Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants.

We have studied aminoglycoside-induced vestibular hair-cell renewal using long-term culture of utricular macula explants from 4-day-old rats. Explanted utricles were exposed to 1 mM of gentamicin for 48 h, during 2nd and 3rd days in vitro (DIV), and then recovering in unsupplemented medium. Utricles were harvested at specified time points from the 2nd through the 28th DIV. The cellular events that occurred within hair cell epithelia during the culture period were documented from serial sectioned specimens. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) with the assistance of morphometric software. Ultrastructural observations were made from selected specimens with transmission electron microscopy (TEM). After 7 DIV, i.e. four days after gentamicin exposure, the density of HCs was 11% of the number of HCs observed in non-gentamicin-exposed control explants. At 28 DIV the HC density was 61% of the number of HCs observed in the control group explant specimens. Simultaneously with this increase in HCs there was a corresponding decline in the number of SCs within the epithelium. The proportion of HCs in relation to SCs increased significantly in the gentamicin-exposed explant group during the 5th to the 28th DIV period of culture. There were no significant differences in the volume estimations of the gentamicin-exposed and the control group explants during the observed period of culture. Morphological observations showed that gentamicin exposure induced extensive loss of HCs within the epithelial layer, which retained their intact apical and basal linings. At 7 to 14 DIV (i.e. 3-11 days after gentamicin exposure) a pseudostratified epithelium with multiple layers of disorganized cells was observed. At 21 DIV new HCs were observed that also possessed features resembling SCs. After 28 DIV a new luminal layer of HCs with several layers of SCs located more basally characterized the gentamicin-exposed epithelium. No mitoses were observed within the epithelial layer of any explants. Our conclusion is that direct transdifferentiation of SCs into HCs was the only process contributing to the renewal of HCs after gentamicin exposure in these explants of vestibular inner ear epithelia obtained from the labyrinths of 4-day-old rats.

Morphological and morphometric characteristics of vestibular hair cells and support cells in long term cultures of rat utricle explants.

A method for long term culture of utricular macula explants is demonstrated to be stable and reproducible over a period of 28 days in vitro (DIV). This culture system for four-day-old rat utricular maculae is potentially suitable for studies of hair cell loss, repair and regeneration processes as they occur in post-natal mammalian inner ear sensory epithelia. The cellular events that occur within utricular macula hair cell epithelia during 28 days of culture are documented from serial sections. Vestibular hair cells (HCs) and supporting cells (SCs) were systematically counted using light microscopy (LM) and the assistance of morphometric computer software. Ultrastructural observations were made with transmission electron microscopy (TEM) for describing the changes in the fine detailed morphological characteristics that occurred in the explants related to time in vitro. After 2 DIV the density of HCs was 77%, at 21 DIV it was 69%, and at 28 DIV it was 52% of HCs present at explantation. Between 2 DIV and 28 DIV there was a 1.7% decrease of the vestibular macula HC density per DIV. The corresponding decrease of SC density within the utricular explants was less than 1% per DIV. The overall morphology of the epithelia, i.e. relationship of HCs to SCs, was well preserved during the first two weeks in culture. After this time a slight deterioration of the epithelia was observed and although type I and type II HCs were identified by TEM observations, these two HC types could no longer be distinguished from one another by LM observations. In preparations cultured for 21 DIV, SC nuclei were located more apical and further away from the basal membrane compared to their position in macula explants fixed immediately after dissection. The loss of cells that occurred was probably due to expulsion from the apical (i.e. luminal) surface of the sensory epithelia, but no lesions of the apical lining or ruptures of the basal membrane were observed. There were no significant changes in the volume of the vestibular HC comprising macular epithelium during the observation period of 28 DIV.

Obesity prevalence in a cohort of women in early pregnancy from a neighbourhood perspective.

BACKGROUND: The evidence of an association between neighbourhood deprivation and overweight is established for different populations. However no previous studies on neighbourhood variations in obesity in pregnant women were found. In this study we aimed to determine whether obesity during early pregnancy varied by neighbourhood economic status. METHODS: A register based study on 94,323 primiparous pregnant women in 586 Swedish neighbourhoods during the years 1992-2001. Multilevel technique was used to regress obesity prevalence on socioeconomic individual-level variables and the neighbourhood economic status. Five hundred and eighty-six neighbourhoods in the three major cities of Sweden, Stockholm, Göteborg and Malmö, during 1992-2001, were included. The majority of neighbourhoods had a population of 4 00010 000 inhabitants. RESULTS: Seven per cent of the variation in obesity prevalence was at the neighbourhood level and the odds of being obese were almost doubled in poor areas. CONCLUSION: Our findings supports a community approach in the prevention of obesity in general and thus also in pregnant women.

The neighbourhood they live in: does it matter to women's smoking habits during pregnancy?

Socioeconomic factors in the neighbourhood are associated with smoking habits in various populations. We studied a 10-year cohort to determine whether women's smoking behaviour during pregnancy can similarly be determined by neighbourhood economic and ethnic factors. The cohort included 127,074 primiparous pregnant women in 592 Swedish neighbourhoods during the years 1992-2001. Multilevel technique was used to regress pregnancy smoking on socioeconomic individual-level variables and neighbourhood characteristics. Seven percent of the variation in pregnancy smoking was at the neighbourhood level and the odds of smoking during pregnancy were doubled in poorer areas. Health education and smoking cessation interventions should be directed at maternity care units in deprived neighbourhoods.

Are there differences in birth weight between neighbourhoods in a Nordic welfare state?

BACKGROUND: The objective of this cohort study was to examine the effect on birth weight of living in a disadvantaged neighbourhood in a Nordic welfare state. Birth weight is a health indicator known to be sensitive to political and welfare state conditions. No former studies on urban neighbourhood differences regarding mean birth weight have been carried out in a Nordic country. METHODS: A register based on individual data on children's birth weight and maternal risk factors was used. A neighbourhood characteristic, i.e. an aggregated measure on income was also included. Connections between individual- and neighbourhood-level determinants and the outcome were analysed using multi-level regression technique. The study covered six hundred and ninety-six neighbourhoods in the three major cities of Sweden, Stockholm, Göteborg and Malmö, during 1992-2001. The majority of neighbourhoods had a population of 4 000-10 000 inhabitants. An average of 500 births per neighbourhood were analysed in this study. RESULTS: Differences in mean birth weight in Swedish urban neighbourhoods were minor. However, gestational length, parity and maternal smoking acted as modifiers of the neighbourhood effects. Most of the observed variation in mean birth weight was explained by individual risk factors. CONCLUSION: Welfare institutions and benefits in Sweden might buffer against negative infant outcomes due to adverse structural organisation of urban neighbourhoods.