Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition

Humans are exposed to the antimicrobial agent triclosan (TCS) through use of TCS‐containing products. Exposed tissues contain mast cells, which are involved in numerous biological functions and diseases by secreting various chemical mediators through a process termed degranulation. We previously demonstrated that TCS inhibits both Ca²⁺ influx into antigen‐stimulated mast cells and subsequent degranulation. To determine the mechanism linking the TCS cytosolic Ca²⁺ depression to inhibited degranulation, we investigated the effects of TCS on crucial signaling enzymes activated downstream of the Ca²⁺ rise: protein kinase C (PKC; activated by Ca²⁺ and reactive oxygen species [ROS]) and phospholipase D (PLD). We found that TCS strongly inhibits PLD activity within 15 minutes post‐antigen, a key mechanism of TCS mast cell inhibition. In addition, experiments using fluorescent constructs and confocal microscopy indicate that TCS delays antigen‐induced translocations of PKCβII, PKCδ and PKC substrate myristoylated alanine‐rich C‐kinase. Surprisingly, TCS does not inhibit PKC activity or overall ability to translocate, and TCS actually increases PKC activity by 45 minutes post‐antigen; these results are explained by the timing of both TCS inhibition of cytosolic Ca²⁺ (~15+ minutes post‐antigen) and TCS stimulation of ROS (~45 minutes post‐antigen). These findings demonstrate that it is incorrect to assume that all Ca²⁺‐dependent processes will be synchronously inhibited when cytosolic Ca²⁺ is inhibited by a toxicant or drug. The results offer molecular predictions of the effects of TCS on other mammalian cell types, which share these crucial signal transduction elements and provide biochemical information that may underlie recent epidemiological findings implicating TCS in human health problems.     

Se - [(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl] 4-chlorobenzoselenolate reduces the nociceptive and edematogenic response by chemical noxious stimuli in mice: Implications of multi-target actions

BackgroundThe present study evaluated the antioxidant, antinociceptive and anti-edematogenic effects of Se-[(2,2-dimethyl-1,3-dioxolan-4-yl) methyl] 4-chlorobenzoselenolate (Se-DMC).MethodsIn vitro experiments were carried out to evaluate Se-DMC antioxidant action. Thiobarbituric acid reactive species levels, 2,2′-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-thylbenzthiazoline-6-sulfonic acid) radicals scavenging and glutathione S-transferase-like activity were determined. Male Swiss mice were orally pretreated with Se-DMC (1, 10 and 50 mg/kg), meloxicam (50 mg/kg) or vehicle 30 min prior to acetic acid or glutamate test. To extend our knowledge of the pharmacological properties of this compound, it was tested in an inflammatory model through ear edema induced by croton oil. The contribution of glutamatergic and serotonergic systems was also investigated.ResultsIn vitro experiments revealed that Se-DMC exerts antioxidant activity. Nociception induced by glutamate or acetic acid was reduced by Se-DMC or meloxicam. Se-DMC diminished the paw edema formation induced by glutamate, while meloxicam did not show any effect. Se-DMC and meloxicam decreased the ear edema formation and protected against the increase in myeloperoxidase activity in mice ear induced by croton oil. The pretreatment of animals with MK-801 did not alter antinociception caused by Se-DMC in the glutamate test. The antinociceptive effect exerted by Se-DMC in the acetic acid test was reverted by the pretreatment of mice with different serotonergic antagonists (WAY100635, ketanserin and pindolol).ConclusionsData presented here showed that the modulation of serotonergic and glutamatergic systems and the anti-inflammatory and antioxidant actions could contribute to the antinociceptive and anti-edematogenic effects of Se-DMC and it supported the therapeutic potential of this compound.     

Migration status and perinatal parameters in a Greek public maternity hospital: an illustration of the “healthy immigrant effect”

Background: Although socioeconomic disparities adversely affect health, studies referring to the “healthy immigrant effect” imply more favorable health outcomes in immigrants than natives. We aimed to investigate the impact of immigration on several perinatal parameters.

Methods: Birth records (01/01/2010???31/12/2014) from a public maternity hospital in Athens, Greece were reviewed for maternal (ethnicity, age, delivery mode) and neonatal (gender, birthweight, gestational age) variables. Immigrants were classified by country of origin, according to Human Development Index. Comparison of results between Greeks and immigrants were made. Stratification by maternal age (< and ≥35 years) was conducted to test for confounding and interaction.

Results: Almost one-third of 7506 deliveries applied to immigrants; 36.3% of Greeks and 19.2% of immigrants [risk ratio (RR)?=?0.53, 95% confidence interval (CI)?=?0.52–0.54] delivered at ≥35 years; 10.5% of Greek and 7.0% of immigrant neonates weighted <2500?g (RR?=?0.67, 95% CI?=?0.61–0.74); 10.9% of Greeks and 8.1% of immigrants were born <37 wks (RR?=?0.74, 95% CI?=?0.67–0.82); 55.7% of Greeks and 48.2% of immigrants delivered by caesarean section (RR?=?0.87, 95% CI?=?0.85–0.88).

Conclusion: We found that immigrant women deliver at a younger age, vaginally, more mature, and heavier neonates. Furthermore, we confirmed that the protective effect of immigrant status could not be explained by maternal age only.     

Clinical Uses of Cervical Vestibular-Evoked Myogenic Potential Testing in Pediatric Patients

To demonstrate the feasibility and clinical significance of cervical vestibular-evoked myogenic potential (cVEMP) test in pediatric patients.Retrospective review study was conducted in a pediatric tertiary care facility. A total of 278 patients were identified with adequate data, including medical notes, results of cVEMP, and imaging studies.Among the total of 278 pediatric patients, only 3 children were not able to finish the cVEMP test successfully. In about 90% of the cases, the cVEMP test was requested to investigate a patient’s hearing loss and/or vestibular complaints. Over 90% of the cVEMP tests were ordered by specialists such as pediatric otolaryngologists or otologists. Obtained cVEMP results provided useful information in clinical diagnosis and management in all cases.It is feasible to conduct cVEMP testing in children, including infants, and cVEMP testing can provide valuable information in the diagnosis and management of hearing loss and vestibular impairment. This simple and noninvasive test should be embraced by pediatric professionals.     

The effectiveness of manual physical therapy interventions in pediatric patients with anterior hip pain: a retrospective study

Objectives: The purposes of this study were to: (1) assess the benefit of adding manual therapy (MT) to physical therapy care in pediatric patients with anterior hip pain; (2) assess the relative risk of adverse reactions when MT is used; and (3) report the types of MT used.

Methods: This study was a retrospective chart review of patients treated in a hospital-based sports medicine clinic. The charts of 201 patients (mean age = 14.23?±?2.15 years) met the inclusion criteria and were reviewed. Patients were grouped into those who received MT during their episode of care, and those who did not. Pain efficiency (change in pain/number of visits), number and type of adverse reactions, as well as frequency and type of manual therapy interventions used, were the outcomes of interest.

Results: The mean pain efficiency was significantly less if manual therapy was performed (MT = 0.60 [95% CI 0.47–0.72], no MT = 0.80 [95% CI 0.71–0.90] p = 0.01). There was no significant difference between groups in risk of adverse reactions (MT = 5, no MT = 5). The number of visits was significantly different between groups (MT = 9.43?±?3.9 sessions, and no MT = 7.6?±?5.2 sessions).

Discussion: MT did not increase the risk of an adverse reaction in pediatric patients with anterior hip pain. While it appears to be a safe intervention, it did not improve pain efficiency or patient adherence. Future research should be performed to assess the effectiveness of MT, when performed by skilled therapists, in pediatric patients with hip pain in a controlled manner.

Level of Evidence: 3b.