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1.
J Hosp Infect ; 108: 55-63, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33122042

RESUMO

The coronavirus disease 2019 pandemic has meant that there is growing pressure on hospital resources, not least the availability of appropriate personal protective equipment (PPE), particularly face masks and respirator masks. Within the field of orthopaedic surgery, it is a common sight to see surgeons wearing 'space suits' (SSs) which comprise a helmet, hood and surgical gown. In this study, the authors made modifications to two different SS systems to incorporate a high-efficiency particulate air (HEPA) filter into the fan inlet to assess their potential as re-usable PPE systems for surgeons with regard to protection from a virus spread via respiratory droplets. The testing was carried out using particle counters upstream and downstream on a mannequin wearing two different SS systems with and without modifications to the fan inlet. The results show that using a layer of HEPA filter, cut to size and sealed to the fan inlet in the helmet, will reduce downstream particulates at the user's mouth by >99.5%; this is equivalent to a respirator mask. HEPA filter material is relatively cheap and can be used repeatedly, making this a viable alternative to disposable, and even resterilized, respirator masks in the setting of a respiratory-droplet-spread viral pandemic.


Assuntos
COVID-19/transmissão , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Procedimentos Ortopédicos/normas , Equipamento de Proteção Individual/provisão & distribuição , Filtros de Ar/estatística & dados numéricos , Filtros de Ar/tendências , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Dispositivos de Proteção da Cabeça , Humanos , Manequins , Máscaras , Procedimentos Ortopédicos/estatística & dados numéricos , Material Particulado/análise , Projetos Piloto , Dispositivos de Proteção Respiratória/estatística & dados numéricos , Dispositivos de Proteção Respiratória/tendências , SARS-CoV-2/genética , Trajes Espaciais/tendências , Trajes Espaciais/virologia
2.
Drug Alcohol Depend ; 207: 107799, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865058

RESUMO

INTRODUCTION: Opioid use disorder (OUD) is common among people in jail and is effectively treated with medications for OUD (MOUD). People with OUD may have an incomplete or inaccurate understanding of OUD and MOUD, and of how to access care. We evaluated an OUD treatment decision making (TDM) intervention to determine whether the intervention increased MOUD initiation post-release. METHODS: We conducted an observational retrospective cohort study of the TDM intervention on initiation of MOUD, individuals with records data indicating confirmed or suspected OUD incarcerated in four eligible jails were eligible to receive the intervention. Time-to-event analyses of the TDM intervention were conducted using Cox proportional hazard modeling with MOUD as the outcome. RESULTS: Cox proportional hazard modeling, with the intervention modeled as having a time-varying effect due to violation of the proportionality assumption, indicated that those receiving the TDM intervention (n = 568) were significantly more likely to initiate MOUD during the first month after release from jail (adjusted hazard ratio 6.27, 95 % C.I. 4.20-9.37), but not in subsequent months (AHR 1.33 95 % C.I. 0.94-1.89), adjusting for demographics, prior MOUD, or felony or gross misdemeanor arrest in the prior year compared to those not receiving the intervention (n = 3174). CONCLUSION: The TDM intervention was associated with a significantly higher relative hazard of starting MOUD, specifically during the first month after incarceration. However, a minority of all eligible people received any MOUD. Future research should examine ways to increase initiation on MOUD immediately after (or ideally during) incarceration.


Assuntos
Terapia Comportamental/métodos , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/psicologia , Educação de Pacientes como Assunto/métodos , Prisioneiros/psicologia , Adolescente , Adulto , Buprenorfina/uso terapêutico , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Tratamento de Substituição de Opiáceos/psicologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Prisões , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
4.
J Child Orthop ; 8(5): 381-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25352372

RESUMO

INTRODUCTION: Developmental dysplasia of the hip (DDH) is the most common congenital musculoskeletal abnormality. Recourse to definitive surgical treatment is not typically taken until over the age of 18-24 months. International consensus regarding age at surgery, degree of dysplasia requiring surgery and type of osteotomy is not available in the literature. STUDY AIMS: To determine variation in timing and type of osteotomy for persistent DDH across the world. METHODOLOGY: Senior authors of recent publications pertaining to hip dysplasia were sampled. Participants' practice relating to age and radiological indications for surgery were determined. RESULTS: Thirty-two surgeons responded from five different geographical regions. No inter-regional consensus was established regarding investigations to determine the need for osteotomy, preferred osteotomy type or ideal age at which to perform an osteotomy. CONCLUSION: International agreement regarding the surgical management of DDH does not exist. This common congenital condition warrants development of a treatment algorithm.

5.
J Physiol ; 591(18): 4621-35, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23774280

RESUMO

The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture. Metabolic differences were then investigated in the basal state or after chronic palmitate treatment. At basal, myocytes from sedentary individuals exhibited higher CD36 and HSP70 protein expression as well as elevated phosphorylation of c-Jun NH2-terminal kinase (JNK) and insulin receptor substrate 1 (IRS1) serine(307) compared to myocytes from active individuals. Despite equal lipid accumulation following palmitate treatment, myocytes from sedentary individuals exhibited delayed acetyl coenzyme A carboxylase phosphorylation compared to the active group. Myocytes from sedentary individuals had significantly higher basal glucose uptake and palmitate promoted insulin resistance in sedentary myocytes. Importantly, myocytes from active individuals were partially protected from palmitate-induced insulin resistance. Palmitate treatment enhanced IRS1 serine307 phosphorylation in myocytes from sedentary individuals and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance, a dysregulated function could have profound effects on health. Therefore the effects of lifestyle on satellite cells needs to be delineated.


Assuntos
Atividade Motora , Músculo Esquelético/metabolismo , Palmitatos/farmacologia , Células Satélites de Músculo Esquelético/metabolismo , Acetil-CoA Carboxilase/metabolismo , Adulto , Antígenos CD36/genética , Antígenos CD36/metabolismo , Glucose/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Fosforilação , Células Satélites de Músculo Esquelético/efeitos dos fármacos
6.
Am J Physiol Endocrinol Metab ; 304(11): E1227-36, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23548615

RESUMO

The purpose of this study was to examine if fat oxidation was affected by menopausal status and to investigate if this could be related to the oxidative capacity of skeletal muscle. Forty-one healthy women were enrolled in this cross-sectional study [premenopausal (n = 19), perimenopausal (n = 8), and postmenopausal (n = 14)]. Estimated insulin sensitivity was obtained from an oral glucose tolerance test. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. Fat oxidation and energy expenditure were measured during an acute exercise bout of 45 min of ergometer biking at 50% of maximal oxygen consumption (Vo2 max). Muscle biopsies from the vastus lateralis of the quadriceps muscle were obtained before and immediately after the exercise bout. Postmenopausal women had 33% [confidence interval (CI) 95%: 12-55] lower whole body fat oxidation (P = 0.005) and 19% (CI 95%: 9-22) lower energy expenditure (P = 0.02) during exercise, as well as 4.28 kg lower lean body mass (LBM) than premenopausal women. Correction for LBM reduced differences in fat oxidation to 23% (P = 0.05), whereas differences in energy expenditure disappeared (P = 0.22). No differences between groups were found in mRNA [carnitine palmitoyltransferase I, ß-hydroxyacyl-CoA dehydrogenase (ß-HAD), peroxisome proliferator-activated receptor-α, citrate synthase (CS), pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)], protein [phosphorylated AMP-activated protein kinase (AMPK), vascular endothelial growth factor, pyruvate dehydrogenase-1Eα, cytochrome oxidase I], or enzyme activities (ß-HAD, CS) in resting skeletal muscle, except for an increased protein level of cytochrome c in the post- and perimenopausal women relative to premenopausal women. Postmenopausal women demonstrated a trend to a blunted exercise-induced increase in phosphorylation of AMPK compared with premenopausal women (P = 0.06). We conclude that reduced whole body fat oxidation after menopause is associated with reduced LBM.


Assuntos
Tecido Adiposo/metabolismo , Exercício Físico/fisiologia , Menopausa/metabolismo , Composição Corporal/fisiologia , Estudos Transversais , Metabolismo Energético/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Oxirredução , Consumo de Oxigênio/fisiologia
7.
Ir J Med Sci ; 180(3): 679-82, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21340751

RESUMO

BACKGROUND: Climate change models predict increasing frequency of extreme weather. One of the challenges hospitals face is how to make sure they have adequate staffing at various times of the year. AIMS: The aim of this study was to examine the effect of this severe inclement weather on hospital admissions, operative workload and cost in the Irish setting. We hypothesised that there is a direct relationship between cold weather and workload in a regional orthopaedic trauma unit. METHODS: Trauma orthopaedic workload in a regional trauma unit was examined over 2 months between December 2009 and January 2010. This corresponded with a period of severe inclement weather. RESULTS: We identified a direct correlation between the drop in temperature and increase in workload, with a corresponding increase in demand on resources. CONCLUSIONS: Significant cost savings could be made if these injuries were prevented. While the information contained in this study is important in the context of resource planning and staffing of hospital trauma units, it also highlights the vulnerability of the Irish population to wintery weather.


Assuntos
Procedimentos Ortopédicos/estatística & dados numéricos , Centros de Traumatologia/organização & administração , Tempo (Meteorologia) , Carga de Trabalho , Redução de Custos , Hospitalização/economia , Humanos , Procedimentos Ortopédicos/economia , Admissão e Escalonamento de Pessoal/organização & administração , Centros de Traumatologia/economia , Centros de Traumatologia/estatística & dados numéricos
8.
Cryo Letters ; 30(1): 1-12, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19274306

RESUMO

In this study we evaluated mitochondrial function after liver cold storage and normothermic reperfusion. The preservation solutions were: modified University of Wisconsin (mod UW) and sucrose-based solution (SBS). After cold preservation liver was re-perfused for 1 hour in vitro with Krebs-Ringer buffer at 37 degree C. Samples of tissue were taken for ATP determination. Mitochondrial respiratory parameters, succinate oxidase complex activity, mitochondrial H+- ATPase and intramitochondrial potassium concentration were assayed. It was shown, that brief (1 hour) cold storage and subsequent normothermic reperfusion revealed no difference in liver ATP content between mod UW and SBS groups but resulted in a gradual decrease of 50 percent after 24-hour storage and reperfusion. Mitochondrial potassium ion concentration increased by 40 percent after 1-hour cold storage in the mod UW as compared to control (P value less than 0.05) and SBS. After brief cold storage ADP and uncoupler-stimulated respiration increased by 120 percent in SBS group, unlike mod UW, when succinate was used as substrate, and was more pronounced after 24 hour. Succinate oxidase complex activity did not change over either cold storage or warm reperfusion. Mitochondrial H+-ATPase activities in SBS and mod UW did not differ and both were inhibited after 24-hour cold storage. Our data demonstrate that low ionic strength preservation solution can substantially modulate mitochondrial energy turnover due to substrate oxidation increase. Many of the changes in mitochondrial function follow brief exposure to low temperatures.


Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Mitocôndrias Hepáticas/metabolismo , Soluções para Preservação de Órgãos/farmacologia , Sacarose/farmacologia , Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Alopurinol/farmacologia , Animais , Glutationa/farmacologia , Insulina/farmacologia , Masculino , Modelos Animais , Oxirredutases/metabolismo , Consumo de Oxigênio/fisiologia , Potássio/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Rafinose/farmacologia , Ratos , Ratos Mutantes
9.
Clin Med (Lond) ; 9(6): 515-8, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20095289

RESUMO

Prescribing errors are a recognised problem on admission to acute medical wards which may be detrimental to patient care. The authors had anecdotal evidence that prescribed medicines do not always reach patients and the aim of this audit was to quantify this problem. Admission prescription charts on two separate occasions were studied in detail and all drugs prescribed but not given in the first 48 hours were recorded along with the reason given for omission. In total, 271 patient charts were analysed. Of these, 20% of prescriptions affecting 17% of patients did not reach patients. The two dominant reasons for medications not being given to patients were that the medication was not available on the ward (38% of omissions) or that the patient was nil by mouth (32% of omissions). In 10% of cases the patient refused the medication, in 19% no reason for omission was given and in only a minority (0.3%) was the patient off the ward. This audit demonstrates that even when medications are prescribed they are not always given. This may lead to increased morbidity and length of stay. Strategies need to be put in place to reduce this problem. The current system that permits omission of medications with inadequate justification must be revised.


Assuntos
Prescrições de Medicamentos , Pacientes Internados , Auditoria Médica , Erros de Medicação/estatística & dados numéricos , Admissão do Paciente , Medicamentos sob Prescrição , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto Jovem
10.
Burns ; 34(8): 1169-75, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18468801

RESUMO

Skin loss following severe burn requires prompt wound closure to avoid such complications as fluid and electrolyte imbalance, infection, immune suppression, and pain. In clinical situations in which insufficient donor skin is available, the development of cultured skin equivalents (dermal matrices seeded with keratinocytes and fibroblasts) may provide a useful alternative. The aim of this study was to assess the suitability of a porcine-derived dermal collagen matrix (Permacol) to function as a cultured skin equivalent in supporting the growth of keratinocytes in vitro and providing cover to full thickness wounds in the BALB C/nude mouse model. A histological comparison was against Glycerol treated-Ethylene Oxide Sterilised Porcine Dermis (Gly-EO Dermis) which has successfully been used as a cultured skin equivalent in previous studies. Both Gly-EO Dermis and to a lesser extent Permacol were able to support the growth of cultured keratinocytes following a 16-day period of cell culture, however, this study was only able to demonstrate the presence of an epidermal layer on Gly-EO dermis 2 weeks after grafting onto full-thickness wounds in the BALB C/nude mouse model.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Colágeno/uso terapêutico , Células Epidérmicas , Queratinócitos/fisiologia , Cicatrização/fisiologia , Animais , Crioprotetores/uso terapêutico , Desinfetantes/uso terapêutico , Epiderme/metabolismo , Óxido de Etileno/uso terapêutico , Glicerol/uso terapêutico , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Animais , Suínos
11.
QJM ; 101(5): 365-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18292099

RESUMO

BACKGROUND: Home parenteral nutrition (HPN) is an established option for patients suffering from intestinal failure, often pending definitive surgery, but sometimes for life or pending intestinal transplant. Care for patients with HPN is provided at centres other than designated intestinal failure units in the UK, but there are few data on outcomes. AIM: To audit the standard of care at one such centre using objective measures to compare with results published from other centres and intestinal failure units. DESIGN: 15-year retrospective audit of paper and computer-based records of all HPN patients (1990-2004). METHODS: Demographic data, major line and metabolic complication rates and mortality were collected and analysed. RESULTS: 88 patients received HPN for a total period of 121 patient-years (median duration 217.8 days, range 18.3-3881.2, median age 40, range 3-73). Principal reasons for HPN were Crohns' disease (35.2%), mesenteric, infarction (11.4%), surgical complications (17.0%), intestinal motility disorder (10.7%). The frequency of major complications were line sepsis (0.35 episodes/patient-year), line occlusion (0.25 episodes/patient-year), subacute bacterial endocarditis (0.02 episodes/patient-year), cholestasis (0.17 episodes/patient-year) and central venous thrombosis (0.03 episodes/patient-year). Indications and complications were all within the range of published data. CONCLUSION: HPN can be delivered effectively outside designated intestinal failure units and the current data are representative of a standard of care.


Assuntos
Serviços Hospitalares de Assistência Domiciliar/normas , Enteropatias/terapia , Nutrição Parenteral no Domicílio/normas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Inglaterra , Métodos Epidemiológicos , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde
12.
Aliment Pharmacol Ther ; 27(2): 120-45, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17922802

RESUMO

BACKGROUND: Enteral nutrition can be associated with gastrointestinal side effects and fibre supplementation has been proposed as a means to normalize bowel function. AIM: To evaluate systematically the effects of fibre supplementation of enteral feeds in healthy volunteers and patients both in the hospital and community settings. METHODS: Electronic and manual bibliographic searches were conducted. Controlled studies in adults or children, comparing fibre-supplemented vs. fibre-free formulae given as the sole source of nutrition for at least 3 days, were included. RESULTS: Fifty-one studies (including 43 randomized-controlled trials), enrolling 1762 subjects (1591 patients and 171 healthy volunteers) met the inclusion criteria. Fibre supplementation was generally well tolerated. In the hospital setting, the incidence of diarrhoea was reduced as a result of fibre administration (OR 0.68, 95% CI: 0.48-0.96; 13 randomized-controlled trials). Meta-regression showed a more pronounced effect when the baseline incidence of diarrhoea was high. In both patients and healthy subjects, fibre significantly reduced bowel frequency when baseline frequency was high and increased it when it was low, revealing a significant moderating effect of fibre. CONCLUSIONS: The review indicates that the fibre-supplemented enteral formulae have important physiological effects and clinical benefits. There is a need to use a consistent approach to undertake more studies on this issue in the community setting.


Assuntos
Constipação Intestinal/induzido quimicamente , Diarreia/induzido quimicamente , Fibras na Dieta/efeitos adversos , Nutrição Enteral/métodos , Adulto , Antibacterianos/uso terapêutico , Criança , Constipação Intestinal/epidemiologia , Defecação/efeitos dos fármacos , Diarreia/epidemiologia , Fibras na Dieta/administração & dosagem , Fibras na Dieta/classificação , Relação Dose-Resposta a Droga , Nutrição Enteral/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fezes/microbiologia , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Clin Exp Allergy ; 37(6): 808-22, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17517094

RESUMO

The aim of this systematic review was to evaluate the efficacy of amino acid-based formulas (AAF) in patients with cow's milk allergy (CMA). Studies were identified using electronic databases and bibliography searches. Subjects eligible for inclusion were patients of any age with CMA or symptoms suggestive of it. Comparisons of interest were AAF vs. extensively hydrolysed formula (eHF), AAF vs. soy-based formula (SF) and AAF vs. cow's milk or cow's milk-based formula. Outcomes of interest were gastrointestinal (GI), dermatological, respiratory and behavioural symptoms as well as growth. A total of 20 studies [three head-to-head randomized controlled trials (RCTs), three cross-over challenge RCTs, seven clinical trials (CTs) and seven case reports (CRs)] were included in the review. In infants with confirmed or suspected CMA, the use of an AAF was shown to be safe and efficacious. Findings from RCT comparisons of AAF with eHF showed that both formulas are equally efficacious at relieving the symptoms of CMA in confirmed or suspected cases. However, infants in specific subgroups (e.g. non-IgE mediated food-induced gastro-enterocolitis-proctitis syndromes with failure to thrive, severe atopic eczema, or with symptoms during exclusive breastfeeding) were more likely overall to benefit from AAF, as intolerance to eHF may occur. In such cases, symptoms persisting despite eHF feeding usually remit on AAF, and catch-up growth may be seen. Meta-analysis of the findings was not possible due to lack of homogenous reporting of outcomes in the original trials. This systematic review shows clinical benefit from use of AAF in both symptoms and growth in infants and children with CMA who fail to tolerate eHF. Further studies are required to determine the relative medical or economic value of initial treatment with AAF in infants at high risk of eHF intolerance.


Assuntos
Aminoácidos , Alimentos Infantis , Fórmulas Infantis , Hipersensibilidade a Leite , Leite Humano , Leite , Leite de Soja , Aminoácidos/efeitos adversos , Animais , Aleitamento Materno/efeitos adversos , Bovinos , Estudos Cross-Over , Bases de Dados Factuais , Dermatite Atópica/dietoterapia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Enterite/dietoterapia , Enterite/imunologia , Enterite/patologia , Insuficiência de Crescimento/dietoterapia , Insuficiência de Crescimento/imunologia , Insuficiência de Crescimento/patologia , Humanos , Imunoglobulina E/imunologia , Lactente , Alimentos Infantis/efeitos adversos , Recém-Nascido , Metanálise como Assunto , Leite/efeitos adversos , Hipersensibilidade a Leite/dietoterapia , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/patologia , Proctite/dietoterapia , Proctite/imunologia , Proctite/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Br J Pharmacol ; 149(8): 1104-12, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17057755

RESUMO

BACKGROUND AND PURPOSE: Carbon monoxide (CO) generated by the enzyme haeme oxygenase-1 (HO-1) during the breakdown of haeme is known to mediate a number of biological effects. Here, we investigated whether CO liberated from two water soluble carbon monoxide-releasing molecules (CO-RMs) exerts inotropic effects on the myocardium. EXPERIMENTAL APPROACH: Rat isolated hearts perfused either at constant flow or constant pressure were used to test the effect of CO-RMs. KEY RESULTS: CORM-3, a fast CO releaser, produced a direct positive inotropic effect when cumulative doses (3, 10 and 30 microg min(-1)) or a single dose (5 microM) were infused at either constant coronary pressure (CCP) or constant coronary flow (CCF). The inotropic effect mediated by CORM-3 was abolished by blockade of soluble guanylate cyclase or Na(+)/H(+) exchanger, but not by inhibitors of L-type Ca(2+) channels and protein kinase C. CORM-3 also caused a slight reduction in heart rate but did not alter coronary flow. In contrast, the slow CO releaser CORM-A1 produced significant coronary vasodilatation when given at the highest concentration (30 mug min(-1)) but exerted no effect on myocardial contractility or heart rate. CONCLUSION AND IMPLICATIONS: A rapid CO release from CORM-3 exerts a direct positive inotropic effect on rat isolated perfused hearts, whereas CO slowly released by CORM-A1 had no effect on myocardial contractility but caused significant coronary vasodilatation. Both cGMP and Na(+)/H(+) exchange appear to be involved in this effect but further work is needed to determine the relative contribution of each pathway in CO-mediated inotropic effect.


Assuntos
Boranos/farmacologia , Monóxido de Carbono/metabolismo , Carbonatos/farmacologia , Cardiotônicos/farmacologia , Miocárdio/metabolismo , Compostos Organometálicos/farmacologia , Alcaloides/farmacologia , Amilorida/análogos & derivados , Amilorida/farmacologia , Animais , Benzofenantridinas/farmacologia , Boranos/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Carbonatos/metabolismo , Inibidores Enzimáticos/farmacologia , Coração/efeitos dos fármacos , Cinética , Masculino , Nifedipino/farmacologia , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos
15.
BJOG ; 113(5): 580-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16579806

RESUMO

OBJECTIVE: To evaluate placental morphology in pregnancies complicated by early- and late-onset pre-eclampsia (PET) with and without fetal growth restriction (FGR) using stereological techniques. DESIGN: A total of 69 pregnant women were studied. Twenty women had pregnancies complicated by PET, 17 by FGR and 16 by both PET and FUR; the remaining 16 were from gestational-age-matched controls. Each group was further classified into early onset (<34 weeks) and late onsets (>34 weeks) based on gestational ages. SETTING: NPIMR at Northwick Park and St Marks Hospital. POPULATION: placentae from pregnant women. METHODS: Formalin-fixed, wax-embedded sections stained with anti-CD34 antibodies and counterstained with haematoxylin. MAIN OUTCOME MEASURES: Volumes, surface areas, lengths, diameters and shape factors of the villous tissues and fetal vasculature in the intermediate and terminal villi of all the groups studied. RESULTS: Terminal villi volume and surface area were compromised in early-onset PET cases, late-onset PET had no impact on peripheral villi or vasculature features. The morphology of the vascular and villous subcomponents in the intermediate and terminal villi was significantly influenced by late-onset FGR, whereas early-onset FGR caused a reduction in placental weight. Length estimates were not influenced by PET, FGR or age of onset. Intermediate arteriole shape factor was significantly reduced in late-onset FGR. CONCLUSIONS: Isolated early-onset PET was associated with abnormal placental morphology, but placentas from late-onset PET were morphologically similar to placentas from gestational-age-matched controls, confirming the existence of two subsets of this condition and supporting the hypothesis that late-onset PET is a maternal disorder and not a placental disease.


Assuntos
Vilosidades Coriônicas/patologia , Retardo do Crescimento Fetal/patologia , Doenças Placentárias/patologia , Placenta/irrigação sanguínea , Pré-Eclâmpsia/patologia , Adulto , Idade de Início , Capilares/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez
16.
Kidney Int ; 69(2): 239-47, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16408112

RESUMO

Low concentrations of carbon monoxide (CO) can protect tissues against ischemia-reperfusion (I-R) injury. We have recently identified a novel class of compounds, CO-releasing molecules (CO-RMs), which exert important pharmacological activities by carrying and delivering CO to biological systems. Here, we examined the possible beneficial effects of CO liberated from CO-RMs on the damage inflicted by cold storage and I-R in isolated perfused kidneys. Hemodynamic and biochemical parameters as well as mitochondrial respiration were measured in isolated perfused rabbit kidneys that were previously flushed with CO-RMs and stored at 4 degrees C for 24 h. Two water-soluble CO-RMs were tested: (1) sodium boranocarbonate (CORM-A1), a boron-containing carbonate that releases CO at a slow rate, and (2) tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), a transition metal carbonyl that liberates CO very rapidly in solution. Kidneys flushed with Celsior solution supplemented with CO-RMs (50 microM) and stored at 4 degrees C for 24 h displayed at reperfusion a significantly higher perfusion flow rate (PFR), glomerular filtration rate, and sodium and glucose reabsorption rates compared to control kidneys flushed with Celsior solution alone. Addition of 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor, prevented the increase in PFR mediated by CO-RMs. The respiratory control index from kidney mitochondria treated with CO-RMs was also markedly increased. Notably, renal protection was lost when kidneys were flushed with Celsior containing an inactive compound (iCO-RM), which had been deliberately depleted of CO. CO-RMs are effective therapeutic agents that deliver CO during kidney cold preservation and can be used to ameliorate vascular activity, energy metabolism and renal function at reperfusion.


Assuntos
Monóxido de Carbono/farmacologia , Rim/efeitos dos fármacos , Preservação de Órgãos , Traumatismo por Reperfusão/prevenção & controle , Animais , Monóxido de Carbono/metabolismo , Temperatura Baixa , Rim/irrigação sanguínea , Rim/fisiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxidiazóis/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Quinoxalinas/farmacologia , Coelhos
17.
Placenta ; 27(6-7): 727-34, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16125226

RESUMO

Both pre-eclampsia (PET) and fetal growth restriction (FGR) pose a heavy burden on fetal and maternal health and may disrupt pregnancy outcome. Using design based stereological techniques, placental vascular and villous morphology were assessed to determine the individual role played by both PET and FGR on placental growth during the third trimester. The following placentas delivered between 25 and 41 weeks of gestation were included into the study; controls (n=16), PET (n=20), FGR (n=17) and PET-FGR (n=16). Each placenta was uniformly randomly sampled and the sampled tissue processed to paraffin. Sections were stained with a CD34 antibody and the following morphometric parameters estimated: volumes, surface areas, length, diameters and the shape factor of the villous (terminal and intermediate) and vascular placental features. For stereologically estimated parameters pure PET had an effect on IVS and terminal villi volume only. FGR alone or when coexisting with PET contributed towards significant reductions in volumetric and surface area terminal villous and vascular features. FGR factors also contributed towards a significant reduction in the lengths of all parameters estimated and in the terminal villi diameter. Additionally, FGR was associated with a significant difference in shape factor indices for both intermediate and terminal villi. This study has shown that PET on its own has limited influence on the placental morphology studied, since the vascular features estimated do not differ stereologically from age matched normal controls. However, placental morphology is different between PET and PET-FGR and between PET-FGR and FGR. PET and FGR may have a cumulative effect on placental villous and vascular morphology as seen in the PET-FGR but there is no synergistic effect. These morphological abnormalities may have major physiological implications in terms of placental function and fetal growth.


Assuntos
Vilosidades Coriônicas/patologia , Retardo do Crescimento Fetal/patologia , Circulação Placentária/fisiologia , Pré-Eclâmpsia/patologia , Adulto , Biomarcadores/metabolismo , Vilosidades Coriônicas/irrigação sanguínea , Vilosidades Coriônicas/metabolismo , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Pré-Eclâmpsia/metabolismo , Gravidez , Terceiro Trimestre da Gravidez
18.
Cell Mol Biol (Noisy-le-grand) ; 51(4): 409-23, 2005 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-16309592

RESUMO

The inducible stress protein heme oxygenase-1 (HO-1) has been linked to tissue and organ protection against the deleterious actions of many pathological conditions, including endotoxin challenge. Similar protection can be achieved by the main products of heme oxygenase activity, namely bilirubin and carbon monoxide (CO). Since the identification of novel chemical compounds that liberate CO in biological systems (CO-releasing molecules or CO-RMs), our group and others have had access to a convenient and simple pharmacological tool that enables to study the role of CO in physiological functions. This article will review the scientific literature published to date on CO-RMs, with emphasis on the in vitro, ex vivo and in vivo experimental models employed to determine the contribution of CO to cellular mechanisms. In addition, we will report on the effect of heme oxygenase-related substances, such as bilirubin, CORM-3 and hemin, in a model of endotoxin-induced hypotension. Among the three different approaches examined, CORM-3 proved the most effective agent in reducing the fall in blood pressure caused by endotoxin. Furthermore, heme oxygenase-related substances affected the endotoxin-stimulated induction and distribution of hepatic HO-1 and inducible nitric oxide synthase (iNOS). Thus, it emerges that CO-RMs could exert important biological actions in the context of endotoxic-mediated dysfunction.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Monóxido de Carbono/metabolismo , Endotoxinas/farmacologia , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Animais , Regulação Enzimológica da Expressão Gênica/genética , Coração/efeitos dos fármacos , Heme Oxigenase-1/genética , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Miocárdio/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley
19.
Cell Mol Biol (Noisy-le-grand) ; 51(4): 425-32, 2005 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-16309593

RESUMO

Emerging evidence reveals that heme oxygenase-1 (HO-1) and its product carbon monoxide (CO) can exert diverse biological and cytoprotective effects. Our group has recently identified a new class of compounds (CO-releasing molecules or CO-RMs) that can carry and deliver CO to biological systems and can be used to examine the physiological properties of CO. Here, we evaluated the influence of endogenously-generated CO (via HO-1 induction by hemin) and CO liberated from exogenously supplied CO-RMs on mitochondrial function. Renal mitochondria were isolated either from rats with increased HO-1 or from untreated animals, the latter being exposed to different concentrations of CO-RMs (10-100 microM). We found that mitochondrial oxygen uptake was significantly reduced in kidneys after HO-1 induction and, in a similar fashion, CO-RMs inhibited mitochondrial function in a concentration-dependent manner. Specifically, a marked depression of state 3 was observed resulting in a significant decrease in respiratory control index (RCI) values. When mitochondria were incubated with the inactive forms of CO-RMs, which are devoid of CO, the respiratory parameters remained unchanged. In summary, the results indicate that HO-1 induction and enhanced CO decrease renal oxygen consumption and alter mitochondrial function suggesting that CO could be a physiological regulator of mitochondrial oxidative phosphorylation.


Assuntos
Monóxido de Carbono/metabolismo , Respiração Celular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Heme Oxigenase (Desciclizante)/metabolismo , Hemina/farmacologia , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley
20.
J Exp Biol ; 208(Pt 13): 2581-93, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15961744

RESUMO

Macaroni penguins were implanted with data loggers to record heart rate (fH), abdominal temperature (Tab) and diving depth during their pre-moult trip (summer) and winter migration. The penguins showed substantial differences in diving behaviour between the seasons. During winter, mean and maximum dive duration and dive depth were significantly greater than during summer, but the proportion of dives within the calculated aerobic dive limit (cADL) did not change. Rates of oxygen consumption were estimated from fH. As winter progressed, the rate of oxygen consumption during dive cycles (sVO2DC)) declined significantly and mirrored the pattern of increase in maximum duration and depth. The decline in sVO2DC) was matched by a decline in minimum rate of oxygen consumption (sVO2min)). When sVO2min) was subtracted from sVO2DC), the net cost of diving was unchanged between summer and winter. We suggest that the increased diving capacity demonstrated during the winter was facilitated by the decrease in sVO2min). Abdominal temperature declined during winter but this was not sufficient to explain the decline in sVO2min). A simple model of the interactions between sVO2min), thermal conductance and water temperature shows how a change in the distribution of fat stores and therefore a change in insulation and/or a difference in foraging location during winter could account for the observed reduction in sVO2min) and hence sVO2DC).


Assuntos
Mergulho/fisiologia , Metabolismo Energético/fisiologia , Estações do Ano , Spheniscidae/fisiologia , Animais , Ilhas Atlânticas , Metabolismo Basal , Temperatura Corporal , Peso Corporal , Feminino , Frequência Cardíaca , Modelos Lineares , Masculino , Consumo de Oxigênio/fisiologia , Fatores de Tempo
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