2-bromoethylamine Hydrobromide Research Articles

Drug-induced papillary necrosis: electrolyte excretion and nephron heterogeneity.

The functional expression of papillary necrosis was investigated in rats following administration of 2-bromoethylamine hydrobromide (BEA). The percentage of filtering superficial and juxtamedullary nephrons was assessed using the qualitative Hanssen technique. There was a marked decrease in the percentage of filtering juxtamedullary nephrons 24 h after the induction of papillary necrosis (as compared with control rats), which was blunted in salt-loaded animals. The percentage of filtering superficial nephrons was the same in all three groups. BEA administration to normal rats was associated with a significant increase in sodium, chloride, phosphate, and calcium excretion. BEA administration to rats on a chloride-restricted diet was associated with chloride wastage. These animals also failed to adapt to a low chloride diet as late as 7 days after the administration of BEA. The phosphaturia observed in intact rats treated with BEA was abolished by parathyroidectomy. BEA-treated rats were able to adapt to a low phosphate diet and to a low magnesium diet. These data demonstrate that papillary necrosis is associated with profound impairment of juxtamedullary nephron filtration and with chloride wastage. In the absence of the papillary structures adaptation to phosphorus or magnesium deprivation is still possible.

Renal function studies in an experimental model of papillary necrosis in the rat.

Twenty four hours after i.v. injection of bromoethylamine-hydrobromide (BEA) in rats, a uniform papillary necrosis is observed. The present study investigates the renal functional and the papillary haemodynamics in response to acute volume expansion (12% of body weight) in this model. Renal function studies were performed in hydropenic and volume expanded sham- or BEA-injected rats. In hydropenic normal animals a GFR of 1.97 +/- 0.14 ml/min, an urinary osmolarity (UOsm) of 1 011 +/- 94.5 mOsm/kg and a fractional sodium excretion (FENa) of 0.18 +/- 0.026% were obtained. In contrast, BEA-treated hydropenic animals showed a lower GFR (1.16 +/- 0.14 ml/min), UOsm (469 +/- 30.31 mOsm/kg) and a higher FENa (0.37 +/- 0.06%). In volume expansion a similar UOsm and FENa were obtained in both groups. The papillary plasma flow (PPF) was measured in each of the experimental groups by the albumin accumulation technique. The mean value in hydropenic normal animals was 50.65 +/- 2.12 m 100 g-1 min-1 and increased to 66.02 +/- 2.00 ml 100 g-1 min-1 after volume expansion (P less than 0.001). In BEA rats the PPF was 58.86 +/- 2.33 ml 100 g-1 min-1 in hydropenia (P less than 0.01 vs. control animals) and remained unchanged after volume expansion. Thus, during hydropenia, BEA-induced papillary necrosis results with a salt wasting state and an urinary concentration defect. After volume expansion no disturbance in sodium excretion capacity was observed. These results are compatible with the nephron-heterogeneity concept in the regulation of sodium excretion. The histological lesions cannot be explained by a decreased renal papillary plasma flow.

Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production.

The inactivation dynamics of rabies virus (PV strain) by binary ethylenimine, and the immunogenic properites and the stability of the vaccines prepared using this agent, were studied. Binary ethylenimine at a final concentration of 0.01 M was prepared wtih 2-bromoethylamine hydrobromide in alkaline solutions, either separately from or in suspensions of rabies virus propagated in BHK cells. The infectivity of virus suspensions containing more than 108 plaque-forming units per 0.1 ml was inactivated in 2 h when the inactivating agent was prepared before its addition to the suspensions, and in3 h when prepared directly in the suspensions. Liquid vaccines prepared in this manner and stored at different temperatures maintained potency for 1 month at 37 degrees C and for 6 months at 4 degrees C and 22 to 25 degrees C. Lyophilized vaccine maintained its potency for 6 months at the three temperatures. The inactivated vaccine mixed with aluminum or oil adjuvant at high dilutions protected guinea pigs against challenge. This safer procedure for rabies virus inactivation offers promise for the production of effective vaccines for the immunization of dogs and cattle.

Functional characterization of drug-induced experimental papillary necrosis

The functional expression of papillary necrosis was investigated with a model of drug-induced papillary necrosis. Bromoethylamine hydrobromide (BEA) administration to rats uniformly resulted in the development of papillary necrosis. All studies were performed 24 hours after BEA administration with the exception of the electrolyte balance studies, which were performed during the 72 hours after the induction of papillary necrosis. GFR was not different between BEA-treated and sham rats. BEA-treated rats had a significantly lower maximal urine osmolality and free water reabsorption than did sham rats. Renal tissue concentrations of sodium, potassium, and water were not different between BEA-treated and sham rats. During water diuresis, free water clearance was not significantly different between the two groups. During sodium bicarbonate administration, maximal bicarbonate reabsorption and urine-blood Pco2 gradient (at comparable urine bicarbonate concentrations) were not significantly different between the two groups. During sodium sulfate infusion, there was no difference in minimum urine pH, ammonium excretion, and net acid excretion between chronically acidotic BEA-injected and sham rats. In rats on "zero" sodium intake, BEA administration resulted in a significant increase in urine flow and sodium excretion, whereas sham rats remained in sodium balance. In rats with restriction of both sodium and chloride, BEA administration resulted in a significant wastage of sodium, chloride, and calcium. There was no difference in potassium excretion between BEA-treated and sham rats during hydropenia, bicarbonate administration, sodium sulfate infusion, or ingestion of a normal potassium diet. When potassium intake was restricted to "zero," BEA-treated rats developed potassium wastage; when potassium intake was increased to 21 mEq/day, BEA-treated rats had a significantly lower potassium excretion than did sham rats. These findings may result from alterations in collecting duct transport, but damage to deep medullary structures may also contribute.

Healed experimental renal papillary necrosis and cortical scarring in the rat from 2-bromoethylamine hydrobromide

Male Sprague-Dawley rats were each given a single subcutaneous injection of an aqueous solution of bromoethylamine hydrobromide (BEA) at dose levels of 80 mg/kg (16 rats), 125 mg/kg (15 rats) and 250 mg/kg (16 rats) or a single subcutaneous injection of water (controls, 15 rats). The dose levels were chosen so as to cause renal papillary injury varying from minor necrotic foci to necrosis and subsequent sloughing of the entire papilla. The animals were killed after 5 months and the kidneys were weighed and examined macroscopically and microscopically for the presence of RPN and cortical scarring. Macroscopically evident RPN occurred in 18 of 43 surviving BEA-treated rats, bilaterally in 16 and unilaterally in 2. Bilateral asymmetry of the extent of sloughing was evident. All kidneys with macroscopic RPN exhibited cortical scarring. Asymmetry of the extent of atrophy and scarring in some animals resulted in a significant unilateral reduction in renal weight and a significant contralateral compensatory hypertrophy. Twenty-three of the 25 BEA-treated rats without macroscopically evident RPN exhibited minor, histologically visible lesions of the renal papillae including necrosis of loops of Henle in the presence of intact collecting ducts. Only 2 of these animals exhibited tiny, unilateral cortical scars, and renal weights did not differ significantly from those of controls. It may therefore be concluded, contrary to certain published proposals: that experimental RPN may be followed by severe renal cortical scarring, reduction in renal size and (in the presence of asymmetrical lesions) compensatory renal hypertrophy, and that necrosis of thin limbs of loops of Henle does not appear to lead to frequent or severe cortical scarring.

Experimental renal papillary necrosis: Effects of beta adrenergic receptor blockade, heparin and hydrocortisone

Renal papillary necrosis was induced in rats by daily subcutaneous injection of 15 mg 2-bromoethylamine hydrobromide (BEA) per 100 g of body weight for 2 successive days. This dose was 50% higher than that reported previously. Beta adrenergic receptor blockade with oxyprenolol did not influence the kidney damage. The administration of heparin did not show any effect. The doses applied did not induce the incoagulability for a sufficient period of time. On the contrary, treatment with hydrocortisone decreased papillary necrosis without inducing increased diuresis.

Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production

Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines.

Drug-induced renal medullary necrosis: II mode of calcification in the kidney

Necrosis of the papillary portion of the renal medulla was produced by administration of 2-bromoethylamine hydrobromide in rats. Following the necrosis, calcification develops in the renal medulla adjacent to the necrosed tissue. The calcium deposit is seen in the vesicular bodies about the basement membranes of the tubules and capillaries and in the collagen fibers of the interstitium. These structures such as the vesicular bodies and collagen fibers appear to serve as nucleation sites for dystrophic calcification.

Condensation of acylpyridines with amines. Part II. Pyrido[1,2-a]pyrido[1′,2′:3,4]imidazo[2,1-c]pyrazi-5,8-di-inium salts from pyridine-2-carbaldehyde and aminoacetaldehyde dimethyl acetal

The anil formed from pyridine-2-carbaldehyde and aminoacetaldehyde dimethyl acetal is converted by acids, in the absence of appreciable quantities of water, into the monoquaternary salts (III). Treatment of these salts with aqueous acids or with alcoholic perchloric acid gives 6,7-dihydro-6-hydroxypyrido[1,2-a]pyrido[1′,2′:3,4]imidazo[2,1-c]pyrazi-5,8-di-inium salts (IV; R = H) or the corresponding methoxy-compounds (IV; R = Me) respectively. Subsequent dehydration of the hydroxy-diquaternary salts (IV; R = H) with thionyl chloride gives the title compounds (V). Pyridine-2-carbaldehyde condenses with 2-bromoethylamine hydrobromide giving 6,7-dihydropyrido[1,2-a]pyrido[1′,2′:3,4]imidazo[2,1-c]pyrazi-5,8-di-inium dibromide (XI; X = Br).

Potential Antiradiation Agents. II. Selenium Analogs of 2-Aminoethylisothiouronium Hydrobromide and Related Compounds1-3

In view of the effectiveness of aminoethyl mercaptan (cysteamine) and of 2-aminoethylisothiouronium (AET) salts in protecting animals against ionizing radiation, efforts were made to prepare even more active analogs of the compounds. Sulfur is considered to be essential to the radioprotective action of cysteamine analogs; however, the selenium analog of cysteamine can shield mice against radiation. Since the atomic radii of sulfur and of selenium are similar, sulfur and selenium analogs may be assumed to have the same ability of fit receptor sites. The selenium analog of AET was prepared by the reaction of selenourea with 2-bromoethylamine hydrobromide. Treatment of the selenouronium salt with NaOH yielded 2-selenoethylguanidine, which was isolated as the flavianate salt. The reaction of 2-aminoethylisoselenouronium hydrobromide with boiling water resulted in the formation of 2-aminoselenazoline. Through the reaction of 2- methylaminoethyl. 2dimethylaminoethyl, and 2-diethylaminoethyl halides with selenourea the corresponding 2-alkylaminoethyl selenouronium salts were obtained. Similarly, 3-aminopropylisoselenouronium hydrobromide was synthesized.

Organic Syntheses

RELIABLE methods are given in this useful volume for the preparation of a further selection of twenty-nine organic compounds. Each of the main structural divisions of organic chemistry is interestingly represented in the list. Among the aliphatic substances are acetylenedicarboxylic acid, from fumaric acid via a-dibromosuccinic acid; allylamine, from allyl isothiocyanate; taurine, from ethanolamine, via -bromoethylamine hydrobromide; and betaine hydrazide hydrochloride (Girard's reagent). The introduction of two of the less familiar elements into aromatic molecules is exemplified by the preparation of 4,4'-difluorobiphenyl, from benzi-dine; and of diphenyl selenide, diphenylselenium dichloride, and triphenylselenonium chloride, starting from diazotized aniline and potassium selenide. The condensation of?-phenylbutyric ester with oxalic ester, followed by cyclization, yields 3,4-dihydro-1,2-naphthalic anhydride, which is then dehydro-genated with sulphur at 230-250°, yielding 1,2-naphthalic anhydride. Organic Syntheses: an Annual Publication of Satisfactory Methods for the Preparation of Organic Chemicals. Vol. 18. Pp. v + 103. (New York: John Wiley and Sons Inc London ; ' Chapman and Hall, Ltd., 1938.) 8s. 6d. net.