, neurokinin type-1 receptor antagonists have been tested as adjuncts for PONV prophylaxis with encouraging results, whereas dexmedetomidine and gabapentinoids emerge as promising alternatives for postcraniotomy pain management. The available data for seizure prophylaxis following craniotomy lacks scientific quality; thus, this remains still a debatable issue. Significantly, a growing body of evidence supports the superiority of levetiracetam over the older antiepileptic drugs (AEDs), in terms of efficacy and safety. SUMMARY: Optimum management of postoperative complications is incorporated as an integral part of the augmented quality of care in patients undergoing craniotomy surgery, aiming to improve outcomes. This review may serve as a benchmark for neuroanesthetists for heightened clinical awareness and prompt institution of well-documented practices.


Assuntos
Craniotomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Humanos , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Convulsões/prevenção & controle , Tromboembolia Venosa/prevenção & controle
15.
Cell Mol Neurobiol ; 36(5): 701-12, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26239244

RESUMO

Hypoxia is the lack of sufficient oxygenation of tissue, imposing severe stress upon cells. It is a major feature of many pathological conditions such as stroke, traumatic brain injury, cerebral hemorrhage, perinatal asphyxia and can lead to cell death due to energy depletion and increased free radical generation. The present study investigates the effect of hypoxia on the unfolded protein response of the cell (UPR), utilizing a 16-h oxygen-glucose deprivation protocol (OGD) in a PC12 cell line model. Expression of glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94), key players of the UPR, was studied along with the expression of glucose-regulated protein 75 (GRP75), heat shock cognate 70 (HSC70), and glyceraldehyde 3-phosphate dehydrogenase, all with respect to the cell death mechanism(s). Cells subjected to OGD displayed upregulation of GRP78 and GRP94 and concurrent downregulation of GRP75. These findings were accompanied with minimal apoptotic cell death and induction of autophagy. The above observation warrants further investigation to elucidate whether autophagy acts as a pro-survival mechanism that upon severe and prolonged hypoxia acts as a concerted cell response leading to cell death. In our OGD model, hypoxia modulates UPR and induces autophagy.


Assuntos
Autofagia/fisiologia , Glucose/metabolismo , Oxigênio/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular , Sobrevivência Celular , Chaperona BiP do Retículo Endoplasmático , Neurônios/metabolismo , Células PC12 , Ratos
16.
Nitric Oxide ; 61: 62-68, 2016 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-27771417

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) has been associated with major perioperative morbidities or mortalities, especially in surgical patients receiving general anesthesia. The severity of the COPD and the degree of bronchial hyperreactivity can determine the perioperative anesthetic risk; therefore they have to be assessed by a thorough preoperative evaluation in order to give the rationale on which to decide for optimum anesthetic management. OBJECTIVE: Aim of the study was to assess the predictive applicability of exhaled Nitric Oxide (NO) in smoking surgical population with COPD, on the basis of morbidity and mortality. METHODS: A prospective, observational study was undertaken in 70 smoking patients diagnosed with COPD scheduled for laparotomy surgery under general anesthesia COPD was evaluated with the GOLD Classification of Air Flow Limitation, the Modified MRC Dyspnoea Scale (mMRC), the BODE Index score and the 6 Minutes Walk Distance (6MWD) using spirometry parameters. All patients were observed for presenting perioperative and postoperative respiratory complications. A cut off value of 19 ppb was determined for fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (FENO50) to differentiate patients poor prognosis from those with favorable outcome. RESULTS: Patients with severe COPD had high BODE index score as well as FENO50. Elevated FENO50 is significantly related to multiple complications (p = 0.004) and postoperative cough (p < 0.001). Patients from the high FENO50 group that were not treated with steroids had a statistically significant higher incidence of extra hospital care need (p < 0.001). Increased FENO50 and ABCD classification are both related with the presentation of multiple complications (Odds ratio = 2.5, 95% CI 1.1 to 5.7, p = 0.028 for ABCD and Odds ratio = 6.39, 95% CI 1.33 to 30.5, p = 0.020 for FENO50). Increased FENO50 and ABCD are related with extra hospital care (p = 0.001 and p = 0.002 respectively) and combined with corticosteroid administration could predict the necessity for extra hospital care (Odds ratio 4.09, 95% CI 1.1 to 15.3, p = 0.036 for corticosteroid treatment, odds ratio 2.4, 95% CI 1.1 to 5.1, p = 0.029 for ABCD and odds ratio 7.93, 95% CI 1.7 to 35.3, p = 0.007 for FENO50). CONCLUSION: The FENO50 may identify high risk smoking surgical patients with COPD receiving general anesthesia. Perioperative and postoperative complications in COPD smoking patients undergoing abdominal surgery can be predicted using not only ABCD GOLD 2011 classification but also the FENO50 as a preoperative marker.


Assuntos
Laparotomia/estatística & dados numéricos , Óxido Nítrico/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Abdome/cirurgia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Testes Respiratórios , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos
17.
Br J Clin Pharmacol ; 82(1): 315-25, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26945547

RESUMO

AIMS: The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. METHOD: A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. RESULTS: The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%). CONCLUSIONS: The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.


Assuntos
Anticonvulsivantes/uso terapêutico , Piracetam/análogos & derivados , Convulsões/prevenção & controle , Anticonvulsivantes/efeitos adversos , Craniotomia/métodos , Humanos , Levetiracetam , Assistência Perioperatória , Fenitoína/efeitos adversos , Fenitoína/uso terapêutico , Piracetam/efeitos adversos , Piracetam/uso terapêutico , Convulsões/etiologia , Neoplasias Supratentoriais/cirurgia , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico
18.
J Anesth ; 30(3): 522-5, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26882921

RESUMO

The aim of this randomized, double-blind clinical trial was to elucidate the impact of general anesthesia alone (GA) or supplemented with epidural anesthesia (EpiGA) on surgical stress response during laparoscopic cholecystectomy, using stress hormones, glucose, and C-reactive protein (CRP), as potential markers. Sixty-two patients scheduled to undergo elective laparoscopic cholecystectomy were randomly assigned into two groups to receive either GA or EpiGA. Stress hormones [cortisol (COR), human growth hormone (hGH), prolactine (PRL)], glucose, and CRP were determined 1 day before surgery, intraoperatively, and upon first postoperative day (POD1). Plasma COR, hGH, PRL, and glucose levels were maximized intraoperatively in GA and EpiGA groups and reverted almost to baseline on POD1. Significant between-group differences were detected for COR and glucose either intraoperatively or postoperatively, but this was not the case for hGH. PRL was elevated in GA group only intraoperatively. Although, CRP was minimally affected intraoperatively, a notable augmentation on POD1, comparable in both groups, was recorded. These results indicate that hormonal and metabolic stress response is slightly modulated by the use of epidural block supplemented by general anesthesia, in patients undergoing laparoscopic cholecystectomy cholecystectomy. Nevertheless, inflammatory reaction as assessed by CRP seems to be unaffected by the anesthesia regimen.


Assuntos
Anestesia Epidural/métodos , Anestésicos/administração & dosagem , Colecistectomia Laparoscópica/métodos , Estresse Fisiológico/fisiologia , Adulto , Anestesia Geral/métodos , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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