Most studies associating different types of malformations with the presence of a single umbilical artery (SUA) are based on small and selected series. Here, we present the results of a study aimed at ...identifying the most frequent, and the most specific anomalies related to SUA. We analyzed 19,909 consecutive newborn infants with congenital malformations, from the Spanish Collaborative Study of Congenital Malformations (ECEMC). To estimate the specificity of the relationship of different congenital defects with SUA, we calculated their relative frequencies (RF) by dividing their frequency in infants with SUA by the corresponding frequency in newborn infants without SUA. Using the different levels of the ECEMC coding system, we calculated the RFs in three steps: (a) a group of individual congenital defects, (b) different groups of malformed infants, and (c) each individual malformation by its clinical presentation in some of the studied groups of malformed infants. The defects most specifically associated with SUA were bilateral renal agenesis and imperforate anus, followed by unilateral renal agenesis, and vertebral defects, the RF of which indicated that they were between 7.99 and 9.93 times more frequent among malformed infants with SUA than among malformed infants without SUA. However, these defects were not as frequent in the group of infants with SUA, as cardiovascular anomalies. Regarding the association of SUA in the groups of malformed infants, the most specific groups were body stalk defects and sirenomelia. Finally, we analyzed the association of the individual defects by different groups of malformed infants in order to identify if the individual defects are associated with SUA in any type of clinical presentation, and in relation to some groups of infants with genetic disorders. The results, together with the embryonic development of the umbilical cord, strongly suggest that not all cases of SUA have the same cause, and that all previously suggested mechanisms may be possible but with different frequencies.
Caveolae are involved in physical compartmentalization between different groups of signaling events. Its main component, CAV1, modulates different pathways in cellular physiology. The emerging ...evidence pointing to the role of CAV1 in cancer led us to study whether different alleles of this gene are associated with colorectal cancer (CRC). Since one of the most characterized enzymes regulated by CAV1 is eNOS, we decided to include both genes in this study. We analyzed five SNPs in 360 unrelated CRC patients and 550 controls from the general population. Two of these SNPs were located within eNOS and three within the CAV1 gene. Although haplotype distribution was not associated with CRC, haplotype TiA (CAV1) was associated with familiar forms of CRC (p<0.05). This was especially evident in CRC antecedents and nuclear forms of CRC. If both CG (eNOS) and TiA (CAV1) haplotypes were taken together, this association increased in significance. Thus, we propose that CAV1, either alone or together with eNOS alleles, might modify CRC heritability.
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This study aimed to investigate the 5‐hydroxytryptamine (5‐HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the ...responses to 5‐HT, sumatriptan, ergotamine, serotonin‐O‐carboxymethyl‐glycyl‐tyrosinamide (SCMGT), α‐methyl 5‐HT (α‐Me) and 2‐methyl 5‐HT (2‐Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists.
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All agonists produced concentration‐dependent contractions of human pulmonary artery and vein preparations. The order of potency (−log EC50 values) was ergotamine (6.88)>5‐HT (6.41)SCMGT (6.20)=sumatriptan (6.19) α‐Me (6.04) in the artery, and ergotamine (7.84)>5‐HT (6.96)>sumatriptan (6.60)=α‐Me (6.56)>SCMGT (6.09) in the vein. The potency of each agonist, except for SCMGT, was greater in vein than in artery preparations. Contractile responses to 5‐HT were similar in intact and endothelium‐denuded preparations but responses to sumatriptan were enhanced in artery rings without endothelium.
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GR127935 (1 nM to 0.5 μM) produced an unsurmountable antagonism of the response to 5‐HT, sumatriptan, ergotamine and SCMGT. Ritanserin (1 nM to 1 μM) also reduced the maximum contractile responses to 5‐HT, ergotamine and α‐Me in artery and vein preparations without affecting those to sumatriptan and SCMGT. In endothelium‐denuded preparations, surmountable antagonism of sumatriptan by GR127935 (in the presence of ritanserin) and of α‐Me by ritanserin (in the presence of GR127935) allowed for the calculation of the apparent pKB values of GR127935 (9.17±0.11 in artery and 9.11±0.05 in vein) and ritanserin (8.82±0.09 in artery and 8.98±0.12 in vein).
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WAY100635 (1 nM to 1 μM), zacopride (1 nM to 1 μM), or SB204070 (1 nM) did not significantly alter the concentration‐response curves for 5‐HT, sumatriptan, ergotamine, SCMGT or 2‐Me in human pulmonary artery or vein thus indicating that 5‐HT1A, 5‐HT3 and 5‐HT4 receptors are presumably not involved in the contractile response to these agonists.
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Binding studies using selective radioligands for different 5‐HT receptors could not detect the presence of 5‐HT1A receptor binding in human pulmonary blood vessels whereas the 5‐HT1B/1D radioligand 3H‐5‐CT significantly labelled a population of specific binding sites in both vessel types. The presence of 5‐HT2A receptors could also be inferred from the level of binding of 3H‐ketanserin to membranes obtained from human pulmonary vessels, although significance could not be reached for arteries. 5‐HT4 specific receptor binding was scarce in veins and absent in the case of arteries.
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These findings indicate that the human pulmonary artery and vein have a mixed functional population of 5‐HT1B/1D and 5‐HT2A receptors mediating the contractile response to 5‐HT which is consistent with results of the binding studies.
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