Comparison of serum and plasma taurine values in Bengal tigers with values in taurine-sufficient and -deficient domestic cats.

A white Bengal tiger was determined to have a central retinal lesion and a central visual defect. Because of the known association between feline central retinal degeneration (CRD) and taurine deficiency in domestic cats, plasma concentrations of taurine were measured in this tiger. Serum concentrations of taurine, methionine, and cystine also were measured in white Bengal tigers, orange Bengal tigers, taurine-sufficient domestic cats, and taurine-deprived and tissue-taurine-depleted visually impaired cats with CRD. Hepatic and brain enzymes responsible for taurine synthesis were identified in tissue specimens from an orange Bengal tiger. Serum taurine concentrations were lower in white vs orange tigers, but were not as low as those in cats with CRD. Thus, we concluded that taurine depletion did not account for the central retinal lesion in the white Bengal tiger.

Rapid determination of total hydroxyproline (HYP) in human urine by HPLC analysis of the phenylisothiocyonate (PITC)-derivative.

A recent development in the preparation for amino acid analysis is the use of phenylisothiocyanate (PITC) as a precolumn derivatizing agent prior to analysis to form a stable derivative. These derivatives can then be separated by reversed phase high pressure liquid chromatography (HPLC). Because of interest in the accurate measurement of urinary hydroxyproline (HYP), PITC was used for derivatization followed by HPLC analysis. Using an automated computer-controlled sampler system, up to 75 samples can be analyzed each 24 h. Technical details, specificity, and reliability of this method are provided. Duplicate measurements of HYP had a coefficient of variation (CV) of 5.5% and with a recovery of HYP in spiked urine samples of 94 to 104%. A sample frozen and thawed 10 times showed no change in the concentration of HYP. When total HYP was measured in 230 healthy women between 20 and 39 years of age, it was found to be 236.62 +/- 146.41 mumoles/L. These samples were researched in 3.5 days using this technique.

HPLC analysis of the phenylisothiocyanate (PITC) derivatives of taurine from physiologic samples.

Taurine is the major free intracellular amino acid. It has become the focus of study by many as a conjugator of bile and as a neurotransmitter and intracellular messenger. In this report we document a technique for measuring taurine in physiologic samples which is rapid, reproducible, and accurate. Any physiologic sample is first derivatized with phenylisothiocyanate (PITC) and separated by reverse phase HPLC, and then taurine is detected by UV at 254 nm. The advantages of this technique for the measurement of taurine are accuracy, small sample size, and reproducibility, and with an automated system many samples can be analyzed.

Development of beta-amino acid transport in the kidney.

This study focuses on the maturation of the renal beta-amino acid transport system and uses dietary manipulation as a probe. The epithelial surface of the renal proximal tubule is responsible for the conservation of ions and organic solutes including beta-amino acids. This beta-amino acid transport system is stimulated during periods of reduced dietary intake and permits increased excretion following dietary excess. We have examined transport of the sulfur-containing beta-amino acid, taurine, as a measure of this renal adaptive response to fluctuations in dietary sulfur amino acid intake and as a substrate for the beta-amino acid transport system. A precession of taurine uptake values by brush border membrane vesicles (BBMV) prepared from nursing rats from youngest to oldest was evident. However, these membranes demonstrate the full renal adaptive response to altered sulfur amino acid intake after the first week of life. This adaptive response is expressed at the brush border surface by transport changes in both directions ("up regulation" and "down regulation"), through changes in the initial rate (15 sec) of Na+-taurine cotransport. No alterations in the lipid microenvironment of the membrane, as detected by altered membrane fluidity, were uncovered. Although vesicles from 7-day-old pups demonstrate adaptation and accumulate taurine to a limited extent, the accumulation of Na+, which energizes uptake, may be altered, thereby preventing full expression of the adaptive response and of transport capacity at this age.

Studies on renal adaptation to altered dietary amino acid intake: tissue taurine responses in nursing and adult rats.

This study examines the effect of a low sulfur amino acid diet (LTD) and a high taurine diet (HTD), compared with a normal diet, on the plasma, urine, muscle, brain and renal cortex levels of taurine in immature and adult rats. Milk taurine from lactating dams reflected the taurine content of the diet, being low in LTD-fed and high in HTD-fed animals. Nursing pups (7, 14 and 21 d old) often had plasma, urine and tissue--renal cortex, heart, skeletal muscle--levels of taurine related to dietary exposure, a situation also found in adult animals. These diets did not influence the urinary excretion of the sulfur-containing alpha-amino acids methionine and cystine but a sulfur aminoaciduria of immaturity was evident. By contrast, the content of taurine in brain was constant regardless of dietary intake of sulfur amino acids. An age-related decline in brain taurine content was found--as noted by others--but this too was influenced by diet. This dual finding of brain taurine constancy despite wide differences in sulfur amino acid intake and changes in the renal handling of taurine as influenced by diet suggest that the renal adaptive response serves to maintain the stability of brain taurine content.

Effect of amino acid intake on brush-border membrane uptake of sulfur amino acids.

Alterations in the intake of sulfur amino acids (SAA) changes the rat renal brush-border membrane uptake of the beta-amino acid, taurine. A low-SAA diet enhances and a high-taurine diet reduces uptake (Chesney et al., Kidney Int. 24: 588-594, 1983). Neither the low-SAA diet nor the high-taurine diet alters the time course or concentration-dependent accumulation of the sulfur amino acids methionine and cystine or of inorganic sulfate. By contrast the uptake of beta-alanine, another beta-amino acid that competes with taurine, is greater in animals on the low-SAA diet. The high-taurine diet does not change beta-alanine uptake. The plasma levels of taurine are altered by dietary change, but not the values for methionine and cystine. This study indicates that renal adaptation is expressed for beta-alanine, a nonsulfur-containing beta-amino acid. By contrast, methionine, cystine, and sulfate, which participate in a variety of synthetic and conjugative processes, are not conserved by the renal brush-border surface following ingestion of either a low-methionine and -cystine diet or high-taurine diet.

Free amino acids and calcium, magnesium and zinc levels in Friedreich's ataxia.

Free amino acid levels and zinc, magnesium and calcium content have been determined in autopsy samples of 9 areas of the brain, two skeletal muscles, and the right ventricle, left ventricle and septum of the heart of a Friedreich's ataxia subject.

Subcellular distribution of neuroactive amino acids in brains of genetically epileptic rats.

The subcellular distribution of amino acids was compared in brains of genetically seizure-susceptible (SS) and genetically seizure-resistant (SR) rats. The total taurine content (mumol/brain) in the P2B, or synaptosomal, fraction in SS rats was only 37% of that of SR rats. Glutamate, glutamine, glycine, alanine, and gamma-aminobutyric acid (GABA) contents were unaltered. No alterations in total content were found in other subcellular fractions for the amino acids studied. SS animals that had never been stimulated to audiogenic seizure had decreased concentrations of taurine (nmol/mg protein) in the P2, P2B, and P2C fractions as compared with SR animals. These fractions contain crude synaptosomes, enriched synaptosomes, and enriched mitochondria, respectively. Phosphoethanolamine concentrations were also decreased in the P2B fractions, but concentrations of other amino acids were unaltered, as compared with SR animals. Twenty-four hours after the intracerebroventricular injection of taurine (6 mumol) in SS animals that had never been convulsed, taurine concentrations were significantly increased in whole brain homogenate and P2 and P2B fractions as compared with SS animals not given taurine. This treatment left unaltered the concentrations of glutamate, glutamine, GABA, and glycine in brain homogenate and P2 fraction. Because decreases in taurine concentration were seen in animals that had not been convulsed, these alterations are intrinsic to the SS strain and are not a consequence of convulsive activity. In view of the antiepileptic action of taurine, and the fact that an impairment of taurine transport in the brain of SS rats had previously been demonstrated, we suggest that a defect in the biochemistry of taurine is partially responsible for the seizure susceptibility of the SS rat.

Relative contribution of the mother, the nurse and endogenous synthesis to the taurine content of the newborn and suckling rat.

The relative contributions have been determined of taurine derived from the mother in utero, via milk during nursing, and from endogenous biosynthesis to the total taurine content of the rat pup between birth and weaning. At birth, 32% of the taurine in the pup has been biosynthesized, and this proportion rises to 83% by day 20 of life. At birth, 67% has been derived from the mother in utero, and by day 20 this has fallen to 4% of the total. This maternal taurine is lost with a half-life of 16 days. There is wide variation in the turnover from different tissues, the pancreas having a half-life of 7 days, and the brain 50 days. However, the amount of maternal taurine in the brain actually increases by 38% over the first 8 days of life. By day 20, 13% of the taurine content of the pup has been obtained from the milk. Taurine turnover in the suckling pup differs from turnover after weaning in that wholebody turnover from the suckling rat is not slower than exchange between organs. In other words, tissues are not in kinetic equilibrium. After animals are weaned, regardless of the taurine content of the diet, taurine is interchanged between organs faster than it is excreted from the animal.

Epilepsy and the concentrations of plasma amino acids in humans.

We have examined the correlation between the presence of epilepsy in humans, and plasma amino acid levels. Subjects were divided into those having pure generalized tonic-clonic seizures (grand mal group), those having generalized tonic-clonic seizures plus other types of epilepsy (mixed group), and those suffering from epilepsies other than grand mal (no grand mal group). Compared to non-epileptic controls, the grand mal group had significantly higher fasting plasma levels of aspartate (100% increase) and glutamate (380% increase) but significant decreases were seen with phenylalanine (?23%), lysine (?27%), and tryptophan (?30%). The no grand mal group showed similar changes except for lysine. The mixed group showed elevations in glutamate, but decreases only in cysteine and methionine. In response to a high protein meal, plasma levels of alanine, cysteine and methionine rose significantly less for the no grand mal group compared to the control group. Increases in aspartate and glutamate concentrations strongly correlated with the prescription of phenytoin. However, the concentrations of these amino acids were not significantly correlated with the actual plasma levels of phenytoin.

Diet and biosynthesis as sources of taurine in the mouse.

The quantitative importance of diet versus biosynthesis as sources of taurine has been established in mice receiving dietary levels of 0.062% [3H]taurine and 0.74% [35S]methionine as sole sulfur-containing amino acids. After 15 days on diets radiolabeled with these levels of taurine and methionine, 16% of total-body taurine had been derived from diet and 24% from biosynthesis. By 30 days, these contributions had risen to 29% and 33%, respectively, and by 61 days to 46%. The half-life of turnover of taurine in the mouse was 18.6 days. These findings indicate that, like the rat and guinea pig, but unlike the cat and human, the mouse exhibits considerable biosynthetic capacity for taurine.

Relative contribution of diet and biosynthesis to the taurine content of the adult rat.

The relative contribution of diet and biosynthesis to the taurine content of the rat has been determined quantitatively under various dietary conditions. Rats were maintained on diets containing [3H]taurine and/or [35S]methionine of known amounts and specific activities, and subsequently the specific activity of taurine in various tissues was determined. This approach gives a quantitative measure of how much taurine is biosynthesized versus how much is derived from the diet regardless of the biosynthetic route or site of biosynthesis in the animal. With no taurine in the diet, over an 87-day period, 54% of the taurine in the animal had been biosynthesized. This fell to 29% if taurine was present in the diet, and the contribution of dietary taurine to body pools rose to 58%. These changes in biosynthetic contributions were not accompanied by an alteration in the rate of biosynthesis but by an alteration in rate of excretion. When the amounts of biosynthesized taurine appearing in the urine over 63 days was added to the amounts found in the carcass, 3.1 mmol were found to be biosynthesized by animals receiving taurine in the diet as compared to 2.9 mmol in animals on a taurine-deficient diet. In any one experiment, the contribution of diet or biosynthesis is invariant from tissue to tissue indicating that the rate of exchange of taurine between tissues is faster than the rate of elimination of taurine from the body.

Radiation effects on pig skin. Exposure to different densities of ionization.

The effects on pig skin from radiations producing different densities of ionization have been determined. For the qualities of radiation employed, erythema was produced at a dose range from 1,240 to 3,440 rads and ulceration at 1,250 to 5,000 rads. In no instance did a radiation-induced neoplasm develop. In determining dose response, two of the most important physical parameters, associated with time of appearance and extent of lesions, were found to be the size of the area irradiated and the density of ionization of the radiations used. These data, on normal tissue tolerance, should be a value in future programs initiated in experimental radiation therapy of both animal and human neoplasia utilizing protons, alpha particles, and carbon ions.

Transcontinental baselines and the rotation of the Earth measured by radio interferometry.

Nine separate very-long-baseline interferometry (VLBI) experiments, carried out in 1972 and 1973 with radio telescopes 3900 kilometers apart, yielded values for the baseline length with a root-mean-square deviation about the mean of less than 20 centitneters. The corresponding fractional spread is about five parts in 10(8). Changes in universal time and in polar motion were also detertnined accurately from these data; the root-mean-square scatter of these results with respect to those based on optical methods were 2.9 milliseconds and 1.3 meters, respectively. Solid-earth tides were apparently detected, but no useful estimate of their amplituide was extracted.