Unexpected death due to chloramine toxicity in a woman with a brain tumor.

It has been known for years that mixing household cleaning products can be hazardous. Nonetheless, from time to time, episodes of pneumonitis from such mixing occur. Although symptoms range from minor upper respiratory irritation to adult respiratory distress syndrome, deaths are very rare. We present the case of a woman with an undiagnosed oligodendroglioma who mixed bleach and ammonia (resulting in the formation of chloramine gas), and died while cleaning her bathroom. To our knowledge, this is the first such death reported from chloramine gas intoxication.

5-Methyltetrahydrofolate is reabsorbed and metabolized in isolated perfused rat kidney.

The renal regulation of folate excretion is an important component in maintaining the body burden of folate. The tubular processes for folate disposition have been examined by a variety of methods to elucidate the mechanism by which renal folate excretion is regulated. Accordingly, the isolated perfused rat kidney technique was evaluated by investigating the clearance and metabolic patterns of 5-methyltetrahydrofolate (5-CH3-H4PteGlu). Kidneys from male Sprague-Dawley rats were perfused in vitro with [3H]5-CH3-H4PteGlu (1-2000 nmol/L). Linear regression analysis of 5-CH3-H4PteGlu excretion vs. filtered load revealed a tubular transport maximum of 7.5 pmol x min-1.g-1. A dual component system for tubular transport of 5-CH3-H4PteGlu was found: a high capacity, nonsaturable system and a low capacity, saturable system represented by the transport maximum. Furthermore, HPLC analysis of urine demonstrated renal uptake and metabolism of the labeled tracer. Tetrahydrofolate was identified as one metabolic product that indicated secretion of this compound. Additional metabolites were identified from kidney samples. Results suggest that 5-CH3-H4PteGlu undergoes net reabsorption by a dual component transport system; some of the reabsorbed 5-CH3-H4PteGlu is metabolized to other products that may be secreted in the urine.

Effects of ethanol on tissue folate incorporation and recovery from folate deficiency in rats.

Studies in folate-deficient alcoholics suggest that ethanol interferes with the recovery of folate status and the hematopoietic response to folate. Previous animal studies have suggested diverse effects of ethanol on intestinal absorption, hepatic metabolism, and urinary excretion of folate. In order to examine the effects of ethanol on folate distribution during folate deficiency, tissue incorporation of a tracer dose of folate was studied in rats chronically fed ethanol-containing and/or folate-deficient diets. Rats fed these diets were also used to study the effect of chronic ethanol consumption on the dietary reversal of folate deficiency by changing the diets (adding folate or replacing ethanol) from 12 to 16 weeks. After 16 weeks, tissue folate depletion was severe in rats fed folate-deficient diets. Plasma and whole body retention of the tracer dose of folate was decreased in folate-deficient rats consuming ethanol. In folate-deficient rats, ethanol consumption increased the incorporation of folate by the kidney and brain, but had no effect in other tissues (liver, lung, spleen, intestine, testis). In ethanol-fed folate-deficient rats that continued to consume ethanol, but with added folate in their diets, urine, plasma, liver, and kidney folate levels returned to control levels in 4 weeks. In the rats that stopped ethanol, but continued low folate diet consumption, no recovery of tissue folate levels was seen in 4 weeks. These results suggest that chronic ethanol consumption can exacerbate folate requirements by inhibiting body retention of small doses of folate. However, these effects are minor because ethanol consumption does not block recovery from folate deficiency when rats are fed sufficient amounts of folate.

Incorporation of 3H-label from folic acid is tissue-dependent in folate-deficient rats.

To study the tissue-specificity of folate deficiency, male Sprague-Dawley rats were fed folate-replete or folate-deficient diets with and without sulfonamide for 16 wk, and then injected with [3H]folic acid (1.5 nmol/kg). Rats were killed after 24 h, and the blood, urine and various organs were prepared for analysis of endogenous and 3H-labeled folate. Endogenous folate levels decreased due to folate deficiency to the greatest extent in the urine and plasma, followed by liver, kidney and other tissues (spleen, testis, lung and intestine), but no decrease was noted in the brain. Of all tissues of folate-deficient rats, the brain showed the greatest increase in incorporation of 3H-label from folate relative to folate-replete rats, with the largest effect in rats that were most deficient in plasma folate. Incorporation of label was increased due to folate deficiency in a number of tissues, with an inverse correlation with the tissue folate concentration. In contrast, hepatic [3H]folate incorporation was lower in folate-deficient rats than in folate-replete rats, with a direct correlation between endogenous folate concentration and the incorporation of labeled folate. These results show that the brain and other organs adapt to the development of folate deficiency because of greater incorporation of folate from exogenous sources. The lower incorporation by the liver of folate-deficient rats may result from the greater incorporation by other tissues.

Effects of chronic ethanol and diet treatment on urinary folate excretion and development of folate deficiency in the rat.

Because the folate deficiency of chronic alcoholism has been proposed to result from ethanol-induced effects on metabolism or urinary excretion of folate, the present study was designed to evaluate the role of chronic ethanol-induced urinary folate loss on folate homeostasis in the rat. Male Sprague-Dawley rats were fed nutritionally sufficient liquid diets for 12 wk with or without ethanol, folate and sulfonamide. Urinary folate excretion was increased in ethanol-fed rats consuming folate-containing diets, but not in rats fed folate deficient diets. Consumption of folate-deficient diets led to a rapid decrease in urinary folate excretion, suggesting renal adaptation to conserve folate. Tissue and plasma levels of folate were mostly unaffected by ethanol ingestion in rats fed folate-containing diets. Ethanol treatment did not consistently enhance tissue folate depletion in rats fed folate-deficient diets. The results suggest that in rats consuming diets containing high levels of folate, chronic ethanol ingestion increased urinary folate excretion, but not to a sufficient magnitude to consistently affect folate homeostasis.

Effects of acute ethanol on urinary excretion of 5-methyltetrahydrofolic acid and folate derivatives in the rat.

Acute ethanol treatment enhances the urinary excretion of endogenous folate. This effect has been implicated in the development of folate deficiency associated with chronic alcoholism. Previous studies have shown that urinary excretion of total [3H]-label after administration of [3H]folic acid is slightly higher in ethanol-treated rats because of conversion of the tracer to forms whose excretion is not affected by ethanol. Since [3H]folic acid is not the physiological substrate for the kidney, studies were performed using a high specific activity 5-methyltetrahydrofolic acid ([3H]5-CH3-H4 folic acid). Male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg, followed by infusion of [3H]5-CH3-H4 folic acid at 5 h. Urine samples were collected to 6 h, when rats were killed, and plasma, liver and kidney samples were collected. Endogenous urinary folate excretion and the fractional urinary excretion of both endogenous and [3H]5-CH3-H4 folic acid at the 5-6 h time period were significantly higher in ethanol-treated rats. The kidney had a tenfold greater specific incorporation of [3H]-label than did the liver. High performance liquid chromatography (HPLC) analysis of the plasma obtained at 6 h showed that 68% of the label was [3H]5-CH3-H4 folic acid, and HPLC analysis of the urine obtained from 5-6 h showed that only 10% of the label was [3H]5-CH3-H4 folic acid. The data indicate that [3H]5-CH3-H4 folic acid was rapidly taken up by the kidney and metabolized to other folate and nonfolate forms, which were then secreted into the renal tubule for excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of acute ethanol on urinary excretion of folate derivatives in the rat.

The ethanol-induced increase in the urinary excretion of folate has been determined to be both a time- and dose-dependent phenomenon and it has been speculated that this loss may enhance the development of folate deficiency. However, ethanol has only a minor effect on the renal clearance of exogenously administered [3H]folic acid [3H]PteGlu) in relation to that of inulin. To clarify this variable effect of ethanol, male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg and placed in metabolic chambers for collection of urine. At 5 hr, [3H]PteGlu was administered and urine samples were collected for 1 hr. At 6 hr, rats were sacrificed with collection of plasma, liver and kidney samples. A significant increase in the urinary excretion of endogenous folates occurred in ethanol-treated rats at both the 4-5- and 5- to 6-hr time periods, but no significant increase in 3H-labeled derivatives was noted in ethanol-treated rats. Subsequent high pressure liquid chromatographic analysis of urine extracts showed that the predominant 3H-labeled PteGlu metabolites were [3H]-5-formimino-H4PteGlu and the formyl-tetrahydrofolates, whereas the major endogenous form was 5-CH3-H4PteGlu. Ethanol administration increased significantly the excretion of the methyl derivative, with minor effects on the other folate forms. These results suggest that there is a selective effect of ethanol on the urinary excretion of specific folate derivatives. Also, inasmuch as no 5-formimino-H4-PteGlu was detected in the plasma, the rodent kidney appears to have the capacity for uptake and metabolism of filtered PteGlu.