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AIMS: Microcystis population and microcystin (MC) dynamics were investigated in western Lake Erie coastal wetlands and downstream beach water. A three-dimensional (3-D) model was developed to quantify how Microcystis population size and structure affect MCs. METHODS AND RESULTS: Real-time PCR, denaturing gradient gel electrophoresis (DGGE) and enzyme-linked immunoabsorbent assay (ELISA) were used. A moderate-low level of Microcystis abundance and MCs were detected with a significant increase along the wetland flow and the spatiotemporal homogeneity of Microcystis populations. The proportion of toxigenic and nontoxgenic genotypes appeared to be more affected by the variation in two major Microcystis PC-IGS genotypes. MC dynamics was associated with the changing Microcystis population size and structure. The 3-D model showed that Microcystis population with greater Microcystis PC-IGS abundance (and simultaneously higher diversity) had more MCs. CONCLUSION: Microcystin variation was significantly affected by Microcystis population size and structure. The 3-D model also revealed the relative importance of Microcystis population size and structure in determining MCs in the Lake Erie costal wetland and downstream beach water. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enriches our understanding of Microcystis population and microcystin ecology in a western Lake Erie coastal wetland and downstream beach water. Our illustrative model brings a new perspective for understanding the ecological relationship between Microcystis population size and structure and MCs.
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Biodiversidad , Lagos/microbiología , Microcistinas/biosíntesis , Microcystis/aislamiento & purificación , Microcystis/metabolismo , Genotipo , Microcystis/genética , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena en Tiempo Real de la Polimerasa , HumedalesRESUMEN
Haemophilia patients with inhibitors require bypassing agents (BPA) like activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) to control bleeds. Adjunct tranexamic acid (TXA) may improve haemostasis. The objective of this study was to investigate safety and haemostatic effect of TXA given in combination with BPA. Healthy volunteers (N = 5) and haemophilia inhibitor patients (N = 6) were enrolled in a prospective case crossover design. Controls were treated with TXA 20 mg kg(-1) orally (O.R.) Patients were treated with aPCC 75 IU kg(-1) intravenous (I.V.) on day 1 followed by TXA 20 mg kg(-1) O.R. combined with aPCC 75 IU kg(-1) I.V. on day 2. A 14-day washout occurred before crossover to rFVIIa 90 µg kg(-1) I.V. ±TXA. Safety evaluation and blood sampling processes were performed at baseline, 15, 30, 60, 120, 180 and 240 min post treatment. Primary outcome was maximum clot firmness (MCF) evaluated by whole blood thromboelastometry using a TF + tissue plasminogen activator-based assay. Healthy controls showed a 20-fold increase in MCF following TXA. Adjunct TXA to aPCC or rFVIIa induced a significant increase in MCF (P < 0.0001) reaching levels indistinguishable from healthy controls treated with TXA (P > 0.05). Infusion of aPCC or rFVIIa alone induced only 3-10 fold increase in MCF from baseline, with a decline in MCF starting after 60-120 min. TXA did not increase the endogenous thrombin potential. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed. Combination of aPCC or rFVIIa with TXA normalizes clot stability in haemophilia patients with inhibitor as compared to healthy controls. No clinical or laboratory adverse events were observed.
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Antifibrinolíticos/uso terapéutico , Factores de Coagulación Sanguínea/uso terapéutico , Hemofilia A/tratamiento farmacológico , Ácido Tranexámico/uso terapéutico , Adulto , Inhibidores de Factor de Coagulación Sanguínea/sangre , Estudios Cruzados , Hemofilia A/sangre , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tromboelastografía , Adulto JovenAsunto(s)
Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Adulto , Anticuerpos Bloqueadores/metabolismo , Teorema de Bayes , Cálculo de Dosificación de Drogas , Factor VIII/inmunología , Humanos , Isoanticuerpos/metabolismo , Cumplimiento de la Medicación , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Medicina de PrecisiónRESUMEN
This paper investigates the effect of glycation on glucose transport in erythrocytes. Glucose transporter function, numbers and erythrocyte phosphorylation rates are simultaneously studied using 30 Caucasian patients with diabetes and 30 Caucasian control volunteers (mean +/- SD where P < or = 0.05; age 48 +/- 8 vs. 45 +/- 8 years [ns]; body mass index [BMI] 31 +/- 7 vs. 27 +/- 5 [P=0.035]; blood glucose 12 +/- 7 vs. 5 +/- 0.6 mmol/L [P=0.001]; HbA1c 8 +/- 2 vs. 5 +/- 0.3% [P=0.0001]; fructosamine 336 +/- 64 vs. 237 +/- 16 micromol/L [P=0.0001]; disease duration 13 +/- 11 years, respectively). Significant differences were found for glucose transporter function, with 3-O-methylglucose uptake rates (108 +/- 49 vs. 146 +/- 55 micromol/L/sec/10(12) cells [P=0.010]); D-glucose influx (64 +/- 30 vs. 117 +/- 45 micromol/L/sec/10(12) cells [P=0.0001]); and D-glucose net transport (31 +/- 22 vs. 74 +/- 55 micromol/L/sec/ 10(12) cells [P = 0.0001]). No differences were found for phosphorylation rates using 2-deoxyglucose (33 +/- 17 vs. 38 +/- 12 micromol/L/sec/10(12) cells [P=0.194]). The number of functional transporters using cytochalasin B studies measured via B(max), was not found to be significantly different between the groups (195 +/- 139 vs. 264 +/- 174 [P=0.206]). However, K(d) was lower for those with diabetes, suggesting higher binding affinity (12 +/- 11 vs. 32 +/- 25 nmol/L [P=0.006]). A negative correlation between HbAlc and D-glucose influx involving both groups was found (r=-0.670, P=0.0001). Glucose transport is shown to be decreased in people who have diabetes compared to normoglycaemic volunteers, whereas the number of glucose transporters is apparently unchanged; however, affinity for binding is increased.
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Diabetes Mellitus Tipo 2/metabolismo , Eritrocitos/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Glucosa/farmacocinética , Adulto , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Citocalasina B/metabolismo , Citocalasina B/farmacología , Eritrocitos/efectos de los fármacos , Glicosilación/efectos de los fármacos , Humanos , Técnicas In Vitro , Persona de Mediana EdadRESUMEN
Concerns have been raised regarding pharmacokinetic performance, efficacy and safety of B-domain-deleted recombinant FVIII (BDD rFVIII). The objective of this study was to perform a retrospective survey of half-life measurements, efficacy and safety in patients with severe haemophilia A, switching treatment from full-length factor VIII (FL FVIII) to BDD rFVIII and then back to FL FVIII. We hypothesized that half-life of FVIII would be equal regardless of product and that total factor consumption and bleeding frequency would be indistinguishable. We report on inhibitor development and outcome following surgery. Patients with severe haemophilia A, exposed to BDD rFVIII were identified from a database. A retrospective analysis of laboratory data and medical notes was undertaken. No significant difference was detected between the half-life measurements during the switch from FL FVIII (T/2 median 9.15 h, range 6.4-22) to BDD rFVIII (T/2 median 9.7, range 4.7-16.8) and back to FL FVIII (T/2 median 9.0, range 5.0-19.5). There was no significant difference in coagulation factor usage (BDD rFVIII median 4803 IU kg(-1) year(-1), range 659-11 304; FL FVIII median 5349, range 1691-10 146), nor bleeds. Eleven received BDD rFVIII to cover surgical procedures, with no reports of excess bleeding. Thirty-three patients received significant exposure to BDD rFVIII and one developed a low titre inhibitor. BDD rFVIII was found to be equivalent to other FVIII products in terms of pharmacokinetics, clinical efficacy and safety in this study group.
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Inhibidores de Factor de Coagulación Sanguínea/farmacocinética , Factores de Coagulación Sanguínea/farmacocinética , Factor VIII/farmacocinética , Hemofilia A/tratamiento farmacológico , Hemorragia/tratamiento farmacológico , Adolescente , Inhibidores de Factor de Coagulación Sanguínea/uso terapéutico , Factores de Coagulación Sanguínea/uso terapéutico , Niño , Preescolar , Estudios Cruzados , Factor VIII/uso terapéutico , Semivida , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cystine and lysine accumulation in vitro in intestinal and renal tissue was studied in eight dogs that form cystine stones. Under conditions which demonstrate in vitro defects in tissue obtained from humans with cystinuria, normal amino acid accumulation occurred in six dogs with the canine disorder. Normal amino acid uptake in tissue and the demonstration of normal to minimum increases in excretion of lysine suggest that the canine disorder is not similar to the human syndrome.
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Aminoácidos/metabolismo , Cistinuria/metabolismo , Mucosa Intestinal/metabolismo , Yeyuno/metabolismo , Corteza Renal/metabolismo , Cálculos Urinarios/metabolismo , Animales , Transporte Biológico , Cistina/metabolismo , Modelos Animales de Enfermedad , Perros , Glicina/metabolismo , Humanos , Lisina/metabolismo , Lisina/orinaRESUMEN
The ability of renal cortical slices to accumulate a monosaccharide is enhanced at temperatures below 37 degrees C. Increase in concentration gradients occurs despite a decrease in total sugar flux. The apparent explanation for this paradox is a proportionally greater inhibition of efflux.
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Glicósidos/metabolismo , Riñón/metabolismo , Temperatura , Animales , Transporte Biológico , Isótopos de Carbono , Técnicas In Vitro , Cinética , RatasRESUMEN
After incubation at 37 degrees C the subsequent uptake of alpha-aminoisobutyric acid, cycloleucine, glycine, and L-proline by newborn (as compared to adult) rat kidney cortex slices is enhanced. The effect is abolished by the presence of cycloheximide, actinomycin D, and high concentrations of the above-mentioned amino acids in the medium during the 37 degrees C incubation prior to measurement of uptake. The data suggest that there is an adaptive control mechanism which is expressed on incubation at 37 degrees C and which can regulate amino acid transport in newborn rat kidney cortex.
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Aminoácidos/metabolismo , Animales Recién Nacidos/metabolismo , Corteza Renal/metabolismo , Ácidos Aminoisobutíricos/metabolismo , Animales , Radioisótopos de Carbono , Cicloheximida/farmacología , Ciclopentanos/metabolismo , Dactinomicina/farmacología , Depresión Química , Glicina/metabolismo , Técnicas In Vitro , Cinética , Leucina/metabolismo , Lisina/metabolismo , Metilglicósidos/metabolismo , Prolina/metabolismo , Ratas , Temperatura , Valina/metabolismoRESUMEN
Nest predation may influence population dynamics of birds on the Arctic Coastal Plain (ACP) of Alaska, USA. Anthropogenic development on the ACP is increasing, which may attract nest predators by providing artificial sources of food, perches, den sites, and nest sites. Enhanced populations or concentrations of human-subsidized predators may reduce nest survival for tundra-nesting birds. In this study, we tested the hypothesis that nest survival decreases in proximity to human infrastructure. We monitored 1257 nests of 13 shorebird species and 619 nests of four passerine species at seven sites on the ACP from 2002 to 2005. Study sites were chosen to represent a range of distances to infrastructure from 100 m to 80 km. We used Cox proportional hazards regression models to evaluate the effects of background (i.e., natural) factors and infrastructure on nest survival. We documented high spatial and temporal variability in nest survival, and site and year were both included in the best background model. We did not detect an effect of human infrastructure on nest survival for shorebirds as a group. In contrast, we found evidence that risk of predation for passerine nests increased within 5 km of infrastructure. This finding provides quantitative evidence of a relationship between infrastructure and nest survival for breeding passerines on the ACP. A posteriori finer-scale analyses (within oil field sites and individual species) suggested that Red and Red-necked Phalaropes combined (Phalaropus fulicarius, P. lobatus) had lower productivity closer to infrastructure and in areas with higher abundance of subsidized predators. However, we did not detect such a relationship between infrastructure and nest survival for Semipalmated and Pectoral Sandpipers (Calidris pusilla, C. melanotos), the two most abundant shorebirds. High variability in environmental conditions, nest survival, and predator numbers between sites and years may have contributed to these inconsistent results. We recommend targeted management actions to minimize anthropogenic effects and suggest new research needed on this issue as expanding development is planned for the ACP of Alaska. In particular, we recommend research on demography of key predators and their importance with respect to nest survival, and experimental studies that better address challenges posed by high natural variability.
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Aves , Ecosistema , Actividades Humanas , Conducta Predatoria , Alaska , Animales , Regiones Árticas , Humanos , Modelos Biológicos , Comportamiento de NidificaciónRESUMEN
INTRODUCTION: Demand for flexible training is increasing. The contribution of such trainees to the trained medical workforce is not clear. METHODS: All full time and flexible trainees in Scotland were 'tracked' at the completion of training. RESULTS: 80% of flexible trainees took up a consultant post of which 93% were in Scotland. 82% of full time trainees took up a consultant post of which 80% were in Scotland. DISCUSSION: Flexible trainees become consultants at the same rate as their full time counterparts. They are commonly geographically tied and are therefore more likely to remain in Scotland and contribute to retention of doctors in this country.
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Educación Médica/métodos , Actitud del Personal de Salud , Humanos , Admisión y Programación de Personal , Escocia , Medicina Estatal/organización & administración , Factores de TiempoRESUMEN
The shared transport system for uptake of L-cystine and L-lysine was examined in isolated rat renal brush-border membrane vesicles for the ionic requirements for activation of the system. No requirement for sodium was seen for either cystine or lysine influx. However, the efflux of lysine from the vesicle was stimulated by Na+. Therefore, the transport system appears to be asymmetric in its requirement for sodium. Two different divalent cations were used in the membrane isolations which resulted in different responses of cystine uptake to the electrogenic movement of K+ out of the vesicle. Membranes prepared by Mg-aggregation showed no stimulation of cystine influx by the imposition of a transient interior negative potential while vesicles prepared by Ca-aggregation did respond to electrogenic stimulation by an outwardly directed K-diffusion potential in the presence of valinomycin. Lysine influx was stimulated by electrogenic potassium efflux in both Mg-prepared and Ca-prepared membranes. No difference in sodium requirement for cystine influx was seen between the vesicles isolated by different cation-aggregation methods.
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Cistina/metabolismo , Riñón/metabolismo , Lisina/metabolismo , Microvellosidades/metabolismo , Animales , Transporte Biológico , Colina/metabolismo , Difusión , Iones , Riñón/efectos de los fármacos , Cinética , Microvellosidades/efectos de los fármacos , Potasio/metabolismo , Ratas , Ratas Endogámicas , Sodio/metabolismo , Valinomicina/farmacologíaRESUMEN
Diamide directly added to renal cortical slices inhibits the uptake of amino acids. Steady-state kinetic analysis indicates an inhibition of alpha-amino acid influx without effect on efflux. The effect could be reversed by addition of pyruvate to the incubation medium. Although there was a good correlation of the transport effect of diamide with its ability to decrease cellular reduced glutathione concentration, there did not appear to be a necessary connection between them. This was shown by the fact that renal cortical slices stored at 4 degrees C have no alteration in amino acid uptake despite the fact that GSH concentration is as low as that seen with diamide. Diamide was shown to have a direct effect on the uptake of glycine by isolated renal brush border membrane vesicles.
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Aminoácidos/metabolismo , Compuestos Azo/farmacología , Diamida/farmacología , Corteza Renal/metabolismo , Ácidos Aminoisobutíricos/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Glucosa/metabolismo , Glutatión/metabolismo , Glicina/metabolismo , Técnicas In Vitro , Corteza Renal/efectos de los fármacos , Masculino , Metilglucósidos/metabolismo , Piruvatos/metabolismo , Ratas , Valina/metabolismoRESUMEN
Cystine and lysine bind to isolated rat renal brush-border vesicles. Three methods to determine the extent of amino acid binding to the membranes have been compared, one relying on the osmotic reactivity of the vesicle, a second by trichloroacetic acid precipitation of membrane-bound material and a third by initial rate analysis. For cystine, all methods yield comparable results at early time points, indicating the trichloroacetic acid method is a simple and valuable tool for binding estimation under initial-rate or near initial-rate conditions. For lysine, initial rate analysis and osmotic perturbation are the methods of choice since lysine co-precipitates with trichloroacetic acid.
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Cistina/metabolismo , Riñón/metabolismo , Lisina/metabolismo , Microvellosidades/metabolismo , Animales , Precipitación Química , Cinética , Concentración Osmolar , Ratas , Ácido TricloroacéticoRESUMEN
BACKGROUND: We recently discovered an autosomal dominant disease causing a progressive dementia. The disease is caused by a point mutation in the gene coding for the serine protease inhibitor (ie, serpin) neuroserpin. The mutation results in an unstable neuroserpin protein that readily aggregates into intraneuronal inclusions that we identify as Collins bodies. The bodies are distributed throughout the cerebral hemispheres but are significantly more numerous in the cortex and the substantia nigra. We have named the disease familial encephalopathy with neuroserpin inclusion bodies (FENIB). OBJECTIVES: To describe the cognitive and neurophysiological changes exhibited by individuals with FENIB and to correlate the phenotypic expression of the disease with the neuropathological findings. DESIGN: Multiple case studies using neuropsychological assessment, electroencephalography (EEG), magnetic resonance imaging (MRI), and single-photon emission computed tomographic (SPECT) studies of family members were performed. Using these measures, we also compared family members in whom the mutation is present with family members in whom the mutation was absent to control for nonspecific familial factors. SUBJECTS: Nine individuals (5 women, aged 31-64 years; 4 men, aged 43-67 years) from 2 generations of family members related to the first reliably identified individual with symptoms of this disease. Symptoms, by self-report and reports of other family members, ranged from asymptomatic to severe dementia. Six of the 9 individuals carried the disease mutation. RESULTS: All subjects with the mutation demonstrated some cognitive changes, with the greatest demonstrated by subjects older than 40 years. The changes included restricted attention, concentration, and response regulation functions, reduced controlled oral fluency (word-list generation), and restricted visuospatial organization. In general, recall memory was not as affected as other cognitive domains. The most severely affected subject demonstrated global dementia with prominent frontal lobe features. Findings on SPECT showed anomalies limited to frontal areas in the less affected subjects and more global, patchy areas of hypoperfusion in the more severely affected subjects. The 3 oldest and most affected subjects demonstrated slowing on EEG findings. The MRI findings were noncontributory except in the 2 most severe cases, which showed global cortical atrophy. CONCLUSIONS: Cognitive changes in mildly to moderately affected subjects were characterized by deficits in frontal and frontal-subcortical area-dependent processes. Continued progressive deterioration of cerebral functions with relative sparing of recall memory suggests a unique dementia associated with this disease.
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Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Trastornos Heredodegenerativos del Sistema Nervioso/patología , Neuropéptidos/genética , Serpinas/genética , Adulto , Trastornos del Conocimiento/diagnóstico por imagen , Electroencefalografía , Salud de la Familia , Femenino , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico por imagen , Humanos , Cuerpos de Inclusión/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Mutación Puntual , Tomografía Computarizada de Emisión de Fotón Único , NeuroserpinaRESUMEN
Two animal models for cystinuria have been examined: the Basenji dog with Fanconi syndrome and cystine stone-forming dogs of various breeds. Brush-border membranes were isolated from these animals and uptake of D-glucose and L-cystine was characterized. Experiments with isolated brush-border vesicles from Basenji dogs with cystinuria as a component of the Fanconi syndrome showed diminished sodium-dependent D-glucose uptake but no decrease in L-cystine uptake even though the cystine defect in vivo was as high as 94% (ie, 6% reabsorption). In contrast, brush-border vesicles isolated from the kidney of a cystine stone-forming dog (Welsh Corgi) with a cystine defect of only 16% (ie, 84% reabsorption) had decreased uptake of cystine compared to values found for Beagle and Basenji vesicles. Thus, cystinuria found in Basenji dogs with the Fanconi syndrome differs from that in classic stone-forming cystinuric dogs. The alteration responsible for the cystinuria of Basenji dogs with Fanconi syndrome does not appear to have a membrane locus and may reflect altered energetics for transport, which are not detected in isolated vesicles. The cystine defect in cystinuric stone-forming dogs does appear to be reflected in the isolated membrane.
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Cistinuria/metabolismo , Síndrome de Fanconi/metabolismo , Aminoácidos/farmacología , Animales , Transporte Biológico , Cistina/metabolismo , Modelos Animales de Enfermedad , Perros , Femenino , Tasa de Filtración Glomerular , Glucosa/metabolismo , Riñón/metabolismo , Cinética , Masculino , Microvellosidades/metabolismo , Sodio/farmacologíaRESUMEN
To comprehend the renal defect underlying the idiopathic Fanconi syndrome in the Basenji dog, we have used isolated renal brush border membrane vesicles to examine two factors that influence membrane nonelectrolyte transport processes, sodium flux and membrane fluidity. We have found that there is no significant difference in the rate of uptake of 100 mmol/L 22Na+ and conclude that the previously observed defects in the sodium gradient-stimulated overshoot of glucose and of proline are not related to an alteration in the flux of sodium at physiological concentrations. Since carrier proteins exist in a lipid milieu, alteration in the physical state of the lipid membrane can determine transport function. Renal brush border preparations from normal and affected animals were studied by measuring fluorescence polarization to assess differences in the physical state of the membranes using the fluorescent probe, DPH, which quantitates inner core membrane fluidity. Membranes from affected dogs consistently showed a higher fluidity as measured by eta, a parameter of DPH fluorescence polarization. Since membrane fluidity is related to lipid composition, the data suggest that there may be an important alteration in the lipids in renal membranes of affected animals.
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Enfermedades de los Perros , Síndrome de Fanconi/veterinaria , Riñón/fisiopatología , Fluidez de la Membrana , Microvellosidades/metabolismo , Sodio/metabolismo , Animales , Transporte Biológico , Membrana Celular/metabolismo , Perros , Síndrome de Fanconi/metabolismo , Síndrome de Fanconi/fisiopatología , Femenino , Riñón/metabolismo , Túbulos Renales/fisiopatología , Cinética , MasculinoRESUMEN
To comprehend the renal defect underlying idiopathic Fanconi syndrome in the Basenji dog, we have focused on delineating the lipid profiles of renal brush border membranes isolated from affected and normal Basenji dogs to establish any physical or compositional changes underlying previously observed transport and membrane-fluidity changes. The lipid composition was studied with respect to total lipid, cholesterol, and phospholipid content, cholesterol to phospholipid ratio, distribution of the major phospholipid classes, and fatty acid composition. Total phospholipid of the isolated renal brush border membranes from Fanconi syndrome dogs analyzed by 31P nuclear magnetic resonance showed no difference compared with that of normal dogs. Examination of total fatty acids in both membranes using gas-liquid chromatography analysis of fatty acid methyl esters showed no difference in the mole percents of the major fatty acids. Our data suggest that changes in bulk membrane fluidity of the Fanconi syndrome dog renal brush border as measured by 1,6-diphenyl-1,3,5-hexatriene cannot be attributed to phospholipid and fatty acid compositional change. In the membranes isolated from affected dog kidney, the cholesterol content determined by gas-liquid chromatography analysis was 66 mol% higher than in membranes isolated from normal dog kidney. This correlates with the higher cholesterol to phospholipid molar ratio of 0.82 +/- 0.08 in the affected animal as compared with 0.58 +/- 0.04 in the normal. Cholesterol content and its microdomain in the membrane bilayer may be important in modulating transport functions. Increased membrane cholesterol content may affect the conformational motility of membrane transport proteins and thus affect their function.
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Perros , Síndrome de Fanconi/metabolismo , Riñón/metabolismo , Metabolismo de los Lípidos , Animales , Colesterol/metabolismo , Cromatografía de Gases , Modelos Animales de Enfermedad , Ácidos Grasos/metabolismo , Femenino , Lípidos/química , Espectroscopía de Resonancia Magnética , Masculino , Microvellosidades/metabolismo , Fosfolípidos/metabolismoRESUMEN
Estrogens are known to increase the renin-angiotensin-aldosterone system and to produce fluid retention, while atrial natriuretic peptide (ANP) induces an increase of the urinary output and tends to return the fluid balance to normal. The aim of this study was to test whether the levels of ANP were decreased during chronic estrogen and progestin administration, thereby possibly decreasing the amount of fluid excreted. The authors also studied women with premenstrual syndrome (PMS), because of the associated fluid retention often described with this syndrome. Levels of ANP, plasma renin activity (PRA), and aldosterone were determined in premenopausal women in the early follicular phase (EFP) and on low-dose oral contraceptives (OC), in postmenopausal patients with and without estrogen replacement therapy (ERT), and in women with PMS associated with fluid retention. The concentrations of ANP and PRA were enhanced in the women on OC, but those of aldosterone were unchanged. No differences were observed in the women on ERT or with PMS. It is concluded that the levels of PRA and ANP are affected by estrogen or progesterone therapy or the combination of the two and this response is dose dependent or additive. Furthermore, ANP and PRA do not seem to play a direct role in PMS.
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Aldosterona/sangre , Factor Natriurético Atrial/sangre , Estrógenos/farmacología , Síndrome Premenstrual/sangre , Renina/sangre , Adulto , Anticonceptivos Orales/farmacología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Glutamate had no significant effect on the uptake of 0.025 mM cystine by isolated rat renal cortical tubules and brushborder membrane vesicles in contrast to lysine which significantly inhibits cystine transport. Glutamate, however, markedly inhibited cystine uptake by rat renal tubule cells grown in a serum-free, hormonally defined media for 5 days. Lysine also inhibited cystine transport in these cultured renal tubule cells.
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Cistina/metabolismo , Glutamatos/farmacología , Corteza Renal/ultraestructura , Túbulos Renales/metabolismo , Microvellosidades/metabolismo , Animales , Transporte Biológico , Membrana Celular/metabolismo , Células Cultivadas , Técnicas de Cultivo , Interacciones Farmacológicas , Ácido Glutámico , Túbulos Renales/efectos de los fármacos , Túbulos Renales/ultraestructura , Lisina/farmacología , Masculino , Microvellosidades/efectos de los fármacos , Microvellosidades/ultraestructura , Ratas , Ratas EndogámicasRESUMEN
To explore the nature of differences in uptake by renal brush border vesicles from animals of different ages, vesicles were isolated from 7-day old and adult rats by a Mg-aggregation method. A number of criteria were compared in vesicles from the young and mature animals. The vesicles isolated from animals of both ages appear similar on electron microscopy, in response to osmotic changes, and in uptake kinetics for L-glucose. Despite these parameters which indicate no basic differences between the membranes of young and mature kidney, differences in proline and sodium handling are seen. When compared to the uptake pattern seen in vesicles from adult animals, the height of the sodium gradient-stimulated proline overshoot is diminished and sodium entry is faster in vesicles of the 7-day old rats. These are the same differences which were found in vesicles prepared by differential centrifugation from 7-day old animals. In addition, although sodium efflux was faster from vesicles of immature kidney and mirrored the faster sodium entry, proline efflux was slower. The data indicate a dissociation of proline and sodium fluxes in brush borders of the young rat kidney.