Comparative study of the analysis of seized samples by GC-MS, H NMR and FT-IR spectroscopy within a Night-Time Economy (NTE) setting.

Rapid analysis of surrendered or seized drug samples provides important intelligence for health (e.g. treatment or harm reduction), and custodial services.

A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain.

Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P -(C5) , of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex.

Betaine is accumulated via transient choline dehydrogenase activation during mouse oocyte meiotic maturation.

Betaine (-trimethylglycine) plays key roles in mouse eggs and preimplantation embryos first in a novel mechanism of cell volume regulation and second as a major methyl donor in blastocysts, but its origin is unknown. Here, we determined that endogenous betaine was present at low levels in germinal vesicle (GV) stage mouse oocytes before ovulation and reached high levels in the mature, ovulated egg. However, no betaine transport into oocytes was detected during meiotic maturation.

Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?

Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved.

Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain-derived neurotrophic factor (proBDNF).

This study describes a fundamental functional difference between the two main polymorphisms of the pro-form of brain-derived neurotrophic factor (proBDNF), providing an explanation as to why these forms have such different age-related neurological outcomes. Healthy young carriers of the Met66 form (present in ∼30% Caucasians) have reduced hippocampal volume and impaired hippocampal-dependent memory function, yet the same polymorphic population shows enhanced cognitive recovery after traumatic brain injury, delayed cognitive dysfunction during aging, and lower risk of late-onset Alzheimer's disease (AD) compared to those with the more common Val66 polymorphism. To examine the differences between the protein polymorphisms in structure, kinetics of binding to proBDNF receptors and in vitro function, we generated purified cleavage-resistant human variants.

Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study.

Background: Betaine is a major osmolyte, also important in methyl group metabolism. Concentrations of betaine, its metabolite dimethylglycine and analog trimethylamine-N-oxide (TMAO) in blood are cardiovascular risk markers. Diabetes disturbs betaine: does diabetes alter associations between betaine-related measures and cardiovascular risk?

Methods: Plasma samples were collected from 475 subjects four months after discharge following an acute coronary admission.

Fenofibrate causes elevation of betaine excretion but not excretion of other osmolytes by healthy adults.

Background: Cross-sectional data suggest that bezafibrate increases betaine excretion in dyslipidemic patients.

Objective: We aimed to demonstrate that fenofibrate induces increased betaine excretion in normal subjects and explore whether other 1-carbon metabolites and osmolytes are similarly affected.

Methods: Urine was collected from 26 healthy adults before and after treatment with fenofibrate (145 mg/day for 6 weeks).

Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes.

Purpose: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes?

Methods: Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32).

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period.

Background: Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers.

Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival and baseline active vitamin B12 levels in post-acute coronary syndromes patients.

Background And Aims: The methylene-tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene is involved in mitochondrial tetrahydrofolate metabolism. Polymorphisms in MTHFD1L, including rs6922269, have been implicated in risk for coronary artery disease (CAD). We investigated the association between rs6922269 and known metabolic risk factors and survival in two independent cohorts of coronary heart disease patients.

Uptake of betaine into mouse cumulus-oocyte complexes via the SLC7A6 isoform of y+L transporter.

Betaine (N,N,N-trimethylglycine) has previously been shown to function in cell volume homeostasis in early mouse embryos and also to be a key donor to the methyl pool in the blastocyst. A betaine transporter (SLC6A20A or SIT1) has been shown to be activated after fertilization, but there is no saturable betaine uptake in mouse oocytes or eggs. Unexpectedly, the same high level of betaine is present in mature metaphase II (MII) eggs as is found in one-cell embryos despite the lack of transport in oocytes or eggs.

Plasma betaine concentrations correlate with plasma cortisol but not with C-reactive protein in an elderly population.

Background: Low plasma betaine concentrations are a feature of seriously ill patients. Increased dietary betaine intake has been associated with lowered systemic inflammation. We aimed to compare plasma cortisol (a stress marker) and C-reactive protein (an inflammation marker) as statistical predictors of plasma betaine concentrations.

Betaine homocysteine methyltransferase is active in the mouse blastocyst and promotes inner cell mass development.

Methyltransferases are an important group of enzymes with diverse roles that include epigenetic gene regulation. The universal donor of methyl groups for methyltransferases is S-adenosylmethionine (AdoMet), which in most cells is synthesized using methyl groups carried by a derivative of folic acid. Another mechanism for AdoMet synthesis uses betaine as the methyl donor via the enzyme betaine-homocysteine methyltransferase (BHMT, EC 2.

Betaine and secondary events in an acute coronary syndrome cohort.

Background: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients.

Methods: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event.

Variability of plasma and urine betaine in diabetes mellitus and its relationship to methionine load test responses: an observational study.

Background: Since betaine is an osmolyte and methyl donor, and abnormal betaine loss is common in diabetes mellitus (>20% patients), we investigated the relationship between betaine and the post-methionine load rise in homocysteine, in diabetes and control subjects. The post-methionine load test is reported to be both an independent vascular risk factor and a measure of betaine sufficiency.

Methods: Patients with type 2 diabetes (n  =  34) and control subjects (n  =  17) were recruited.

The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments.

Background: Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease.

Methods: The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic.

Betaine excretion correlates with plasma homocysteine when plasma lipids are elevated.

Objectives: To reconcile observing a positive correlation of betaine excretion with homocysteine in lipid disorder patients but not other study groups.

Design And Methods: Correlations were estimated in subgroups of a control group and the lipid disorder patients.

Results: Plasma non high-density lipoprotein (non-HDL) cholesterol differed (p<0.

Measurement of marine osmolytes in mammalian serum by liquid chromatography-tandem mass spectrometry.

Osmolytes are accumulated intracellularly to offset the effects of osmotic stress and protect cellular proteins against denaturation. Because different taxa accumulate different osmolytes, they can also be used as "dietary biomarkers" to study foraging. Potential osmolyte biomarkers include glycine betaine, trimethylamine N-oxide (TMAO), homarine, dimethylsulfoniopropionate (DMSP), and the osmolyte analog arsenobetaine (AsB).

Plasma lipids and betaine are related in an acute coronary syndrome cohort.

Background: Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these.

Trimethylaminuria: causes and diagnosis of a socially distressing condition.

Trimethylaminuria is a disorder in which the volatile, fish-smelling compound, trimethylamine (TMA) accumulates and is excreted in the urine, but is also found in the sweat and breath of these patients. Because many patients have associated body odours or halitosis, trimethylaminuria sufferers can meet serious difficulties in a social context, leading to other problems such as isolation and depression. TMA is formed by bacteria in the mammalian gut from reduction of compounds such as trimethylamine-N-oxide (TMAO) and choline.

Fibrates plus betaine: a winning combination?

Because most of the cardiac risk remains despite successful statin therapy there has been renewed interest in fibrate therapy for persisting hyperlipidaemia. Fibrate therapy lowers triglycerides but causes the urinary loss of betaine, which is an essential metabolite that is involved in osmoregulation, in methyl group metabolism, and which also affects lipid partitioning in the body. Loss of betaine is associated with an elevation of homocysteine and may compromise the potential benefits of fibrate therapy.

The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism.

Betaine is an essential osmolyte and source of methyl groups and comes from either the diet or by the oxidation of choline. Its metabolism methylates homocysteine to methionine, also producing N,N-dimethylglycine. Betaine insufficiency is associated with the metabolic syndrome, lipid disorders and diabetes, and may have a role in vascular and other diseases.