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OBJECTIVE: Morbidity in fetuses affected by gastroschisis is mainly the result of bowel ischaemic and inflammatory processes. Experimental studies on animal models show that clearing amniotic fluid from the digestive secretions by amnioexchange procedures reduces the inflammatory process. We evaluated the benefit of the amnioexchange procedure for fetal gastroschisis in humans. DESIGN: Prospective, interventional, randomised study. SETTING: Eight referral centres for fetal medicine. POPULATION: Pregnant women carrying a fetus with gastroschisis. METHODS: We compared, in utero, amnioexchange with a sham procedure. The protocol included, in both arms, steroid injections at 30 weeks of gestation and the use of postnatal minimal enteral feeding. MAIN OUTCOME MEASURES: The primary outcome was a composite variable based on the duration of ventilation and parenteral nutrition. Secondary outcomes were the effectiveness and safety of the amnioexchange procedure, including the rate of perinatal death, time to full enteral feeding, primary closure, and late feeding disorders. RESULTS: Sixty-four patients were randomised. There was no difference in the composite criteria between the amnioexchange and control groups. Based on an intention-to-treat analysis, there were no significant between-group differences in pregnancy outcome or complications. When studying the relationship between digestive compounds and amniotic fluid inflammatory markers, a clear correlation was found between bile acid and both ferritin and interleukin 1ß (IL1ß). CONCLUSIONS: In humans, amnioexchange, as described in our protocol, is not an option for fetal care; however, we provide supplementary proof of the involvement of inflammation in the pathogenicity of gastroschisis and suggest that future research should aim at reducing inflammation. ClinicalTrials.gov: NCT00127946. TWEETABLE ABSTRACT: A prospective, interventional, randomised study shows no benefit of amnioexchange for fetal gastroschisis in humans.
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Líquido Amniótico/química , Cloruros/administración & dosificación , Drenaje/métodos , Enfermedades Fetales/terapia , Gastrosquisis/terapia , Atención Prenatal/métodos , Cloruro de Sodio/administración & dosificación , Adulto , Biomarcadores/análisis , Cloruros/farmacocinética , Drenaje/efectos adversos , Femenino , Enfermedades Fetales/diagnóstico , Gastrosquisis/diagnóstico , Edad Gestacional , Humanos , Mediadores de Inflamación/análisis , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Cloruro de Sodio/farmacocinéticaRESUMEN
BACKGROUND/AIMS: Excessive salt intake and left ventricular hypertrophy (LVH) are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3) plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. METHODS: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. RESULTS: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. CONCLUSION: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.
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Presión Sanguínea/efectos de los fármacos , Cardiomegalia/etiología , Cloruro de Sodio/farmacocinética , Proteína Desacopladora 3/genética , Animales , Cardiomegalia/metabolismo , Ecocardiografía , Metabolismo Energético/efectos de los fármacos , Corazón/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Miocardio/patología , Proteína Desacopladora 3/deficienciaRESUMEN
Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1 hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1 hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1 hr-1 for 5 hr.
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Bromuros/sangre , Solución Salina/farmacocinética , Animales , Anticonvulsivantes/sangre , Anticonvulsivantes/envenenamiento , Bromuros/envenenamiento , Perros/sangre , Perros/metabolismo , Femenino , Infusiones Intravenosas/veterinaria , Soluciones Isotónicas/administración & dosificación , Soluciones Isotónicas/farmacocinética , Compuestos de Potasio/sangre , Compuestos de Potasio/envenenamiento , Solución de Ringer/administración & dosificación , Solución de Ringer/farmacocinética , Solución Salina/administración & dosificación , Cloruro de Sodio/administración & dosificación , Cloruro de Sodio/farmacocinéticaRESUMEN
Marine teleosts can absorb imbibed seawater (SW) to maintain water balance, with esophageal desalination playing an essential role. NaCl absorption from luminal SW was enhanced 10-fold in the esophagus of SW-acclimated eels, and removal of Na+ or Cl- from luminal SW abolished the facilitated absorption, indicating coupled transport. Mucosal/serosal application of various blockers for Na+/Cl- transporters profoundly decreased the absorption. Among the transporter genes expressed in eel esophagus detected by RNA-seq, dimethyl amiloride-sensitive Na+/H+ exchanger (NHE3) and 4,4'-diisothiocyano-2,2'-disulfonic acid-sensitive Cl-/[Formula: see text] exchanger (AE) coupled by the scaffolding protein on the apical membrane of epithelial cells, and ouabain-sensitive Na+-K+-ATPases (NKA1α1c and NKA3α) and diphenylamine-2-carboxylic acid-sensitive Cl- channel (CLCN2) on the basolateral membrane, may be responsible for enhanced transcellular NaCl transport because of their profound upregulation after SW acclimation. Upregulated carbonic anhydrase 2a (CA2a) supplies H+ and [Formula: see text] for activation of the coupled NHE and AE. Apical hydrochlorothiazide-sensitive Na+-Cl- cotransporters and basolateral Na+-[Formula: see text] cotransporter (NBCe1) and AE1 are other possible candidates. Concerning the low water permeability that is typically seen in marine teleost esophagus, downregulated aquaporin genes (aqp1a and aqp3) and upregulated claudin gene (cldn15a) are candidates for transcellular/paracellular route. In situ hybridization showed that these upregulated transporters and tight-junction protein genes were expressed in the absorptive columnar epithelial cells of eel esophagus. These results allow us to provide a full picture of the molecular mechanism of active desalination and low water permeability that are characteristic to marine teleost esophagus and gain deeper insights into the role of gastrointestinal tracts in SW acclimation.
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Anguilas/fisiología , Esófago/fisiología , Absorción Gastrointestinal/fisiología , Aguas Salinas/farmacocinética , Tolerancia a la Sal/fisiología , Simportadores de Cloruro de Sodio-Potasio/fisiología , Animales , Permeabilidad de la Membrana Celular/fisiología , Activación del Canal Iónico/fisiología , Agua de Mar , Cloruro de Sodio/farmacocinéticaRESUMEN
BACKGROUND: The number of cardiac cycles that need to be reviewed by echocardiography before a significant intrapulmonary shunt can be excluded remains unclear. METHODS: We retrospectively identified patients with cirrhosis who underwent technetium-99 m-labeled macroaggregated albumin scanning. The kinetics of bubble appearance after the injection of agitated saline during transthoracic echocardiograms were assessed in these patients. RESULTS: For the 64 eligible patients, the mean ± SD age was 56 ± 9 years. The median (IQR) shunt fraction by radionuclide scanning was 7.7% (2.8%-19.9%). Microbubbles were seen in the left atrium (LA) and left ventricle (LV) at a median (IQR) of 4 (2-5) and 4 (2-5) beats, respectively. The number of heart cycles before microbubbles appeared in the LA or LV was inversely associated with the nuclear scanning shunt fraction (R = -0.42, P = .001, R = -0.46, P < .001, respectively). If no microbubbles were detected by heart cycle 7, the shunt fraction was uniformly less than 3%. Patients with arterial oxygen <60 mm Hg, compared to ≥60 mm Hg, had earlier appearance of microbubbles in the left heart chambers (2.6 ± 1.9 vs 4.0 ± 2.3 beats, P = .046). CONCLUSIONS: In patients with advanced cirrhosis suspected of having hepatopulmonary syndrome, a greater shunt fraction during nuclear scanning was associated with more pronounced hypoxemia and a prompt and more intense appearance of microbubbles in the left-sided heart chambers. Patients with a shunt fraction above 3% have microbubbles in the LA or LV at some point during the first seven heart cycles.
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Medios de Contraste/farmacocinética , Ecocardiografía/métodos , Cardiopatías/diagnóstico por imagen , Aumento de la Imagen/métodos , Cirrosis Hepática/complicaciones , Microburbujas , Cloruro de Sodio/farmacocinética , Femenino , Cardiopatías/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
In vitro, replacing KCl with potassium glutamate (KGlu), the Escherichia coli cytoplasmic salt and osmolyte, stabilizes folded proteins and protein-nucleic acid complexes. To understand the chemical basis for these effects and rank Glu- in the Hofmeister anion series for protein unfolding, we quantify and interpret the strong stabilizing effect of KGlu on the ribosomal protein domain NTL9, relative to the effects of other stabilizers (KCl, KF, and K2SO4) and destabilizers (GuHCl and GuHSCN). GuHSCN titrations at 20 ° C, performed as a function of the concentration of KGlu or another salt and monitored by NTL9 fluorescence, are analyzed to obtain R-values quantifying the Hofmeister salt concentration (m3) dependence of the unfolding equilibrium constant K(obs) [r-value = −d ln K(obs)/dm3 = (1/RT) dΔG(obs) ° /dm3 = m-value/RT]. r-Values for both stabilizing K+ salts and destabilizing GuH+ salts are compared with predictions from model compound data. For two-salt mixtures, we find that contributions of stabilizing and destabilizing salts to observed r-values are additive and independent. At 20 ° C, we determine a KGlu r-value of 3.22 m(−1) and K2SO4, KF, KCl, GuHCl, and GuHSCN r-values of 5.38, 1.05, 0.64, −1.38, and −3.00 m(−1), respectively. The KGlu r-value represents a 25-fold (1.9 kcal) stabilization per molal KGlu added. KGlu is much more stabilizing than KF, and the stabilizing effect of KGlu is larger in magnitude than the destabilizing effect of GuHSCN. Interpretation of the data reveals good agreement between predicted and observed relative r-values and indicates the presence of significant residual structure in GuHSCN-unfolded NTL9 at 20 ° C.
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Escherichia coli/metabolismo , Ácido Glutámico/química , Ácido Glutámico/farmacocinética , Dominios y Motivos de Interacción de Proteínas , Desplegamiento Proteico , Proteínas Ribosómicas/química , Proteínas Ribosómicas/metabolismo , Cinética , Pliegue de Proteína , Sales (Química)/química , Sales (Química)/farmacocinética , Cloruro de Sodio/química , Cloruro de Sodio/farmacocinética , TermodinámicaRESUMEN
PURPOSE: To assess whether and to what extent irrigation fluid absorption occurs during laser vaporization (LV) of the prostate using the 180 W XPS™ GreenLight laser. METHODS: This prospective investigation was performed in a tertiary care center with a consecutive series of patients undergoing 180 W LV of the prostate. Intraoperative irrigation was performed with isotonic saline containing 1 % ethanol. The volume of irrigation fluid absorption was calculated from periodically performed breath ethanol measurements during LV. Additionally, intraoperative changes in biochemical and hematological blood parameters were assessed. RESULTS: Positive breath ethanol tests were detectable in 22 of 54 patients. The median absorption volume in these patients was 950 ml (range 208-4579 ml). Ten patients absorbed more than 2000 ml. Absorbers had smaller prostates, more capsular perforations and injuries to venous sinuses, and more total energy was applied with higher output power. Five patients had transient symptoms potentially related to fluid absorption. A significant drop in hemoglobin, hematocrit, venous pH and bicarbonate and an increase in chloride were detectable in the absorber group. These changes were significantly different in the non-absorber group. CONCLUSIONS: Absorption of irrigation fluid did occur in a relevant proportion of patients undergoing XPS™ GreenLight LV. High-volume absorption (≥2000 ml), which might be clinically relevant, was detectable in almost 20 % of all procedures. Absorption of saline irrigation fluid does not result in a classical TUR syndrome, but fluid and chloride overload can lead to serious complications, particularly in cardiovascular high-risk patients. Thus, patients with symptoms potentially related to fluid absorption should be monitored carefully.
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Absorción Fisiológica , Etanol/farmacocinética , Complicaciones Intraoperatorias/etiología , Terapia por Láser , Prostatectomía/métodos , Cloruro de Sodio/farmacocinética , Irrigación Terapéutica , Anciano , Anciano de 80 o más Años , Pruebas Respiratorias , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
INTRODUCTION: Transurethral resection risks excessive absorption of irrigating fluid with potentially severe or life-threatening consequences. We determined the amount of absorbed saline irrigation fluid during photoselective vaporisation of the prostate (PVP) and bipolar transurethral resection of the prostate (bTURP). PATIENTS AND METHODS: Patients at our institution treated by one of these methods were monitored by the alcometric method: ethanol is added to the irrigation fluid and blood alcohol is measured with a breathalyser. Various possible correlations were investigated. RESULTS: Data from 71 patients (36 PVP, 35 bTURP) were analysed. Detection of any absorption was more frequent under bTURP (71% of patients) than under PVP (39%; p = 0.006). Absorption in the volume range 500-1,000 ml was conspicuously more frequent in the bTURP procedure than in PVP. CONCLUSIONS: Presence of absorption was more frequent under bTURP than under PVP. However, high-volume absorption was more frequent during bTURP than in PVP.
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Absorción Fisiológica , Etanol/farmacocinética , Síntomas del Sistema Urinario Inferior/metabolismo , Síntomas del Sistema Urinario Inferior/cirugía , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/cirugía , Cloruro de Sodio/farmacocinética , Resección Transuretral de la Próstata/métodos , Anciano , Pruebas Respiratorias , Humanos , Masculino , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Irrigación TerapéuticaRESUMEN
PURPOSE: Absorption of irrigation fluid was not detected during GreenLight™ laser vaporization of the prostate using the first generation 80 W laser. However, data are lacking on intraoperative irrigation fluid absorption using the second generation 120 W high power laser. We assessed whether fluid absorption occurs during high power laser vaporization of the prostate. MATERIALS AND METHODS: We performed this prospective investigation at a tertiary referral center in patients undergoing 120 W laser vaporization for prostatic bladder outlet obstruction. Normal saline containing 1% ethanol was used for intraoperative irrigation. The expired breath ethanol concentration was measured periodically during the operation using an alcometer. The volume of saline absorption was calculated from these concentrations. Intraoperative changes in hematological and biochemical blood parameters were also recorded. RESULTS: Of 50 investigated patients 22 (44%) had a positive breath ethanol test. Median absorption volume in the absorber group was 725 ml (range 138 to 3,452). Ten patients absorbed more than 1,000 ml. Absorbers had a smaller prostate, more capsular perforation, higher bleeding intensity and more laser energy applied during the operation. Three patients (13%) had symptoms potentially related to fluid absorption. Hemoglobin, hematocrit and serum chloride were the only blood parameters that changed significantly in the absorber group. The changes were significantly different than those in nonabsorbers. CONCLUSIONS: Fluid absorption occurs frequently during high power laser vaporization of the prostate. This should be considered in patients who present with cardiopulmonary or neurological symptoms during or after the procedure.
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Absorción Fisiológica , Etanol/farmacocinética , Cuidados Intraoperatorios/efectos adversos , Complicaciones Intraoperatorias/etiología , Terapia por Láser , Cloruro de Sodio/farmacocinética , Resección Transuretral de la Próstata/métodos , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Etanol/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cloruro de Sodio/administración & dosificación , Irrigación Terapéutica/efectos adversosRESUMEN
Infusion fluids are often given to restore blood pressure (volume resuscitation), but may also be administered to replace ongoing losses, match insensible losses, correct electrolyte or acid-base disorders, or provide glucose. The development of new infusion fluids has provided clinicians with a wide range of products. Although the choice for a certain infusion fluid is often driven more by habit than by careful consideration, we believe it is useful to approach infusion fluids as drugs and consider their pharmacokinetic and pharmacodynamic characteristics. This approach not only explains why infusion fluids may cause electrolyte and acid-base disturbances, but also why they may compromise kidney function or coagulation. In this teaching case, we present a 19-year-old patient in whom severe hypernatremia developed as a result of normal saline solution infusion and explore the pharmacokinetic and pharmacodynamic effects of frequently used infusion fluids. We review clinical evidence to guide the selection of the optimal infusion fluid.
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Hipernatremia/inducido químicamente , Riñón/fisiopatología , Sustitutos del Plasma/efectos adversos , Cloruro de Sodio/efectos adversos , Desequilibrio Hidroelectrolítico/inducido químicamente , Acidosis/etiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/complicaciones , Volumen Sanguíneo , Parálisis Cerebral/complicaciones , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Coloides/efectos adversos , Coloides/uso terapéutico , Cuidados Críticos , Soluciones Cristaloides , Epilepsia/complicaciones , Resultado Fatal , Femenino , Fluidoterapia , Infecciones por Bacterias Grampositivas/etiología , Humanos , Hidrocefalia/cirugía , Hipernatremia/terapia , Discapacidad Intelectual/complicaciones , Soluciones Isotónicas/efectos adversos , Soluciones Isotónicas/química , Soluciones Isotónicas/farmacocinética , Soluciones Isotónicas/uso terapéutico , Complicaciones Posoperatorias/inducido químicamente , Infecciones Relacionadas con Prótesis/etiología , Resucitación/métodos , Cloruro de Sodio/farmacocinética , Cloruro de Sodio/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND AND AIMS: The activity of H(+)-ATPase is essential for energizing the plasma membrane. It provides the driving force for potassium retention and uptake through voltage-gated channels and for Na(+) exclusion via Na(+)/H(+) exchangers. Both of these traits are central to plant salinity tolerance; however, whether the increased activity of H(+)-ATPase is a constitutive trait in halophyte species and whether this activity is upregulated at either the transcriptional or post-translation level remain disputed. METHODS: The kinetics of salt-induced net H(+), Na(+) and K(+) fluxes, membrane potential and AHA1/2/3 expression changes in the roots of two halophyte species, Atriplex lentiformis (saltbush) and Chenopodium quinoa (quinoa), were compared with data obtained from Arabidopsis thaliana roots. KEY RESULTS: Intrinsic (steady-state) membrane potential values were more negative in A. lentiformis and C. quinoa compared with arabidopsis (-144 ± 3·3, -138 ± 5·4 and -128 ± 3·3 mV, respectively). Treatment with 100 mm NaCl depolarized the root plasma membrane, an effect that was much stronger in arabidopsis. The extent of plasma membrane depolarization positively correlated with NaCl-induced stimulation of vanadate-sensitive H(+) efflux, Na(+) efflux and K(+) retention in roots (quinoa > saltbush > arabidopsis). NaCl-induced stimulation of H(+) efflux was most pronounced in the root elongation zone. In contrast, H(+)-ATPase AHA transcript levels were much higher in arabidopsis compared with quinoa plants, and 100 mm NaCl treatment led to a further 3-fold increase in AHA1 and AHA2 transcripts in arabidopsis but not in quinoa. CONCLUSIONS: Enhanced salinity tolerance in the halophyte species studied here is not related to the constitutively higher AHA transcript levels in the root epidermis, but to the plant's ability to rapidly upregulate plasma membrane H(+)-ATPase upon salinity treatment. This is necessary for assisting plants to maintain highly negative membrane potential values and to exclude Na(+), or enable better K(+) retention in the cytosol under saline conditions.
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Adenosina Trifosfatasas/metabolismo , Arabidopsis/fisiología , Atriplex/fisiología , Chenopodium quinoa/fisiología , Proteínas de Plantas/metabolismo , Cloruro de Sodio/farmacocinética , Membrana Celular/fisiología , Transporte Iónico , Cinética , Potenciales de la Membrana , Raíces de Plantas/fisiología , Salinidad , Tolerancia a la Sal , Plantas Tolerantes a la Sal/fisiología , Intercambiadores de Sodio-Hidrógeno/metabolismoRESUMEN
BACKGROUND: We measured the spread of radiocontrast in the interscalene space after injection under low (<15 psi) and high (>20 psi) pressures. METHODS: Nine healthy volunteers received ultrasound-guided injections of 10 mL radio-opaque NaCl 0.9% in both interscalene spaces. Spread of injectate as assessed by computed tomography scan and discomfort on injection were recorded. RESULTS: Under both opening pressure conditions, injectate contacted 3 brachial plexus roots and spilled over the surface of the anterior and/or middle scalene muscles underneath the cervical fascia. CONCLUSIONS: Regardless of injection pressure, the interscalene space was filled with 10 mL of radiocontrast injectate.
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Bloqueo del Plexo Braquial , Plexo Braquial/diagnóstico por imagen , Medios de Contraste/farmacocinética , Músculo Esquelético/diagnóstico por imagen , Cloruro de Sodio/farmacocinética , Tomografía Computarizada por Rayos X , Adulto , Bélgica , Medios de Contraste/administración & dosificación , Femenino , Voluntarios Sanos , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Presión , Cloruro de Sodio/administración & dosificación , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent entity in elderly men. If medical treatment fails, monopolar transurethral resection of the prostate (TUR-P) is still considered as the standard treatment. The proportion of high-risk patients with cardiac comorbidities increases and TUR-P goes along with a relevant perioperative risk. Especially large volume influx of irrigation fluid and transurethral resection syndrome (TUR syndrome) represent serious threats to these patients. Using isotonic saline as irrigation fluid like in transurethral laser vaporization (TUV-P), TUR syndrome can be prevented. However, no prospective trial has ever assessed occurrence or extent of irrigation fluid absorption in Thulium Laser TUV-P. METHODS/DESIGN: This is a single-center prospective trial, investigating, if absorption of irrigation fluid occurs during Thulium Laser TUV-P by expired breath ethanol test. The expired breath ethanol technique is an established method of investigating intraoperative absorption of irrigation fluid: A tracer amount of ethanol is added to the irrigation fluid and the absorption of irrigation fluid can be calculated by measuring the expiratory ethanol concentrations of the patient with an alcohol breathalyzer. Fifty consecutive patients undergoing TUV-P at our tertiary referral center are included into the trial. Absorption volume of irrigation fluid during Thulium Laser TUV-P is defined as primary endpoint. Pre- to postoperative changes in bladder diaries, biochemical and hematological laboratory findings, duration of operation and standardized questionnaires are assessed as secondary outcome measures. DISCUSSION: The aim of this study is to assess the safety of Thulium Laser TUV-P in regard to absorption of irrigation fluid.
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Pruebas Respiratorias , Terapia por Láser , Hiperplasia Prostática/cirugía , Tulio , Absorción Fisiológica , Adulto , Pruebas Respiratorias/métodos , Etanol/farmacocinética , Humanos , Complicaciones Intraoperatorias/etiología , Periodo Intraoperatorio , Soluciones Isotónicas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/metabolismo , Cloruro de Sodio/farmacocinética , Resección Transuretral de la Próstata/métodosRESUMEN
In humans, when plasma sodium concentration rises slightly beyond 140 mM, vascular endothelium sharply stiffens and nitric oxide release declines. In search of a vascular sodium sensor, the endothelial glycocalyx was identified as being a negatively charged biopolymer capable of selectively buffering sodium ions. Sodium excess damages the glycocalyx and renders vascular endothelium increasingly permeable for sodium. In the long term, sodium accumulates in the interstitium and gradually damages the organism. It was discovered that circulating red blood cells (RBC) 'report' surface properties of the vascular endothelium. To some extent, the RBC glycocalyx mirrors the endothelial glycocalyx. A poor (charge-deprived) endothelial glycocalyx causes a poor RBC glycocalyx and vice versa. This observation led to the assumption that the current state of an individual's vascular endothelium in terms of electrical surface charges and sodium-buffering capabilities could be read simply from a blood sample. Recently, a so-called salt blood test was introduced that quantifies the RBC sodium buffer capacity and thus characterizes the endothelial function. The arguments are outlined in this article spanning a bridge from cellular nano-mechanics to clinical application.
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Permeabilidad de la Membrana Celular/fisiología , Endotelio Vascular/metabolismo , Eritrocitos/metabolismo , Glicocálix/metabolismo , Hipertensión , Sodio/metabolismo , Transporte Biológico/fisiología , Endotelio Vascular/patología , Eritrocitos/patología , Espacio Extracelular/metabolismo , Humanos , Hipertensión/metabolismo , Hipertensión/patología , Hipertensión/fisiopatología , Cloruro de Sodio/farmacocinéticaRESUMEN
CONTEXT: Inhaled hygroscopic aerosols will absorb water vapor from the warm and humid air of the human lung, thus growing in size and consequently changing their deposition properties. OBJECTIVE: The objectives of the present study are to study the effect of a stochastic lung structure on individual particle growth and related deposition patterns and to predict local deposition patterns for different hygroscopic aerosols. MATERIALS AND METHODS: The hygroscopic particle growth model proposed by Ferron et al. has been implemented into the stochastic asymmetric lung deposition model IDEAL. Deposition patterns were calculated for sodium chloride (NaCl), cobalt chloride (CoCl2 · 6H2O), and zinc sulfate (ZnSO4 · 7H2O) aerosols, representing high, medium and low hygroscopic growth factors. RESULTS: Hygroscopic growth decreases deposition of submicron particles compared to hydrophobic particles with equivalent diameters due to a less efficient diffusion mechanism, while the more efficient impaction and sedimentation mechanisms increase total deposition for micron-sized particles. Due to the variability and asymmetry of the human airway system, individual trajectories of inhaled particles are associated with individual growth factors, thereby enhancing the variability of the resulting deposition patterns. DISCUSSION AND CONCLUSIONS: Comparisons of model predictions with several experimental data for ultrafine and micrometer-sized particles indicate good agreement, considering intersubject variations of morphometric parameters as well as differences between experimental conditions and modeling assumptions.
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Contaminantes Atmosféricos/farmacocinética , Exposición por Inhalación/análisis , Pulmón/metabolismo , Modelos Biológicos , Material Particulado/farmacocinética , Absorción , Aerosoles , Contaminantes Atmosféricos/toxicidad , Cobalto/farmacocinética , Cobalto/toxicidad , Humanos , Pulmón/efectos de los fármacos , Material Particulado/toxicidad , Cloruro de Sodio/farmacocinética , Cloruro de Sodio/toxicidad , Procesos Estocásticos , Distribución Tisular , Agua/química , Sulfato de Zinc/farmacocinética , Sulfato de Zinc/toxicidadRESUMEN
To define roles for reactive oxygen species (ROS) and epithelial sodium channel (ENaC) in maintaining lung fluid balance in vivo, we used two novel whole animal imaging approaches. Live X-ray fluoroscopy enabled quantification of air space fluid content of C57BL/6J mouse lungs challenged by intratracheal (IT) instillation of saline; results were confirmed by using conventional lung wet-to-dry weight ratios and Evans blue as measures of pulmonary edema. Visualization and quantification of ROS produced in lungs was performed in mice that had been administered a redox-sensitive dye, hydro-Cy7, by IT instillation. We found that inhibition of NADPH oxidase with a Rac-1 inhibitor, NSC23766, resulted in alveolar flooding, which correlated with a decrease in lung ROS production in vivo. Consistent with a role for Nox2 in alveolar fluid balance, Nox2(-/-) mice showed increased retention of air space fluid compared with wild-type controls. Interestingly, fluoroscopic analysis of C57BL/6J lungs IT instilled with LPS showed an acute stimulation of lung fluid clearance and ROS production in vivo that was abrogated by the ROS scavenger tetramethylpiperidine-N-oxyl (TEMPO). Acute application of LPS increased the activity of 20 pS nonselective ENaC channels in rat type 1 cells; the average number of channel and single-channel open probability (NPo) increased from 0.14 ± 0.04 to 0.62 ± 0.23. Application of TEMPO to the same cell-attached recording caused an immediate significant decrease in ENaC NPo to 0.04 ± 0.03. These data demonstrate that, in vivo, ROS has the capacity to stimulate lung fluid clearance by increasing ENaC activity.
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Canales Epiteliales de Sodio/metabolismo , Líquido Extracelular/metabolismo , Glicoproteínas de Membrana/fisiología , NADPH Oxidasas/fisiología , Alveolos Pulmonares/enzimología , Canales de Sodio/metabolismo , Superóxidos/metabolismo , Aminoquinolinas/farmacología , Animales , Líquido Extracelular/diagnóstico por imagen , Técnicas de Inactivación de Genes , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/farmacocinética , Pulmón/diagnóstico por imagen , Pulmón/enzimología , Pulmón/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , NADPH Oxidasa 2 , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Neuropéptidos/antagonistas & inhibidores , Neuropéptidos/metabolismo , Técnicas de Placa-Clamp , Alveolos Pulmonares/metabolismo , Pirimidinas/farmacología , Radiografía , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Cloruro de Sodio/administración & dosificación , Cloruro de Sodio/farmacocinética , Proteínas de Unión al GTP rac/antagonistas & inhibidores , Proteínas de Unión al GTP rac/metabolismo , Proteína de Unión al GTP rac1RESUMEN
PURPOSE: To characterize the effects of pressure-driven brain infusions using high field intra-operative MRI. Understanding these effects is critical for upcoming neurodegeneration and oncology trials using convection-enhanced delivery (CED) to achieve large drug distributions with minimal off-target exposure. MATERIALS AND METHODS: High-resolution T2-weighted and diffusion-tensor images were acquired serially on a 7 Tesla MRI scanner during six CED infusions in nonhuman primates. The images were used to evaluate the size, distribution, diffusivity, and temporal dynamics of the infusions. RESULTS: The infusion distribution had high contrast in the T2-weighted images. Diffusion tensor images showed the infusion increased diffusivity, reduced tortuosity, and reduced anisotropy. These results suggested CED caused an increase in the extracellular space. CONCLUSION: High-field intra-operative MRI can be used to monitor the distribution of infusate and changes in the geometry of the brain's porous matrix. These techniques could be used to optimize the effectiveness of pressure-driven drug delivery to the brain.
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Encéfalo/anatomía & histología , Encéfalo/metabolismo , Infusiones Intraventriculares , Imagen por Resonancia Magnética Intervencional/métodos , Cloruro de Sodio/administración & dosificación , Cloruro de Sodio/farmacocinética , Animales , Macaca mulatta , Presión , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución TisularRESUMEN
BACKGROUND: Protective effects of saturated hydrogen (H(2)) saline on cardiac ischaemia-reperfusion (I/R) injury have been demonstrated previously. This study was designed to show that hydrogen-rich saline is protective in preventing lung I/R injury in rats. METHODS: Adult male Sprague-Dawley rats underwent 45 min occlusion of the right lung roots and 120 min reperfusion. Rats were divided randomly into three groups: sham-operated control group, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment (0.6 mmol/L, 0.5 ml/kg/d). Three days of intraperitoneal injection of hydrogen-rich saline before the reperfusion combined with immediate administration of hydrogen-rich saline after the reperfusion were performed. Following reperfusion, the lung tissue and the pulmonary artery was immediately obtained and the W/D ratio, pulmonary artery contraction and relaxation ability, H-E staining, TUNEL staining, caspase-3, MDA, 8-OHdG content and measurement of such biomarkers as WBC, CRP were measured or carried out. RESULTS: Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL. CONCLUSIONS: It is concluded that hydrogen-rich saline is a novel, simple, safe and effective method to attenuate pulmonary I/R injury.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Hidrógeno/farmacología , Daño por Reperfusión/tratamiento farmacológico , Cloruro de Sodio/farmacocinética , 8-Hidroxi-2'-Desoxicoguanosina , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/fisiopatología , Animales , Biomarcadores/sangre , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangre , Masculino , Malondialdehído/sangre , Arteria Pulmonar/metabolismo , Arteria Pulmonar/fisiopatología , Edema Pulmonar/sangre , Edema Pulmonar/tratamiento farmacológico , Edema Pulmonar/fisiopatología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/sangre , Daño por Reperfusión/fisiopatología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/fisiopatologíaRESUMEN
Trifolium alexandrinum L. was transformed with the Arabidopsis HARDY gene that belongs to the stress-related AP2/ERF (APETALA2/ethylene responsive element binding factors) superfamily of transcription factors. The fresh weights of the transgenic lines L2 and L3 were improved by 42 and 55% under drought stress and by 38 and 95% under salt stress compared to the wild type, respectively. The dry weights were similarly improved. Overexpression of HARDY improved the instantaneous water use efficiency (WUE) under drought stress by reducing transpiration (E) and under salt stress by improving photosynthesis (A), through reducing Na+ accumulation in leaves, and reducing E. However, HARDY improved the growth of drought-stressed transgenic plants as compared to the wild type by delaying water depletion from soil and preventing rapid decline in A. L2 and L3 had thicker stems and in case of L3, more xylem rows per vascular bundle, which may have made L3 more resistant to lodging in the field. Field performance of L2 and L3 under combined drought and salt stress was significantly better than that of the wild type in terms of fresh and dry weights (40%, 46% and 31%, 40%, respectively). The results provide further evidence for the efficiency of overexpression of a single gene in improving tolerance to abiotic stress under field conditions.