Nitrogen retention, limitation

Bacitracin is markedly nephrotoxic if administered systemically, producing proteinuria, hematuria, and nitrogen retention. Hypersensitivity reactions (eg, skin rashes) are rare. Because of its marked toxicity when used systemically, it is limited to topical use. Bacitracin is poorly absorbed. Topical application results in local antibacterial activity without significant systemic toxicity. The small amounts of bacitracin that are absorbed are excreted by glomerular filtration. 

The prevalence of skeletal disease among patients with nonterminal renal failure is not known. The majority of such patients do not complain of skeletal symptoms and their serum alkaline phosphatase activities are not markedly elevated. The mean for all patients in one study (15) was 1.5 times the upper reference limit for adults. In some patients with nonterminal renal failure, systemic acidosis is out of proportion to the degree of nitrogenous retention, and it currently seems that acidotic patients are more liable to develop skeletal abnormalities. Mean serum alkaline phosphatase in a group of such patients was 3.5 times the upper reference limit, with individual values of almost 10 times the upper reference limit (15). The rise in total serum alkaline phosphatase, which is largely due to increases in the bone isoenzyme (15, P15), shows a significant positive correlation with the severity of parathyroid osteopathy, irrespective of the presence or absence of concurrent osteomalacia (P15). 

An HPLC method for the analysis of etodolac and its metabolites in equine serum and urine was developed [32]. Serum (1 mL) or urine (0.5 mL) samples were extracted with iso-octane/isopropanol (95 5, v/v) after addition of ibuprofen as internal standard, diluting with 1 or 2 mL of distilled water, and adjusting the pH to 1 with 1 M HC1. The organic layer was evaporated under a stream of nitrogen, the residue dissolved in 100 pL of mobile phase, and a 20 pL aliquot injected on to the HPLC system. The HPLC system consisted of a pre-column, a 250 x 4 mm (7 pm particles) LiChrosorb RP-18 column at 25°C, isocratic elution with 1% acetic acid/acetonitrile (50 50, v/v) at a flow rate of 1.3 mL/min, and UV detector at 227 nm. The retention time of etodolac was 8.5 minutes. The method was linear over the range of 0.1-20 pg/mL in serum, and in 0.5-800 pg/mL range in urine. The limits of quantitation were 40 ng/mL in... 

The simplest approach to qualitative or semiquantitative analysis of products that are gases at ambient temperature (e.g., C02, S02, some nitrogen oxides, perhaps H20, etc.) is through retention with a refrigerant in a vacuum apparatus. Measurements are then made of the pressure exerted on subsequent volatilization of the condensed gases present within a vessel of known volume. By the use of several cold traps, estimations of the compositions of a limited range of simple mixtures are sometimes possible. 

The laboratories of Stec (24) and the author (26-28) have reported that the nitrogen anions of phosphoramidates react with carbonyl compounds (benzalde-hyde or CO2) to incorporate an atom of oxygen bonded to phosphorus at the expense of the nitrogen substituent, and that this reaction proceeds with retention of configuration at phosphorus. This stereochemically useful reaction, known as the Wittig-Staudinger reaction, is not limited to carbonyl compounds but can also be used with thiocarbonyls or selenocarbonyls to produce chiral phospho-rothioates or phosphoroselenates with retention of configuration at phosphorus (27). The primary application of this reaction has been in the preparation of both... 

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