Seminal plasma does not aid in the transport of phenolsulfonphthalein across the uterotubal junction in mares.

This study tested the hypothesis that the presence of prostaglandin E2 in seminal plasma would aid in the transport of phenolsulfonphthalein (PSP) across the uterotubal junction. Five mares in estrus were inseminated during estrus with PSP dissolved in phosphate-buffered saline and during the subsequent estrus with PSP added to a standard insemination dose. Serum and urine samples were obtained at hours 0, 1, 2, and 3 following treatment and examined for the presence of PSP. Phenolsulfonphthalein could not be detected in any of the urine samples collected from mares following either treatment. None of the serum samples collected following intrauterine installation of PSP in PBS contained PSP. Phenolsulfonphthalein was detected in serum samples from 1 mare following insemination with semen containing PSP. Components in seminal plasma such as PGE2 did not facilitate the transport of PSP across the uterotubal junction as had been hypothesized.

Le plasma séminal ne facilite pas le transport de la phénolsulfonphtaléine au travers de la jonction utéro-tubaire des juments. Cette étude a testé l'hypothèse voulant que la présence de la prostaglandine E2 dans le plasma séminal facilite le transport de la phénolsulfonphtaléine (PSP) au travers de la jonction utéro-tubaire. Cinq juments en oestrus ont été inséminées avec de la PSP dissoute dans une solution saline tamponnée au phosphate et, durant l'oestrus subséquent, avec de la PSP ajoutée à une dose d'insémination standard. Des prélèvements de sérum et d'urine ont été obtenus aux heures 0, 1, 2 et 3 ainsi qu'après le traitement et examinés pour déceler la présence de la PSP. La phénolsulfonphtaléine n'a pas pu être détectée dans aucun des échantillons d'urine prélevés auprès des juments après l'un ou l'autre des traitements. Aucun des échantillons de sérum prélevés après l'installation intra-utérine de la PSP dans PBS ne contenait de PSP. La phénolsulfonphtaléine a été détectée dans des échantillons de sérum provenant d'une jument après l'insémination avec du sperme contenant de la PSP. Des composants dans le plasma séminal comme le PGE2 n'ont pas facilité le transport de la PSP au travers de la jonction utéro-tubaire conformément à l'hypothèse émise.(Traduit par Isabelle Vallières).

Phenolphthalein metabolite inhibits catechol-O-methyltransferase-mediated metabolism of catechol estrogens: a possible mechanism for carcinogenicity.

Phenolphthalein (PT), used in over-the-counter laxatives, has recently been identified as a multisite carcinogen in rodents, but the molecular species responsible for the carcinogenicity is not known. A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s. The above data, when taken together, suggest that chronic administration of PT may enhance metabolic redox cycling of both PT-CAT and the catechol estrogens and this, in turn, may contribute to PT-induced tumorigenesis.

Glucuronidation and biliary excretion of phenolphthalein in temperature-acclimated steelhead trout (Salmo gairdneri).

Conjugative metabolism and biliary excretion of phenolphthalein (PP) were studied in steelhead trout (Salmo gairdneri) acclimated to 10, 14 or 18 degrees C. Significant seasonal effects were found on liver weight to body weight ratio and conjugative metabolism but not biliary excretion of free plus conjugate of PP. Temperature did not significantly interact with these relationships. PP was excreted in bile as parent compound and the glucuronide conjugate at all temperatures. Saturation of the excretory process was apparent at a dose of approximately 10 mumol/kg (i.p.) at 10 and 14, but not 18 degrees C.

A screening method for establishing laxative abuse.

Abuse of laxatives, most of them belonging to the group of colonic stimulants or cathartics, can cause various disorders. Extensive diagnostic work can be avoided by early toxicological screening of the suspected patients with respect to laxatives. Because no screening method of this kind was available, we developed a procedure with which all phenolic and anthraquinone laxatives--except sodium picosulfate--can be detected in urine. This method is based on high-performance thin-layer chromatography in two systems after pretreatment of a 20-mL urine sample with beta-glucuronidase and subsequent column extraction. The procedure is very sensitive: at least 32 h after a single dose of bisacodyl, danthron, phenolphthalein, or sennoside, the drug can be detected in the urine. Bisoxatin and oxyphenisatin are still detectable in the urine 18 h after intake. The method is also highly specific; none of 73 other drugs interfered in either of the two chromatographic systems. This procedure can be helpful for the early diagnosis of laxative abuse.

Qualitative and quantitative analysis of some synthetic, chemically acting laxatives in urine by gas chromatography-mass spectrometry.

A method for the qualitative and quantitative simultaneous analysis of dioxyanthraquinone, desacetyl-Bisacodyl, phenolphthalein and Oxyphenisatin in human urine using gas chromatography-mass spectrometry (GC-MS) has been developed. The compounds were extracted from urine at pH 7.5 with diethyl ether using Extrelut extraction columns, followed by evaporation and trimethylsilylation. The method used electron beam ionization GC-MS employing a computer-controlled multiple-ion detector (mass fragmentography). The recovery from urine for the various compounds was between 80% and 100%. The detection limit for these compounds was in the range 0.01--0.05 micrograms/ml of urine. The method proved to be suitable for measuring urine concentrations for at least four days after administration of a single oral low therapeutic dose of the laxatives to sixteen healthy volunteers.

Validity of oral bioavailability estimates of phenolsulfonphthalein based on total urinary excretion from rats.

Urinary recovery of phenolsulfonphthalein from rats were determined after intracardial (0.075 mg) and oral (1.5 mg) doses. Although trace quantities of conjugated metabolites could be identified by TLC, the levels present did not introduce significant error into estimates of total phenolsulfonphthalein excretion if samples were assayed directly by colorimetric methods for only unchanged dye. The absolute availability of phenolsulfonphthalein based on urinary recovery under the present experimental conditions was estimated at 10.6%.

Diarrhea, red diapers, and child abuse: clinical alertness needed for recognition; clinical skill needed for success in management.

Three children were chronically given phenolphthalein in the form of laxatives by emotionally disturbed mothers. All children had repeated hospitalizations and extensive diagnostic testing because of recurrent intractable unexplained diarrhea. One child died. Pink-red urine and stool were passed at some time during their illnesses. The presence of phenolphthalein was tested for by application of dilute acid of dilute alkali to the diapers causing respectively disappearance of deepening of the pink-red color. Cases went undiagnosed for prolonged intervals because mothers seemed exemplary. Evidence of their psychiatric illnesses was found once the possibility was considered. Phenolphthalein poisoning should be tested for in any case of intractable diarrhea when objective evidence of intestinal mucosal damage cannot be found. The condition represents a heretofore unrecognized variant of child abuse of battering.

Renal excretion of chlorphenol red and related organic acids in the intact flounder Pseudopleuronectes americanus.

Renal clearance experiments were performed on unanesthetized winter flounder from which bladder urine was collected continuously and caudal vein blood was sampled periodically; renal tissue was also obtained terminally for comparison of test organic acid content in vivo and after incubation in vitro. Urine flow rates and inulin U/P (urine to plasma concentration) ratios were relatively constant for a given fish and averaged 1.0 ml/hr X kg fish and 2.6, respectively. In contrast, U/P ratios for all three test acids cycled from minima of near 100 to maxima of over 1000 roughly every 24 hr when plasma concentrations of unbound acid were below 1 micron; correction of plasma protein binding was required in the case of chlorphenol red, but not PAH or Diodrast. Both in vivo and in vitro the organic acid content of renal tissue was intermediate between plasma and urine concentrations. These results demonstrate that kidneys of intact flounder exhibit the remarkable concentrative capacity for exogenous organic acids previously observed with isolated tubules and suggest that the tubular urine concentration is established in two steps by cell transport first at the peritubular and second at the luminal membrane. The anterior kidney position and the magnitude of maximal PAH and Diodrast clearances, about 1000 ml/hr X kg flounder, are consistent with most of the cardiac output returning to the heart through the renal portal circulation; a regulatory shunt bypassing the peritubular capillaries is proposed to explain cycling of organic acid clearances to minimal values.

Surreptitious laxative ingestion. Delayed recognition of a serious condition: a case report.

A 46-year-old man with chronic diarrhea underwent exhaustive investigations, including laparotomy, but a definitive diagnosis could not be made. It was not until a colonoscopic biopsy demonstrated the pigment of melanosis coli that the surreptitious use of laxatives was considered seriously. This diagnosis was confirmed by simple chemical tests that demonstrated phenolphthalein in the feces and urine.