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AIM: Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS: Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS: Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION: Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.
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Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Barorreflejo/fisiología , Ejercicios Respiratorios , Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/fisiopatología , Frecuencia Cardíaca/fisiología , Hiperoxia , Terapia por Inhalación de Oxígeno , Anciano , Albuminuria/etiología , Sistema Nervioso Autónomo/fisiopatología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.
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Cesárea/efectos adversos , Terapia de Presión Negativa para Heridas/métodos , Obesidad/cirugía , Complicaciones del Embarazo/cirugía , Infección de la Herida Quirúrgica/prevención & control , Adulto , Vendajes/estadística & datos numéricos , Dinamarca , Femenino , Humanos , Obesidad/complicaciones , Embarazo , Factores de Riesgo , Nivel de Atención/estadística & datos numéricos , Infección de la Herida Quirúrgica/etiología , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
Bone mass in childhood is highly influenced by puberty. At the same age, bone mass was higher for pubertal than pre-pubertal children. A high level of tracking during 7 years from childhood through puberty was shown, indicating that early levels of bone mass may be important for later bone health. INTRODUCTION: Bone mass development in childhood varies by sex and age, but also by pubertal stage. The objectives of this study were to (1) describe bone mass development in childhood as it relates to pubertal onset and to (2) determine the degree of tracking from childhood to adolescence. METHODS: A longitudinal study with 7 years of follow-up was initiated in 2008 to include 831 children (407 boys) aged 8 to 17 years. Participants underwent whole body dual-energy X-ray absorptiometry (DXA) scanning, blood collection to quantify luteinizing hormone levels, and Tanner stage self-assessment three times during the 7-year follow-up. Total body less head bone mineral content, areal bone mineral density, and bone area were used to describe development in bone accrual and to examine tracking over 7 years. RESULTS: Bone mass in pubertal children is higher than that of pre-pubertal children at the same age. Analysing tracking with quintiles of bone mass Z-scores in 2008 and 2015 showed that more than 80% of participants remained in the same or neighbouring quintile over the study period. Tracking was confirmed by correlation coefficients between Z-scores at baseline and 7-year follow-up (range, 0.80-0.84). CONCLUSIONS: Bone mass is highly influenced by pubertal onset, and pubertal stage should be considered when examining children's bone health. Because bone mass indices track from childhood into puberty, children with low bone mass may be at risk of developing osteoporosis later in life.
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Envejecimiento/fisiología , Densidad Ósea/fisiología , Desarrollo Óseo/fisiología , Pubertad/fisiología , Absorciometría de Fotón/métodos , Adolescente , Antropometría/métodos , Niño , Femenino , Estudios de Seguimiento , Humanos , MasculinoRESUMEN
Objective: To investigate associations between obesity-linked systemic factors and gene expression indicative for the inflammatory and fibrotic processes in the infrapatellar fat pad (IFP), in a population of obese patients with end-stage knee osteoarthritis (KOA). Methods: We collected human IFPs from 48 patients with a mean body mass index (BMI) of 35.44 âkg/m2 during total knee replacement procedures. These patients were part of a randomized controlled trial and met the criteria of having OA and a BMI of ≥30 âkg/m2. Blood samples were collected to assess serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and leptin. Total body composition was measured using dual-energy X-ray absorptiometry. Gene expressions of IL6, TNFA, COL1A1, IL1B, ASMA, PLOD2 in the IFP were analyzed. Results: Univariate analysis resulted in a positive correlation between BMI and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression (r2 â= â0.13). In univariate analyses of obesity-linked systemic factors and PLOD2, significant correlations were found for lean mass (r2 â= â0.20), fat mass (r2 â= â0.20), serum cholesterol (r2 â= â0.17), serum triglycerides (r2 â= â0.19) and serum leptin (r2 â= â0.10). A multiple linear regression model indicated fat mass to be a strong predictor of PLOD2 production in the IFP (r2 â= â0.22, P â= â0.003). Conclusion: Our study demonstrates the positive association between fat mass and PLOD2 expression in the IFP of obese end-stage knee OA patients. This may indicate that within this patient population the fibrotic process in the IFP is influenced by systemic adipose tissue, next to local inflammatory processes.
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Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group exercise and relaxation intervention showed an adherence rate of 76%, whereas the patients failed to comply with the home-based exercise. The hospital-based intervention initiated at time of diagnosis encouraged former sedentary lung cancer patients to participation and was undertaken safely by cancer patients with advanced stages of disease, during treatment. The patients experienced physical, functional and emotional benefits. This study confirmed that supervised training in peer-groups was beneficial, even in a cancer population with full-blown symptom burden and poor prognosis.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Terapia por Ejercicio , Neoplasias Pulmonares/terapia , Terapia por Relajación , Carcinoma Pulmonar de Células Pequeñas/terapia , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/psicología , Disnea/etiología , Disnea/terapia , Terapia por Ejercicio/psicología , Fatiga/etiología , Fatiga/terapia , Estudios de Factibilidad , Femenino , Grupos Focales , Estado de Salud , Humanos , Entrevistas como Asunto , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/psicología , Masculino , Persona de Mediana Edad , Motivación , Fuerza Muscular , Cooperación del Paciente , Terapia por Relajación/psicología , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Carcinoma Pulmonar de Células Pequeñas/psicologíaRESUMEN
PURPOSE: Local anesthesia for open inguinal hernia repair is recommended by guidelines but is rarely used in clinical practice in several countries. This study aimed to explore physician's considerations in choosing type of anesthesia and barriers for implementing local anesthesia for open hernia repair in clinical practice. METHODS: We performed individual semi-structured interviews of surgeons and anesthesiologists. Transcribed data were condensed, coded, categorized, and formulated into themes in an inductive qualitative content analysis. RESULTS: Twenty two participants from seven public hospitals were included in the study. Participants described a standardized setup for general anesthesia with use of intravenous propofol/remifentanil and a laryngeal mask and were generally satisfied with this setup. Their considerations in choosing anesthesia could be described in four themes: (1) Intraoperative pain and quality of surgical technique, (2) Communication and teaching, (3) Logistics, and (4) Clinical routines. CONCLUSION: Participants considered intraoperative pain and quality of surgical technique, communication and teaching, logistics, and clinical routines as important factors when choosing anesthesia for open inguinal hernia repair and these factors acted as barriers for implementing of local anesthesia in Danish public hospitals. In this setting, implementation strategies should, therefore, be multimodal to address these barriers. The potential workload in such an effort should be justified by evidence supporting specific types of local anesthesia comapared with general anesthesia with use of propofol/remifentanil and a laryngeal mask.
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Hernia Inguinal , Propofol , Anestesia Local , Hernia Inguinal/cirugía , Herniorrafia/métodos , Humanos , Dolor/cirugía , RemifentaniloRESUMEN
BACKGROUND AND AIMS: Obesity is an increasing problem in patients after total knee replacement. The aim of this study was to investigate whether a weight loss intervention before primary total knee replacement would improve quality of life, knee function, mobility, and body composition 1 year after surgery. MATERIAL AND METHODS: Patients scheduled for total knee replacement due to osteoarthritis of the knee and obesity were randomized to a control group receiving standard care or to an intervention group receiving 8-week low-energy diet before total knee replacement. Patient-reported quality of life, 6-Min Walk Test, and body composition by dual-energy X-ray absorptiometry were assessed before intervention for the diet group, and within 1 week preoperatively for both groups, and the changes in outcome from baseline to 1 year after total knee replacement were compared between groups. The number of participants was lower than planned, which might introduce a type-2 error and underestimate the trend for a better outcome after weight loss. RESULTS: The analyses are based on a total of 76 patients, 38 in each group. This study showed major improvement in both study groups in quality of life and knee function, though no statistically significant differences between the groups were observed 1 year after total knee replacement. The average weight loss after 8-week preoperative intervention was 10.7 kg and consisted of a 6.7 kg reduction in fat mass. One year after total knee replacement, the participants in the diet group managed to maintain the weight reduction, whereas there was no change in the control group. CONCLUSION: The results suggest that it is feasible and safe to implement an intensive weight loss program shortly before total knee replacement. The preoperative intervention resulted in a 10% body weight loss, improved body composition, lower cardiovascular risk factors, and sustained s-leptin.
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Artroplastia de Reemplazo de Rodilla , Obesidad/dietoterapia , Osteoartritis de la Rodilla/cirugía , Periodo Preoperatorio , Calidad de Vida , Recuperación de la Función , Pérdida de Peso , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Composición Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
To address the problem of manure-based environmental pollution in the pork industry, we have developed the phytase transgenic pig. The saliva of these pigs contains the enzyme phytase, which allows the pigs to digest the phosphorus in phytate, the most abundant source of phosphorus in the pig diet. Without this enzyme, phytate phosphorus passes undigested into manure to become the single most important manure pollutant of pork production. We show here that salivary phytase provides essentially complete digestion of dietary phytate phosphorus, relieves the requirement for inorganic phosphate supplements, and reduces fecal phosphorus output by up to 75%. These pigs offer a unique biological approach to the management of phosphorus nutrition and environmental pollution in the pork industry.
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6-Fitasa/química , 6-Fitasa/genética , Animales Modificados Genéticamente , Fósforo/química , Saliva/enzimología , Animales , Western Blotting , Suplementos Dietéticos , Inmunohistoquímica , Estiércol , Glándula Parótida/metabolismo , Fosfatos/farmacología , Fósforo/metabolismo , Glándulas Salivales/metabolismo , Porcinos , TransgenesRESUMEN
Aeration tank settling is a control method allowing settling in the process tank during high hydraulic load. The control method is patented. Aeration tank settling has been applied in several waste water treatment plants using the present design of the process tanks. Some process tank designs have shown to be more effective than others. To improve the design of less effective plants, computational fluid dynamics (CFD) modelling of hydraulics and sedimentation has been applied. This paper discusses the results at one particular plant experiencing problems with partly short-circuiting of the inlet and outlet causing a disruption of the sludge blanket at the outlet and thereby reducing the retention of sludge in the process tank. The model has allowed us to establish a clear picture of the problems arising at the plant during aeration tank settling. Secondly, several process tank design changes have been suggested and tested by means of computational fluid dynamics modelling. The most promising design changes have been found and reported.
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Arquitectura y Construcción de Instituciones de Salud , Modelos Estructurales , Purificación del Agua/instrumentación , Aerobiosis , Precipitación Química , Movimientos del Agua , Purificación del Agua/métodosRESUMEN
BACKGROUND: From 2012-2015, the Departments of Obstetrics and Gynecology and of Pediatrics at the University of Copenhagen conducted a project, "Internationalization at Home ", offering clinical teaching in English. The project allowed international students to work with Danish speaking students in a clinical setting. Using semi-quantitative questionnaires to 89 clinicians about use of English and need for training, this paper considers if Danish clinical doctors are prepared to teach in English. RESULTS: The majority self-assessed their English proficiency between seven and eight on a 10 unit visual analogue scale, with 10 equivalent to working in Danish, while 15 % rated five or less. However, one-fourth found teaching and writing in English to be twice as difficult than in Danish, and 12 % rated all teaching tasks in English at four or less compared to Danish. The self-assessed need for additional English skills was perceived low. CONCLUSION: Teaching in English was rated as 30 % more difficult than in Danish, and a significant subgroup of doctors had difficulties in all forms of communication in English, resulting in challenges when introducing international students in non-native English speaking medical departments.
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Educación Médica , Lenguaje , Médicos , Dinamarca , Humanos , Lingüística , Autoevaluación (Psicología) , EscrituraRESUMEN
BACKGROUND: Epidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15-19 years. OBJECTIVE: The aim of this study was to investigate the association between shift work at young age and the risk of developing MS. METHODS: We performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15-19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors. RESULTS: We found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08-1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01-1.06, p=0.002). Duration of shift work in years was not associated with risk of MS. CONCLUSION: This study supports a statistically significant association between shift work at age 15-19 years and MS risk.
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Empleo , Esclerosis Múltiple/epidemiología , Adulto , Factores de Edad , Estudios de Casos y Controles , Dinamarca/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Factores de RiesgoRESUMEN
BACKGROUND: Cardiovascular ischemic events may occur more frequently in hypertensive patients with activated renin-angiotensin systems. We tested the hypothesis that angiotensin II (Ang II) may contribute to atherosclerosis by increasing expression of vascular inflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1). METHODS AND RESULTS: Rats infused with norepinephrine or Ang II for 6 days developed similar hypertensive responses, but only Ang II-treated rats exhibited significant increases in aortic VCAM-1 protein and mRNA expression. Oral losartan treatment (50 mg. kg(-1). d(-1)) inhibited Ang II-induced hypertension and aortic VCAM-1 mRNA expression. Ang II treatment significantly increased VCAM-1 mRNA expression in cultured rat aortic smooth muscle cells (RASMCs). Ang II also induced nuclear NF-kappaB-like binding activity and transactivated an NF-kappaB-driven VCAM-1 promoter. Losartan and proteasome inhibitors blocked Ang II-induced NF-kappaB activation and VCAM-1 mRNA accumulation. IkappaB-alpha overexpression in RASMCs inhibited Ang II-induced VCAM-1 promoter transactivation. CONCLUSIONS: Ang II may contribute to atherogenesis by activation of VCAM-1 through proteasome dependent, NF-kappaB-like transcriptional mechanisms.
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Angiotensina II/farmacología , Arteriosclerosis/fisiopatología , Sistema Renina-Angiotensina/fisiología , Molécula 1 de Adhesión Celular Vascular/biosíntesis , Animales , Presión Sanguínea/efectos de los fármacos , Células Cultivadas , Expresión Génica/efectos de los fármacos , Hipertensión/fisiopatología , Inmunohistoquímica , Masculino , Norepinefrina/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Angiotensina/fisiología , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin, which is a critical cofactor for NO synthase (NOS). In addition, previous literature suggests that inactivation of NO(*) by increased vascular production superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states. We sought to determine whether these 2 seemingly disparate mechanisms were related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent relaxation while having no effect in vessels from control mice. Treatment of normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*-) production, seemingly from eNOS, because this effect was absent in vessels lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-) with NO(*) but also through interactions between peroxynitrite and tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase.
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Apolipoproteínas E/deficiencia , Biopterinas/análogos & derivados , Endotelio Vascular/fisiología , Pterinas , Vasodilatación/fisiología , Acetilcolina/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Aorta Torácica/fisiología , Apolipoproteínas E/genética , Biopterinas/metabolismo , Calcimicina/farmacología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Femenino , Técnicas In Vitro , Ionóforos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Nitratos/farmacología , Óxido Nítrico Sintasa/deficiencia , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Nitroglicerina/farmacología , Pteridinas/farmacología , Superóxidos/metabolismo , Superóxidos/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
OBJECTIVES: Nitroglycerin (NTG) is metabolized to nitric oxide (NO) in vascular smooth muscle cells. It is currently not clear whether prolonged exposure to NTG and tolerance development directly affects endogenous NO-mediated vasodilation in vivo. This study investigates NO-mediated vasodilation in conscious chronically catheterized rats before and after development of nitrate tolerance. The effect of the thiol compound N-acetylcysteine (NAC), which may affect NTG responsiveness, was also studied. METHODS: Nitrate tolerance was induced by a 72-h intravenous infusion of NTG and confirmed by a 65-68% reduction in the hypotensive response to NTG (P < 0.05). The hypotensive effects of acetylcholine (ACh) and sodium nitroprusside, (SNP) and possible NAC-mediated changes in the responses to these compounds were examined in nontolerant and nitrate-tolerant rats. Furthermore, the hypertensive response to the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) was measured. RESULTS: Nitrate tolerance was associated with a significantly attenuated hypotensive response to ACh (before 24 +/- 1 mmHg; after 17 +/- 2 mmHg, n = 7, P < 0.05). Similarly, the response to SNP was reduced from 32 +/- 1 mmHg to 26 +/- 3 mmHg (n = 7, P < 0.05). NTG-vehicle (placebo) did not affect the response to ACh and SNP (P > 0.05). NAC augmented the effect of NTG, ACh and SNP in both nontolerant and nitrate-tolerant animals (P < 0.05). The hypertensive response to L-NAME (n = 8), was reduced by 67% (from 34 +/- 6 mmHg to 11 +/- 1 mmHg, P < 0.05) after induction of nitrate tolerance. CONCLUSIONS: The results suggest (1) that nitrate tolerance in vivo is associated with cross tolerance to NO-mediated vasodilation produced by both exogenous and endogenous nitrovasodilators and (2) that also responses to nitrovasodilator agents other than NTG are improved by the addition of NAC.
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Nitratos/metabolismo , Óxido Nítrico/fisiología , Vasodilatación/fisiología , Acetilcolina/farmacología , Acetilcisteína/farmacología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Tolerancia a Medicamentos , Femenino , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nitroglicerina/farmacología , Nitroprusiato/farmacología , Ratas , Ratas Wistar , Vasodilatación/efectos de los fármacosRESUMEN
OBJECTIVE: Both disruption of the endothelial nitric oxide synthase (eNOS) gene and pharmacological inhibition of the NOS produce modest hypertension. It is unclear if and to what extent NOS isoforms other than eNOS contribute to this effect and how loss of one copy of the eNOS gene might impact on vascular reactivity or eNOS protein expression. METHODS: We examined protein expression, vascular reactivity, activity of soluble guanylate cyclase, blood pressure and heart rate in mice completely lacking the eNOS gene (eNOS-/-), wild-type mice (eNOS+/+) and mice heterozygotic for the eNOS gene (eNOS+/-). RESULTS: While eNOS-/- mice had mild hypertension and bradycardia, eNOS+/- mice were normotensive. In control mice, oral administration of L-NAME (approximately 100 mg/kg/day x 21 days) increased blood pressure to levels observed in eNOS-/- mice. In eNOS-/- mice, chronic oral administration of L-NAME had no effect on blood pressure, suggesting that inhibition of other NOS isoforms unlikely contribute to hypertension. L-NAME treatment induced bradycardia in both control and eNOS-/- mice, suggesting that both eNOS and other isoforms of NOS might be involved in heart rate control. Studies of aortic rings from eNOS-/- mice revealed a complete lack of endothelium-dependent vascular relaxation in response to acetylcholine and the calcium ionophore A23187 and an increase in sensitivity to phenylephrine, serotonin and nitroglycerin. Aortic rings from eNOS+/- mice demonstrated only minor alterations of responses to nitroglycerin and a normal relaxation to either acetylcholine or A23187 compared to vessels from eNOS-/+. Western analysis demonstrated that eNOS expression was virtually identical between eNOS+/+ and eNOS+/- mice and was absent in eNOS-/- mice. The activity of lung-isolated soluble guanylate cyclase was identical in the three strains of mice. CONCLUSIONS: We conclude that loss of one copy of the eNOS gene, as observed in heterozygotic animals, has no effect on vascular reactivity, blood pressure or eNOS protein expression. Isoforms of NOS, other than eNOS are unlikely involved in blood pressure regulation but may participate in heart rate control.
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Hemodinámica/genética , Hipertensión/genética , Isoenzimas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Animales , Aorta Torácica , Presión Sanguínea/genética , Western Blotting , Inhibidores Enzimáticos/farmacología , Eliminación de Gen , Expresión Génica , Guanilato Ciclasa/metabolismo , Frecuencia Cardíaca/genética , Heterocigoto , Hipertensión/metabolismo , Técnicas In Vitro , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Vasoconstricción/genéticaRESUMEN
Experiments in cultured vascular smooth muscle cells have shown that angiotensin II (Ang II) stimulates expression of endothelin-1. We sought to examine role of endothelin-1 in the effects of Ang II in vivo. Ang II infusion in rats (0.7 mg/kg per day for 5 days) was associated with marked increases in vascular smooth muscle endothelin-1 levels, as assessed by immunostaining. Administration of the selective endothelin type A (ET(A)) receptor antagonist PD 155080 (50 mg/kg per day) abrogated the hypertensive response to a 5-day infusion of Ang II (0.7 mg/kg per day), as did losartan (25 mg/kg per day). ET(A) receptor blockade during Ang II-mediated hypertension was associated with marked elevations of plasma endothelin-1 levels. Ang II-mediated hypertension was associated with heightened vascular responsiveness to a variety of vasoconstrictor agents except endothelin-1. Blockade of ET(A) receptor invariably corrected this vasoconstrictor hyperresponsiveness. We conclude that some of the vascular effects of Ang II thought to be unique to this hormone are likely mediated by endothelin-1.
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Angiotensina II/fisiología , Dioxoles/farmacología , Antagonistas de los Receptores de Endotelina , Endotelina-1/fisiología , Hipertensión/fisiopatología , Análisis de Varianza , Angiotensina II/administración & dosificación , Antagonistas de Receptores de Angiotensina , Animales , Antihipertensivos/farmacología , Aorta Torácica/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Presión Sanguínea/efectos de los fármacos , Endotelina-1/sangre , Imidazoles/farmacología , Técnicas In Vitro , Losartán , Masculino , Fenilefrina/farmacología , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina A , Serotonina/farmacología , Coloración y Etiquetado , Tetrazoles/farmacología , Factores de Tiempo , Vasoconstrictores/farmacologíaRESUMEN
Expression in the mouse salivary glands may be used as a model system for studies involving oral cavity delivery of gene products. Previously, sequences from the mouse Psp gene were used to build a minigene construct denoted 'Lama'. This construct was used as a cassette for expression of human factor VIII light chain in mouse saliva. However, whereas the endogenous Psp mRNA is the most abundant protein-coding transcript in the parotid glands, the Lama mRNA was expressed below 1% of the level of Psp mRNA in these glands. Here, we show that a 25-kb cosmid-derived DNA fragment (PspX25) carrying the structural gene and large flanking areas of Psp is expressed in all 14 analysed lines in the parotid glands. The average level of transgene expression was estimated to be 45% of that of the endogenous Psp gene. More importantly, it was possible to transfer PspX25's ability for high-level parotid gland expression to the Lama construct.
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Glándulas Salivales/fisiología , Proteínas y Péptidos Salivales/genética , Animales , Secuencia de Bases , Regulación de la Expresión Génica , Ratones , Ratones Transgénicos , ARN Mensajero/genética , Secuencias Reguladoras de Ácidos Nucleicos , TransgenesRESUMEN
[structure: see text]. A new method for intramolecular glycosylation, in which the donor and acceptor were linked via a 3,5-dinitrosalicylic acid derivative, was developed. Simply dissolving the tethered glycoside in CH3NO2 and warming to 40-60 degrees C led to formation of 1,4-linked disaccharides under neutral, hence, exceptionally mild, conditions.
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Disacáridos/síntesis química , Glicosilación , HidrólisisRESUMEN
Protoplast fusions between Brassica napus and Orychophragmus violaceus for transfer of valuable traits to oilseed rape resulted in 257 somatic hybrid plants. Hybridity was confirmed by morphological, cytological and molecular means. Symmetric fusions gave rise to 131 plants. Fifty eight of these plants had an intermediate morphology and contained nuclear DNA corresponding to the sum of the parental species. All 131 plants were sterile with no pollen grains observed upon flowering. Another 126 plants were derived from asymmetric fusions in which protoplasts of the donor parent O. violaceus were irradiated by 100 or 200-Gy X-rays prior to fusion. Morphologically these plants showed a larger variation compared to the plants regenerated from symmetric fusion experiments. In contrast to plants obtained from symmetric fusions, fertile hybrids were recovered among regenerants from the asymmetric fusions. Twenty four of these plants released viable pollen grains and 14 of the determined 17 plants set seeds after either selfing or backcrossing to B. napus. Fourteen male-sterile plants were identified with female fertility. This observed male sterility most-likely originated from alloplasmic recombination and would be of great potential for the development of a new cytoplasmic male sterility system. The fatty acid composition of the fertile hybrids and their progenies showed a biased distribution towards the B. napus parent, which has a high erucic acid-content type. However, increased levels of palmitic and linoleic acids compared to B. napus were found in subsequent generations, as well as a reduced level of erucic acid.
RESUMEN
A well known complication in the treatment of infectious endocarditis is development of neutropenia caused by treatment with antibiotics in high concentrations over long periods. Neutropenia often necessitates discontinuation of antibiotic treatment. Three patients with infectious endocarditis who developed neutropenia are reported. The patients were treated with granulocyte colony stimulating factor (G-CSF), a haematopoietic growth factor that stimulates neutrophils. G-CSF induced an immediate increase in white blood cell count, primarily neutrophils. G-CSF may be effective in ameliorating neutropenia in patients who receive antibiotics for treatment of infectious endocarditis.