17 research outputs found
Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis
BACKGROUND: Chromosome 9p21 has recently been shown to be a risk region for a broad range of vascular diseases. Since carotid intima-media thickness (IMT) and plaque are independent predictors for vascular diseases, the association between 9p21 and these two phenotypes was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Carotid segment-specific IMT and plaques were obtained in 1083 stroke- and myocardial infarction-free volunteers. We tested the genotypes and haplotypes of key single nucleotide polymorphisms (SNPs) on chromosome 9p21 for the associations with carotid IMT and plaque. Multivariate permutation analyses demonstrated that carriers of the T allele of SNP rs1333040 were significantly associated with thicker common carotid artery (CCA) IMT (p=0.021) and internal carotid artery (ICA) IMT (p=0.033). The risk G allele of SNP rs2383207 was associated with ICA IMT (p=0.007). Carriers of the C allele of SNP rs1333049 were found to be significantly associated with thicker ICA IMT (p=0.010) and the greater risk for the presence of carotid plaque (OR=1.57 for heterozygous carriers; OR=1.75 for homozygous carriers). Haplotype analysis showed a global p value of 0.031 for ICA IMT and 0.115 for the presence of carotid plaque. Comparing with the other haplotypes, the risk TGC haplotype yielded an adjusted p value of 0.011 and 0.017 for thicker ICA IMT and the presence of carotid plaque respectively. Further analyzing the data separated by sex, the results were significant only in men but not in women. CONCLUSIONS: Chromosome 9p21 had a significant association with carotid atherosclerosis, especially ICA IMT. Furthermore, such genetic effect was in a gender-specific manner in the Han Chinese population
Trigonometric Regressive Spectral Analysis Reliably Maps Dynamic Changes in Baroreflex Sensitivity and Autonomic Tone: The Effect of Gender and Age
BACKGROUND: The assessment of baroreflex sensitivity (BRS) has emerged as prognostic tool in cardiology. Although available computer-assisted methods, measuring spontaneous fluctuations of heart rate and blood pressure in the time and frequency domain are easily applicable, they do not allow for quantification of BRS during cardiovascular adaption processes. This, however, seems an essential criterion for clinical application. We evaluated a novel algorithm based on trigonometric regression regarding its ability to map dynamic changes in BRS and autonomic tone during cardiovascular provocation in relation to gender and age. METHODOLOGY/PRINCIPAL FINDINGS: We continuously recorded systemic arterial pressure, electrocardiogram and respiration in 23 young subjects (25+/-2 years) and 22 middle-aged subjects (56+/-4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex- and spectral analysis was performed using the algorithm of trigonometric regressive spectral analysis. There was an age-related decline in spontaneous BRS and high frequency oscillations of RR intervals. Changes in autonomic tone evoked by cardiovascular provocation were observed as shifts in the ratio of low to high frequency oscillations of RR intervals and blood pressure. Respiration at 0.1 Hz elicited an increase in BRS while head-up tilt and Valsalva manoeuvre resulted in a downregulation of BRS. The extent of autonomic adaption was in general more pronounced in young individuals and declined stronger with age in women than in men. CONCLUSIONS/SIGNIFICANCE: The trigonometric regressive spectral analysis reliably maps age- and gender-related differences in baroreflex- and autonomic function and is able to describe adaption processes of baroreceptor circuit during cardiovascular stimulation. Hence, this novel algorithm may be a useful screening tool to detect abnormalities in cardiovascular adaption processes even when resting values appear to be normal
Anticancer Potential of 3-(Arylideneamino)-2- Phenylquinazoline-4(3H)-One Derivatives
Different quinazoline derivatives have showed wide
spectrum of pharmacological activities. Some 3-
(arylideneamino)-phenylquinazoline-4(3H)-ones have
been reported to possess antimicrobial activity. The
present study has been undertaken to evaluate the
anticancer effect of these quinazolinone derivatives.
The quinazolinone derivatives were synthesized as
reported earlier. Compounds containing NO2, OH,
OCH3, or OH and OCH3 as substituent(s) on the
arylideneamino group were named as P(3a), P(3b),
P(3c), and P(3d) respectively. Out of these, P(3a)
and P(3d) showed better cytotoxic activity than P(3b)
and P(3c) on a panel of six cancer cell lines of different
origin, namely, B16F10, MiaPaCa-2, HCT116, HeLa,
MCF7, and HepG2, though the effect was higher in
B16F10, HCT116, and MCF7 cells. P(3a) and P(3d)
induced death of B16F10 and HCT116 cells was
associated with characteristic apoptotic changes like
cell shrinkage, nuclear condensation, DNA
fragmentation, and annexin V binding. Also, cell cycle
arrest at G1 phase, alteration of caspase-3, caspase-
9, Bcl-2 and PARP levels, loss of mitochondrial
membrane potential, and enhanced level of cytosolic
cytochrome c were observed in treated B16F10 cells.
Treatment with multiple doses of P(3a) significantly
increased the survival rate of B16F10 tumor bearing
BALB/c mice by suppressing the volume of tumor
while decreasing microvascular density and mitotic
index of the tumor cells