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Biomedical subjects

J A Sturman

Publications and source records attributed to J A Sturman.

At least 19 recordsLinked to original sources

The role of taurine in infant nutrition.

The importance of taurine in the diet of pre-term and term infants has not always been clearly understood and is a topic of interest to students of infant nutrition. Recent evidence indicates that it should be considered one of the "conditionally essential" amino acids in infant nutrition. Plasma values for taurine will fall if infants are fed a taurine-free formula or do not have taurine provided in the TPN solution. Urine taurine values also fall, which is indicative of an attempt by the kidney to conserve taurine. The very-low-birth-weight infant, for a variety of reasons involving the maturation of tubular transport function, cannot maximally conserve taurine by enhancing renal reabsorption and, hence, is potentially at greater risk for taurine depletion than larger pre-term or term infants, and certainly more than older children who have taurine in their diet. Taurine has an important role in fat absorption in pre-term and possibly term infants and in children with cystic fibrosis. Because taurine-conjugated bile acids are better emulsifiers of fat than glycine-conjugated bile acids, the dietary (or TPN) intake has a direct influence on absorption of lipids. Taurine supplementation of formulas or TPN solutions could potentially serve to minimize the brain phospholipid fatty acid composition differences between formula-fed and human milk-fed infants. Taurine appears to have a role in infants, children, and even adults receiving most (> 75%) of their calories from TPN solutions in the prevention of granulation of the retina and electroencephalographic changes. Taurine has also been reported to improve maturation of auditory-evoked responses in pre-term infants, although this point is not fully established. Clearly, taurine is an important osmolyte in the brain and the renal medulla. At these locations, it is a primary factor in the cell volume regulatory process, in which brain or renal cells swell or shrink in response to osmolar changes, but return to their previous volume according to the uptake or release of taurine. While there is a dearth of clinical studies in man concerning this volume regulatory response, studies in cats, rats, and dog kidney cells indicate the protective role of taurine in hyperosmolar stress. The infant depleted of taurine may not be able to respond to hyper- or hyponatremic stress without massive changes in neuronal volume, which has obvious clinical significance. The fact that the brain content of taurine is very high at birth and falls with maturation may be a protective feature, or compensation for renal immaturity Defining an amino acid as "conditionally essential" requires that deficiency result in a clinical consequence or consequences which can be reversed by supplementation. In pre-term and term infants, taurine insufficiency results in impaired fat absorption, bile acid secretion, retinal function, and hepatic function, all of which can be reversed by taurine supplementation. Therefore, this small beta-amino acid, taurine, is indeed conditionally essential.

Animals

Dietary beta-alanine results in taurine depletion and cerebellar damage in adult cats.

We have used the taurine analogue, beta-alanine, to perturb the taurine concentrations in taurine-supplemented and taurine-deprived adult cats. By using 5% beta-alanine in the drinking water for 20 weeks, both groups of cats had greatly reduced brain taurine concentrations. Taurine-supplemented cat brain accumulated relatively small amounts of beta-alanine whereas taurine-deprived cats accumulated large amounts of beta-alanine. The cerebellum of cats treated with beta-alanine had a number of pathological changes compared with similar cats drinking water alone. The changes were more severe in the taurine-deprived cats, and included reduced numbers of granule and Purkinje cells, with many of those remaining appearing pyknotic and dying. Long swollen fibers were seen in the white matter, resembling Rosenthal fibers described in some human cerebellar diseases. There was also prominent gliosis. Using antibodies to beta-alanine and taurine, beta-alanine was localized in Purkinje cell soma and dendrites, in Golgi II cells, and in some granule cells, especially in taurine-deprived cats treated with beta-alanine. Taurine appears to have been virtually eliminated from Purkinje and granule cells, and concentrated in Golgi II cells and glia. We conclude that beta-alanine is responsible for these neurotoxic pathological changes.

Administration, Oral

Effect of K+- and kainate-mediated depolarization on survival and functional maturation of GABAergic and glutamatergic neurons in cultures of dissociated mouse cerebellum.

The effect of the depolarizing agents, an elevated potassium concentration (25 mM) or kainic acid (50 microM) on neuronal survival and differentiation was investigated in cultures of dissociated neurons from cerebella of 7-day-old mice. When maintained in the presence of an antimitotic agent such cultures consist primarily of glutamatergic and GABAergic neurons. Cell survival was monitored by measurement of DNA, and differentiation by determining uptake and depolarization coupled release of glutamate (D-aspartate as label) and GABA. The depolarizing agents were added separately or together either from the start of the culture period (7-8 days) or at day 5 in culture. The main findings are that K+ depolarization is important for differentiation of glutamatergic neurons but not for GABAergic neurons. This depolarizing signal is important during the early phase of development in culture. For glutamatergic neurons, kainate may replace K+ as a depolarizing signal whereas in case of the GABAergic neurons, kainate was toxic particularly during the late phase of development. It was further observed that the glutamatergic neurons when maintained in a medium with 5 mM K+ during the first 5 days in culture became sensitive to kainate toxicity when this amino acid was added at day 5. This was not the case when the medium contained 25 mM K+ from the start of the culture period.

Animals

Altered GABA distribution in hamster brain is an early molecular consequence of infection by scrapie prions.

Antibodies specific for GABA, glutamate and taurine were used to study the distribution of these amino acid neurotransmitters during the progression of scrapie in hamsters. Immunohistochemical distribution of glutamate and taurine were unaffected in scrapie hamsters compared with controls, but the distribution of GABA was altered by 21 days after inoculation. We found both a greater number of neurons showing GABA-like immunoreactivity and more intense staining in those neurons in scrapie-inoculated hamster brains, particularly in the hippocampus, inferior colliculus, frontal cortex and cerebellum. The overall concentrations of aspartate, GABA, glutamate and taurine, measured in seven different brain regions by PITC-amino acid analysis, were not significantly different between normal and scrapie-affected hamsters. The subtle alteration in GABA metabolism detected in this scrapie model suggests that PrPSc interacts directly with a component of the GABA system.

Animals

Taurine in pediatric nutrition.

The past 20 years have seen the status of taurine change from an end product of methionine and cysteine metabolism and substance conjugated to bile acids to that of an important, and sometimes essential, nutrient. It is now added to most synthetic human infant formulas and pediatric parenteral solutions throughout the world. This article describes the research that led to this end.

Animals

Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats.

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.

Animals

Excitatory amino acid receptors in membranes from cultured human retinal pigment epithelium.

The presence of specific, saturable receptor sites for excitatory amino acids (EAA) in membranes from cultured human retinal pigment epithelium (RPE) was established through the binding of [3H]L-glutamate (L-Glu). The age of the donors ranged from 6 days to 33 years. The affinity of the binding (KB) sites was between 1.2 and 1.5 microM, and did not change with the age of the donor, whereas the Bmax was slightly increased (8.6 to 13.0 pmol/mg) in membranes from the 33 year-old compared to the 29 day-old donor. The efficacy profile of agonists and antagonists acting at EAA receptors for displacing [3H]L-Glu was L-Glu = L-Aspartate > 2-amino-4-phosphonovalerate (AP5) > N-methyl-D-Aspartate (NMDA) > 1-aminocyclopentane-1,3 dicarboxylate (trans-ACPD) > 2-amino-3-phosphonopropionate (AP3). These data suggest the presence of either an NMDA-receptor sensitive to the metabotropic agonist trans-ACPD or alternatively, the presence of two different populations of receptors with similar affinity for the agonist: NMDA and metabotropic. Glycine highly stimulated Glu-binding; this effect was inversely related to the age of the donor. Taurine and to a lesser extent GABA, mimicked this effect. Stimulation by glycine was dose-dependent, insensitive to strychnine and 80% inhibited by 7-chlorokynurenate. This effect was also present in human RPE-derived fibroblasts, human scleral fibroblasts and the human lymphoblastoid cell line NB76, all continuously dividing cells. The results further support the possibility of the participation of EAA receptors in the regulation of phagocytosis in RPE.

Adolescent

Taurine in toad brain and blood under different conditions of osmolality: an immunohistochemical study.

The concentrations of taurine in blood and brain regions of the toad Bufo boreas have been measured. Most of these values are considerably lower than those found in mammals. Using an antibody prepared against conjugated taurine, the distribution of taurine in three brain regions of the toad has been visualized. The possible osmoregulatory functions of taurine have been investigated by making toads hyper- or hypo-osmotic in vivo. Induction of hypoosmolality is accompanied by a massive taurine tide in blood plasma, but has no immediate effects upon the taurine concentrations in the brain areas studied. However, histochemical visualization indicates a marked redistribution of taurine between cellular components and extracellular space of brain tissues. This may indicate that taurine has an osmoregulatory function in brain tissue under hypo-osmotic conditions. Hyperosmolality results in no elevation of the taurine concentration in blood plasma of toads, but rather in a very gradual decline of total plasma taurine content over a prolonged time period. Histochemical studies reveal little change in frontal cortex after 1 hour but deeper staining of many neurons in optic lobe accompanied by greater staining in the extracellular fluid. By 3 hours there is a depletion of taurine from all compartments of cerebral cortex tissues. No evidence of any prolonged direct osmoregulatory role for taurine is indicated under hyperosmotic conditions. A possible indirect osmoregulatory function of taurine is discussed.

Animals

Visualization of taurine, GABA and glutamate in developing feline cerebellum by immunohistochemistry.

The localization of taurine, GABA and glutamate in developing feline cerebellum was performed using antibodies raised against the amino acids conjugated to bovine serum albumin with glutaraldehyde. Distinct patterns of immunostaining were observed for each of the amino acids. Taurine-like immunoreactivity reached a peak at 4 weeks after birth, as did GABA-like immunoreactivity, whereas glutamate-like immunoreactivity was greatest in the mature cerebellum. Purkinje cells are all taurine-positive in cerebellum from neonatal animals, whereas in the mature cerebellum they appear to contain only GABA and glutamate, with virtually no taurine, in contrast to observations reported with rodent cerebellum. Ultrastructural studies and immunogold labelling visualized by electron microscopy show that the band of taurine-like immunoreactivity observed in newborn feline cerebellum is localized within dendrites, axons and glial processes. Granule cells migrating through this region also show prominent taurine-like immunoreactivity.

Animals

Immunohistochemical localization of taurine in rat renal tissue: studies in experimental disease states.

Taurine, a sulfur amino acid, is present in abundant amounts in cells throughout the body. The kidney regulates taurine balance by modulating proximal tubule reabsorption in response to fluctuations in dietary intake of this nutrient. There is no information about the localization of taurine within the kidney in normal and diseased renal parenchyma. Therefore, using an antibody to a taurine-glutaraldehyde-BSA conjugate, we examined the distribution of taurine in renal tissue. Normal rats, those with streptozocin diabetes, puromycin aminonucleoside nephropathy, bilateral ureteral ligation, and 5/6 nephrectomy were studied. In normal animals, taurine was found primarily in medullary tubules, with minimal staining of proximal tubules and glomeruli. There was increased taurine staining of all structures, especially medullary tubules, in rats with streptozocin diabetes and puromycin aminonucleoside nephropathy. These changes were more pronounced in diabetic rats and were unrelated to renal medullary osmolality. The distribution of taurine within the kidney was unchanged in the models of acute and chronic renal failure. Alterations in the immunohistochemical localization of taurine correlated with the beneficial effect of this amino acid to preserve renal function in the rats with chronic diabetes and puromycin aminonucleoside nephropathy. These results suggest that taurine is preferentially localized in the medullary regions of the kidney, where it exerts a protective effect against renal injury in select disease states.

Animals

Taurine distribution in different cat muscles as visualized by immunohistochemistry: changes with stimulus state.

The distribution of endogenous taurine in the cardiac pectinate muscle, the intestinal wall smooth muscle and in nine striated muscles of the cat was studied by immunohistochemistry. It was found that taurine-like immunoreactivity (TLI) is distributed homogeneously in the cardiac and smooth muscles selected where it is present in every single fibre. In contrast, TLI appeared unevenly distributed in eight out of nine skeletal muscles, the soleus being atypical. Under resting conditions, TLI is present in only a portion of the fibre population, the proportion being specific for each muscle. Under nerve stimulation the TLI negative/positive ratio increased, suggesting release activity, while an opposite trend occurred after denervation. Glutamate-like immunoreactivity (GLI), although present in every fibre, showed a stronger reaction in those fibres positive to taurine, suggesting parallel movements of both amino acids. Results are discussed in terms of two functional possibilities.

Animals