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1.
Eur J Clin Microbiol Infect Dis ; 34(10): 2017-21, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26205664

RESUMEN

In Europe, infections with Puumala hantavirus cause nephropathia epidemica. Presently the risk factors predicting severe kidney damage after Puumala virus infection are not well known. The objective of the study was to investigate environmental and individual factors predicting severe kidney damage caused by serologically established Puumala infections. In a nationwide cohort study we investigated all serologically established Puumala infections in Southern Denmark from 1996 to 2012. A total of 184 patients had serologically verified Puumala virus infection. In patients with Puumala virus infections the decrease of platelet counts preceded acute kidney failure. Multivariable logistic regression demonstrated that recent activities in the forest, platelet counts, and flu-like symptoms predicted estimated glomerular filtration rates less than 30 mL/min/1.73 m(²), but not age, gender, fever, nor abdominal pain. Severe kidney damage in Puumala infections in Southern Denmark is associated with the risk of recent activities in the forest.


Asunto(s)
Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Fiebre Hemorrágica con Síndrome Renal/sangre , Fiebre Hemorrágica con Síndrome Renal/complicaciones , Adulto , Estudios de Cohortes , Dinamarca , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Virus Puumala , Factores de Riesgo
2.
Acta Physiol (Oxf) ; 213(2): 481-91, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25069877

RESUMEN

AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse mesenteric arteries with an EC50 of 25 nm, but large mouse renal arteries or rat descending vasa recta only at >100-fold higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar concentration range was endothelium-dependent and absent in vessels of Trpv1 -/- mice. The TRPV4 agonist GSK1016790A relaxed large conducting renal arteries, mesenteric arteries and vasa recta with EC50 of 18, 63 nm and ~10 nm respectively. These effects were endothelium-dependent and inhibited by a TRPV4 antagonist, AB159908 (10 µm). Capsaicin and GSK1016790A produced vascular dilation in isolated mouse perfused kidneys with EC50 of 23 and 3 nm respectively. The capsaicin effects were largely reduced in Trpv1 -/- kidneys, and the effects of GSK1016790A were inhibited in Trpv4 -/- kidneys. CONCLUSION: Our results demonstrate that two TRPV channels have unique sites of vasoregulatory function in the kidney with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We suggest that TRPV1/4 channels are potent therapeutic targets for site-specific vasodilation in the kidney.


Asunto(s)
Riñón/irrigación sanguínea , Canales Catiónicos TRPV/metabolismo , Animales , Presión Sanguínea/fisiología , Capsaicina/farmacología , Endotelio Vascular/efectos de los fármacos , Riñón/efectos de los fármacos , Masculino , Arterias Mesentéricas/efectos de los fármacos , Ratones , Ratas Sprague-Dawley , Canales Catiónicos TRPV/genética , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología
3.
Exp Clin Endocrinol Diabetes ; 121(10): 614-23, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24122240

RESUMEN

To estimate medication costs in individuals with diagnosed diabetes, undetected diabetes, impaired glucose regulation and normal blood glucose values in a population-based sample by age and sex.Using the KORA F4 follow-up survey, conducted in 2006-2008 (n=2611, age 40-82 years), we identified individuals' glucose tolerance status by means of an oral glucose tolerance test. We assessed all medications taken regularly, calculated age-sex specific medication costs and estimated cost ratios for total, total without antihyperglycemic drugs, and cardiovascular medication, using multiple 2-part regression models.Compared to individuals with normal glucose values, costs were increased in known diabetes, undetected diabetes and impaired glucose regulation, which was more pronounced in participants aged 40-59 years than in those aged 60-82 years (cost ratios for all medications: 40-59 years: 2.85; 95%-confidence interval: 1.78-4.54, 2.00; 1.22-3.29 and 1.53; 1.12-2.09; 60-82 years: 2.04; 1.71-2.43, 1.17; 0.90-1.51 and 1.09; 0.94-1.28). Compared to individuals with diagnosed diabetes, costs were significantly lower among individuals with impaired glucose regulation across all age and sex strata, also when antihyperglycemic medication was excluded (40-59 years: 0.60; 0.36-0.98, 60-82 years: 0.74; 0.60-0.90; men: 0.72; 0.56-0.93; women: 0.72; 0.54-0.96).We could quantify age- and sex-specific medication costs and cost ratios in individuals with diagnosed diabetes, undetected diabetes and impaired glucose regulation compared to those with normal glucose values, using data of a population-based sample, with oral glucose tolerance test-based identification of diabetes states. These results may help to validly estimate cost-effectiveness of screening and early treatment or prevention of diabetes.


Asunto(s)
Diabetes Mellitus/economía , Tamizaje Masivo/economía , Adulto , Anciano , Anciano de 80 o más Años , Costos y Análisis de Costo , Diabetes Mellitus/epidemiología , Diabetes Mellitus/prevención & control , Femenino , Estudios de Seguimiento , Alemania , Prueba de Tolerancia a la Glucosa/economía , Humanos , Masculino , Persona de Mediana Edad
4.
Acta Physiol (Oxf) ; 207(3): 546-64, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23253200

RESUMEN

Recent preclinical data indicate that activators of transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) may improve the outcome of ischaemic acute kidney injury (AKI). The underlying mechanisms are unclear, but may involve TRPV1 channels in dorsal root ganglion neurones that innervate the kidney. Recent data identified TRPV4, together with TRPV1, to serve as major calcium influx channels in endothelial cells. In these cells, gating of individual TRPV4 channels within a four-channel cluster provides elementary calcium influx (calcium sparklets) to open calcium-activated potassium channels and promote vasodilation. The TRPV receptors can also form heteromers that exhibit unique conductance and gating properties, further increasing their spatio-functional diversity. This review summarizes data on electrophysiological properties of TRPV1/4 and their modulation by endogenous channel agonists such as 20-HETE, phospholipase C and phosphatidylinositide 3-kinase (PI3 kinase). We review important roles of TRPV1 and TRPV4 in kidney physiology and renal ischaemia reperfusion injury; further studies are warranted to address renoprotective mechanism of vanilloid receptors in ischaemic AKI including the role of the capsaicin receptor TRPV1 in primary sensory nerves and/or endothelium. Particular attention should be paid to understand the kidneys' ability to respond to ischaemic stimuli after catheter-based renal denervation therapy in man, whereas the discovery of novel pharmacological TRPV modulators may be a successful strategy for better treatment of acute or chronic kidney failure.


Asunto(s)
Enfermedades Renales/metabolismo , Riñón/metabolismo , Canales Catiónicos TRPV/metabolismo , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/fisiopatología , Animales , Humanos , Activación del Canal Iónico , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/inervación , Riñón/fisiopatología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Ligandos , Potenciales de la Membrana , Insuficiencia Renal/metabolismo , Insuficiencia Renal/fisiopatología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Transducción de Señal , Canales Catiónicos TRPV/efectos de los fármacos
5.
Am J Transplant ; 13(1): 167-73, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23094759

RESUMEN

We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells confirmed that the tumor was of female donor's origin in male kidney recipients. Recent literature associated increased urokinase-plasminogen-activator-receptor (uPAR) and plasma soluble urokinase-plasminogen-activator-receptor (suPAR) levels with metastatic malignancies. Now we found that, compared to baseline levels, both deceased-donor kidney recipients showed increased uPAR transcripts in mononuclear cells as well as increased plasma suPAR levels after the diagnosis of metastatic angiosarcomas, i.e. 4 months after donor tumor transmission. These results show an association of uPAR/suPAR in donor tumor transmission of metastatic angiosarcomas in humans.


Asunto(s)
Hemangiosarcoma/etiología , Trasplante/efectos adversos , Adulto , Secuencia de Bases , Cartilla de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Tomografía de Emisión de Positrones , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tomografía Computarizada por Rayos X
7.
Kidney Int ; 72(3): 231-2, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17653228

RESUMEN

Prevention of ototoxicity after the administration of aminoglycoside antibiotics has been notably difficult, in particular in patients with chronic kidney disease. Feldman et al. report that oral administration of 600 mg N-acetylcysteine twice daily significantly ameliorates gentamicin-induced ototoxicity in hemodialysis patients. That approach may help to prevent aminoglycoside-induced hearing loss in these high-risk patients in daily practice.


Asunto(s)
Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Pérdida Auditiva/prevención & control , Acetilcisteína/administración & dosificación , Acetilcisteína/efectos adversos , Administración Oral , Aminoglicósidos/efectos adversos , Aminoglicósidos/uso terapéutico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Bacteriemia/prevención & control , Gentamicinas/efectos adversos , Gentamicinas/uso terapéutico , Pérdida Auditiva/inducido químicamente , Humanos , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Diálisis Renal/métodos
8.
J Hum Hypertens ; 21(1): 60-7, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17024133

RESUMEN

The time-dependent incidence of cardiovascular events points to an important role of chronobiology for arterial properties. To evaluate arterial properties in patients with essential hypertension, we assessed arterial vascular tone during sleep at night in patients with essential hypertension and normotensive control subjects. Vascular tone was continuously quantified by the reflective index obtained by non-invasive digital photoplethysmography and an algorithm for continuous, investigator-independent, automatic analysis of digital volume pulse. During the first half of the night, the reflective index was significantly higher in 31 patients with essential hypertension compared to 30 normotensive control subjects (30.0+/-0.2 vs 28.8+/-0.2; P=0.001). In patients with essential hypertension, the reflective index significantly increased from 30.0+/-0.2 in the first half (from 2301 to 0230) to 30.7+/-0.2 in the second half (from 0231 to 0600) of the night (n=31; P=0.027). In normotensive control subjects the reflective index also significantly increased from 28.8+/-0.2 in the first half of the night to 30.2+/-0.2 in the second half of the night (n=30; P=0.001). An increase of the reflective index tone indicated systemic vasoconstriction as confirmed by cold pressure tests and a significant correlation between arterial vascular tone and sympathetic nerve activity measured by microneurography from the peroneal nerve. Photoplethysmographic determination of arterial vascular tone demonstrated a significant increase of systemic arterial vascular tone in patients with essential hypertension during the first half of the night compared to normotensive control subjects.


Asunto(s)
Hipertensión/fisiopatología , Músculo Liso Vascular/fisiopatología , Anciano , Ritmo Circadiano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pletismografía
9.
Am J Transplant ; 6(7): 1624-30, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16827863

RESUMEN

It is important whether impairment of renal allograft function may deteriorate arterial stiffness in renal transplant recipients. In a cross-sectional study, arterial vascular characteristics were non-invasively determined in 48 patients with renal allograft using applanation tonometry and digital photoplethysmography. Mean age was 51 +/- 2 years (mean +/- SEM), and studies were performed 17 +/- 1 months after transplantation. The stage of chronic kidney disease was based on the glomerular filtration rate. We observed a significant association between the stage of chronic kidney disease and arterial stiffness of large arteries S1 and small arteries S2 in renal transplant recipients (each p < 0.05 by non-parametric Kruskal-Wallis test between groups). Multivariate linear regression analysis showed that male gender of patients with renal allograft (p < 0.01) reduced glomerular filtration rate (p = 0.01), and older age of kidney donor (p = 0.04) were independently associated with an increase of large artery stiffness S1. Furthermore, a significant association between the stage of chronic kidney disease and arterial vascular reactivity during reactive hyperemia was observed (p < 0.05 by non-parametric Kruskal-Wallis test between groups). It is concluded that impairment of renal allograft function is associated with an increased arterial stiffness in renal transplant recipients.


Asunto(s)
Trasplante de Riñón , Riñón/irrigación sanguínea , Riñón/fisiopatología , Adulto , Estudios Transversales , Femenino , Humanos , Riñón/cirugía , Masculino , Persona de Mediana Edad , Trasplante Homólogo
10.
Kidney Int Suppl ; (100): S8-10, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16612403

RESUMEN

A widespread, rather general, definition of contrast-induced nephropathy (CIN) is an impairment in renal function occurring within 3 days following the intravascular administration of contrast media (CM) and the absence of an alternative aetiology. In spite of the vast clinical importance of CIN, its understanding and the pathophysiology behind CIN remain incomplete. Many studies have been performed; however, they have provided no widely accepted conclusion so far. Here the possible mechanisms underlying CIN are outlined, which span from altered rheological properties, perturbation of renal haemodynamics, regional hypoxia, auto-, and paracrine factors (adenosine, endothelin, reactive oxygen species) to direct cytotoxic effects. Although these potential mediators of CIN will be discussed separately, several factors may act in concert to perturb kidney function after exposure to contrast media. From the current knowledge of the mechanisms causing CIN, it is not possible to recommend a certain class of contrast media, except to avoid large doses of CM of the first generation. From a pathophysiological perspective, volume expansion is effective in avoiding CIN, since water permeability of the collecting ducts will decrease and enhance fluid excretion. Hence, CM in the distal portions of the tubular system is diluted, which implies reduced fluid viscosity and a lower risk of obstruction.


Asunto(s)
Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Túbulos Renales Distales/fisiopatología , Colorantes/farmacocinética , Medios de Contraste/administración & dosificación , Humanos , Túbulos Renales Distales/efectos de los fármacos , Mitocondrias/fisiología , Concentración Osmolar , Especies Reactivas de Oxígeno/metabolismo , Sales de Tetrazolio/farmacocinética , Tiazoles/farmacocinética
12.
Minerva Med ; 96(4): 277-85, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16179894

RESUMEN

Hypertension in chronic hemodialysis patients is very common, and associated with cardiovascular morbidity and mortality. On the other hand, normalization of blood pressure in this patient population results in improvement of survival in the long-term. Drug therapy for hypertension in hemodialysis patients includes mainly angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta-blockers and diuretics, but guidelines for the use of specific classes of antihypertensive medications do not exist for end-stage renal disease (ESRD) patients on maintenance hemodialysis treatment. In survival analyses, some studies are in favour for the ACE inhibitors, other studies report reduced risk of cardiovascular mortality by using calcium channel blockers. Beta blockers seem to be ideal antihypertensive agents, since sympathetic nerve activity is inappropriately increased in ESRD patients. Most studies indicate that hypertension control is still not adequate in the majority of chronic hemodialysis patients. Randomized, controlled clinical trials are needed to determine the most advantageous antihypertensive agent(s) to use in ESRD patients on chronic hemodialysis therapy.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Diálisis Renal , Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diuréticos/uso terapéutico , Humanos
13.
MMW Fortschr Med ; 146(22): 31-4, 2004 May 27.
Artículo en Alemán | MEDLINE | ID: mdl-15373106

RESUMEN

The antihypertensive agents of first choice include ACE-inhibitors, angiotensin receptor blockers, beta blockers, calcium antagonists and diuretic agents. For the selection of medicaments, the individual patient risk profile of decisive importance. In particular a metabolic syndrome, diabetes mellitus, disturbed renal function and/or a disturbed electrolyte household must be considered. For initial treatment monotherapy or a low-dose combination regime is suggested. If the response is inadequate, possible options include increasing the dose, changing the medicament, (sequential monotherapy) or, in the sense of stepped treatment, introduction of further combination drugs. Resistance to therapy should prompt consideration of a number of causes, in particular noncompliance on the part of the patient.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/administración & dosificación , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/uso terapéutico , Complicaciones de la Diabetes , Diuréticos/administración & dosificación , Diuréticos/uso terapéutico , Sinergismo Farmacológico , Quimioterapia Combinada , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertensión/complicaciones , Cooperación del Paciente , Insuficiencia Renal/complicaciones , Factores de Riesgo
14.
Eur Respir J ; 23(4): 601-4, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15083761

RESUMEN

Obstructive sleep apnoea syndrome (OSAS) is a common disorder in obesity. Leptin, an adipocyte-derived signalling factor, plays an important role in metabolic control. There is growing evidence that leptin regulation is altered in OSAS. Therefore, the aim of this study was to test the hypothesis that effective treatment will influence leptin levels in OSAS patients. Serum leptin levels were determined in 86 consecutive patients (aged 57.5 +/- 11.0 yrs) with polysomnographically verified OSAS. In addition, leptin levels were reassessed and treatment efficacy was evaluated by polysomnography after 6 months of therapy. Patients were treated with continuous or bilevel positive airway pressure, a mandibular advancement device or conservatively, depending on the clinical symptoms. Mean serum leptin levels did not change with treatment in the whole study group (7.3 +/- 5.0 versus 7.5 +/- 4.8 ng.mL-1), however, leptin levels decreased in effectively treated patients (8.5 +/- 5.0 versus 7.4 +/- 5.1 ng.mL-1) while they increased in ineffectively treated patients (5.0 +/- 4.0 versus 7.7 +/- 4.1 ng.mL-1). Furthermore, not only was there a significant and independent correlation between the change in leptin levels with treatment and the change in body mass index, but also with the change in apnoea/hypopnoea index. Effective treatment of sleep-disordered breathing may have significant effects on leptin levels in obstructive sleep apnoea syndrome patients. Changes in leptin levels are related to changes in apnoea/hypopnoea index in obstructive sleep apnoea syndrome patients.


Asunto(s)
Leptina/sangre , Apnea Obstructiva del Sueño/terapia , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Presión de las Vías Aéreas Positiva Contínua , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Avance Mandibular/instrumentación , Persona de Mediana Edad , Oxígeno/sangre , Cooperación del Paciente , Polisomnografía , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/clasificación , Resultado del Tratamiento
15.
Minerva Cardioangiol ; 51(5): 525-30, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14551521

RESUMEN

Radiocontrast-induced nephropathy is the 3rd most common cause of in-hospital acute renal failure after hypotension and surgery. Radio-graphic contrast media are used at a progressive rate for several diagnostic and therapeutic applications. Prevention of radiocontrast-induced nephropathy will become more important, including risk of patient impairment and costs. Radiocontrast-induced ne-phropathy is due to vasoconstriction-mediated renal medullary ischemia and direct toxic damage to renal tubular epithelial cells. These effects may in part be mediated by generation of reactive oxygen species. Several prospective, randomized, placebo-controlled studies in patients with moderate renal insufficiency showed that the prophylactic oral administration of acetylcysteine at a dose of 600 mg twice daily along with hydration prevents the reduction in renal function after radiocontrast administration. Recently, intravenous administration of acetyl-cysteine has also been shown to be effective. Use of acetylcysteine together with hydration is the treatment of choice to prevent radiocontrast-induced nephropathy.


Asunto(s)
Acetilcisteína/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Medios de Contraste/efectos adversos , Depuradores de Radicales Libres/uso terapéutico , Humanos
16.
J Clin Invest ; 112(2): 256-64, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12865413

RESUMEN

NO prevents atherogenesis and inflammation in vessel walls by inhibition of cell proliferation and cytokine-induced endothelial expression of adhesion molecules and proinflammatory cytokines. Reduced NO production due to inhibition of either eNOS or iNOS may therefore reinforce atherosclerosis. Patients with end-stage renal failure show markedly increased mortality due to atherosclerosis. In the present study we tested the hypothesis that uremic toxins are responsible for reduced iNOS expression. LPS-induced iNOS expression in mononuclear leukocytes was studied using real-time PCR. The iNOS expression was blocked by addition of plasma from patients with end-stage renal failure, whereas plasma from healthy controls had no effect. Hemofiltrate obtained from patients with end-stage renal failure was fractionated by chromatographic methods. The chromatographic procedures revealed a homogenous fraction that inhibits iNOS expression. Using gas chromatography/mass spectrometry, this inhibitor was identified as phenylacetic acid. Authentic phenylacetic acid inhibited iNOS expression in a dose-dependent manner. In healthy control subjects, plasma concentrations were below the detection level, whereas patients with end-stage renal failure had a phenylacetic acid concentration of 3.49 +/- 0.33 mmol/l (n = 41). It is concluded that accumulation of phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. That mechanism may contribute to increased atherosclerosis and cardiovascular morbidity in patients with end-stage renal failure.


Asunto(s)
Fallo Renal Crónico/sangre , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/biosíntesis , Fenilacetatos/sangre , Adulto , Anciano , Animales , Western Blotting , Línea Celular , Supervivencia Celular , Células Cultivadas , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Leucocitos Mononucleares/enzimología , Leucocitos Mononucleares/metabolismo , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Ratones , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II , Nitritos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Eur J Clin Invest ; 32(10): 732-7, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12406020

RESUMEN

BACKGROUND: Angiotensin-converting enzyme inhibitors may affect reactive oxygen species in humans in vitro and in vivo. In the present study we evaluated whether angiotensin-converting enzyme inhibitors may affect NAD(P)H oxidase activity. MATERIALS AND METHODS: The production of reactive oxygen species was measured spectrophotometrically in mononuclear leukocytes using the fluorescent dye, dichlorofluorescein diacetate. The effects of quinaprilat, captopril, enalaprilat and lisinopril on phorbol myristate acetate-induced reactive oxygen species generation were investigated in vitro. The effects of quinaprilat, captopril, enalaprilat and lisinopril on the NAD(P)H oxidase activity of the mononuclear leukocytes were measured photometrically. In addition, reactive oxygen species were measured before and 4 h after oral administration of quinapril. RESULTS: In vitro, the addition of quinaprilat (72 +/- 6% of control; mean +/- SEM; n= 19; P < 0.001) and captopril (48 +/- 2% of control; n= 19; P < 0.001) significantly reduced the phorbol-12-myristate-13-acetate-induced reactive oxygen species generation by the mononuclear leukocytes, whereas enalaprilat and lisinopril showed no effect. The effect of captopril on phorbol-12-myristate-13-acetate-induced reactive oxygen species generation in vitro was concentration-dependent. Quinaprilat and captopril significantly inhibited the NAD(P)H oxidase activity. After the oral administration of 10 mg of quinapril the phorbol-12-myristate-13-acetate-induced reactive oxygen species generation by the mononuclear leukocytes was significantly decreased from 1981 +/- 292% to 988 +/- 141% (n = 14; P < 0.01). CONCLUSION: Quinapril and captopril decrease the production of reactive oxygen species.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Captopril/farmacología , Isoquinolinas/farmacología , Leucocitos Mononucleares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tetrahidroisoquinolinas , Células Cultivadas , Relación Dosis-Respuesta a Droga , Enalaprilato/farmacología , Fluoresceínas , Colorantes Fluorescentes , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Lisinopril/farmacología , NADPH Oxidasas/antagonistas & inhibidores , Quinapril , Acetato de Tetradecanoilforbol/farmacología
18.
J Comput Biol ; 8(3): 325-37, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11535179

RESUMEN

Tandem mass spectrometry fragments a large number of molecules of the same peptide sequence into charged molecules of prefix and suffix peptide subsequences and then measures mass/charge ratios of these ions. The de novo peptide sequencing problem is to reconstruct the peptide sequence from a given tandem mass spectral data of k ions. By implicitly transforming the spectral data into an NC-spectrum graph G (V, E) where /V/ = 2k + 2, we can solve this problem in O(/V//E/) time and O(/V/2) space using dynamic programming. For an ideal noise-free spectrum with only b- and y-ions, we improve the algorithm to O(/V/ + /E/) time and O(/V/) space. Our approach can be further used to discover a modified amino acid in O(/V//E/) time. The algorithms have been implemented and tested on experimental data.


Asunto(s)
Algoritmos , Espectrometría de Masas/métodos , Análisis de Secuencia de Proteína/métodos , Ovalbúmina/análisis , Ovalbúmina/química
19.
Res Exp Med (Berl) ; 200(3): 155-68, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11426667

RESUMEN

Hyperhomocyst(e)inemia is commonly accepted as an independent atherosclerotic risk factor. In most hemodialysis patients, serum homocyst(e)ine is markedly elevated and may contribute to premature atherosclerosis in these patients. Whereas the beneficial effect of folate supplementation on serum homocyst(e)ine has been extensively studied, there are less detailed studies on the effects of cobalamin and pyridoxal phosphate alone, or in combination with folate. We examined the effect of a four-week course of intravenous treatment with folate (1.1 mg), cobalamin (1.0 mg), and pyridoxal phosphate (5.0 mg), administered once (group 1), twice (group 2) or thrice (group 3) weekly in 33 hemodialysis patients divided in three groups of 11 patients. All patients were followed for a further four weeks after treatment was stopped. Serum homocyst(e)ine, cobalamin, folate and pyridoxal phosphate, as well as the metabolites of homocyst(e)ine, methylmalonate, 2-methylcitrate and cystathionine, were determined before, during and after treatment. Baseline serum homocyst(e)ine correlated significantly with serum folate (P=0.0149), cobalamin (P=0.0047) and pyridoxal phosphate (P=0.0408). Correlations independent from the other metabolites or vitamins were found for methylmalonate (P=0.003) and folate (P=0.029). All regimens increased serum cobalamin significantly (in group 1 from 444 +/- 215 to 17,303 +/- 11,989 pg/ml, P<0.01; in group 2 from 542 +/- 633 to 44,896 +/- 15,772 pg/ml, P<0.001; in group 3 from 548 +/- 394 to 77,961 +/- 31,546 pg/ml, P<0.001), but did not increase any of the other vitamin levels. Serum homocyst(e)ine was lowered significantly by 39.8% +/- 31.9% (P<0.05) with two and by 30.1% +/- 26.9% (P<0.05) with three vitamin dosages weekly, but not with one dosage weekly. Since methylmalonate is known to be a sensitive marker of cobalamin deficiency, the data support an important influence of cobalamin levels on baseline homocyst(e)ine levels. Increasing cobalamin levels and additional treatment with folate and pyridoxal phosphate 156 may decrease serum homocyst(e)ine in the same way as high doses of folate alone.


Asunto(s)
Homocisteína/sangre , Fallo Renal Crónico/sangre , Diálisis Renal , Complejo Vitamínico B/administración & dosificación , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Hematínicos/administración & dosificación , Hematínicos/sangre , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Piridoxina/administración & dosificación , Piridoxina/sangre , Análisis de Regresión , Vitamina B 12/administración & dosificación , Vitamina B 12/sangre , Complejo Vitamínico B/sangre
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