Expression of hypoxia‐inducible factor‐1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

Late renal graft loss is associated with interstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) is thought to facilitate fibrosis through interaction with TGF‐β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF‐1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty‐nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF‐1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF‐1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF‐1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF‐1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1‐10‐72‐318‐13)     

Ankle torque steadiness is related to muscle activation variability and coactivation in children with cerebral palsy

The aims of this study were to: (1) investigate the significance of muscle activation variability and coactivation for the ability to perform steady submaximal ankle torque (torque steadiness) in healthy children and those with cerebral palsy (CP), and (2) assess ankle function during isometric contractions in those children. Fourteen children with CP who walked with equinus foot deformity and 14 healthy (control) children performed maximal and steady submaximal ankle dorsi‐ and plantarflexions. Dorsiflexion torque steadiness was related to agonist and antagonist muscle activation variability as well as the plantarflexor coactivation level in children with CP (r > 0.624, P < 0.03). Moreover, children with CP displayed reduced maximal torque and submaximal torque steadiness of both dorsi‐ and plantarflexion compared with controls (P < 0.05). Both muscle groups may benefit from strength training, as they exhibit poor submaximal control and weakness in children with CP. Muscle Nerve, 2009     

Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF-transgenic mice

The inflammatory cytokine tumour necrosis factor (TNF) can both induce oligodendrocyte and myelin pathology and promote proliferation of oligodendrocyte progenitor cells and remyelination. We have compared the response of the oligodendrocyte lineage to anterograde axonal (Wallerian) and terminal degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus in TNF-transgenic mice with the response in genetically normal mice. Transectioning of the entorhino-dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly larger levels in the TNF-transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF-transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed a tendency towards a greater increase in the number of juxtaposed, potentially proliferating oligodendrocytes. Noteworthy, at day 5 we also observed upregulation of MBP mRNA expression in adjacent hippocampal subregions with lesion-induced axonal sprouting, which were devoid of axonal degeneration, raising the possibility that sprouting axons provide trophic stimuli to the oligodendrocyte lineage. Twenty-eight days after lesioning, oligodendrocyte numbers and MBP mRNA expression were reduced to near normal levels. However, oligodendrocyte densities in the TNF-transgenic mice were significantly lower than in nontransgenics. We conclude that the early response of the oligodendrocyte lineage to axonal lesioning and lesion-induced axonal sprouting appears unaffected by the supranormal TNF levels in the TNF-transgenic mice. TNF may, however, have long-term inhibitory effects on the oligodendrocyte response to axonal lesioning.     

A role for interferon-gamma in focal cerebral ischemia in mice

The pro-inflammatory cytokine interferon-gamma (IFNgamma) has traditionally been associated with inflammatory CNS disease and more recently with ischemia-induced pathology. Using a murine model of focal cerebral ischemia, we found no evidence for induction of IFNgamma mRNA after permanent middle cerebral artery occlusion. In addition, we found that mice deficient in IFNgamma or IFNgamma receptors developed neocortical infarcts similar in size to those in wild type. In contrast, MBP promoter-IFNgamma-transgenic mice consistently developed significantly larger infarcts than non-transgenic mice. Because IFNgamma is a potent activator of microglia-macrophages, we investigated the involvement of microglial-macrophage-derived TNF in the larger infarcts. Numbers of TNF mRNA-expressing microglia-macrophages and levels of TNF mRNA and TNF in IFNgamma-transgenic and non-transgenic mice were similar. Furthermore, the ischemic brain damage in IFN-gamma-transgenic mice was unaffected by recombinant soluble TNF receptor I. Taken together, the data argues against a role for IFNgamma in cerebral ischemia under normal conditions. However, when present, IFNgamma significantly exacerbates ischemia-induced brain damage by mechanisms that appear to be independent of TNF or synergistic neurotoxic interactions of IFNgamma and TNF Irrespective of the mechanism(s) involved, this enhancing effect of IFNgamma on ischemia-induced neurotoxicity may need to be considered in diseases where immune IFNgamma is involved, such as multiple sclerosis.     

Myelinated nerve fibres in the subcortical white matter of cerebral hemispheres are preserved in alcoholic subjects

Previous studies have found that the primary change in the brain of chronic alcoholics is a selective loss of white matter in cerebral hemispheres. It is unknown whether the loss of white matter is due to alcohol-induced degeneration of axons in white matter, and this hypothesis has never been tested. We used a newly developed stereological method to investigate whether the length and diameter of myelinated fibres change in the subcortical white matter of male alcoholic subjects. We found no significant differences between control and alcoholic subjects with respect to the total volume, total length, and mean diameter of myelinated fibres in white matter. Our results do not find any support for the hypothesis that chronic alcoholic subjects may suffer from a degeneration of axons (myelinated fibres) in white matter in cerebral hemispheres.     

Diagnosing dental caries in populations with different levels of dental fluorosis

The aim of this study was to assess the reliability of the Nyvad visual–tactile caries-diagnostic criteria when used among children who have been lifelong residents in areas with 'optimal' or low concentrations of fluoride in the drinking water. In each of two areas with drinking water fluoride concentrations of 0.3 and 1.1 ppm (0.3 and 1.1 mg/l) fluoride, respectively, 150 children were clinically examined twice, 2 wk apart, for dental fluorosis, using the Thylstrup-Fejerskov index (TF index), and for dental caries using the Nyvad visual–tactile caries criteria. The prevalence of dental fluorosis was 45% in the 1.1 ppm fluoride area and 21% in the 0.3 ppm fluoride area. When the results of the duplicate caries recordings were compared at the surface level, only minute differences were observed in the percentage agreement (91.7 and 90.7%, respectively) and in the kappa values (0.73 and 0.72, respectively). When individual DFS counts were compared across examinations using Bland–Altman plots and estimation of prediction intervals for the differences, we observed a greater variability of the differences between recordings among children from the low-fluoride area. Contrary to our expectations, a pronounced dental fluorosis background did not reduce the reliability of the caries recordings, which appeared to be slightly less reliable at very low levels of dental fluorosis.     

Coping with life-threatening events was associated with better self-perceived health in a naval cross-sectional study

Objective

We studied the relationship between experiencing and coping with life-threatening events and self-perceived health in navy personnel operating mainly under peaceful circumstances.

Methods

The data were collected in a cross-sectional study from a questionnaire sent by mail at the end of 2002 to all employees in the Royal Norwegian Navy (N=3878) as part of a general health study. Both military and civilian personnel with different types of work on ships and ashore participated in the study. Logistic regression analyses were performed to study the relationship between the number of life-threatening events, occupational status, sex, age, and the extent of putting these events behind. The possible trends between the degree of putting the events behind and each of the eight SF-36 scales were calculated by bivariate correlations.

Results

Military personnel had experienced life-threatening events more often than civilians, but the military personnel appeared 5.5 times more likely to have put such events behind themselves than the civilians. The extent of having put life-threatening events behind oneself was clearly correlated to self-perceived health as measured by the SF-36 subscales bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These associations had linear appearances.

Conclusion

Navy personnel who have experienced a life-threatening event and have not been able to put this event behind them are more likely to report a reduced self-perceived health.