Control of sodium and potassium homeostasis by renal distal convoluted tubules.

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

Control of sodium and potassium homeostasis by renal distal convoluted tubules

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

Biópsia hepática com agulha tru-cut guiada por videolaparoscopia em caprinos / Videolaparoscopic guided hepatic biopsy with tru-cut needle in goats

Descreve-se a técnica de biópsia hepática com agulha tru-cut guiada por videolaparoscopia em 12 caprinos machos, castrados, hígidos, sem raça definida, distribuídos em dois grupos (G): G1, com cinco animais de 12 meses e G2, com sete de seis meses de idade. O procedimento foi realizado sob anestesia geral intravenosa com o animal em decúbito lateral esquerdo. O pneumoperitônio e a laparoscopia foram procedidos no flanco direito, aproximadamente a 10cm ventral aos processos transversos das vértebras lombares. A agulha tru-cut foi introduzida no 11º espaço intercostal direito, a aproximadamente 12cm ventral à coluna vertebral, para punção e remoção de fragmento do lobo hepático direito. O tempo operatório médio foi de 23 minutos e cinco segundos. A hemorragia causada pela perfuração hepática cessou em dois minutos em 75 por cento dos animais e em três minutos, nos 25 por cento restantes. Nas avaliações clínicas feitas no pré-jejum e às 24, 48 e 72 horas após a biópsia, não foram observadas alterações (P>0,05) da temperatura retal, das frequências cardíaca e respiratória e dos movimentos rumenais nos dois grupos. A biópsia hepática com agulha tru-cut guiada por videolaparoscopia foi considerada eficaz para uso em caprinos, permitindo a obtenção de fragmentos hepáticos suficientes para exame histológico.

The videolaparoscopic guided hepatic biopsy with tru-cut needle is described in 12 healthy, no defined breed, castrated male goats. Animals were distributed in two groups: G1 (n=5) 12-month-old animals; and G2 (n=7) six-month-old animals. The procedure was performed with the animal in left lateral recumbency and under total intravenous anesthesia. Pneumoperitoneum and laparoscopy were performed in the right flank, approximately 10cm ventral to the transverse processes of the lumbar vertebrae. The tru-cut needle was inserted into the right eleventh intercostal space, around 12cm ventral to the spinal column, for punching and removal of a fragment from the right hepatic lobe. The average time spent in the surgical procedure was 23 minutes and five seconds. The hemorrhage caused by the liver biopsy ceased in two minutes (75 percent) and in three minutes in the other animals (25 percent). In the clinical evaluations performed during the pre-fasting period and 24, 48, and 72 hours after the biopsy procedure, neither group presented alterations (P>0.05) evaluated by rectal temperature; and cardiac, respiratory, and rumen frequencies. The videolaparoscopic guided hepatic biopsy with tru-cut needle was considered efficacious to be used in goats, providing hepatic tissue fragments suitable for histological examination.