Determinants of bronchial responsiveness at school age in prematurely born children

The bronchial challenge test using isocapnic hyperventilation of cold air (IHCA) was used to evaluate bronchial responsiveness in 63 offspring of multiple pregnancies when they were 8-15 years old. At birth, 27 (43%) children had had intrauterine growth retardation (IUGR, birth weight <-2 SD, or birth weight difference between twin pairs >1.3 SD). The median birth weight was 2,050 g (range, 800-3, 150), and the median gestational age was 35 weeks (range, 28-38). None of the children had asthma or suffered from asthma-like symptoms. In the interpretation of the IHCA test, a fall of 9% or more in the forced expiratory volume in 1 sec (FEV(1)) was considered as abnormal, and these children were classified as "cold air responders." The number of responders was 16 (25%); their baseline FEV(1)/forced vital capacity ratio (FEV(1)/FVC) and forced expiratory flow between 25-75% FVC (FEF(25-75)), but not FEV(1) were significantly lower than the corresponding values in nonresponders. No differences were found in perinatal or neonatal factors between responders or nonresponders. Eight (30%) of the 27 IUGR and 8 (22%) of the 36 appropriate for gestational age (AGA) children were IHCA responders. In particular, IUGR was not correlated with maximal FEV(1) falls following the IHCA test. Respiratory infections after the neonatal period were equally common in IUGR and AGA children; but infections were associated with subsequent IHCA responsiveness. Adenoidectomy, tonsillectomy, and/or myringotomy had been performed significantly more often in the responders than in the nonresponders. At least one of the above invasive procedures had been performed in 20 (32%) of the children; this group was termed the "ENT (ear, nose, throat) surgery group." Fifty-six percent of the responders, but only 26% of the nonresponders, belonged to the ENT surgery group (P = 0.02). We conclude that intrauterine growth retardation or prematurity is not associated with abnormal cold air responsiveness in the IHCA test.     

Effects of long-term estrogen replacement therapy versus combined hormone replacement therapy on nitric oxide-dependent vasomotor function

Postmenopausal hormone replacement therapy (HRT) with estrogen may increase production of the predominant endothelium-derived vasodilator nitric oxide (NO) and consequently improve vascular reactivity. In contrast, concurrent progestin therapy may oppose this beneficial effect. We studied the effect of long-term estrogen HRT and combined HRT on vasomotor function and on plasma nitrate, which reflects the amount of NO in the circulation. As lipid peroxidation affects NO production and impairs endothelial function, we also measured the amount of the in vivo lipid peroxidation marker urinary 8-iso-prostaglandin F(2 alpha). The study group comprised 15 women receiving estradiol valerate HRT (mean age, 56 yr; treatment duration, 10.5 yr) and 15 women receiving combined HRT with estradiol valerate and levonorgestrel (mean age, 58 yr; treatment duration, 11.3 yr). The peak flow velocity (PFV) and pulsatility index of the common carotid and internal carotid artery and the abdominal aorta were measured by ultrasonography after long-term HRT (baseline), after a 4-wk pause and again 3 wk after reintroducing HRT. A statistically significant interaction between the groups and time points was observed in the PFV of the internal carotid artery (P = 0.011). In women taking estradiol valerate, the PFV values decreased significantly after withdrawal of HRT (P = 0.007) and increased again to the baseline level after reintroduction of therapy (P < 0.001). In women receiving combined HRT, the PFV remained stable over all study periods. At baseline, the PFV of women taking estradiol valerate correlated with the plasma nitrate concentration in the common carotid artery (r = 0.646; P = 0.009) and in the abdominal aorta (r = 0.579; P = 0.024). For pulsatility index and urinary 8-iso-prostaglandin F(2 alpha) excretion, there were no significant differences between the groups. Our results suggest that the favorable effects of long-term estrogen treatment on blood flow are at least partly mediated through NO. The addition of levonorgestrel to the treatment regimen appears to abolish this effect.     

Body-image dissatisfaction is strongly associated with chronic dysphoria

Background

Individual depressive symptoms may contribute to the risk of chronic depression. This study aimed to explore which symptoms predict chronic dysphoria, a hallmark of depression.

Methods

1057 participants from the population-based Young Finns study were examined for four times during a 16-year period. Those with a modified Beck’s Depression Inventory score in the upper third at all four screenings were considered to have chronic dysphoria (n=135). Participants with only one high depression score formed the reference group of transient dysphoria (n=179). Individual items of the Inventory were analyzed in terms of their association with dysphoria status and chronicity, controlling for potential confounding factors, such as personality assessed using the Temperament and Character Inventory.

Results

Body-image dissatisfaction was strongly associated with chronically elevated dysphoria (Bonferroni-corrected p=0.006). The degree of body-image dissatisfaction was associated with the probability for chronic dysphoria in a dose–response manner, with the estimated probability ranging from 0.01 to 0.60 as a function of item response. The association remained after adjustments for a wide range of personality characteristics.

Limitations

The study relied on self-reports of mood and personality, and lacked information on external opinion on participants appearances. The requirement of full time-series data may have resulted in attrition-related bias.

Conclusions

Body-image dissatisfaction was a strong predictor of chronic depression characterized by dysphoria. This finding suggests that dysfunctional attitude towards oneself might represent a potentially important target for cognitive therapies and preventive interventions.     

Induction of Hyaluronan Cables and Monocyte Adherence in Epidermal Keratinocytes

Hyaluronan attached to cell surface can form at least two very different structures; a pericellular coat close to plasma membrane and hyaluronan chains coalesced into “cables” that can span several cell lengths. The hyaluronan in cables, induced by many inflammatory agents, can bind leukocytes, whereas that in the pericellular coat does not contribute to leukocyte binding. Therefore, this structural change seems to have a major role in inflammation. In the present study we checked whether cells of squamous epithelium, like epidermal keratinocytes, can form hyaluronan cables and bind leukocytes. In addition, we checked whether hyaluronan synthesis is affected during the induction of cables. Control keratinocytes expressed pericellular hyaluronan as small patches on plasma membrane. But when treated with inflammatory agents or stressful conditions (tunicamycin, interleukin-1β, tumor necrosis factor-α, and high glucose concentration), hyaluronan organization changed into cable-like structures that avidly bound monocytes. Simultaneously, the total amount of secreted hyaluronan was slightly decreased, and the expression levels of hyaluronan synthases (Has1–3) and CD44 were not significantly changed. The results show that epidermal keratinocytes can form cables and bind leukocytes under inflammatory provocation and that these effects are not dependent on stimulation of hyaluronan secretion.     

Cyanobacteria produce a high variety of hepatotoxic peptides in lichen symbiosis

Lichens are symbiotic associations between fungi and photosynthetic algae or cyanobacteria. Microcystins are potent toxins that are responsible for the poisoning of both humans and animals. These toxins are mainly associated with aquatic cyanobacterial blooms, but here we show that the cyanobacterial symbionts of terrestrial lichens from all over the world commonly produce microcystins. We screened 803 lichen specimens from five different continents for cyanobacterial toxins by amplifying a part of the gene cluster encoding the enzyme complex responsible for microcystin production and detecting toxins directly from lichen thalli. We found either the biosynthetic genes for making microcystins or the toxin itself in 12% of all analyzed lichen specimens. A plethora of different microcystins was found with over 50 chemical variants, and many of the variants detected have only rarely been reported from free-living cyanobacteria. In addition, high amounts of nodularin, up to 60 μg g(-1), were detected from some lichen thalli. This microcystin analog and potent hepatotoxin has previously been known only from the aquatic bloom-forming genus Nodularia. Our results demonstrate that the production of cyanobacterial hepatotoxins in lichen symbiosis is a global phenomenon and occurs in many different lichen lineages. The very high genetic diversity of the mcyE gene and the chemical diversity of microcystins suggest that lichen symbioses may have been an important environment for diversification of these cyanobacteria.     

Repeated metal ion measurements in patients with high risk metal-on-metal hip replacement

Purpose

Conventional follow-up methods are not sufficient to identify adverse soft tissue reactions in patients with metal-on-metal hip replacements. The national guidelines regarding metal ion measurements are debatable. The aims of our study were to investigate (1) if there is a clinically significant change in whole blood (WB) cobalt (Co) or chrome (Cr) levels in repeated WB assessment in patients operated on with ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) in the repeated WB metal ion assessment.

Methods

We identified all patients (n = 254) with unilateral ASR implants who had second blood sample taken eight to 16 months after the first.

Results

WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with a high risk HR device. In contrast to this, 50 % of patients with THRs had metal ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group.

Conclusion

In patients with a high risk HR, repeated metal ion measurement did not provide useful information for clinical decision-making. In patients with a LD MoM THR repeated measurements revealed a large number of patients with metal ion levels exceeding SUL and might thus be clinically beneficial.     

Comparison of indirect diagnostic methods for hypolactasia

The aim of this study was to continue our previously published work and to compare the different indirect diagnostic methods for hypolactasia with the lactase to sucrase ratio obtained by jejunal biopsy. The following tests were performed in 63 adult patients: the breath hydrogen test, the lactose tolerance test with ethanol (serum galactose measurement after oral lactose load with ethanol), the urinary lactose tolerance test (urinary galactose measurement after oral lactose load with ethanol), and the strip test (like the former but using a special test strip for urinary galactose). Specificities of all these tests were good (96-98%). The 3-h breath hydrogen test was less sensitive (69%) than the other methods (81-94%). The strip test is recommended for the general practitioner for the diagnosis of this common cause of abdominal complaints.     

Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1β expression ratio and preserved NO/urea ratio following LPS-stimulation in vitro

In humans, usual aging, differently from successful aging, is associated with deregulation of proinflammatory/anti-inflammatory cytokine balance. The corresponding data from rat studies are limited. Therefore, we examined (i) cytokine messenger RNA (mRNA) profile of fresh peritoneal cells from 6- (adult), 24- (old), and 31-month-old (long-lived) AO rats and (ii) proinflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine, NO, and urea production in their LPS-stimulated cultures. Comparing with adult rats, cells from old ones expressed lower amount of TNF-α and IL-6 mRNAs, but greater amount of IL-1β mRNA. On the other hand, cells from long-lived rats exhibited a dramatic increase in IL-10 mRNA expression followed by diminished TNF-α and IL-6 mRNA expression, and comparable expression of IL-1β mRNA relative to adult rats. Consequently, IL-10/IL-1β mRNA ratio was greater in cells from long-lived rats than in adult and old rats. In LPS-stimulated peritoneal cell cultures (contained ≥95 % macrophages) from old rats, concentration of common proinflammatory cytokines was higher than in those from adult rats. Comparing with adult and old rats, in LPS-stimulated macrophage cultures from long-lived rats, TNF-α and IL-6 concentrations were lower; IL-1β concentration was comparable or greater (in respect to adult rats), whereas that of IL-10 was strikingly higher. Consistently, in macrophage cultures from long-lived rats, NO (iNOS activity marker)/urea (arginase activity marker) ratio was less and not different from that in old and adult rats, respectively. The study suggests that macrophages from long-lived rats, differently from those of old ones, have substantial ability to limit proinflammatory mediator production, which may contribute to their longevity.