PubMed · 5180208
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D G James. 1967-01-06. Furosemide (Lasix).. https://pubmed.ncbi.nlm.nih.gov/5180208/
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The binding conformations of oxyphenbutazone (OXY), Nepsilon-dansyl-L-lysine (DNS-LYS), and furosemide (FU) to human serum albumin (HSA) have been investigated by molecular dynamics (MD) calculations and transferred nuclear Overhauser effect (TRNOE) measurements. We have combined distance information obtained from the Conformational Analyzer with Molecular Dynamics And Sampling (CAMDAS) calculation and experimental NOE spectroscopy measurements to determine a "binding conformation" for each drug which binds to site I of HSA. For OXY, only one conformer (conf9) among the conformer set generated by MD calculation satisfied the distance restraint conditions obtained from TRNOE measurements. For DNS-LYS and FU, 17 and 5 conformers satisfied distance restraint conditions, respectively. The structure of conf9 of OXY was taken as a "template" to choose binding conformers for DNS-LYS and FU. By fitting the "template" to the 17 conformers of DNS-LYS and 5 conformers of FU, we could efficiently obtain one binding conformer for DNS-LYS (conf144) and FU (conf26). It is suggested from the feature of the binding conformation that the three-dimensional location of a hydrophobic aromatic ring, alkyl chain, and electronegative functional group is important for binding to site I of HSA. This method, which combines MD calculations and NOE information, is thought to be effective for determining the binding conformation of drugs to HSA.
The routine use of ultrasonography has resulted in an explosion in the number of conditions reported to be associated with nephrocalcinosis. It has also been increasingly recognized that urolithiasis and nephrocalcinosis can coexist in the same patient. The two conditions most commonly associated with nephrocalcinosis in childhood are the use of furosemide in infancy and the treatment of patients with hypophosphatemic rickets with phosphate and vitamin D preparations. Although originally thought to be related to hypercalciuria, more recent studies in humans and research animals indicate a multifactorial etiology for furosemide-related nephrocalcinosis. In patients with hypophosphatemic rickets, it seems that the dose of phosphate and in particular the development of secondary hyperparathyroidism play a central role in the development of nephrocalcinosis. Among the entities recently reported to be associated with nephrocalcinosis are some that characteristically include Fanconi's syndrome. These findings dispute the previous teaching of lack of renal calcifications in this syndrome, which involves proximal renal tubular acidosis. The diagnosis of nephrocalcinosis requires a metabolic work-up to identify the offending factor. When identified, appropriate intervention should be instituted.
Arguments against the use of diuretic renography in the assessment of newborn hydronephrosis include immature function of neonatal kidneys, previously reported poor diuretic response and nonreproducible drainage patterns. To address these concerns we reviewed the initial and followup renal scans of 17 neonates with hydronephrosis without ureterectasis diagnosed by perinatal ultrasonography. All patients were evaluated with an initial diuretic renal scan up to the age of 28 days, and all had normal cystograms. A total of 19 dilated kidneys was studied of which 13 ultimately required pyeloplasty and 6 were managed nonsurgically. Patient study parameters included age and weight at the time of each renal scan, side of hydronephrosis, differential function of each kidney, pre-diuretic and post-diuretic urine output, and drainage half-time of each kidney. The diuretic renal scans followed a standardized protocol. There was no statistically significant difference between neonatal and followup differential function (p > 0.05), and the correlation coefficient was highly significant (r = 0.968). Comparison of response to diuretic stimulation (ml./kg. per minute) revealed no statistically significant difference as the patients aged with brisk urine output 3 to 5 times greater than previously reported. The distribution and mean drainage half-times for normal nonhydronephrotic kidneys were similar when comparing those performed as neonates and at followup. Hydronephrotic kidneys managed nonsurgically maintained almost identical patterns. Those repaired surgically demonstrated appropriate improvement in drainage but function remained unchanged. These results refute each of the criticisms against the use of diuretic renography to evaluate neonatal hydronephrosis and demonstrate its reliability in neonates.