Observations on the Effects of a New Diuretic-S1520

S1520, a sulphonamide-derived diuretic, was administered to healthy volunteers and patients with oedema. A therapeutic effect was produced by doses of 10 - 20 mg. The onset of action was within 3 hours and persisted for up to 36 hours. Natriuresis, chloruresis and increasing kaliuresis were observed with continued administration. The probable site of drug action was on the distal tubule. Patients with severe renal failure or hyponatraemia did not show a therapeutic response, and the maximal efficacy of the drug was considered to be less than that of furosemide

Experience with chronic haemodialysis in Johannesburg

Since 1966 the treatment for patients with end-stage renal disease in Johannesburg has primarily been renal transplantation. This has required an adequate programme of regular dialysis. All patients were treated at the central hospital or at two small satellite units. A total of 158 patients, mean age 34,2 years (88 males) have been dialysed. The mean duration on dialysis prior to transplantation was 5,6 months (range 1 week - 23 months). The commonest cause of renal failure in males was chronic glomerulonephritis (63%), whereas in females it was analgesic nephropathy (39%). Twenty-seven patients (17%) died while on dialysis, including 6 who had had unsuccessful transplantations. Renal osteodystrophy was diagnosed in 30% of the patients. Hepatitis has been endemic among both patients and staff. Nephrectomies were done in 106 patients. Ten patients had operations for peptic ulcer and 5 parathyroidectomies were performed. The number of patients unsuccessfully transplanted, or who died, was less than the number of new patients requiring treatment. In addition, an increasing proportion of patients have become 'relatively untransplaotable'. This has led to overloading of facilities.S. Afr. Med. J., 48, 1821 (1974

Lipocalin 2 modulates the cellular response to amyloid beta

The production, accumulation and aggregation of amyloid beta (Aß) peptides in Alzheimer's disease (AD) are influenced by different modulators. Among these are iron and iron-related proteins, given their ability to modulate the expression of the amyloid precursor protein and to drive Aß aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to Aß1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aß1-42 stimulation decreases the dehydrogenase activity and survival of wild-type astrocytes, astrocytes lacking the expression of Lcn2 are not affected. This protection results from a lower expression of the proapoptotic gene Bim and a decreased inflammatory response. Altogether, these findings show that Aß toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.Cell Death and Differentiation advance online publication, 23 May 2014; doi:10.1038/cdd.2014.68.We thank Dr. Ioannis Sotiropoulos for reagents and comments. Sandro Da Mesquita and Ana Catarina Ferreira are recipients of PhD fellowships and Fernanda Marques is recipient of a postdoctoral fellowship by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal)/FEDER. This work was supported by a grant from FCT/FEDER (EXPL/NEUOSD/2196/2013)

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage