864 research outputs found

    Distribution of dopamine- and cAMP-dependent phosphoprotein (DARPP-32) in the developing and mature kidney

    Get PDF
    Distribution of dopamine- and cAMP-dependent phosphoprotein (DARPP-32) in the developing and the mature kidney. DARPP-32 is a dopamine- and cAMP-regulated inhibitor of protein phosphatase-1 (PP-1). Dopamine and DARPP-32 regulate sodium reabsorption in renal tubules by inhibiting the activity of Na+,K+-ATPase. We here report the pre- and postnatal distributions of DARPP-32 in the kidney as demonstrated by immunoblotting and immunohistochemistry. With immunoblotting we examined the abundance of DARPP-32 and the functionally similar but more widespread inhibitor of PP-1, inhibitor-1 (I-1). We compared their relative abundance in the renal cortex, renal medulla and neostriatum from the brain, where DARPP-32 is greatly enriched. DARPP-32 levels in the adult rat were fourfold higher in the neostriatum than in the renal medulla and 13-fold higher than in the renal cortex. I-1 levels were approximately the same in the neostriatum and in the renal medulla and 2.5-fold higher in neostriatum than in the renal cortex. Between postnatal day 10 (PN10) and 40 (PN40) DARPP-32 abundance increased 1.3-fold in the neostriatum, 1.4-fold in the renal cortex and sixfold in the medulla. The abundance of I-1 did not increase in the striatum from PN10 to PN40 but increased 1.5-fold in the renal cortex and threefold in the renal medulla. Thus, during the time of maturation of tubular transport function, the levels of both PP-1 inhibitors increased in the kidney, the largest increase being found in the renal medulla. With immunohistochemistry strong DARPP-32-like-immunoreactivity (DARPP-32-LI) was detected in the ureteral buds from gestational day 18 and up to postnatal day 8 when nephrogenesis was completed. No I-1-like immunoreactivity (I-1-LI) was found in the ureteral buds. From gestational day 21, DARPP-32-LI was identified in the proximal convoluted tubules. After postnatal day 8, DARPP-32-LI increased greatly in the medullary tubules of the thick ascending limb of Henle. These results suggest two separate roles for DARPP-32 in renal function. During tubulogenesis, DARPP-32 may participate in differentiation/proliferation. In the mature kidney, DARPP-32 participates in the regulation of sodium excretion

    Coexisting NPY and NE synergistically regulate renal tubular Na+, K+-ATPase activity

    Get PDF
    Coexisting NPY and NE synergistically regulate renal tubular Na+, K+-ATPase activity. The sympathetic renal nerves are of central importance for the regulation of sodium balance. Sodium excretion decreases following renal nerve activation and increases following denervation. These effects have been attributed to norepinephrine (NE) acting on α-adrenergic receptors. In the present study, using isolated permeabilized rat renal proximal convoluted tubule (PCT) cells, neuropeptide Y (NPY) was shown to stimulate Na+, K+-ATPase activity. This 36-amino acid peptide is a messenger molecule in the sympathetic nervous system which is co-stored with NE and dopamine-β-hydroxylase (DBH), the NE synthesizing enzyme in the renal nerves. The effect is likely to be mediated via the NPY Y2 receptor, a pertussis toxin (PTX)-sensitive G-protein, and calcium. It is partically antagonized by α-adrenergic antagonists, and enhanced by the subthreshold doses of α-adrenergic agonists. Our results suggest an important role for this peptide in the regulation of the sodium balance in the kidney

    Effect of vesicoureteral reflux on renal function in children with recurrent urinary tract infections

    Get PDF
    Effect of vesicoureteral reflux on renal function in children with recurrent urinary tract infections. The functional damage caused by vesicoureteral reflux (VUR) has been examined by unilateral clearance studies in 22 children with recurrent urinary tract infection (UTI) and representing 23 kidneys with large VUR, 7 kidneys with small to moderate VUR and 14 kidneys without VUR. Inulin clearance, Na+ excretion and glucose reabsorption were determined. In kidneys without or with small and moderate VUR, UTI had no effect on renal function if treated. In kidneys with large VUR extending into the pelvis and dilating the ureter, there was a gradual deterioration of glomerular filtration rate (GFR) that was accelerated after the age of 6yr. Before puberty more than 50% of renal function was lost despite strict medical care of the UTI. If this functional loss was unilateral, hyperfunction of the contralateral kidney was generally observed. Maximal glucose reabsorption was depressed in proportion to GFR. In kidneys with unilaterally low GFR, the fractional Na+ excretion was consistently increased as compared to the contralateral kidney with normal GFR. This adaptive increase in Na+ excretion must therefore be of intrarenal origin.Effet du reflux vésico-urétéral sur la fonction chez l'enfant atteint d'infection urinaire récidivante. L'altération de la fonction rénale déterminée par le reflux vésico-urétéral (VUR) a été étudiée par clearance unilatérale chez 22 enfants atteints d'infection urinaire récidivante (UTI). L'étude a porté sur 23 reins avec reflux importants, 7 reins avec reflux minime ou moyen et 14 reins sans reflux. La clearance de l'inuline, l'excrétion de Na et la réabsorption de glucose ont été déterminés. L'infection urinaire récidivante n'a pas d'effets sur la fonction des reins sans reflux ou avec reflux minime ou moyen. Dans les reins avec reflux important atteignant le bassinet et dilatant l'uretère on observe une détérioration progressive de la filtration glomérulaire, détérioration qui est plus rapide après l'âge de 6 ans. Avant la puberté, plus de 50% de la fonction rénale sont perdus malgré un traitement strict de l'infection urinaire récidivante. Quand cette diminution de la fonction est unilatérale, une augmentation de la fonction controlatérale est habituellement observée. La réabsorption maximale de gluclose est diminuée en proportion du débit de filtration glomérulaire. L'excrétion fractionnelle de sodium par les reins dont la filtration glomérulaire est diminuée est nettement plus grande que celle du rein controlatéral dont la filtration glomérulaire est normale. Il semble donc que cette adaptation dans l'excrétion du sodium doive être d'origine intrarénale

    Copper Inhibits the Water and Glycerol Permeability of Aquaporin-3

    Get PDF
    Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several other tissues. Erythrocytes are, together with kidney and liver, the main targets for copper toxicity. Here we report that both water and glycerol permeability of human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the natural buffer system in our body, doses in the range of those observed in Wilson disease and in copper poisoning caused significant inhibition. AQP7, another aquaglyceroporin, was insensitive to copper. Three extracellular amino acid residues, Trp128, Ser152, and His241, were identified as responsible for the effect of copper on AQP3. We have previously shown that Ser152 is involved in regulation of AQP3 by pH. The fact that Ser152 mediates regulation of AQP3 by copper may explain the phenomenon of exquisite sensitivity of human erythrocytes to copper at acidic pH. When AQP3 was co-expressed with another AQP, only glycerol but not water permeability was inhibited by copper. Our results provide a better understanding of processes that occur in severe copper metabolism defects such as Wilson disease and in copper poisoning

    It pays to promote joint PhD programmes between academia and the private sector

    Get PDF
    The prosperity of a country is closely related to its level of education to fuel research and innovation. Doctoral graduates have attained the highest education level and should be the key players in research and innovation. The number of doctoral graduates is increasing rapidly in most/many countries, but is less well correlated to changes in prosperity of a country.The innovative medicines initiative (IMI) was established to help Europe strengthen its position in biomedical research and development. During its planning stage IMI observed large gaps in the scientific interaction between academia and industry in Europe, and that undergraduate students were not realizing the career opportunities within biomedical R&D. A major objective for the education and training section of IMI, the European Medicines Research Training Network (EMTRAIN, http://www.emtrain.eu), has therefore been to work out a framework for public private partnership PhD (PPP-PhD) and to create a cohort of networking, industry-aware scientists

    Antenatal Corticosteroids and Postnatal Fluid Restriction Produce Differential Effects on AQP3 Expression, Water Handling, and Barrier Function in Perinatal Rat Epidermis

    Get PDF
    Loss of water through the immature skin can lead to hypothermia and dehydration in preterm infants. The water and glycerol channel aquaglyceroporin-3 (AQP3) is abundant in fetal epidermis and might influence epidermal water handling and transepidermal water flux around birth. To investigate the role of AQP3 in immature skin, we measured in vivo transepidermal water transport and AQP3 expression in rat pups exposed to clinically relevant fluid homeostasis perturbations. Preterm (E18) rat pups were studied after antenatal corticosteroid exposure (ANS), and neonatal (P1) rat pups after an 18 h fast. Transepidermal water loss (TEWL) and skin hydration were determined, AQP3 mRNA was quantified by RT-PCR, and in-situ hybridization and immunocytochemistry were applied to map AQP3 expression. ANS resulted in an improved skin barrier (lower TEWL and skin hydration), while AQP3 mRNA and protein increased. Fasting led to loss of barrier integrity along with an increase in skin hydration. These alterations were not paralleled by any changes in AQP3. To conclude, antenatal corticosteroids and early postnatal fluid restriction produce differential effects on skin barrier function and epidermal AQP3 expression in the rat. In perinatal rats, AQP3 does not directly determine net water transport through the skin

    Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

    Get PDF
    <p>Abstract</p> <p>Introduction</p> <p>Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus.</p> <p>Case presentation</p> <p>Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus.</p> <p>Conclusions</p> <p>In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.</p
    corecore