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Biomedical subjects

M Lever

Publications and source records attributed to M Lever.

At least 19 recordsLinked to original sources
PubMed2004

Trigonelline is not responsible for the acute increase in plasma homocysteine following ingestion of instant coffee.

OBJECTIVE: To determine whether trigonelline contributes to the effect of coffee on homocysteine (Hcy). DESIGN AND INTERVENTIONS: This was a randomised crossover study. Subjects consumed 50 mg trigonelline, 5 g of instant coffee (approximately 50 mg trigonelline) or water, consumed as a single dose in 100 ml, with 1 week between each treatment. Blood samples were drawn fasting and hourly for 8 h. Urine samples were collected pretreatment and every 2 h for 8 h. SETTING: Christchurch Clinical Studies Trust, Christchurch, New Zealand. SUBJECTS: Eight healthy male subjects. RESULTS: Instant coffee raised plasma Hcy concentrations compared with water (P=0.019) and trigonelline (P=0.037). Plasma Hcy concentrations were not different between water and trigonelline treatments (P=0.789). The change in plasma Hcy concentration was higher (mean+/-s.e.) 4 h (0.7+/-0.2 micromol/l, P=0.006), 5 h (0.7+/-0.2 micromol/l, P=0.013) and 7 h (0.7+/-0.2 micromol/l, P=0.024) following coffee consumption. Urinary glycine betaine excretion was increased by coffee but not by trigonelline. CONCLUSION: Ingestion of instant coffee acutely elevated plasma Hcy; however, trigonelline is not responsible for this rise. SPONSORSHIP: Supported by the Health Research Council, the Canterbury Medical Foundation, the Foundation of Research, Science and Technology.

Adult↗
PubMed2001

Near infra-red spectra of urea with glycine betaine or trimethylamine N-oxide are additive.

Glycine betaine and trimethylamine-N-oxide counteract urea denaturation in solutions containing urea and the methylamine in the mole ratio of 2:1. Near infra-red difference spectra (water spectrum subtracted) of solutions containing both urea with either glycine betaine or trimethylamine-N-oxide can be predicted from the spectra of the single solutes, with r(2)>0.999 both using the spectrum from 1200 to 2100 nm (where most absorbance is attributable to hydrogen bonding) and using an extended range 1000 to 2500 nm, which includes solute specific bands. Thus urea and the kosmotropes appear to interact with water independently and the counteraction cannot be attributed to specific interactions between them. The spectrum of aqueous glycine betaine can be predicted from tetramethylammonium and formate ions (r(2)=0.998), suggesting that independent interactions of the quaternary amine, and of the carboxyl function, with water are dominant. The exceptional properties of glycine betaine do not arise from specific intramolecular interactions between the charged groups.

Betaine↗
PubMed2001

Glycine betaine excretion is not directly linked to plasma glucose concentrations in hyperglycaemia.

Diabetes mellitus subjects, type 1 and type 2, have increased glycine betaine excretion compared to normal subjects that correlated with plasma glucose and HbA(1C) concentrations. The current study was undertaken to determine whether elevated glucose concentration directly increases glycine betaine excretion in an animal model. Non-pregnant female Coopworth sheep received an intravenous glucose load (12.5,25 and 50% w/v; rate 200 ml/h) for 6 h followed by a 12 h physiological saline washout (0.9% w/v). Plasma and urine samples were analyzed for glycine betaine and glucose. Urine volumes and osmolality were also measured. Using the non-parametric Kruskal Wallis analysis of variance test we found no difference in glycine betaine excretion between glucose loaded and saline infused control animals (P=0.861). However, a significant negative correlation (r=-0.28, P<0.001) was observed between urine osmolality and glycine betaine excretion independent of treatment. We conclude that acute elevations of plasma glucose concentrations did not result in increased glycine betaine excretion and is therefore unlikely to be directly responsible for elevated glycine betaine excretion observed in diabetes mellitus subjects.

Animals↗
PubMed2001

Some ways of looking at compensatory kosmotropes and different water environments.

Hydration of macromolecular structures determines biological activity. Stabilizing solutes are kosmotropic (increase order of water) rather than chaotropic (decrease order). Preferential hydration of surfaces is a thermodynamic consequence of the solution behavior of kosmotropic solutes, but inconsistencies imply interactions such as the hydration of specific sites within macromolecules. Thermodynamic measures require bulk pure solutes; here simpler measures of the effects on bulk water, water at surfaces and hydration water of probes have been applied to solutes including natural stabilizers, analogues and example chaotropes. Changes in the near-infrared spectra, water proton NMR chemical shifts and relaxation times measure changes in the bulk liquid; HPLC-column retention of solutes indicate interactions with hydration water at different surfaces, and fluorescence probes detect effects on functional group hydration water. Ab initio calculations and Monte-Carlo simulations of the solutes in water measure the energetics of the solute-water interactions, the dipole moments of these molecules, their charge distributions and the effect of the solute molecules on the structure of water. The rankings of the test solutes by these measures are not consistent. Thus, stabilizing solutes are not interchangeable in biological systems and the intracellular replacement of one by another could affect the integration of cell metabolism.

Chromatography, High Pressure Liquid↗
PubMed2001

Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations.

BACKGROUND: Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is a known feedback inhibitor of BHMT. We postulated that DMG might accumulate in CRF and contribute to hyperhomocysteinemia by inhibiting BHMT activity. METHODS: Plasma and urine concentrations of GB and DMG were measured in 33 dialysis patients (15 continuous ambulatory peritoneal dialysis and 18 hemodialysis), 33 patients with CRF, and 33 age-matched controls. Concentrations of fasting plasma total homocysteine (tHcy), red cell and serum folate, vitamins B(6) and B(12), serum zinc, and routine biochemistry were also measured. Groups were compared, and determinants of plasma tHcy were identified by correlations and stepwise linear regression. RESULTS: Plasma DMG increased as renal function declined and was twofold to threefold elevated in dialysis patients. Plasma GB did not differ between groups. The fractional excretion of GB (FE(GB)) was increased tenfold, and FED(MG) was doubled in CRF patients compared with controls. Plasma tHcy correlated positively with plasma DMG, the plasma DMG:GB ratio, plasma creatinine, and FE(GB) and negatively with serum folate, zinc, and plasma GB. In the multiple regression model, only plasma creatinine, plasma DMG, or the DMG:GB ratio was independent predictors of tHcy. CONCLUSIONS: DMG accumulates in CRF and independently predicts plasma tHcy concentrations. These findings suggest that reduced BHMT activity is important in the pathogenesis of hyperhomocysteinemia in CRF.

Adult↗
PubMed1999

Elevated glycine betaine excretion in diabetes mellitus patients is associated with proximal tubular dysfunction and hyperglycemia.

In an ambulatory population of diabetic subjects (Type 1 and Type 2), the urine excretion of the renal osmolyte, glycine betaine, was compared to known markers of glycemic control, renal dysfunction and to the excretion of related betaines, including trigonelline, proline betaine, carnitine and acetyl-carnitine. Of the 85 subjects, 20 patients had urine glycine betaine concentrations above the reference range for normal subjects. Plasma glycine betaine concentrations were within reference ranges for normal subjects. Patients with elevated glycine betaine excretion tended to have lower plasma glycine betaine concentrations, but this did not reach statistical significance. One way analysis of variance found excretion is independent of treatment, duration of diagnosed diabetes, blood pressure and body mass index (BMI). An association between glycine betaine excretion and glycemic control was observed with statistically significant correlations occurring with both plasma glucose (r = 0.43, P < 0.001) and glycated haemoglobin (HbA1c) (r = 0.35, P < 0.005). The excretion of carnitine, acetyl-carnitine and proline betaine were related to glycine betaine excretion (r = 0.49, P < 0.001; r = 0.40, P < 0.001; r = 0.27, P < 0.05, respectively). Urine carnitine and acetyl-carnitine concentrations were also related to plasma glucose concentrations (r = 0.30, P < 0.01). Increased urine retinol binding protein concentrations (RBP), a marker of proximal tubular dysfunction, correlated with elevated urine glycine betaine excretion and plasma HbA1c (r = 0.28, P < 0.01). These results suggest poor glycemic control is associated with the increase in urine glycine betaine, carnitine, acetyl-carnitine and RBP excretion in diabetic patients. However, < 50% of the observed increase in glycine betaine excretion has been accounted for by the variables measured, suggesting other unidentified processes may also be involved.

Adult↗
PubMed1999

Inhibitors of bacterial growth in urine: what is the role of betaines?

It has long been recognised that some individuals produce urine that is inhibitory to uropathogens. This may be partly explained by inhibitors. Several inhibitors have been identified in urine including urea and organic acids. Bacteria adapt to high osmolarity by activating osmoregulated betaine porters and accumulating organic osmolytes intracellularly. The preferred substrate is glycine betaine, which is present in urine, and promotes rapid growth by balancing osmotic forces and stabilising macromolecular structures against the toxicity of urea and low pH. Other dietary betaines such as trigonelline may also be taken but enhance urea toxicity. The importance of such compounds in vivo is unknown.

Bacteria↗
PubMed1999

Osmoprotective activity, urea protection, and accumulation of hydrophilic betaines in Escherichia coli and Staphylococcus aureus.

The hydrophilic betaines, deanol betaine, triethanol betaine, diethanolthetin and methylethanolthetin, and also thioxanium betaine and citrulline betaine, were accumulated by Escherichia coli. All betaines tested had significant osmoprotective activity for E. coli and, with the exception of citrulline betaine and diethanolthetin, also demonstrated urea protection. Staphylococcus aureus accumulated only methylethanolthetin, deanol betaine and thioxanium betaine: the first two had an osmoprotective effect but conferred no urea protection. Diethanolthetin and thioxanium betaine significantly decreased urea tolerance for S. aureus.

Betaine↗
PubMed1998

Exclusion and retention of compensatory kosmotropes by HPLC columns.

With water as the elution solvent, zwitterionic solutes and polyols were retained on HPLC columns, more than was water, by totally hydrophobic packing materials. Relative retentions were systematically affected by oxygen functional groups in the packing material, explicable as specific retention of water. Reproducible elution sequences of 20 solutes at a variety of hydrophobic surfaces (aromatic and both long- and short-alkyl aliphatic surfaces) showed there is a general process, consistent with interactions with hydration water at the surface having solvent properties distinct from bulk water. Early eluting solutes included glycine, sarcosine and taurine. Glycine betaine followed both these and N,N-dimethylglycine. The natural betaines propionobetaine and dimethylsulfoniopropionate also preceded glycine betaine. Dimethylsulfoxide was strongly retained, as (to a lesser extent) was proline betaine. Polyols eluted in the sequence sorbitol, trehalose, glycerol. Changes in the chemical nature of the surface or base material affected relative retentions of water and solutes. The presence of hydrogen-bonding functions increased retention of polyols, as well as water, relative to zwitterionic solutes. Specific effects retention, constraining models based on the formation of low-density water.

Aluminum Oxide↗
PubMed1998

Osmoprotective properties and accumulation of betaine analogues by Staphylococcus aureus.

Betaines were evaluated as potential antistaphylococcal agents for urinary tract infections. Staphylococcus aureus accumulated all tested betaines except trigonelline. S. aureus transport systems were less sensitive to carbon chain length than those of Escherichia coli. Betaines were accumulated in the absence of osmotic stress, and 10-fold more in hyperosmotic medium. Most betaines increased the osmotolerance of S. aureus in defined minimal medium. Unlike E. coli, S. aureus did not significantly accumulate a second betaine in the presence of glycine betaine. Betaines are less likely to be useful in treating staphylococcal than E. coli urinary infections.

Anti-Bacterial Agents↗
PubMed1996

Natural and synthetic betaines counter the effects of high NaCl and urea concentrations.

Escherichia coli was used as a model system to evaluate a range of betaines for their ability to protect against salt and urea stresses. Betaine structure determined the salt and urea protective effects. Dimethylthetin conferred salt protection similar to glycine betaine, whereas dimethylsulfoniopropionate (DMSP) was less effective than either glycine betaine or dimethylthetin, but similar to propionobetaine (its nitrogen analogue). Hydrophobic alpha-substituents altered salt tolerance. Valine betaine with an aliphatic side group conferred salt tolerance similar to glycine betaine. Betaines containing phenyl groups (phenylglycine, phenylalanine and N-phenylglycine betaines) did not confer salt protection, growth being similar to, or less than the control (no betaine). Hydrophobic groups decreased the ability to protect against urea stresses; valine betaine conferred poor urea tolerance. The addition of an hydroxyl group increased the ability of a betaine to protect against urea denaturation. Proline betaine, an effective salt protector, conferred poor urea tolerance. Increasing the charge separation in the betaine molecule decreased the ability to confer urea tolerance. Thiolanium, pyridinium and triethylglycine betaines, with larger cationic functions, conferred no urea tolerance to E. coli.

Betaine↗
PubMed1996

Is the ability of urinary tract pathogens to accumulate glycine betaine a factor in the virulence of pathogenic strains?

The regulation of intracellular concentrations of organic solutes, including glycine betaine, is an important adaptive response to osmotic stress for Escherichia coli. The clinical significance of glycine betaine to uropathogens is not clear. Clinical isolates of E. coli, Klebsiella pneumoniae, Enterobacter species, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, S. saprophyticus, and Enterococcus faecalis accumulated glycine betaine from hyperosmotic media. The addition of glycine betaine to hyperosmotic minimal medium accelerated the growth rates of all species tested except P. mirabilis. However, when clinical strains of E. coli were transferred from urine with low osmolality to hyperosmotic urine, there was no slowing of the growth rate. There was no difference in growth rates of E. coli isolates from acute pyelonephritis, cystitis, and asymptomatic bacteriuria nor from fecal isolates. The ability to accumulate osmolytes, although it may be a factor in the adaptation to hypertonic environments, was not related to virulence.

Adolescent↗
PubMed1996

Accumulation of natural and synthetic betaines by a mammalian renal cell line.

Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2-5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels. Inhibition studies to distinguish the betaine ports were performed by the addition of proline. Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation. Because alpha-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.

Animals↗
PubMed1995

Competitive accumulation of betaines by Escherichia coli K-12 and derivative strains lacking betaine porters.

Escherichia coli was grown in hyperosmotic media containing both glycine betaine and one other betaine. E. coli K-12 derivative WG439 (putP- proP- proU-) did not accumulate any of 15 betaines. Strains WG445 (putP- proP- proU+), WG443 (putP- proP+ proU-) and the control strains all accumulated less betaine, (CH3)3N(+)-(CH2)n-COO-, when n was greater than 1. Accumulation was not detectable when n = 5. Both L- and D-isomers of alpha-substituted betaines were accumulated by both strains WG443 and WG445, the D-isomers more slowly. Hydroxylated alpha-substituted betaines were accumulated relatively more through the osmoregulated transport protein ProU than through ProP. In actively growing cultures glycine betaine appeared to be the preferred substrate for accumulation, but the proportion of the second accumulated betaine increased as cultures approached stationary phase.

Amino Acid Transport Systems↗
PubMed1995

Short-term response of nonurea organic osmolytes in human kidney to a water load and water deprivation.

The cells of the inner medulla of the mammalian kidney accumulate high concentrations of nonurea organic osmolytes. The organic osmolytes found in the kidney include glycine betaine and sorbitol. This study was designed to measure changes in the urinary excretion of glycine betaine and sorbitol and the plasma concentration of glycine betaine in response to an acute water load (20 ml/kg) or acute water deprivation in young healthy males. In response to a water load the urinary excretion of glycine betaine and sorbitol increased parallel with or shortly after urinary urea excretion. The increase in urinary urea and sorbitol excretions preceded maximum minute volume, whereas peak glycine betaine excretion was closely related to maximum urine minute volume. Subsequently, urea, sorbitol, and glycine betaine excretion rates returned to baseline. In contrast, during water deprivation no change in glycine betaine, sorbitol, and urea urinary excretions occurred during the study period. Plasma glycine betaine concentration was stable during both diuresis and antidiuresis. We conclude that the organic osmolytes glycine betaine and sorbitol are components of a physiological and dynamic system in response to an acute water diuresis.

Adult↗
PubMed1994

Abnormal glycine betaine content of the blood and urine of diabetic and renal patients.

In normal human plasma the concentrations of the renal osmolyte, glycine betaine, are usually between 20 and 70 mumol/l, in adult males (median 44 mumol/l) higher than in females (34 mumol/l). Concentrations are lower in renal disease (median 28 mumol/l) and normal in diabetes. Urinary excretion of glycine betaine shows no sex difference and is frequently elevated both in renal disease and in diabetes (medians: normal, 6.2, renal 12.3 and diabetes, 39.7 mmol/mol creatinine). The elevation in diabetes does not strongly correlate with known renal disease, nor with either urinary microalbumin or plasma creatinine. There is no correlation with glycated haemoglobin. The positive correlation with the excretions of another renal osmolyte, sorbitol, was highly significant in diabetic subjects. In the diabetic group there was also a significant negative correlation between plasma glycine betaine and urine microalbumin.

Adult↗