Anti-inflammatory effects of locally applied enzyme-loaded ultradeformable vesicles on an acute cutaneous model

Superoxide dismutase (SOD) and catalase (CAT) are active scavengers of reactive oxygen species and were incorporated into ultradeformable vesicles with the aim of increasing enzyme bioavailability (skin delivery). These special very adaptable vesicles have been formulated and optimized for enzyme transport in order to penetrate into or across the intact skin barrier. Anti-inflammatory activity of SOD-loaded, CAT-loaded and of SOD- and CAT-loaded ultradeformable vesicles applied epicutaneously was measured using different protein doses on the skin, on an arachidonic acid-induced mouse ear oedema. The biological anti-oedema activity is a measurement of drug-targeting potentiation in the organ. Delivery by means of deformable vesicles was compared to conventional vesicles or the absence of an enzyme carrier mediated transport. This was done at various times following prophylactic application of the test formulations. Positive reference groups were treated epicutaneously with several low molecular weight non-steroidal anti-inflammatory drugs (NSAIDs). The latter included indomethacin (3 mg kg(-1)), etofenamate (30 mg kg(-1)) and piroxicam (11 mg kg(-1)) and reduced the oedema by 94 +/- 4%, 81 +/- 4% and 42 +/- 5%, respectively, if measured 30 min after ear treatment with a NSAID. Of the enzyme-loaded carriers tested, only the enzyme-loaded ultradeformable vesicles reduced the swelling of ears significantly: SOD (90 mu g kg(-1)), CAT (250 mu g kg(-1)) and SOD (90 mu g kg(-1)) plus CAT (250 mu g kg(-1)) reduced the oedema by 70 +/- 12%, 65 +/- 10% and 61 +/- 19%, respectively, at t = 30 min. Aqueous enzyme solutions and empty carriers had no such effect. The combination of two enzymes resulted in no increased therapeutic effect, but the results are inconclusive since only two dose combinations were tested. The results presented in this study suggest that antioxidant enzymes delivered by means of ultradeformable lipid vesicles can serve as a novel region-specific treatment of inflammation.. - Fundacao para a Ciencia e para a Tecnologia [POCTI/1999/FCB/35787]. - Professor Gregor Cevc is acknowledged for the discussion of the results. The work was financially supported by Fundacao para a Ciencia e para a Tecnologia, project POCTI/1999/FCB/35787

Laser Phototherapy as Topical Prophylaxis Against Head and Neck Cancer Radiotherapy-Induced Oral Mucositis: Comparison Between Low and High/Low Power Lasers

Background and Objective: Oral mucositis is a dose-limiting and painful side effect of radiotherapy (RT) and/or chemotherapy in cancer patients. The purpose of the present study was to analyze the effect of different protocols of laser phototherapy (LPT) on the grade of mucositis and degree of pain in patients under RT. Patients and Methods: Thirty-nine patients were divided into three groups: G1, where the irradiations were done three times a week using low power laser; G2, where combined high and low power lasers were used three time a week; and G3, where patients received low power laser irradiation once a week. The low power LPT was done using an InGaAlP laser (660 nm/40 mW/6 J cm(-2)/0.24 J per point). In the combined protocol, the high power LPT was done using a GaAlAs laser (808 nm, 1 W/cm(2)). Oral mucositis was assessed at each LPT session in accordance to the oral-mucositis scale of the National Institute of the Cancer-Common Toxicity criteria (NIC-CTC). The patient self-assessed pain was measured by means of the visual analogue scale. Results: All protocols of LPT led to the maintenance of oral mucositis scores in the same levels until the last RT session. Moreover, LPT three times a week also maintained the pain levels. However, the patients submitted to the once a week LPT had significant pain increase; and the association of low/high LPT led to increased healing time. Conclusions: These findings are desired when dealing with oncologic patients under RT avoiding unplanned radiation treatment breaks and additional hospital costs. Lasers Surg.Med. 41:264-270,2009. (C) 2009Wiley-Liss, Inc.FAPESP (The State of Sao Paulo Research Foundation)[57578-8/2005]CNPq (The National Council of Scientific and Technological Development)[552210/2005

A pragmatic multi-center trial of goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery

Background: Intraoperative fluid therapy guided by mechanical ventilation-induced pulse-pressure variation (PPV) may improve outcomes after major surgery. We tested this hypothesis in a multi-center study. Methods: The patients were included in two periods: a first control period (control groupn = 147) in which intraoperative fluids were given according to clinical judgment. After a training period, intraoperative fluid management was titrated to maintain PPV < 10% in 109 surgical patients (PPV group). We performed 1:1 propensity score matching to ensure the groups were comparable with regard to age, weight, duration of surgery, and type of operation. The primary endpoint was postoperative hospital length of stay. Results: After matching, 84 patients remained in each group. Baseline characteristics, surgical procedure duration and physiological parameters evaluated at the start of surgery were similar between the groups. The volume of crystalloids (4500 mL [3200-6500 mL] versus 5000 mL [3750-8862 mL]P = 0.01), the number of blood units infused during the surgery (1.7 U [0.9-2.0 U] versus 2.0 U [1.7-2.6 U]P = 0.01), the fraction of patients transfused (13.1% versus 32.1%P = 0.003) and the number of patients receiving mechanical ventilation at 24 h (3.2% versus 9.7%P = 0.027) were smaller postoperatively in PPV group. Intraoperative PPV-based improved the composite outcome of postoperative complications OR 0.59 [95% CI 0.35-0.99] and reduced the postoperative hospital length of stay (8 days [6-14 days] versus 11 days [7-18 days]P = 0.01). Conclusions: In high-risk surgeries, PPV-directed volume loading improved postoperative outcomes and decreased the postoperative hospital length of stay.DIXTAL BIOMEDICA INDUSTRIA E COMERCIO LIDAUniv Sao Paulo, Fac Med, Hosp Clin, Div Anestesia, Av Eneas Carvalho de Aguiar,255 2 Andar, BR-05403900 Sao Paulo, SP, BrazilHosp Padre Albino, Catanduva Med Sch, Catanduva, SP, BrazilUniv Fed Sao Paulo, Hosp Sao Paulo, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Hosp Sao Paulo, Sao Paulo, SP, BrazilWeb of Scienc

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Symptoms of anxiety and depression in patients with persistent asthma : a cross-sectional analysis of the INSPIRERS studies

ObjectivesAnxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms.MethodsThis is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6 +/- 16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score &gt;= 8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built.ResultsAccording to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression.ConclusionAt least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies

I Diretriz Brasileira de Cardio-Oncologia da Sociedade Brasileira de Cardiologia

Inst Canc Estado Sao Paulo, BR-01246 Sao Paulo, BrazilUniv Sao Paulo, Hosp Clin, Fac Med, Inst Coracao, BR-05508 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Inst Cardiol, Sao Paulo, BrazilUniv Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Serv Cardiol, BR-90046900 Porto Alegre, RS, BrazilUniv Hosp, Brasilia, DF, BrazilHosp Procardiaco, Ctr Insuficiencia Cardiaca, Rio De Janeiro, BrazilUniv Pernambuco, Recife, PE, BrazilUniv Fed Amazonas, Fdn Ctr Oncol Amazonas, Manaus, Amazonas, BrazilMonte Tabor Hosp Sao Rafael, Salvador, BA, BrazilFdn Beneficencia Hosp & Cirurgia, Clin Coracao, Aracaju, SE, BrazilHosp Socor, Ecoctr, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Inst Cardiol, Sao Paulo, BrazilWeb of Scienc