RESUMO
Aim: In this study, we aimed to investigate the efficacy of a helicopter emergency medical service (HEMS) facilitated pathway for in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) for patients with an out of hospital cardiac arrest (OHCA) in a semi-rural setting. Methods: We retrospectively reviewed all patients with an OHCA attended by a UK HEMS service between 1 January 2018 and 20 September 2021, when a dedicated ECPR pathway was in effect to facilitate transport of eligible patients to the nearest ECLS centre. The primary endpoint was the number of patients meeting ECPR eligibility criteria at three pre-defined time points: at HEMS dispatch, during on-scene evaluation and upon arrival in hospital. Results: During the study period, 162 patients attended met ECPR pathway dispatch criteria. After on-scene evaluation, 74 patients (45%) had a return of spontaneously circulation before arrival of HEMS, 60 (37%) did not meet eligibility criteria regarding initial rhythm or etiology of the OHCA, and 15 (9%) had deteriorated (mainly into asystole) and were no longer suitable candidates upon arrival of HEMS. Eleven patients were eligible for ECPR and transported to hospital in arrest, and a further two patients were transported for post-ROSC ECLS. Nine patients deteriorated during transport and were no longer suitable ECPR candidates upon arrival. ECLS was successfully initiated in two patients (one intra-arrest, and one post-ROSC). Conclusion: In-hospital ECPR is of limited value for patients with refractory OHCA in a semi-rural setting, even when a dedicated pathway is in place. Potentially eligible patients often cannot be transported within an appropriate timeframe and/or deteriorate before arrival in hospital.
RESUMO
The primary objective of this study was to evaluate the long-term effects of variables that could be measured early in life on first lactation milk production. The secondary objective was to evaluate the long-term effects of treatment for bovine respiratory disease (BRD), within the first 120 days of life, on survivability to 850 days and reproductive success. Data from Holstein heifer calves was collected from 1 October, 2015-31 January, 2020 and included milk consumption (MC; n = 10,431), bodyweight (BW; n = 9,825), average daily gain (ADG; n = 6,194), heifer conception age (n = 10,112), and 305-day first lactation milk production (305 M; n = 5,823), and treatment records for BRD (n = 12,485). Calves were fed pasteurized whole milk through an automated calf feeding system for 60 days (range, 48 - 126 days), with a 30% crude protein (CP) and 5% crude fat enhancer added at 20 g/L milk. Calves were weighed at birth, weaning, and several other times prior to 2 years of age. Daily BW were predicted for individual animals using a third order orthogonal polynomial to model individual BW regressions. Daily BW predictions were used to calculate ADG and BW predictions on specific days of interest. Season born, ADG (0-400 days), milk production potential, and heifer conception age had a significant impact on 305-day first lactation milk production (all P ≤ 0.05; r2 = 0.31). A retrospective cohort study was conducted utilizing data collected from a commercial farm with cohorts defined by BRD status. Calves treated for BRD from 61 to 120 days old had a significantly lower chance of survival to 850 days of age than animals not treated for BRD. Additionally, calves treated for BRD from 61 to 120 days old had reduced risk of pregnancy. The results show the impact of early life on future milk production, survivability, and pregnancy risk on a commercial dairy herd.
Assuntos
Doenças dos Bovinos , Leite , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Colostro , Dieta/veterinária , Feminino , Humanos , Lactação , Gravidez , Estudos Retrospectivos , DesmameAssuntos
Cianose/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Fíbula/diagnóstico por imagem , Osteonecrose/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Atresia Tricúspide/diagnóstico por imagem , Adulto , Cianose/complicações , Cianose/terapia , Humanos , Masculino , Osteonecrose/etiologia , Osteonecrose/terapia , Radiografia , Atresia Tricúspide/complicações , Atresia Tricúspide/terapiaRESUMO
Laboratory studies were conducted to determine the sublethal effects of exposure to selected larvicides on the critical swimming speed (Ucrit) of crimson-spotted rainbowfish, Melanotaenia duboulayi (Castlenau). This native fish is common throughout southeastern Queensland, and it is increasingly being distributed as a biological control agent of mosquitoes. The selected larvicides included, two organophosphate (OP) compounds (temephos and pirimiphos-methyl), two microbial larvicides (Bacillus thuringiensis spp. israelensis [Bti] de Barjac and Bacillus sphaericus [Bs] Neide), and an insect growth regulator (IGR) (s-methoprene). Exposure to the OP temephos at 10 times the effective field concentration (EFC; 0.33 mg/liter), and OP pirimiphos-methyl at the EFC (0.50 mg/liter), resulted in a significant reduction in the Ucrit of M. duboulayi under controlled conditions. Conversely, exposure to the microbial (Bti and Bs) and IGR (s-methoprene) larvicides at 10 times the EFC had no effect on the Ucrit of M. duboulayi. Accordingly, these products are suitable for integrated pest management programs in Australia.
Assuntos
Culicidae , Peixes/fisiologia , Inseticidas/toxicidade , Compostos Organotiofosforados/toxicidade , Natação/fisiologia , Temefós/toxicidade , Animais , Relação Dose-Resposta a Droga , Larva/efeitos dos fármacos , Metoprene/toxicidadeRESUMO
BACKGROUND: It has been shown that exposure in intense exposure in swine barn facilities is associated with increased respiratory symptoms and reduction in pulmonary functions. This study investigated if systemic response could be predicted by FEV(1) response following swine barn exposure. METHODS: Naïve males were tested at baseline, low and high endotoxin and dust levels. Subjects were classified as "more responsive" (n = 9) or "less responsive" (n = 11) based on FEV(1) reduction following high endotoxin exposure. Health measures included pulmonary function testing, blood samples and nasal lavage. Environmental samples were collected from the barn. RESULTS: White blood cells and blood lymphocytes at low exposure were significantly greater in those who were "more responsive" compared to those who were "less responsive". There was a significant increase in blood lymphocytes, serum IL6, total nasal lavage cells and nasal IL8 at high exposure among "more responsive" subjects compared to "less responsive" subjects. CONCLUSIONS: Respiratory response to high-level endotoxin and dust exposure predicts evidence of inflammatory response throughout a range of endotoxin and dust exposures.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poeira/análise , Endotoxinas/efeitos adversos , Abrigo para Animais , Hipersensibilidade/epidemiologia , Exposição Ocupacional/efeitos adversos , Doenças Respiratórias/epidemiologia , Suínos , Adolescente , Adulto , Poluentes Ocupacionais do Ar/análise , Criação de Animais Domésticos , Animais , Biomarcadores/análise , Estudos Cross-Over , Endotoxinas/análise , Humanos , Hipersensibilidade/imunologia , Interleucina-6/análise , Interleucina-8/análise , Masculino , Exposição Ocupacional/análise , Testes de Função Respiratória , Doenças Respiratórias/imunologia , Estatísticas não ParamétricasRESUMO
AIMS: Endothelin-1 (ET-1) promotes endothelial cell growth. Endothelial cell proliferation involves the activation of Ca2+-activated K+ channels. In this study, we investigated whether Ca2+-activated K+ channels with big conductance (BK(Ca)) contribute to endothelial cell proliferation induced by ET-1. METHODS: The patch-clamp technique was used to analyse BK(Ca) activity in endothelial cells derived from human umbilical cord veins (HUVEC). Endothelial proliferation was examined using cell counts and measuring [3H]-thymidine incorporation. Changes of intracellular Ca2+ levels were examined using fura-2 fluorescence imaging. RESULTS: Characteristic BK(Ca) were identified in cultured HUVEC. Continuous perfusion of HUVEC with 10 nmol L(-1) ET-1 caused a significant increase of BK(Ca) open-state probability (n = 14; P < 0.05; cell-attached patches). The ET(B)-receptor antagonist (BQ-788, 1 micromol L(-1)) blocked this effect. Stimulation with Et-1 (10 nmol L(-1)) significantly increased cell growth by 69% (n = 12; P < 0.05). In contrast, the combination of ET-1 (10 nmol L(-1)) and the highly specific BK(Ca) blocker iberiotoxin (IBX; 100 nmol L(-1)) did not cause a significant increase in endothelial cell growth. Ca2+ dependency of ET-1-induced proliferation was tested using the intracellular Ca2+-chelator BAPTA (10 micromol L(-1)). BAPTA abolished ET-1 induced proliferation (n = 12; P < 0.01). In addition, ET-1-induced HUVEC growth was significantly reduced, if cells were kept in a Ca2+-reduced solution (0.3 mmol L(-1)), or by the application of 2 aminoethoxdiphenyl borate (100 micromol L(-1)) which blocks hyperpolarization-induced Ca2+ entry (n = 12; P < 0.05). CONCLUSION: Activation of BK(Ca) by ET-1 requires ET(B)-receptor activation and induces a capacitative Ca2+ influx which plays an important role in ET-1-mediated endothelial cell proliferation.
Assuntos
Ácido Egtázico/análogos & derivados , Células Endoteliais/fisiologia , Endotelina-1/fisiologia , Canais de Potássio Cálcio-Ativados/fisiologia , Cálcio/metabolismo , Cálcio/fisiologia , Contagem de Células , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Células Cultivadas , Quelantes/farmacologia , Meios de Cultura , Relação Dose-Resposta a Droga , Ácido Egtázico/farmacologia , Condutividade Elétrica , Células Endoteliais/efeitos dos fármacos , Antagonistas do Receptor de Endotelina B , Humanos , Potenciais da Membrana/fisiologia , Oligopeptídeos , Peptídeos/farmacologia , Piperidinas , Canais de Potássio Cálcio-Ativados/antagonistas & inibidoresAssuntos
Araceae/efeitos dos fármacos , Arsênio/farmacologia , Cádmio/farmacologia , Mercúrio/farmacologia , Poaceae/efeitos dos fármacos , Raphanus/efeitos dos fármacos , Poluentes do Solo/farmacologia , Araceae/crescimento & desenvolvimento , Araceae/metabolismo , Combinação de Medicamentos , Poaceae/crescimento & desenvolvimento , Poaceae/metabolismo , Raphanus/crescimento & desenvolvimento , Raphanus/metabolismoRESUMO
We have previously shown that vitamin C supplementation affects recovery from an unaccustomed bout of demanding exercise, with the most pronounced effect being that on plasma interleukin-6 concentration. However, because of the proposed role of interleukin-6 in the regulation of metabolism, it was unclear whether this represented a reduced response to muscle damage or some form of interaction with the metabolic demands of the activity. Therefore, the aim of the present study was to investigate the effect of the same form of supplementation on a bout of exercise that initiated similar muscle damage but had a low metabolic cost. Fourteen male subjects were allocated to either a placebo (P) or a vitamin C (VC) group. The VC group consumed 200 mg of ascorbic acid twice a day for 14 days prior to a bout of exercise and for the 3 days after exercise. The P group consumed identical capsules that contained 200 mg lactose. Subjects performed 30 min of downhill running at a gradient of -18% and recovery was monitored for up to 3 days after exercise. Plasma VC concentrations in the VC group increased following supplementation. Nevertheless, downhill running provoked a similar increase in circulating markers of muscle damage (creatine kinase activity and myoglobin concentration) and muscle soreness in P and VC groups. Similarly, although downhill running increased plasma interleukin-6, there was no effect from VC supplementation. These results suggest that vitamin C supplementation does not affect interleukin-6 concentrations following eccentric exercise that has a low metabolic component.
Assuntos
Ácido Ascórbico/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Exercício Físico , Interleucina-6/sangue , Músculo Esquelético/fisiopatologia , Dor/induzido quimicamente , Dor/fisiopatologia , Adulto , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Creatina Quinase/sangue , Método Duplo-Cego , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Mioglobina/sangue , Miosite/induzido quimicamente , Miosite/fisiopatologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologiaRESUMO
Physical stress induced in healthy volunteers by the Loughborough intermittent shuttle test (LIST) was used to validate a newly developed whole-blood cell culture system (Instant leukocyte culture system (ILCS). Exercise induced immune modulation was investigated through measurement of cytokine levels after activating leukocytes in peripheral blood ex vivo using the physiologic stimulant lipopolysaccharide (LPS). LPS induced production of three different cytokines, interferon gamma (IFNgamma), interleukin-6 (IL-6), and interleukin-10 (IL-10). IFNgamma levels were significantly decreased (P = 0.02 and P = 0.001 ) and IL-10 levels significantly increased (P= 0.04 and 0.03) after exercise. LPS induced IL-6 production was only marginally further increased by exercise. In conclusion, the ILCS system provided a reliable ex vivo method, showing common as well as subject specific features in the time course of the immune modulation caused by the LIST protocol. This system will be useful for studies of the elderly, where cytokine standardisation is notoriously difficult.
Assuntos
Coleta de Amostras Sanguíneas/métodos , Exercício Físico/fisiologia , Leucócitos/imunologia , Coleta de Amostras Sanguíneas/normas , Técnicas de Cultura de Células/métodos , Técnicas de Cultura de Células/normas , Citocinas/biossíntese , Teste de Esforço/métodos , Humanos , Lipopolissacarídeos/imunologia , Masculino , Estresse Fisiológico/imunologiaRESUMO
It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P<0.0001) and soluble intercellular adhesion molecule-1 (P<0.0001) in the elderly group. The anti-inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-beta levels were significantly (P<0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population.
Assuntos
Envelhecimento/imunologia , Citocinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Nível de Saúde , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Solubilidade , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta1RESUMO
STUDY OBJECTIVES: Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method. DESIGN: Retrospective chart review. SETTING: Tertiary-care university clinical pulmonary function laboratory. PATIENTS: One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge. INTERVENTION: Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures. MEASUREMENTS AND RESULTS: There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up. CONCLUSIONS: The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.
Assuntos
Asma/diagnóstico , Testes de Provocação Brônquica/métodos , Cloreto de Metacolina , Adolescente , Adulto , Idoso , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
OBJECTIVES: Heart function is variably impaired after cardiopulmonary bypass. We hypothesized that, similar to other myocardial injury states, cardiopulmonary bypass leads to enhanced activity of nitric oxide synthase and matrix metalloproteinases. METHODS: We obtained right atrial biopsy specimens and plasma samples at the onset and termination of cardiopulmonary bypass in 10 patients. Biopsy specimens were analyzed for nitric oxide synthase activity by using a citrulline assay, whereas plasma and tissue were analyzed for matrix metalloproteinase-9 and matrix metalloproteinase-2 activity by using zymography. Tissue inhibitor of metalloproteinase-4 was analyzed by means of Western blotting. The cellular expression of inducible nitric oxide, endothelial nitric oxide synthase, matrix metalloproteinase-2, and matrix metalloproteinase-9 was determined in right atrial biopsy samples from 3 additional patients by using the appropriate conjugated antibodies. RESULTS: Nitric oxide synthase activity increased from the beginning to the end of bypass (4.46 +/- 1.07 vs 16.77 +/- 4.86 pmol citrulline/mg of protein per minute, respectively; P =.018). Pro-matrix metalloproteinase-9 activity increased in hearts (199 +/- 41 vs 660 +/- 177 density units/mg protein; P =.008) and plasma (14.1 +/- 4.6 vs 52.2 +/- 5.9 density units/mg protein; P =.008). Pro-matrix metalloproteinase-2 activity increased in the heart (201 +/- 23 vs 310 +/- 35 density units/mg protein, P <.05) but not in plasma. Tissue inhibitor of metalloproteinase-4 expression in the heart decreased (1574 +/- 280 vs 864 +/- 153 density units, P =.014). CONCLUSIONS: Cardiopulmonary bypass activates enzymes mediating acute inflammation and organ injury (ie, nitric oxide synthase, matrix metalloproteinase-9, and matrix metalloproteinase-2). Decreased tissue inhibitor of metalloproteinase-4 expression allows relatively unopposed increases in matrix metalloproteinase tissue activity. We postulate that these changes play a role in the pathogenesis of heart dysfunction after bypass surgery.
Assuntos
Ponte de Artéria Coronária , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Miocárdio/enzimologia , Óxido Nítrico Sintase/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-IdadeRESUMO
Inappropriate shock therapy is a frequent problem in patients with implantable cardioverter-defibrillators (ICDs), caused mostly by supraventricular rhythms. Self-terminating ventricular arrhythmias (STVAs), however, may also lead to inappropriate shock discharges even in ICDs with abortive shock capabilities. The aim of this study was to evaluate the clinical performance of a specific ventricular tachycardia/ventricular fibrillation (VT/VF) reconfirmation algorithm implemented in current ICD devices from Medtronic to prevent inappropriate shock discharges due to STVAs. A total of 161 STVA episodes were documented in 59 of 150 patients (39%) within a mean follow-up of 30 +/- 20 months and resulted in 25 inappropriate shock discharges in 15 of 150 patients (10%) despite activation of the reconfirmation algorithm. The first synchronization interval of the algorithm was met in 92% of STVA episodes with and even 38% of STVA episodes without shock delivery. A reduced incidence of inappropriate shocks due to STVAs was found with tachycardia/fibrillation detection intervals (TDI/FDI) programmed to shorter cycle lengths < or =280 ms or the use of the first 2 cycles after the end of charging to be considered for reconfirmation only. Thus, inappropriate shocks due to STVAs still occur in 10% of patients with ICDs despite activation of a specific VT/VF reconfirmation algorithm, and are mainly caused by meeting the first synchronization interval that therefore should be shortened in cycle length. Moreover, to reduce the likelihood of inappropriate shocks, the VF reconfirmation algorithm should be optimized by basing the synchronization intervals exclusively on the FDI with short cycle lengths or using the first 2 cycles for reconfirmation only.
Assuntos
Algoritmos , Desfibriladores Implantáveis , Taquicardia Ventricular/terapia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não ParamétricasRESUMO
BACKGROUND: Pleural tuberculosis can resolve spontaneously, suggesting that the inflammatory process may represent a protective immune response. However, pleural tuberculosis is strongly associated with HIV infection. It has been suggested that cell-mediated immune responses may be reduced, and direct bacterial invasion may have a role in pathogenesis, in HIV-positive cases. To test this hypothesis, we compared production of the pro-inflammatory cytokines, interferon (IFN)-gamma and tumour necrosis factor(TNF)-alpha, production of the immunosuppressive cytokine, interleukin (IL)-10, and mycobacterial culture positivity, in HIV-negative and HIV-positive patients with pleural tuberculosis. METHODS: Cytokine levels were measured in serum and pleural fluid, and in supernatants of blood and pleural fluid stimulated in vitro using mycobacterial antigens. Intracellular IFN-gamma and TNF-alpha production was measured after stimulation with phorbol myristate acetate and ionomycin in vitro. RESULTS: IFN-gamma was strikingly elevated in serum and pleural fluid in HIV-positive, compared to HIV-negative subjects (P < or = 0.02). TNF-alpha was elevated, but this was not statistically significant. IL-10 levels were higher in serum (P < 0.001), but similar in pleural fluid. IFN-gamma responses to soluble mycobacterial antigen in vitro were reduced in peripheral blood (P = 0.006), but not pleural fluid, of HIV-positive subjects. Intracellular cytokine staining suggested that CD8+ T cells were a major source of IFN-gamma in HIV-positive subjects. The proportion of subjects with a positive culture for Mycobacterium tuberculosis from pleural fluid was higher in the HIV-positive group. CONCLUSIONS: HIV-positive patients with pleural tuberculosis show elevated production of IFN-gamma, for which CD8+ T cells may be a major source. Mycobacterium tuberculosis can proliferate despite high levels of pro-inflammatory cytokines.
Assuntos
Infecções por HIV/imunologia , Soronegatividade para HIV/imunologia , Soropositividade para HIV/imunologia , Interleucina-18/biossíntese , Mycobacterium tuberculosis/imunologia , Tuberculose Pleural/imunologia , Adulto , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Feminino , Infecções por HIV/complicações , Soropositividade para HIV/complicações , HIV-1 , Humanos , Interleucina-10/biossíntese , Masculino , Subpopulações de Linfócitos T/classificação , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Whether acute and direct percutaneous transluminal coronary angioplasty improves the incidence of nonsustained ventricular tachycardia in patients surviving acute myocardial infarction is not known. In 400 consecutively studied patients, Lown classification IVb on Holter monitoring was only associated with arrhythmia morbidity, whereas reduced ejection fraction was related to total and cardiac mortality and arrhythmia morbidity.
Assuntos
Angioplastia Coronária com Balão , Eletrocardiografia Ambulatorial , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Taquicardia Ventricular/diagnóstico , Angiografia Coronária , Interpretação Estatística de Dados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Taquicardia Ventricular/etiologia , Resultado do TratamentoRESUMO
Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.
Assuntos
Moléculas de Adesão Celular/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Eicosanoicos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Inflamação/sangue , Idoso , Ácido Araquidônico/farmacologia , Moléculas de Adesão Celular/sangue , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Ácidos Graxos/sangue , Ácidos Graxos/química , Ácidos Graxos Ômega-6 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fagocitose/efeitos dos fármacos , Fosfolipídeos/sangue , Fosfolipídeos/química , Explosão Respiratória , Ácido alfa-Linolênico/farmacologia , Ácido gama-Linolênico/farmacologiaRESUMO
Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. Male subjects <40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males >55 years of age (both P<0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P=0.073). Subgroups of 16 males aged <40 years and 12 elderly subjects (>55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.
Assuntos
Envelhecimento/sangue , Moléculas de Adesão Celular/sangue , Gorduras Insaturadas na Dieta/farmacologia , Óleos de Peixe/farmacologia , Adulto , Idoso , Método Duplo-Cego , Selectina E/sangue , Ácido Eicosapentaenoico/sangue , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Solubilidade , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
BACKGROUND: Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen tension and pulse oximetry. OBJECTIVES: To assess the value of the monitoring of finger pulse oximetry during routine methacholine challenges in a clinical pulmonary function laboratory with regard to both safety and the possibility that a significant fall in oxygen saturation as measured by pulse oximetry (SpO(2)) might be a useful surrogate for determining the response to methacholine. METHODS: Two hundred consecutive patients undergoing diagnostic methacholine challenges in the pulmonary function laboratory of a tertiary-care, university-based referral hospital were studied. Methacholine challenges were performed by the standardized 2-min tidal breathing technique, and the DeltaFEV(1) was calculated from the lowest postsaline solution inhalation to the lowest postmethacholine inhalation value. SpO(2) was measured immediately prior to each spirogram, and the DeltaSpO(2) was measured from the lowest postsaline solution inhalation value to the lowest postmethacholine inhalation value. We examined the data for safety (ie, any SpO(2) value < 90). Based on previous reports, we used a DeltaSpO(2) of > or = 3 as significant and looked at the sensitivity, specificity, and positive and negative predictive values for DeltaSpO(2) > or = 3 vis-à-vis a fall in FEV(1) of > or = 15%. RESULTS: There were 119 nonresponders (DeltaFEV(1), < 15%) and 81 responders. The baseline FEV(1) percent predicted was slightly but significantly lower in the responders (responders [+/- SD], 91.6 +/- 15%; nonresponders, 96.4 +/- 14%; p < 0.05). DeltaSpO(2) was 3.1 +/- 1.6 in the responders and 1.6 +/- 1.8 in the nonresponders (p < 0. 001). There was a single recording in one patient of SpO(2) < 90 (88). A DeltaSpO(2) > or = 3 had a sensitivity of 68%, a specificity of 73%, a positive predictive value of 63%, and negative predictive value of 77% for a fall in FEV(1) > or = 15%. CONCLUSIONS: Pulse oximetry is not routinely useful for safety monitoring during methacholine challenge. DeltaSpO(2) is not helpful in predicting a positive spirometric response to methacholine. However, the negative predictive value is adequate to allow the DeltaSpO(2) to be used as an adjunct in assessing a negative result of a methacholine test in patients who have difficulty performing spirometry.