How long does it take to diagnose young-onset dementia? A comparison with late-onset dementia.

INTRODUCTION: Dementia occurring in young people may be difficult to recognize. We compared the time to diagnosis between young- (YOD, age < 65) and late-onset dementia (LOD). METHODS: Time between the onset of symptoms and the diagnosis was measured in YOD and LOD patients consecutively seen in a cognitive neurology clinic. Multivariable regression analyses were performed to identify determinants of time to diagnosis. RESULTS: Mean time to diagnosis in 95 YOD patients was 11.2 months longer than in 73 LOD patients (p = 0.022). The delay was driven by a longer time taken by YOD patients to be seen in the specialist centre, which in turn was related to the presence of language disturbances and coexisting depression. DISCUSSION: Young people take longer than elderly people to receive a dementia diagnosis because they take longer to be referred to dementia specialist centres. More awareness on YOD is needed in primary care and the public.

Genistein effects on Ca2+ handling in human umbilical artery: inhibition of sarcoplasmic reticulum Ca2+ release and of voltage-operated Ca2+ channels.

Isoflavones are a group of natural phytoestrogens including the compound genistein. Health beneficial effects have been attributed to the consumption of this compound, but the fact that it has estrogen-like activity has raised doubts regarding its potential risk in infants, newborns, or in the fetus and placenta during pregnancy. This work is aimed at studying genistein effects on Ca2+ handling by smooth muscle cells of the human umbilical artery (HUA). Using fluorometric techniques, we found that in these cells genistein reduces the intracellular Ca2+ peak produced by serotonin. The same result could be demonstrated in absence of extracellular Ca2+, suggesting that the isoflavone reduces Ca2+ release from the sarcoplasmic reticulum. Force measurement experiments strengthen these results, since genistein reduced the peak force attained by intact HUA rings stimulated by serotonin in a Ca2+-free solution. Moreover, genistein induced the relaxation of HUA rings precontracted either with serotonin or a depolarizing high-extracellular K+ solution, hinting at a reduction of extracellular Ca2+ entry to the cell. This was confirmed by whole-cell patch-clamp experiments where it was shown that the isoflavone inhibits ionic currents through voltage-operated Ca2+ channels. In summary, we show that genistein inhibits two mechanisms that could increase intracellular Ca2+ in human umbilical smooth muscle cells, behaving in this way as a potential vasorelaxing substance of fetal vessels. Taking into account that genistein is able to cross the placental barrier, these data show that isoflavones may have important implications in the regulation of feto-maternal blood flow in pregnant women who consume soy-derived products as part of their meals.

Efectos de la genisteína en los niveles del Ca2+ citosólico en células musculares de arteria umbilical humana / Genistein effects on Ca2+ handling in human umbilical artery: inhibition of sarcoplasmic reticulum Ca2+ release and of voltage-operated Ca2+ channels

Isoflavones are a group of natural phytoestrogens including the compound genistein.Health beneficial effects have been attributed to the consumption of this compound,but the fact that it has estrogen-like activity has raised doubts regarding itspotential risk in infants, newborns, or in the fetus and placenta during pregnancy.This work is aimed at studying genistein effects on Ca2+ handling by smooth musclecells of the human umbilical artery (HUA). Using fluorometric techniques, we foundthat in these cells genistein reduces the intracellular Ca2+ peak produced by serotonin.The same result could be demonstrated in absence of extracellular Ca2+, suggestingthat the isoflavone reduces Ca2+ release from the sarcoplasmic reticulum.Force measurement experiments strengthen these results, since genistein reduced thepeak force attained by intact HUA rings stimulated by serotonin in a Ca2+-free solution.Moreover, genistein induced the relaxation of HUA rings precontracted eitherwith serotonin or a depolarizing high-extracellular K+ solution, hinting at a reductionof extracellular Ca2+ entry to the cell. This was confirmed by whole-cell patchclampexperiments where it was shown that the isoflavone inhibits ionic currentsthrough voltage-operated Ca2+ channels. In summary, we show that genisteininhibits two mechanisms that could increase intracellular Ca2+ in human umbilical smooth muscle cells, behaving in this way as a potential vasorelaxing substance offetal vessels. Taking into account that genistein is able to cross the placental barrier,these data show that isoflavones may have important implications in the regulationof feto-maternal blood flow in pregnant women who consume soy-derived productsas part of their meals(AU)

Las isoflavonas son un grupo de fitoestrógenosnaturales que incluyen la genisteína. Alconsumo de este compuesto se le han atribuidoefectos beneficiosos para la salud, pero su actividadsimilar a los estrógenos permite pensaren efectos indeseados en niños o en el feto o laplacenta durante el embarazo. En este trabajose estudian los efectos de la genisteína sobre elmanejo de Ca2+ por las células de músculo lisode la arteria umbilical humana (AUH).Mediante la utilización de técnicas fluorométricasse observó que la genisteína reduce elpico de Ca2+ intracelular producido por la serotonina en estas células incluso en ausenciade Ca2+ extracelular, lo que sugiere que la isoflavonareduce la liberación de Ca2+ a partir delretículo sarcoplásmico. Los experimentos demedida de fuerza refuerzan estos resultados, yaque la genisteína redujo la fuerza pico desarrolladapor serotonina en anillos intactos deAUH en una solución libre de Ca2+. Además,la genisteína indujo la relajación de anillos deAUH precontraídos con serotonina o con unasolución despolarizante de alto K+ extracelular,lo que apunta a una reducción de la entradade Ca2+ desde el exterior de la célula. Con latécnica de “patch-clamp” en configuración decélula entera, los resultados confirmaron que laisoflavona inhibe corrientes iónicas a través decanales de Ca2+ operados por el voltaje. Enresumen, mostramos que la genisteína inhibedos mecanismos que incrementan el Ca2+intracelular en células de músculo liso deAUH, comportándose de esta manera comoun potencial vasorrelajante de los vasos fetales.Dado que la genisteína atraviesa la barrera placentaria,estos datos muestran que las isoflavonaspodrían tener consecuencias en la regulacióndel flujo materno-fetal en mujeres embarazadasque incluyan productos derivados de lasoja como parte de sus dietas(AU)

Genistein inhibits contractile force, intracellular Ca2+ increase and Ca2+ oscillations induced by serotonin in rat aortic smooth muscle.

The soy-derived isoflavones genistein and daidzein affect the contractile state of different kinds of smooth muscle. We describe acute effects of genistein and daidzein on contractile force and intracellular Ca2+ concentration ([Ca2+]i) in in situ smooth muscle of rat aorta. Serotonin (5-HT) (2 microM) or a depolarizing high K+ solution produced the contraction of aortic rings, which were immediately relaxed by 20 microM genistein and by 20 microM daidzein. Accordingly, both 5-HT and a high K+ solution increased the [Ca2+]i in in situ smooth muscle cells. Genistein strongly inhibited the [Ca2+]i increase evoked by 5-HT (74.0 +/- 7.3%, n = 11, p < 0.05), and had a smaller effect on high K+ induced [Ca2+]i increase (19.9 +/- 4.0%, n = 7, p < 0.05). The K+ channels blocker tetraethylammonium (TEA) (0.5 mM) diminished genistein effects on 5-HT-induced [Ca2+]i increase. Interestingly, during prolonged application of 5-HT, the [Ca2+]i oscillated and a short (90 s) preincubation with genistein (20 microM) significantly diminished the frequency of the oscillations. This effect was totally abolished by TEA. In conclusion, in rat aortic smooth muscle, genistein is capable of diminishing the increase in [Ca2+]i and in force evoked by 5-HT and high K+ solution, and of decreasing the frequency of [Ca2+]i oscillations induced by 5-HT. The short time required by genistein, and the relaxing effect of daidzein suggest that tyrosine kinases inhibition is not involved. The small inhibiting effect of genistein on the [Ca2+]i increase evoked by high K+ and the effect of TEA point to the activation by genistein of calcium-activated K+ channels.

Genistein inhibits contractile force, intracellular Ca2+ increase and Ca2+ oscillations induced by serotonin in rat aortic smooth muscle

The soy-derived isoflavones genistein and daidzein affect the contractile state ofdifferent kinds of smooth muscle. We describe acute effects of genistein and daidzeinon contractile force and intracellular Ca2+ concentration ([Ca2+]i) in in situ smoothmuscle of rat aorta. Serotonin (5-HT) (2 ìM) or a depolarizing high K+ solution producedthe contraction of aortic rings, which were immediately relaxed by 20 ìMgenistein and by 20 ìM daidzein. Accordingly, both 5-HT and a high K+ solutionincreased the [Ca2+]i in in situ smooth muscle cells. Genistein strongly inhibited the[Ca2+]i increase evoked by 5-HT (74.0 ± 7.3%, n=11, p<0.05), and had a smallereffect on high K+ induced [Ca2+]i increase (19.9 ± 4.0%, n=7, p<0.05). The K+ channelsblocker tetraethylammonium (TEA) (0.5 mM) diminished genistein effects on 5-HT-induced [Ca2+]i increase. Interestingly, during prolonged application of 5-HT,the [Ca2+]i oscillated and a short (90 s) preincubation with genistein (20 ìM) significantlydiminished the frequency of the oscillations. This effect was totally abolishedby TEA. In conclusion, in rat aortic smooth muscle, genistein is capable of diminishingthe increase in [Ca2+]i and in force evoked by 5-HT and high K+ solution, andof decreasing the frequency of [Ca2+]i oscillations induced by 5-HT. The short timerequired by genistein, and the relaxing effect of daidzein suggest that tyrosine kinasesinhibition is not involved. The small inhibiting effect of genistein on the [Ca2+]iincrease evoked by high K+ and the effect of TEA point to the activation by genisteinof calcium-activated K+ channels (AU)

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Genistein inhibits contractile force, intracellularCa2+ increase and Ca2+ oscillations induced byserotonin in rat aortic smooth muscle

The soy-derived isoflavones genistein and daidzein affect the contractile state ofdifferent kinds of smooth muscle. We describe acute effects of genistein and daidzeinon contractile force and intracellular Ca2+ concentration ([Ca2+]i) in in situ smoothmuscle of rat aorta. Serotonin (5-HT) (2 ìM) or a depolarizing high K+ solution producedthe contraction of aortic rings, which were immediately relaxed by 20 ìMgenistein and by 20 ìM daidzein. Accordingly, both 5-HT and a high K+ solutionincreased the [Ca2+]i in in situ smooth muscle cells. Genistein strongly inhibited the[Ca2+]i increase evoked by 5-HT (74.0 ± 7.3%, n=11, p<0.05), and had a smallereffect on high K+ induced [Ca2+]i increase (19.9 ± 4.0%, n=7, p<0.05). The K+ channelsblocker tetraethylammonium (TEA) (0.5 mM) diminished genistein effects on 5-HT-induced [Ca2+]i increase. Interestingly, during prolonged application of 5-HT,the [Ca2+]i oscillated and a short (90 s) preincubation with genistein (20 ìM) significantlydiminished the frequency of the oscillations. This effect was totally abolishedby TEA. In conclusion, in rat aortic smooth muscle, genistein is capable of diminishingthe increase in [Ca2+]i and in force evoked by 5-HT and high K+ solution, andof decreasing the frequency of [Ca2+]i oscillations induced by 5-HT. The short timerequired by genistein, and the relaxing effect of daidzein suggest that tyrosine kinasesinhibition is not involved. The small inhibiting effect of genistein on the [Ca2+]iincrease evoked by high K+ and the effect of TEA point to the activation by genisteinof calcium-activated K+ channels (AU)

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The Na+/Ca2+ exchanger is active and working in the reverse mode in human umbilical artery smooth muscle cells.

The data presented in this work suggest that in human umbilical artery (HUA) smooth muscle cells, the Na(+)/Ca(2+) exchanger (NCX) is active and working in the reverse mode. This supposition is based on the following results: (i) microfluorimetry in HUA smooth muscle cells in situ showed that a Ca(2+)-free extracellular solution diminished intracellular Ca(2+) ([Ca(2+)](i)), and KB-R7943 (5microM), a specific inhibitor of the Ca(2+) entry mode of the exchanger, also decreased [Ca(2+)](i) (40.6+/-4.5% of Ca(2+)-free effect); (ii) KB-R7943 produced the relaxation of HUA rings (-24.7+/-7.3gF/gW, n=8, p<0.05); (iii) stimulation of the NCX by lowering extracellular Na(+) increases basal [Ca(2+)](i) proportionally to Na(+) reduction (Delta fluorescence ratio=0.593+/-0.141 for Na(+)-free solution, n=8) and HUA rings' contraction (peak force=181.5+/-39.7 for 130mM reduction, n=8), both inhibited by KB-R7943 and a Ca(2+)-free extracellular solution. In conclusion, the NCX represents an important Ca(2+) entry route in HUA smooth muscle cells.