Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9

Keratinocytes are continuously in contact with external stimuli and have the capacity to produce several soluble mediators. Pathogen-associated molecular patterns (PAMPs) are recognized, among others, by Toll-like receptors (TLRs). The functional responses of keratinocytes to different PAMPs have not yet been fully established. Here we show that keratinocytes constitutively express TLR1, 2, 3, 4, 5, 6, 9, and 10 mRNA, but not TLR7 and 8. Stimulation of keratinocytes with TLR3, 4, 5, and 9 ligands resulted in differential immune-associated responses. Tumor necrosis factor-alpha, CXC chemokine ligand 8 (CXCL8), CCL2, and C chemokine ligand 20 (CCL20) release was enhanced in response to all PAMPs tested, in a time- and dose-dependent manner. Only TLR9 ligand CpG-oligodeoxynucleotides (ODNs) and TLR3 ligand poly-I:C could additionally induce type I IFNs. CCL27 production was selectively induced by poly-I:C and flagellin, whereas CXCL9 and CXCL10 were exclusively induced by CpG-ODNs and/or poly-I:C. Upregulation of ICAM-1, HLA-DR, HLA-ABC, FasR, and CD40 was mainly observed in response to poly-I:C, flagellin, and lipopolysaccharide. Furthermore, PAMP triggering resulted in the phosphorylation of phosphorylated-IkappaB alpha and in the nucleus translocation of NF-kappaB p65. Altogether, these findings stress an unexpectedly multifaceted role of keratinocytes in innate immunity as evident by their differential, TLR-mediated responses to PAMPs associated with different classes of pathogens.     

No difference in in vitro susceptibility to HIV type 1 between high-risk HIV-negative Ethiopian commercial sex workers and low-risk control subjects

Host factors such as increased beta-chemokine production, HIV-1 coreceptor expression level, and HIV-1 coreceptor polymorphism have been thought to influence susceptibility to HIV-1 infection. To determine the protective role of these factors in Ethiopians who remained HIV-1 uninfected, despite multiple high-risk sexual exposures, we studied 21 Ethiopian women who had been employed as commercial sex workers (CSWs) for five or more years. The HIV-1-resistant CSWs were compared with low-risk age-matched female controls who had a comparable CD4+ cell percentage and mean fluorescence intensity (MFI). Genetic polymorphism in the CCR5, CCR2b, or SDF-1 genes appeared not to be associated with resistance in the Ethiopian CSWs. Expression levels of CCR5 and CXCR4 on naive, memory, and total CD4+ T cells tended to be higher in the resistant CSWs, while the production of beta-chemokines RANTES, MIP-1alpha, and MIP-1beta by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was lower compared with low-risk HIV-1 negative controls. In vitro susceptibility of PHA-stimulated PBMCs to primary, CCR5-restricted, Ethiopian HIV-1 isolates was comparable between resistant CSWs and low-risk controls. In vitro susceptibility was positively correlated to CD4+ cell mean fluorescence intensity and negatively correlated to CCR5 expression levels, suggesting that infection of PBMCs was primarily dependent on expression levels of CD4 and that CCR5 expression, above a certain threshold, did not further increase susceptibility. Our results show that coreceptor polymorphism, coreceptor expression levels, beta-chemokine production, and cellular resistance to in vitro HIV-1 infection are not associated with protection in high-risk HIV-1-negative Ethiopian CSWs.     

In vitro replication capacity of HIV-2 variants from long-term aviremic individuals

To establish whether efficient suppression of virus replication in HIV-2-infected individuals is associated with low replicative capacity of HIV-2, replication kinetics of HIV-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating HIV-1 variants from asymptomatics and long-term nonprogressors (AS/LTNP). On average, HIV-2 from aviremic individuals had lower replication rates than HIV-1 variants from AS/LTNP in cells of 8 donors (0.45 log10 [range 0.14-0.77] vs. 0.58 log10 [range 0.32-0.99] pg RT/ml/day, P = 0.036). The relatively low replication rate of HIV-2 compared to HIV-1 variants was not related to different sensitivities to inhibition by CD8+ T cells or different degrees of infectivity. HIV-2 replication rates increased with progressive infection and with switch from CCR5 to CXCR4 usage. The relatively low replicative capacity of HIV-2 variants from aviremic individuals likely contributes to the low viral load and benign course of infection in these individuals.     

The effect of dietary components on inflammatory lung diseases – a literature review

Anti-inflammatory treatment in chronic inflammatory lung diseases usually involves glucocorticosteroids. With patients suffering from serious side effects or becoming resistant, specific nutrients, that are suggested to positively influence disease progression, can be considered as new treatment options. The dietary inflammatory index is used to calculate effects of dietary components on inflammation and lung function to identify most potent dietary components, based on 162 articles. The positive effects of n-3 PUFAs and vitamin E on lung function can at least partially be explained by their anti-inflammatory effect. Many other dietary components showed only small or no effects on inflammation and/or lung function, although the number of weighted studies was often too small for a reliable assessment. Optimal beneficial dietary elements might reduce the required amounts of anti-inflammatory treatments, thereby decreasing both side effects and development of resistance as to improve quality of life of patients suffering from chronic inflammatory lung diseases.     

Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study

Please cite this paper as: Becker J, van Rijswijk J, Versteijnen B, Evers A, van den Akker E, van Beek E, Bolte A, Rijnders R, Mol B, Moons K, Porath M, Drogtrop A, Schuitemaker N, Willekes C, Westerhuis M, Visser G, Kwee A. Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study. BJOG 2012;119:1410-1416. Objective To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. Design Retrospective cohort study. Setting Three academic and six non-academic teaching hospitals in the Netherlands. Population Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36?weeks of gestation. Methods We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(?) clinical guidelines. Main outcome measures Number and type of ST-events. Results Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. Conclusions Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.     

Differential tropism of clinical HIV-1 isolates for primary monocytes and promonocytic cell lines.

Previously we demonstrated a correlation between a nonsyncytium-inducing (NSI), non-T-cell line tropic phenotype of HIV-1 isolates and the capacity to replicate in primary monocyte-derived macrophages (MDM). Here we demonstrate that these NSI, monocytotropic HIV-1 isolates lack the capacity to replicate in two promonocytic cell-lines, HL60 and U937. In contrast, most syncytium-inducing (SI) HIV-1 isolates with tropism for T-cell lines and generally non-monocytotropic were able to establish a productive infection in promonocytic cell lines. Similar differences in tropism for monocytes and promonocytic cell lines were observed with infectious molecular clones. Our results indicate that virological studies on promonocytic cell lines do not necessarily pertain to the HIV-1 infection of monocytes in vivo.     

Stepwise compared with rapid application of vacuum in ventouse extraction procedures

Objective To compare a one-step (rapid) application of negative pressure (vacuum) with conventional stepwise application for ventouse extraction following a prolonged second stage of labour.
Design Randomised controlled study.
Setting Teaching Hospital.
Participants Forty-seven women were randomised to the rapid vacuum group and 47 to the stepwise group.
Main outcome measures Duration of ventouse procedure, effectiveness of methods of application, morbidity of mother and infant.
Results There was no significant difference in frequency of detachment of the cup after rapid or stepwise application of vacuum. A reduction in mean duration of the ventouse procedure of 6 min was realised without significant difference in maternal or neonatal morbidity.
Conclusion Rapid application of vacuum significantly reduces the duration of a ventouse extraction procedure without compromise to efficiency and safety.