A- vitamiini signaloi niin kuulo kuin näköaistin kehittymisen

J Neurobiol. 2006 Jun;66(7):687-704. Retinoid signaling in inner ear development.

Romand R, Dollé P, Hashino E.

Institut Clinique de la Souris and Institut de Génétique et de Biologie Moléculaire et cellulaire, B.P. 10142, 67404 Illkirch Cedex, France. romand(at) igbmc.u-strasbg.fr

Abstract

The inner ear originates from an embryonic ectodermal placode and rapidly develops into a three-dimensional structure (the otocyst) through complex molecular and cellular interactions. Many genes and their products are involved in inner ear induction, organogenesis, and cell differentiation. Retinoic acid (RA) is an endogenous signaling molecule that may play a role during different phases of inner ear development, as shown from pathological observations. To gain insight into the function of RA during inner ear development, we have investigated the spatio-temporal expression patterns of major components of RA signaling pathway, including cellular retinoic acid binding proteins (CRABPs), cellular retinoid binding proteins (CRBPs), retinaldehyde dehydrogenases (RALDHs), catabolic enzymes (CYP26s), and nuclear receptors (RARs). Although the CrbpI, CrabpI, and -II genes are specifically expressed in the inner ear throughout development, loss-of-function studies have revealed that these proteins are dispensable for inner development and function. Several Raldh and Cyp26 gene transcripts are expressed at embryological day (E) 9.0-9.5 in the otocyst and show mainly complementary distributions in the otic epithelium and mesenchyme during following stages. From Western blot, RT-PCR, and in situ hybridization analysis, there is a low expression of Raldhs in the early otocyst at E9, while Cyp26s are strongly expressed. During the following days, there is an up-regulation of Raldhs and a down-regulation for Cyp26s. Specific RA receptor (Rar and Rxr) genes are expressed in the otocyst and during further development of the inner ear. At the otocyst stage, most of the components of the retinoid pathway are present, suggesting that the embryonic inner ear might act as an autocrine system, which is able to synthesize and metabolize RA necessary for its development. We propose a model in which two RA-dependent pathways may control inner ear ontogenesis: one indirect with RA from somitic mesoderm acting to regulate gene expression within the hindbrain neuroepithelium, and another with RA acting directly on the otocyst. Current evidence suggests that RA may regulate several genes involved in mesenchyme-epithelial interactions, thereby controlling inner ear morphogenesis. Our investigations suggest that RA signaling is a critical component not only of embryonic development, but also of postnatal maintenance of the inner ear.

(c) 2006 Wiley Periodicals, Inc.

PMID: 16688766 [PubMed - indexed for MEDLINE]

Vauvojen A-vitamiinitarpeesta kommentti

Pidän vääränä päätöksenä (Ruotsissa 2008) lopettaa A-vitamiinin anto lapsilta ja siirtymistä pelkkiin D-vitamiinitippoihin AD-tippojen sijasta. kuten nyt Ruotsissa on tehty. Siitä voi vauva-ja lapsikuolleisuus lisääntyä sekä silmän kehityshäiriöt voivat lisääntyä: lasiaisen kokoomuksen, optisen taiton ja synkronisten silmälihastoimintojen alueella voi alkaa tulla jälleen enemmän häiriötä. A-vitamiini vaikuttaa koko silmän ja näköaistin alueeseen kyynelkanavia ja luomireunoja ja sarveiskalvon pintoja myöten optisen tarkentumisen ohella. Mutta västövaikutusta saa tietysti odottaa seuraaviin suosituksiin asti.

Nyt Lansetti kirjoittaa: Jo vauvan 5 ensimmäisen elinpäivän aikana annettu A-vitamiini saattaa olla hyödyllinen. Tosin tässä tutkimuksessa ei mainita muitten sairauksien osuutta.

he Lancet, Volume 376, Issue 9753, Pages 1643 - 1644, 13 November 2010

doi:10.1016/S0140-6736(10)61895-8Cite or Link Using DOI

Published Online: 13 October 2010 Neonatal vitamin A supplementation and infant survival
Original Text
Betty Kirkwood, Jean Humphrey b, Larry Moulton b, Jose Martines c
Vitamin A supplementation given to neonates within a few days of birth has been proposed as a strategy to improve infant survival. A meta-analysis of five trials showed no overall survival benefit, but confidence intervals were wide and did not exclude the possibility of an important benefit (relative risk 0·92, 95% CI 0·75—1·12).1 Three large randomised controlled trials are currently ongoing in Ghana, India, and Tanzania to resolve this issue.
An additional randomised controlled trial testing the same intervention in low birthweight infants was published earlier this year by Benn and colleagues.2 Overall, this trial found no effect on infant mortality but reported a significant interaction with sex. Benn and colleagues combined these results with those of their previous trial in Guinea-Bissau3 and presented the pooled findings indicating that boys tended to benefit but that there was a significantly harmful effect on girls' survival.
We have now done a meta-analysis of all studies published to date that have assessed the survival effect of vitamin A given to neonates within a few days of birth, including the previously unpublished sex-specific data from a study in Zimbabwe.
In this new meta-analysis, we included both individually randomised and cluster-randomised8 placebo controlled trials. For trials with a factorial design, we included the comparison of all neonates given vitamin A with all neonates who were given placebo.6—8 Thus, in the pair of studies from Guinea Bissau, both normal and low birthweight neonates were included.1, 2 Similarly, in the study from Zimbabwe, neonates of mothers who were HIV positive, HIV negative, or with unknown HIV status were included.4, 6 We used author-reported effect sizes on mortality during infancy for pooling using the “metan” command in Stata (version 11) software. Because there was substantial heterogeneity in results across studies, we used a random effects model to pool the results.
This new meta-analysis indicates that there is no differential effect of the intervention in boys and girls (figure). The overall effect on risk of death during infancy is 0·93 (95% CI 0·80—1·07), the effect in boys is 0·84 (0·65—1·09) and that in girls is 0·98 (0·82—1·17). It is notable that only the studies from Guinea-Bissau reported a trend for harmful effect of the intervention in girls. By contrast, only the study from Zimbabwe reported a trend for a harmful effect of the intervention in boys.

Ultrahivenaine arsenikki ja vahingolliset määrät

Ultrahivenaineeksi mainittu arsenikki on tunnettu toksiini suuremmissa määrissä. Lansetti esittää artikkelissa näitä rajoja mortaliteetin ja morbiditeetin suhteen.
Kohorttitutkimukseen otettiin 11 746 vuosina 2000 - 2002 BanglaDeshissa. kontrolliryhmän juomavedessä oli arsenikkia alle 10 ug litrassa, siis veden käytön olless esim 2-3 litraa, olisi henkilöön tullut päivässä korkeintaan 20- 30 ug arseenia vedestä, mikä on vielä ultahivenaineen aluetta.
Tätä ryhmää verrattiin niihin joiden juoma vedessä oli 150- 864 ug arseenia litrassa.

The Lancet, Volume 376, Issue 9753, Page 1641, 13 November 2010

doi:10.1016/S0140-6736(10)62089-2Cite or Link Using DOI Arsenic exposure from drinking water and mortality in Bangladesh

Original Text

Marie Vahter, Nazmul Sohel c, Kim Streatfield b, Lars Åke Persson c

Maria Argos and co-workers (July 24, p 252)1 assess the association between arsenic in drinking water and mortality in rural Bangladesh. A cohort of 11 746 was recruited between 2000 and 2002 and followed up biennially. Compared with individuals with less than 10 μg/L arsenic in the main drinking water source used at baseline, those with 150—864 μg/L showed an increased risk of all-cause mortality (adjusted hazard ratio 1·68, 95% CI 1·26—2·23). This association was similar when exposure was expressed as creatinine-adjusted total arsenic in urine. This might, however, be biased owing to low creatinine excretion in malnourished people and co-excretion of creatinine and arsenic.2

Argos and colleagues also claim that the association between arsenic exposure and mortality has not been prospectively investigated by use of individual-level data. However, we published results of a population-based cohort study in Bangladesh a year ago.3 Our study assessed mortality data collected prospectively during 1991—2000 in an established health and demographic surveillance system in the rural region of Matlab (population size 115 903). This study was erroneously cited by Argos and colleagues as a retrospective study based on group-level data. In fact, data on individual long-term arsenic exposure through drinking water were based on personal interviews about historic water use (for each calendar year 1970—90) and arsenic in all 13 286 tubewells. Because the deceased people could not be interviewed, we used household long-term average arsenic concentration in drinking water as an exposure estimate, which in a subsample of 1000 living individuals was found to correlate with individual long-term average exposure (r=0·94).

The results showed that even low concentrations of arsenic in water (10—49 μg/L) were associated with a significantly increased risk of all non-accidental mortality (adjusted hazard ratio 1·16, 95% CI 1·06—1·26).3 Additionally, we found an increased risk of death due to cancer (1·44, 1·06—1·95) and infectious diseases (1·30, 1·13—1·49) at arsenic concentrations of 50—149 μg/L, and increased risk of cardiovascular death from 150 μg/L and above (1·51, 1·31—1·75).

We declare that we have no conflicts of interest.