Urinary excretion of anthocyanins in humans after cranberry juice ingestion

Cranberry, which is rich in polyphenols, including anthocyanins and proanthocyanidins, has been found to have various effects beneficial to human health, including prevention of urinary tract infections. These effects have been associated with polyphenols in the fruit. We investigated the excretion of anthocyanins in human urine after ingestion of cranberry juice. Eleven healthy volunteers consumed 200 ml of cranberry juice containing 650.8 microg total anthocyanins. Urine samples were collected within 24 h before and after consumption. Six of 12 anthocyanins identified in cranberry were quantified in human urine by HPLC coupled with electrospray ionization and tandem mass spectrometry (HPLC-ESI-MS-MS). Among these, peonidin 3-O-galactoside, the second most plentiful anthocyanin in the juice, was found most abundantly in urine within 24 h, corresponding to 41.5 nmol (56.1% of total anthocyanins). The urinary levels of anthocyanins reached a maximum between 3 and 6 h after ingestion, and the recovery of total anthocyanins in the urine over 24 h was estimated to be 5.0% of the amount consumed. This study found high absorption and excretion of cranberry anthocyanins in human urine.     

Urinary excretion of aldosterone metabolite Kelly-M1 in patients with adrenal dysfunction

Using tetrahydroaldosterone antibody a radioimmunoassay was developed to measure substance Kelly-M1 (K-M1) in human urine. The normal values were lower than observed by Kelly et al. who discovered the catabolite after giving large doses of exogenous aldosterone. While in essential hypertension the excretion of K-M1 was predominantly within the normal range, elevated values were found in most cases of 21-hydroxylase deficiency, both the simple virilizing and salt losing form, primary aldosteronism, renal hypertension and cystinosis. Our findings suggest that K-M1 may be formed from 21-deoxyaldosterone and/or by microbial intervention from aldosterone or its metabolites.     

Urinary prostaglandin e2 excretion in chronic renal disease

To ascertain whether renal prostaglandin E₂ production is impaired in chronic renal disease we measured urinary prostaglandin E₂ in 25 female renal patients, and in 38 female normal volunteers. Prostaglandin E₂ averaged 337 ± 63 ng/24 hr in 25 female renal patients, which was significantly higher (P < 0.01) than values in normal female subjects (166 ± 17 ng/24 hr). None of the renal patients excreted less than 50 ng/24 hr, whereas normals when treated with indomethacin averaged 30 ± 10 ng/24 hr (n=8). There were no significant correlations between prostaglandin E₂ and creatinine clearance, or urine volume. No difference in prostaglandin E₂ was encountered between hypertensive and normotensive renal patients. Our results indicate that renal prostaglandin E₂ production is increased rather than decreased in renal disease. The failure to demonstrate decreased urinary prostaglandin E2 excretion in renal hypertension sharply contrasts with the situation in essential hypertension.     

Synthesis of a quaternary polyprenyl ammonium salt

Reaction of primary C(55)-allylic alcohol moraprenol (WT(3)C(7-9)-OH, a polyprenol from mulberry leaves) with triethylamine in the presence of phosphorus oxychloride leads to a quaternary ammonium chloride with a good yield (72%) and high cis-stereoselectivity of the terminal isoprene unit. Cationic polyprenyl derivatives may be useful for transfection and immunological studies.     

Dipeptidyl peptidase IV is a target for covalent adduct formation with the acyl glucuronide metabolite of the anti-inflammatory drug zomepirac

The nonsteroidal anti-inflammatory drug zomepirac (ZP) is metabolised to a chemically reactive acyl glucuronide conjugate (ZAG) which can form covalent adducts with proteins. In vivo, such adducts could initiate immune or toxic responses. In rats given ZP, the major band detected in liver homogenates by immunoblotting with a polyclonal ZP antiserum was at 110 kDa. This adduct was identified as ZP-modified dipeptidyl peptidase IV (DPP IV) by immunoblotting using the polyclonal ZP antiserum and monoclonal DPP IV antibodies OX-61 and 236.3. In vitro, ZAG, but not ZP itself, covalently modified recombinant human and rat DPP IV. Both monoclonal antibodies recognized DPP IV in livers from ZP- and vehicle-dosed rats. Confirmation that the 110 kDa bands which were immunoreactive with the ZP and DPP IV antibodies represented the same molecule was obtained from a rat liver extract reciprocally immunodepleted of antigens reactive with these two antibodies. Furthermore, immunoprecipitations with OX-61 antibody followed by immunolotting with ZP antiserum, and the reciprocal experiment, showed that both these antibodies recognised the same 110 kDa molecule in extracts of ZP-dosed rat liver. The results verify that DPP IV is one of the protein targets for covalent modification during hepatic transport and biliary excretion of ZAG in rats.     

Urinary cyclic AMP excretion is increased in Macaca fascicularis and Macaca mulatta compared to humans

Changes in parathyroid hormone and its second messenger cyclic AMP have been implicated in the pathogenesis of osteoporosis. Nonhuman primate models have been useful in the study of osteoporosis, but the physiology of mineral metabolism in certain species is different than in humans. We investigated parameters of mineral metabolism in 15 normal adult female cynomolgus and 14 normal adult female rhesus monkeys. In both species, urinary cyclic AMP was increased compared with humans, and the nephrogenous cyclic AMP in the cynomolgus monkeys was also elevated. Despite this, there was no evidence for hyperparathyroidism in either species as evaluated by serum or plasma phosphorus and midregion-specific and/or aminoterminal-specific immunoreactive parathyroid hormone. Given the increasing use of nonhuman primates in the study of osteoporosis, understanding basic changes in mineral metabolism is important before pathologic effects of bone loss can be understood.     

Mutants of Saccharomyces cerevisiae resistant to a quaternary ammonium salt

Three quaternary ammonium salts were compared in respect of their ability to select resistant mutants of S. cerevisiae. The mutants tolerating slightly higher IM compound concentration were analysed. They appeared to be the products of nuclear gene mutation segregating monogenically but strongly influenced by genetic background. The mutant IMR when transformed to rho degrees lost resistance below the level of minimal inhibitory concentration of original strain. Possible hypothesis explaining this phenomenon is presented.     

High biliary and systemic excretion of a glucuronide during its hepatic synthesis

Using isolated perfused rat liver and ¹⁴C-p-nitrophenol as a model substrate for glucuronidation, evidence was obtained that during synthesis of p-nitrophenyl-glucuronide biliary excretion of the metabolite is much higher than would be expected from concentrations of the metabolite in the circulation. Isotopic dilution experiments indicate that newly synthesized glucuronide is in a pool which is readily available for biliary excretion but is not easily miscible, or diluted, by the glucuronide in the circulation.     

Urinary excretion of taurine in epilepsy

Evidence that taurine (2-aminoethanesulfonic acid) is related to the epilepsies is supported by work with both experimental animals and hurmans. It may function as a neurotransmitter or modulator of neurotransmission. Investigators using an automated amino acid analyzer reported lower mean urinary taurine excretion among epileptics. However, Rao et al. reported higher taurine excretion among epileptics using an older method. Analyses of the same epileptic and control urines by both methods coupled with paper and molecular size chromatography indicate that substances in addition to taurine are co-eluted with taurine using the older method, yielding spuriously high values. The resolution of this disparity is important because the urinary excretion of taurine may reflect primarily the influence of taurine transport alleles which may be polygenic components in the idiopathic epilepsies.