Limited Relationship between Cervico-Vaginal Fluid Cytokine Profiles and Cervical Shortening in Women at High Risk of Spontaneous Preterm Birth

Objective: to determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship. Methods: this prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay. Results: all 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001]. Conclusions: although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length

The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival

Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Long-term follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-α levels negatively correlated to tumour proliferation (ρ=−0.697, P=0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (ρ=0.452, P=0.05) and apoptosis (ρ=0.587, P=0.01). Patient survival correlates to tumour pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI⩽0.6% and TNF-α levels ⩾8148 pg ml−1 correlate to improved survival (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNF-α and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected

The metabolic modulator trimetazidine triggers autophagy and counteracts stress-induced atrophy in skeletal muscle myotubes

It has recently been demonstrated that trimetazidine (TMZ), an anti-ischemic antianginal agent, is also able to improve exercise performance in patients with peripheral arterial disease. TMZ is a metabolic modulator, and the mechanisms underlying its cytoprotective anti-ischemic activity could be ascribed, at least in cardiomyocytes, to optimization of metabolism. However, regarding the cytoprotection exerted by TMZ on skeletal muscle and allowing the improvement of exercise performance, no information is yet available. In the present study, we investigated in detail the protective effects of this drug on invitro skeletal muscle models of atrophy. Experiments carried out with murine C2C12 myotubes treated with TMZ revealed that this drug could efficiently counteract the cytopathic effects induced by the proinflammatory cytokine tumor necrosis factor- and by the withdrawal of growth factors. Indeed, TMZ significantly counteracted the reduction in myotube size induced by these treatments. TMZ also increased myosin heavy chain expression and induced hypertrophy in C2C12 myotubes, both effects strongly suggesting a role of TMZ in counteracting atrophy invitro. In particular, we found that TMZ was able to activate the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin2 pathway and to reduce the stress-induced transcriptional upregulation of atrogin-1, muscle ring finger protein1, and myostatin, all of which are key molecules involved in muscle wasting. Moreover, this is the first demonstration that TMZ induces autophagy, a key mechanism involved in muscle mass regulation. On the basis of these results, it can be hypothesized that the improvement in exercise performance previously observed in patients could be ascribed to a cytoprotective mechanism exerted by TMZ on skeletal muscle integrity

Maternal request: a reason for rising rates of cesarean section?

OBJECTIVE: The rising rate of cesarean sections (CS), especially those on maternal request, is an important obstetric care issue. The aim of this two-point cross-sectional study was to evaluate the prevalence of CS and their indications. METHODS: We performed a retrospective chart review of the indications of all CS performed at a tertiary care clinic in Switzerland in 2002 and 2008. Chi-square, Student's t and Mann-Whitney U tests were performed to identify significant differences. RESULTS: The number of CS rose from 23.3% (371 out of 1,594 total life births) in 2002 to 27.5% (513 out of 1,866) in 2008 (p = 0.005). Of all deliveries, the rate of CS on maternal request and, among these, especially those requested after previous CS, increased significantly (2.1 vs. 5.1% and 0.3 vs. 1.2%, respectively). The number of CS due to previous traumatic birth experience nearly doubled (0.7 vs. 1.2%, not significant). Maternal and fetal complications were rare but not negligible in the subset of low-risk patients requesting CS. CONCLUSIONS: The study demonstrated a significant increase in CS on maternal request, especially in case of previous CS. The findings of this study support the need for specific counseling strategies for women requesting delivery by CS