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1.  The effect of trichostatin-A and tumor necrosis factor on expression of splice variants of the MaxiK and L-type channels in human myometrium 
The onset of human parturition is associated with up-regulation of pro-inflammatory cytokines including tumor necrosis factor (TNF) as well as changes in ion flux, principally Ca2+ and K+, across the myometrial myocytes membrane. Elevation of intra-cellular Ca2+ from the sarcoplasmic reticulum opens L-type Ca2+ channels (LTCCs); in turn this increased calcium level activates MaxiK channels leading to relaxation. While the nature of how this cross-talk is governed remains unclear, our previous work demonstrated that the pro-inflammatory cytokine, TNF, and the histone deacetylase inhibitor, Trichostatin-A (TSA), exerted opposing effects on the expression of the pro-quiescent Gαs gene in human myometrial cells. Consequently, in this study we demonstrate that the different channel splice variants for both MaxiK and LTCC are expressed in primary myometrial myocytes. MaxiK mRNA expression was sensitive to TSA stimulation, this causing repression of the M1, M3, and M4 splice variants. A small but not statistically significantly increase in MaxiK expression was also seen in response to TNF. In contrast to this, expression of LTCC splice variants was seen to be influenced by both TNF and TSA. TNF induced overall increase in total LTCC expression while TSA stimulated a dual effect: causing induction of LTCC exon 8 expression but repressing expression of other LTCC splice variants including that encoding exons 30, 31, 33, and 34, exons 30–34 and exons 40–43. The significance of these observations is discussed herein.
PMCID: PMC4097961  PMID: 25076912
parturition; MaxiK; LTCC; splice variants; TNF; TSA
2.  MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group 
Trials  2012;13:13.
MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR.
Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented.
Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years.
As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.
PMCID: PMC3395865  PMID: 22314083
Vitamin D; cholecalciferol; supplementation; trial; osteoporosis; DXA; pregnancy; neonate
3.  Comparison of human uterine cervical electrical impedance measurements derived using two tetrapolar probes of different sizes 
We sought to compare uterine cervical electrical impedance spectroscopy measurements employing two probes of different sizes, and to employ a finite element model to predict and compare the fraction of electrical current derived from subepithelial stromal tissue.
Cervical impedance was measured in 12 subjects during early pregnancy using 2 different sizes of the probes on each subject.
Mean cervical resistivity was significantly higher (5.4 vs. 2.8 Ωm; p < 0.001) with the smaller probe in the frequency rage of 4–819 kHz. There was no difference in the short-term intra-observer variability between the two probes. The cervical impedance measurements derived in vivo followed the pattern predicted by the finite element model.
Inter-electrode distance on the probes for measuring cervical impedance influences the tissue resistivity values obtained. Determining the appropriate probe size is necessary when conducting clinical studies of resistivity of the cervix and other human tissues.
PMCID: PMC1684260  PMID: 17125510

Results 1-3 (3)