Vasopressin regulation of sodium transport in the distal nephron and collecting duct.

Arginine vasopressin (AVP) is released from the posterior pituitary gland during states of hyperosmolality or hypovolemia. AVP is a peptide hormone, with antidiuretic and antinatriuretic properties. It allows the kidneys to increase body water retention predominantly by increasing the cell surface expression of aquaporin water channels in the collecting duct alongside increasing the osmotic driving forces for water reabsorption. The antinatriuretic effects of AVP are mediated by the regulation of sodium transport throughout the distal nephron, from the thick ascending limb through to the collecting duct, which in turn partially facilitates osmotic movement of water. In this review, we will discuss the regulatory role of AVP in sodium transport and summarize the effects of AVP on various molecular targets, including the sodium-potassium-chloride cotransporter NKCC2, the thiazide-sensitive sodium-chloride cotransporter NCC, and the epithelial sodium channel ENaC.

Characterization of a novel phosphorylation site in the sodium-chloride cotransporter, NCC.

The sodium-chloride cotransporter, NCC, is essential for renal electrolyte balance. NCC function can be modulated by protein phosphorylation. In this study, we characterized the role and physiological regulation of a novel phosphorylation site in NCC at Ser124 (S124). Novel phospho-specific antibodies targeting pS124-NCC demonstrated a band of 160 kDa in the kidney cortex, but not medulla, which was preabsorbed by a corresponding phosphorylated peptide. Confocal microscopy with kidney tubule segment-specific markers localized pS124-NCC to all distal convoluted tubule cells. Double immunogold electron microscopy demonstrated that pS124-NCC co-localized with total NCC in the apical plasma membrane of distal convoluted tubule cells and intracellular vesicles. Acute treatment of Munich-Wistar rats or vasopressin-deficient Brattleboro rats with the vasopressin type 2 receptor-specific agonist dDAVP significantly increased pS124-NCC abundance, with no changes in total NCC plasma membrane abundance. pS124-NCC levels also increased in abundance in rats after stimulation of the renin-angiotensin-aldosterone system by dietary low sodium intake. In contrast to other NCC phosphorylation sites, the STE20/SPS1-related proline-alanine-rich kinase and oxidative stress-response kinases (SPAK and OSR1) were not able to phosphorylate NCC at S124. Protein kinase arrays identified multiple kinases that were able to bind to the region surrounding S124. Four of these kinases (IRAK2, CDK6/Cyclin D1, NLK and mTOR/FRAP) showed weak but significant phosphorylation activity at S124. In oocytes, (36)Cl uptake studies combined with biochemical analysis showed decreased activity of plasma membrane-associated NCC when replacing S124 with alanine (A) or aspartic acid (D). In novel tetracycline-inducible MDCKII-NCC cell lines, S124A and S124D mutants were able to traffic to the plasma membrane similarly to wildtype NCC.

[The value of palpation as basis for decision on lymph node excision]. / Vaerdien af palpation som grundlag for lymfeknudeeksairese.

The purpose of the study was to evaluate palpation of the regional lymph nodes in control examinations of patients with malignant disease. A retrospective review of the medical records of 188 cases in which the patients had had an extirpation of the regional lymph nodes was performed. We have compared the preoperative findings through palpation with the histological diagnosis. The patients were grouped according to the region in which the lymph node removal had been done. The specificity of palpation when the histological diagnosis was malignant was (with 95% confidence limits), in the axilla 0.65 (0.54-0.75), in the inguinal region 0.86 (0.75-0.94) on the neck 0.83 (0.52-0.98) and in the suprahyoid region 0.58 (0.28-0.85). In conclusion, palpation of regional lymph nodes is not a sufficient control examination in the estimation of the course of malignant disease. Supplementary examination methods are recommended.

Autosomal recessive epidermolysis bullosa simplex. A case report.

We report a male child with autosomal recessive epidermolysis bullosa simplex presenting at birth. The patient subsequently developed cutaneous atrophy, nail dystrophy, milia and alopecia. He had growth retardation and anaemia, but there were no other associated abnormalities. Electron microscopy showed epidermolytic cleavage. The family history indicated an autosomal recessive mode of inheritance.

Short-contact treatment at home with Micanol.

The efficacy of home treatment of psoriasis with a new dithranol formulation, Micanol, was investigated in three studies. They were carried out according to a randomized, within-patient comparison design. In a 4-week pilot study Micanol was compared with placebo (10 patients) and in two 6-week studies Micanol was compared with dithranol 1% in petrolatum (33 patients) and with dithranol 1% in Amitase stick (16 patients). Micanol was found to be effective and well suited for treatment at home in all studies. The vehicle itself did not improve the psoriasis plaques. The rate of clinical improvement was faster for dithranol in petrolatum and Amitase stick than for Micanol. The prevalence and severity of erythema, burning and staining of skin and clothing were far less for Micanol. Approximately half the number of patients preferred dithranol in petrolatum or Amitase stick and the other half preferred Micanol.

Different sensitising acrylic monomers in Napp printing plate.

3 chemically pure fractions were isolated from Napp printing plate and subsequently identified by means of nuclear magnetic resonance, infrared spectrophotometry and elemental analysis. 1 of the fractions elicited positive test reactions in 3 Napp-allergic printers, and another fraction also elicited a positive test reaction in 1 of the printers. The 2 allergens were 2-hydroxyethyl methacrylate and N,N'-methylene-bis-acrylamide. The 1st of the 2 allergens was also demonstrated in another printing plate, Nyloprint WD.

Secondary acrylamides in Nyloprint printing plate as a source of contact dermatitis.

Several chemically pure fractions have been isolated from Nyloprint printing plates. 5 of the fractions elicited positive patch test reactions in 7 Nylonprint allergic printers. 4 of the 5 components were analysed by means of nuclear magnetic resonance, infrared spectrophotometry, mass spectrometry and elemental analysis. The fractions were identified as N,N'-methylene-bis-acrylamide. N,N'-[oxybis(methylene)]bis-2-propenamide, N,N'-[1,2-ethanediylbis(oxymethylene)]-2-propenamide, and a new compound N-[(2-hydroxyethoxy)-methyl]-2-propenamide. All of the analysed fractions have the common feature of being secondary acrylamides.

Functional studies in patients with the glucagonoma syndrome.

Four patients with glucagon-producing tumours of the pancreas were investigated. Fasting plasma glucagon concentrations ranged from 209--625 pmol/l. Plasma insulin concentrations were normal except in one patient, where the tumour also produced insulin (558 pmol/l). Intravenous glucose (25 g/m2) depressed the glucagon concentration in two patients, while no change was noted in the others. Intravenous arginine stimulated glucagon secretion in three patients, but not in the fourth. Intravenous somatostatin suppressed glucagon secretion in all three patients investigated. All patients had abnormally low plasma levels of individual amino acids; glucogenic and branched-chain amino acids were equally depressed. Surgical removal of the tumours led to complete recovery from dermatosis and the glucagon levels were normalized. Postoperative tests were performed in three patients. The alpha-cell responsiveness to iv glucose was restored. Glucose tolerance (Kg-value) was improved in one patient (0.73 to 1.65), persistently low in one patient (0.75 to 0.72) and impaired in the third patient (1.35 to 1.09). It is concluded that none of these functional tests will be of diagnostic value in cases suspected of glucagonomas. The results also show that glucose homeostasis is remarkably unaffected by the extreme hyperglucagonaemia of these patients and that hypoaminoacidaemia is an important consequence of chronic hyperglucagonaemia.