Tacrolimus-induced hypomagnesemia and hypercalciuria requires FKBP12 suggesting a role for calcineurin.

Calcineurin inhibitors (CNIs) are immunosuppressive drugs used to prevent graft rejection after organ transplant. Common side effects include renal magnesium wasting and hypomagnesemia, which may contribute to new-onset diabetes mellitus, and hypercalciuria, which may contribute to post-transplant osteoporosis. Previous work suggested that CNIs reduce the abundance of key divalent cation transport proteins, expressed along the distal convoluted tubule, causing renal magnesium and calcium wasting.

NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity.

Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies.

Functionomics of NCC mutations in Gitelman syndrome using a novel mammalian cell-based activity assay.

Gitelman syndrome (GS) is an autosomal recessive salt-wasting tubular disorder resulting from loss-of-function mutations in the thiazide-sensitive NaCl cotransporter (NCC). Functional analysis of these mutations has been limited to the use of Xenopus laevis oocytes. The aim of the present study was, therefore, to analyze the functional consequences of NCC mutations in a mammalian cell-based assay, followed by analysis of mutated NCC protein expression as well as glycosylation and phosphorylation profiles using human embryonic kidney (HEK) 293 cells.

Alternative splice variant of the thiazide-sensitive NaCl cotransporter: a novel player in renal salt handling.

The thiazide-sensitive NaCl cotransporter (NCC) is an important pharmacological target in the treatment of hypertension. The human SLC12A3 gene, encoding NCC, gives rise to three isoforms. Only the third isoform has been extensively investigated.

Interleukin 18 function in atherosclerosis is mediated by the interleukin 18 receptor and the Na-Cl co-transporter.

Interleukin-18 (IL18) participates in atherogenesis through several putative mechanisms. Interruption of IL18 action reduces atherosclerosis in mice. Here, we show that absence of the IL18 receptor (IL18r) does not affect atherosclerosis in apolipoprotein E-deficient (Apoe(-/-)) mice, nor does it affect IL18 cell surface binding to or signaling in endothelial cells.

AQP9 expression in glioblastoma multiforme tumors is limited to a small population of astrocytic cells and CD15(+)/CalB(+) leukocytes.

Aquaporin-9 (AQP9) is a membrane protein channel that is permeable to a range of small solutes, including glycerol, urea and nucleobases. Expression of AQP9 in normal brain is limited, while widespread AQP9 expression has previously been reported in human glioblastoma. However, the specific cellular expression of AQP9 in glioblastoma remains unclear.

Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding.

Aquaporin 11 (AQP11) is a protein channel expressed intracellularly in multiple organs, yet its physiological function is unclear. Aqp11 knockout (KO) mice die early due to malfunction of the kidney, a result of hydropic degeneration of proximal tubule cells. Here we report the generation of liver-specific Aqp11 KO mice, allowing us to study the role of AQP11 protein in liver of mice with normal kidney function.

Aquaporin-9 and urea transporter-A gene deletions affect urea transmembrane passage in murine hepatocytes.

In mammals, the majority of nitrogen from protein degradation is disposed of as urea. Several studies have partly characterized expression of urea transporters (UTs) in hepatocytes, where urea is produced. Nevertheless, the contribution of these proteins to hepatocyte urea permeability (P(urea)) and their role in liver physiology remains unknown.

Aquaporin-9 protein is the primary route of hepatocyte glycerol uptake for glycerol gluconeogenesis in mice.

It has been hypothesized that aquaporin-9 (AQP9) is part of the unknown route of hepatocyte glycerol uptake. In a previous study, leptin receptor-deficient wild-type mice became diabetic and suffered from fasting hyperglycemia whereas isogenic AQP9(-/-) knock-out mice remained normoglycemic. The reason for this improvement in AQP9(-/-) mice was not established before.

Do premotor interneurons act in parallel on spinal motoneurons and on dorsal horn spinocerebellar and spinocervical tract neurons in the cat?

It has previously been established that ventral spinocerebellar tract (VSCT) neurons and dorsal spinocerebellar tract neurons located in Clarke's column (CC DSCT neurons) forward information on actions of premotor interneurons in reflex pathways from muscle afferents on α-motoneurons. Whether DSCT neurons located in the dorsal horn (dh DSCT neurons) and spinocervical tract (SCT) neurons are involved in forwarding similar feedback information has not yet been investigated. The aim of the present study was therefore to examine the input from premotor interneurons to these neurons.

An unusual solution after bilateral lower extremity amputation.

The authors present a case of a 40-year-old male with devastating amputation trauma of both lower extremities. Reconstruction of the right lower extremity was solved by the unusual use of inserted vascularized bone-skin graft from the left crus with a simultaneous replantation of the right foot. The result after 3.

[Primary adenocarcinoma of the appendix].

The authors published experience with the treatment of four patients with primary adenocarcinoma of the appendix and an analysis of 20 patients with primary adenocarcinoma of the appendix treated in the North Moravia region during a ten-year period (1980-1989). The incidence of the disease is rare. Usually it is manifested by symptoms imitating acute appendicitis.

Investigation of protein metabolism with respect to amino acid administration.

A comparative study of the protein metabolism of two groups of patients having suffered major trauma (group I, n = 26, and group II, n = 16) and of two groups having undergone major surgery (group III, n = 10, and group IV, n = 9) was performed from the 2nd to the 11th day of treatment. All of the patients received approximately 35 kcal/kg body weight/day. In addition the patients in groups I and III received a 10% amino acid solution containing 0.

Changes in essential fatty acids in plasma lipid fractions of traumatized patients.

Changes in the fatty acid pattern of plasma lipid in four different groups of polytraumatized patients were investigated. All of the patients received amino acid solutions containing 0.24 gN/day/kg body weight and 30 kal/day/kg body weight (BW).

[A case of severe multiple trauma (author's transl)].

A case of severe multiple trauma sustained in a road accident is reported. The aim of the report is to show the determing role played by diagnostic and surgical methods and therapeutic possibilities available in the intensive care unit (shock treatment, controlled respiration, parenteral feeding, haemodialysis) in winning the five-months' battle for the life of the patient. Early haemodyalisis as supporting therapy in respiratory failure and conservation treatment of intestinal fistulae are important.

[A retrospective study of the impressions and psychic reactions experienced by patients in a traumatological intensive care unit (author's transl)].

30 persons who had been treated for an average of 22 days on a traumatological intensive care unit were asked to comment on their impressions and experiences. 80% of the patients had been in need of artificial respiration; but this had not unduly distressed them and they remembered it only vaguely. The major worry in 30% of the cases was awareness of their condition and the fear of permanent physical and mental disablement.

[Changes of the essential fatty acids in plasmalipid fractions of polytraumatized patients with different parenteral nutrition (author's transl)].

In two groups of polytraumatized patients we investigated changes in the fatty acid pattern of plasma-lipids during the phase of total parenteral nutrition. For parenteral nutrition we gave L-amino acid solutions in a dose of 0.24 g N/kg body weight/day.

Transthoracic electrical impendance in anaesthesia and intensive care.

Pulmonary fluid accumulation plays an important role in the development of post-traumatic pulmonary insufficiency. Yet initially diagnosis may be difficult. The measurement of transthoracic electrical impedance was used to detect early pulmonary fluid overload.