Biomedical subjects

K Sugden

Publications and source records attributed to K Sugden.

At least 19 recordsLinked to original sources

PubMed2005

Association analysis of monoamine genes with measures of depression and anxiety in a selected community sample of siblings.

Evidence indicates the genetic susceptibility to depression and anxiety is both overlapping and dimensional. In the current study, a quantitative phenotype had been created from several depression and anxiety-related measures in order to index this common genetic susceptibility (G). This has been studied in 119 sibships comprising 312 individuals, selected for extreme scores on G, from a community-based sample of 34,371 individuals. In a pathway based candidate gene study, we examined five microsatellite markers located within or nearby to five serotonin system genes (5HT2C, 5HT1D, 5HT1B, TPH1, and MAOB). Statistical analysis, carried out using QTDT, gave a significant association with a microsatellite downstream of TPH1. Further analysis included a life-events composite as a co-variable, this lead to a stronger association of TPH1. To our knowledge, this is the first study to report an association of the 3' end of TPH1 with continuous measures of depression and anxiety.

Alleles↗

PubMed2004

Gene-environment interaction analysis of serotonin system markers with adolescent depression.

We report analyses from a study of gene-environment interaction in adolescent depression. The sample was selected from 1990 adolescents aged 10-20 years: those with depression symptoms in the top or bottom 15% were identified and divided into high or low environmental risk groups. DNA was obtained from 377 adolescents, representing the four quadrants of high or low depression and high or low environmental risk. Markers within, or close to, each of the serotonergic genes 5HTT, HTR2A, HTR2C, MAOA (monoamine oxidase type A) and tryptophan hydroxylase (TPH) were genotyped. Environmental risk group was a nonsignificant predictor and sex was a significant predictor of the depression group. HTR2A and TPH significantly predicted the depression group, independent of the effects of sex, environmental risk group and their interaction. In addition, there was a trend for an effect of 5HTTLPR, which was significant in female subjects. Furthermore, there was a significant genotype-environmental risk interaction for 5HTTLPR in female subjects only, with the effect being in the same direction as another recent study, reaffirming that an important source of genetic heterogeneity is exposure to environmental risk.

Adolescent↗

PubMed2002

The dopamine D4 receptor and the hyperactivity phenotype: a developmental-epidemiological study.

Attention-deficit hyperactivity disorder (ADHD) affects 2-6% of school-age children and is a precursor of behavioural problems in adolescence and adulthood. Underlying the categorical definition of ADHD are the quantitative traits of activity, impulsivity, and inattention which vary continuously in the population. Both ADHD and quantitative measures of hyperactivity are heritable, and influenced by multiple genes of small effect. Several studies have reported an association between clinically defined ADHD and the seven-repeat allele of a 48-bp tandem repeat polymorphism in the third exon of the dopamine D4 receptor gene (DRD4). We tested this association in a large, unselected birth cohort (n = 1037) using multiple measures of the hyperactivity phenotype taken at multiple assessment ages across 20 years. This longitudinal approach allowed us to ascertain whether or not DRD4 has a general effect on the diagnosed (n = 49) or continuously distributed hyperactivity phenotype, and related personality traits. We found no evidence to support this association.

Adolescent↗

PubMed1999

High-performance liquid chromatography study of the pharmacokinetics of various spin traps for application to in vivo spin trapping.

In vivo spin trapping is potentially a very useful tool to investigate the role of free radicals in physiologic processes and disease development. Unfortunately, knowledge on the stability and distribution of spin traps in living systems is limited. Therefore, in our study, we selected 11 acyclic and cyclic nitrone spin traps with diverse properties to determine their pharmacokinetics in mice. At varying times after intraperitoneal administration, we measured the concentration of the spin traps in the liver, heart, and blood. Our results showed that most spin traps were rapidly absorbed and were approximately evenly distributed throughout the mouse body. It was also found that most of the traps were relatively stable in vivo with more than half of the injected amount still available for spin trapping free radicals after an hour. Two of the 11 tested spin traps, however, decomposed after injection. These results indicate that for a successful in vivo spin trapping experiment, the stability of the spin trap is not of major concern, but the time course of distribution may be important.

Animals↗

PubMed1989

Application of a modified colorimetric enzyme assay to monitor plasma paracetamol levels following single oral doses to non-patient volunteers.

A modified enzyme-based colorimetric method has been used to determine plasma paracetamol profiles following single dose (2 x 500 mg) administration of three dosage forms to non-patient volunteers. The assay is linear over the concentration range 0.15-60 micrograms ml-1 with a coefficient of variation of 9.1% at the 1.5 micrograms ml-1 level. It is rapid, requiring small sample volumes; compares favourably with other techniques such as HPLC; and is not subject to interference from paracetamol metabolites and other drugs. Administration of paracetamol as two different dosage forms, as a solid tablet and as a dispersible tablet, resulted in no statistically significant difference in pharmacokinetic parameters between treatments.

Acetaminophen↗

PubMed1989

Determination of underivatised efaroxan and idazoxan in blood plasma by capillary gas chromatography with mass-selective detection.

Sensitive and specific methods for the determination of efaroxan and idazoxan in blood plasma have been developed based on solvent extraction, chromatographic separation and quantification by selected-ion monitoring using a quadruple mass-selective detector. The use of a short non-polar bonded-phase capillary gas chromatography (GC) column facilitated rapid separation of the compounds of interest from internal standards, metabolites and endogenous material. Of equal significance was the ability to chromatograph these basic compounds without prior derivatisation. The application of bonded-phase capillary GC coupled to selected-ion monitoring resulted in robust analytical procedures with sub-ng ml(-1) sensitivity and high selectivity.

Adrenergic alpha-Antagonists↗

PubMed1988

Determination of idazoxan in plasma by radioreceptor assay.

A radioreceptor assay to determine the plasma concentration of idazoxan, a potent, highly selective antagonist for the alpha(2)-adrenoreceptor, is described. The assay is based upon a technique in which plasma extracts containing idazoxan compete with radiolabelled ligand for binding sites on receptor-rich tissue prepared from beef brain cortex. Using a logistic data-fit the limit of detection is of the order of 1 ng ml(-1) and represents a 10-fold increase in sensitivity over that from an established HPLC procedure. Comparison of human plasma data from the two assays indicates a correlation coefficient of 0.92 (N = 27) although the chromatographic method gave consistently higher values than the binding assay. The binding assay requires no sample extraction or pretreatment of plasma and its accuracy, precision and inherent specificity are such that the method represents a useful alternative to HPLC for therapeutic drug monitoring.

Journal Article↗

PubMed1988

Gastrointestinal dynamics and pharmacology for the optimum design of controlled-release oral dosage forms.

This article encompasses a brief discussion of the principles of pharmacodynamics of different types of drugs and the mechanisms of absorption at different sites in the gastrointestinal tract. The importance of factors such as the pH, the unstirred layer or microclimate, gastric emptying, intestinal contact time, metabolism in the gut wall, and bacterial degradation in the colon is discussed. Methods that can be used to alter the absorption of drugs such as formulation in a viscous form, a form that floats in the stomach, position release forms, combination with other drugs that may influence absorption, etc. are examined in detail.

Administration, Oral↗

PubMed1987

Viscosity of food gums determined in vitro related to their hypoglycemic actions.

Experiments were carried out in vitro and in normal human subjects to evaluate alternative food-grade viscous polysaccharides as agents for reducing postprandial hyperglycemia and to assess the relationship between the in vitro and in vivo performance of the polysaccharides. A 1:1 mixture of xanthan and locust bean gum (X/LBG) had the greatest viscosity at equivalent concentrations and shear rates and was more effective than guar gum, xanthan, or locust-bean gum at inhibiting glucose movement in vitro. It was not, however, more efficient in lowering postprandial blood glucose and plasma insulin in human subjects when incorporated in a drink containing 50 g glucose. When the different gums were acidified and reneutralized to mimic conditions in the gut, there was a better correlation between viscosity and blood glucose and plasma insulin levels. This effect may explain why X/LBG was no more effective than the other gums in reducing postprandial hyperglycemia in man.

Adolescent↗

PubMed1983