The oxysterol receptor LXRß protects against DSS- and TNBS-induced colitis in mice.

We examined the function of the oxysterol receptors (LXRs) in inflammatory bowel disease (IBD) through studying dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and by elucidating molecular mechanisms underlying their anti-inflammatory action. We observed that Lxr-deficient mice are more susceptible to colitis. Clinical indicators of colitis including weight loss, diarrhea and blood in feces appeared earlier and were more severe in Lxr-deficient mice and particularly LXRß protected against symptoms of colitis. Addition of an LXR agonist led to faster recovery and increased survival. In contrast, Lxr-deficient mice showed slower recovery and decreased survival. In Lxr-deficient mice, inflammatory cytokines and chemokines were increased together with increased infiltration of immune cells in the colon epithelium. Activation of LXRs strongly suppressed expression of inflammatory mediators including TNFα. While LXRα had anti-inflammatory effects in CD11b(+) immune cell populations, LXRß in addition had anti-inflammatory effects in colon epithelial cells. Lack of LXRß also induced CD4(+)/CD3(+) immune cell recruitment to the inflamed colon. Expression of both LXRA and LXRB was significantly suppressed in inflamed colon from subjects with IBD compared with non-inflamed colon. Taken together, our observations suggest that the LXRs could provide interesting targets to reduce the inflammatory responses in IBD.

Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice.

AIMS/HYPOTHESIS: Liver X receptor (LXR)α regulates the genes involved in cholesterol, fatty acid and glucose metabolism. Soy protein (SP) consumption reduces the hepatic accumulation of cholesterol and triacylglycerol, and improves insulin sensitivity. However, it is not known whether these effects are mediated via LXRα. We therefore investigated whether the consumption of SP regulates metabolic changes in cholesterol metabolism and insulin sensitivity via LXRα. METHODS: Wild-type (WT) and Lxrα(-/-) (Lxrα, also known as Nr1h3) mice were fed an SP diet with or without cholesterol for 28 days. The expression of LXRα target genes was measured in liver and intestine, as were hepatic lipid content and faecal bile acid concentration. Oral glucose and insulin tolerance tests were also performed. Hepatocytes were used to study the effect of isoflavones on LXR activity. RESULTS: The livers of WT and Lxrα(-/-) mice fed an SP high-cholesterol diet showed less steatosis than those fed casein. The SP diet increased the expression of the ATP-binding cassette (ABC) sub-family genes Abca1, Abcg5 and Abcg8 in the liver and intestine, as well as increasing total faecal bile acid excretion and insulin sensitivity in WT mice compared with mice fed a casein diet. However, these effects of SP were not observed in Lxrα(-/-) mice. The SP isoflavone, genistein, repressed the activation of LXRα target genes by T0901317, whereas it stimulated the activation of LXRß target genes. The AMP-activated protein kinase inhibitor, compound C, had the opposite effects to those of genistein. CONCLUSIONS/INTERPRETATION: Our results suggest that SP isoflavones stimulate the phosphorylation of LXRα or LXRß, resulting in different biological effects for each LXR isoform.

Late miscarriage and preterm birth after treatment with clindamycin: a randomised consent design study according to Zelen.

OBJECTIVE: To screen for bacterial vaginosis (BV) and to investigate the effect of treatment with vaginal clindamycin in order to observe the effect on late miscarriage and delivery prior to 37 completed weeks (primary outcome). DESIGN: Randomised consent design for clinical trials according to Zelen. SETTING: Southeast region of Sweden. POPULATION: A total of 9025 women were screened in early pregnancy. METHODS: A total of 819 women with a Nugent score of 6 and above were considered to have BV and treated according to Zelen allocation. The incidence of late miscarriage and spontaneous (noniatrogenic) preterm birth was assessed. MAIN OUTCOME MEASURES: Late miscarriage and spontaneous preterm delivery before 37 weeks. RESULTS: Therapy with vaginal clindamycin had no significant impact on the incidence of spontaneous preterm delivery prior to 37 completed weeks; OR 0.90, 95% CI 0.40-2.02 (primary outcome variable). However, only 1 of 11 women in the treatment group versus 5 of 12 in the control group delivered prior to 33 completed weeks; OR 0.14, 95% CI 0.02-0.95. Treatment was associated with 32 days longer gestation for the 23 participants who had late miscarriage or spontaneous preterm birth (P= 0.024, Mann-Whitney U test) and significantly fewer infants had a birthweight below 2,500 g (secondary outcome). A follow up of infants born preterm 4 years postnatally indicated that extending gestational age did not increase the number of sequelae. CONCLUSIONS: Clindamycin vaginal cream therapy was associated with significantly prolonged gestation and reduced cost of neonatal care in women with BV. Early screening for BV and treatment with clindamycin saved approximately 27 euro per woman.

Bacterial vaginosis--a microbiological and immunological enigma.

The development of bacterial vaginosis (BV) among women of childbearing age and the resulting quantitative and qualitative shift from normally occurring lactobacilli in the vagina to a mixture of mainly anaerobic bacteria is a microbiological and immunological enigma that so far has precluded the formulation of a unifying generally accepted theory on the aetiology and clinical course of BV. This critical review highlights some of the more important aspects of BV research that could help in formulating new basic ideas respecting the biology of BV, not least the importance of the interleukin mediators of local inflammatory responses and the bacterial shift from the normally occurring lactobacilli species: L. crispatus, L. gasseri, L. jensenii, and L. iners to a mixed flora dominated by anaerobic bacteria.

Diagnosis of bacterial vaginosis: need for validation of microscopic image area used for scoring bacterial morphotypes.

BACKGROUND: The diagnosis of bacterial vaginosis (BV) is often made according to Nugent's classification, a scoring system based on bacterial counting of Gram stained slides of vaginal secretion. However as the image area of the microscope field will influence the number of morphotypes seen there is a need to standardise the area. METHODS: A graph intended for recalculation of number of bacterial morphotypes seen by the observer using 1000 x magnification from various microscope set-ups was constructed and applied to data sets typical for scoring BV. The graph was used in recalculation of Nugent scores, which were also compared with the Ison/Hay scores to evaluate the consequences for the diagnosis of BV. RESULTS: The observed image area differed by 300% among the investigated microscope set-ups. In two different data sets, one treatment study and one screening study, a considerable change in the number of women classified as intermediate was seen when the graph was used to standardise the image area. The recalculated numbers were also compared to the Ison/Hay classification. Weighted kappa indexes between the different methods were 0.84, 0.88, and 0.90, indicating that the methods are comparable. CONCLUSION: Because of the considerable differences among image areas covered by different microscope set-ups used in Nugent and Ison/Hay scoring, there is a need to standardise the area in order to reach comparable scores reflecting the diagnosis of BV in different laboratories. The differences in the intermediate group will have a considerable effect on the results from both treatment and prevalence studies, even though the kappa indexes indicate very good agreement between the methods used.

An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.

An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

Ambiguities in colour constancy and shape from shading.

A new visual phenomenon--called the AMBEGUJAS phenomenon--is presented, together with some descriptive data from two initial exploratory experiments. The phenomenon is basically one of shape from shading, but ambiguous as to both shape and colour. There are two spontaneously alternating and mutually exclusive perceived 3-D shapes, and--as the most surprising observation--the colour impressions of these two shapes are markedly different. The stimulus situation is very simple with two differently coloured illuminations (with sharp edges) adjacently cast onto a flat, grey striped surface. In one 3-D shape almost the whole chromatic content disappears, and the surface goes towards its veridically grey colour. In the other the perceived object assumes the two illumination colours as clear surface colours. The decolorised percept is interpreted as a striking example of colour constancy: a perceptual solution with the classical 'discounting of the illuminant'. Experiments show that the phenomenon is robust and appears in varying display layouts and different combinations of chromatic illuminations.

Slight steroid-sparing effect of intravenous immunoglobulin in children and adolescents with moderately severe bronchial asthma.

Twenty subjects (aged 6-20 years) with moderately severe bronchial asthma participated in an open controlled trial with intravenous immunoglobulin (IVIG) given as five monthly infusions with a mean dose of 0.8 g/kg body weight. A follow-up was performed 4 and 14 months after the treatment period. Nine of 14 children in the treatment group completed the trial. Two children experienced severe headache after the first infusion, another two patients were taken off the study for reasons unrelated to the IVIG therapy, and one patient dropped out from lack of motivation. In six of the IVIG-treated children, there was a reduction in the daily intake of inhaled steroids at an unchanged or reduced histamine reactivity. Of the remaining three children, two showed a reduction in bronchial hyperreactivity, but their steroid dose was not reduced. Six patients participated in a reference group to determine seasonal variations of symptoms. One of them improved during the study period, and the condition of the other five deteriorated, as indicated by increased medication without reduced histamine reactivity. After 14 months, there were no significant differences in clinical symptoms, nor in sensitivity to histamine between the treated patients and the controls, as the condition had improved also in the latter. We have thus been able to confirm, in a group larger than those in previously published reports, some clinical improvement of asthma by IVIG therapy at a lower dose than previously used and in children with only moderately severe disease. The effect was still present 4 months after the termination of IVIG therapy but not after 14 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinctness of perceived three-dimensional form induced by modulated illumination: effects of certain display and modulation conditions.

The present study concerns the distinctness of the 3-D shape induced on flat displays by space-modulated illumination ("shape from shading"). The displays that we used varied in structure, hue contrast, lightness contrast, and in the number of reflectance edges present. The modulations of the illumination were a square-wave grating, a gradual modulation (a blurred grating), and an "O'Brien modulation," which combines an edge and a gradient. The displays were compared, using the paired comparison method, as to the distinctness of the perceived 3-D form. The results showed that the structure and chromatic color of the display were important factors facilitating the distinctness of the induced 3-D shape under all the modulation conditions. The results are discussed in relation to the "vector model" for color constancy, proposed in earlier papers.