Biological effects of particles from the paris subway system

Particulate matter (PM) from atmospheric pollution can easily deposit in the lungs and induce recruitment of inflammatory cells, a source of inflammatory cytokines, oxidants, and matrix metalloproteases (MMPs), which are important players in lung structural homeostasis. In many large cities, the subway system is a potent source of PM emission, but little is known about the biological effects of PM from this source. We performed a comprehensive study to evaluate the biological effects of PM sampled at two sites (RER and Metro) in the Paris subway system. Murine macrophages (RAW 264.7) and C57Bl/6 mice, respectively, were exposed to 0.01-10 microg/cm2 and 5-100 microg/mouse subway PM or reference materials [carbon black (CB), titanium dioxide (TiO2), or diesel exhaust particles (DEPs)]. We analyzed cell viability, production of cellular and lung proinflammatory cytokines [tumor necrosis factor alpha (TNFalpha), macrophage inflammatory protein (MIP-2), KC (the murin analog of interleukin-8), and granulocyte macrophage-colony stimulating factor (GM-CSF)], and mRNA or protein expression of MMP-2, -9, and -12 and heme oxygenase-1 (HO-1). Deferoxamine and polymixin B were used to evaluate the roles of iron and endotoxin, respectively. Noncytotoxic concentrations of subway PM (but not CB, TiO2, or DEPs) induced a time- and dose-dependent increase in TNFalpha and MIP-2 production by RAW 264.7 cells, in a manner involving, at least in part, PM iron content (34% inhibition of TNF production 8 h after stimulation of RAW 264.7 cells with 10 microg/cm2 RER particles pretreated with deferoxamine). Similar increased cytokine production was transiently observed in vivo in mice and was accompanied by an increased neutrophil cellularity of bronchoalveolar lavage (84.83+/-0.98% of polymorphonuclear neutrophils for RER-treated mice after 24 h vs 7.33+/-0.99% for vehicle-treated animals). Subway PM induced an increased expression of MMP-12 and HO-1 both in vitro and in vivo. PM from the Paris subway system has transient biological effects. Further studies are needed to better understand the pathophysiological implications of these findings.     

Synaptic release of zinc from brain slices: factors governing release, imaging, and accurate calculation of concentration

Cerebrocortical neurons that store and release zinc synaptically are widely recognized as critical in maintenance of cortical excitability and in certain forms of brain injury and disease. Through the last 20 years, this synaptic release has been observed directly or indirectly and reported in more than a score of publications from over a dozen laboratories in eight countries. However, the concentration of zinc released synaptically has not been established with final certainty. In the present work we have considered six aspects of the methods for studying release that can affect the magnitude of zinc release, the imaging of the release, and the calculated concentration of released zinc. We present original data on four of the issues and review published data on two others. We show that common errors can cause up to a 3000-fold underestimation of the concentration of released zinc. The results should help bring consistency to the study of synaptic release of zinc.     

Leveraging nanochannels for universal,zero-order drug delivery in vivo

Drug delivery is essential to achieve effective therapy. Herein we report on the only implantable nanochannel membrane with geometrically defined channels as small as 2.5 nm that achieves constant drug delivery in vivo. Nanochannels passively control the release of molecules by physico-electrostatic confinement, thereby leading to constant drug diffusion. We utilize a novel design algorithm to select the optimal nanochannel size for each therapeutic agent. Using nanochannels as small as 3.6 and 20 nm, we achieve sustained and constant plasma levels of leuprolide, interferon α-2b, letrozole, Y-27632, octreotide, and human growth hormone, all delivered at clinically-relevant doses. The device was demonstrated in dogs, rats, and mice and was capable of sustaining target doses for up to 70 days. To provide evidence of therapeutic efficacy, we successfully combined nanochannel delivery with a RhoA pathway inhibitor to prevent chronic rejection of cardiac allografts in a rat model. Our results provide evidence that the nanochannel platform has the potential to dramatically improve long-term therapies for chronic conditions.     

Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts

The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT-PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10(-13)-10(-6) M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3.     

Complete sequence of a Kyrgyzstan swine hepatitis E virus (HEV) isolated from a piglet thought to be experimentally infected with human HEV

Hepatitis E virus (HEV) was identified by RT-PCR amplification with degenerate ORF2 primers in the stool of a piglet experimentally inoculated with a stool suspension from a patient with acute hepatitis during an outbreak of non-A, non-B hepatitis in Kyrgyzstan. Further characterization by sequencing of the complete genome and phylogenetic analysis showed that the piglet isolate was most closely related to HEV genotype 3. Because the original human stool specimen used to inoculate the piglet was no longer available, stool samples from three patients obtained during the same outbreak were sequenced and found to be HEV genotype 1. These findings suggest that the HEV isolated from the swine stool was probably an HEV enzootic in Kyrgyzstan and not the virus inoculated from the human stool.     

Claudin-3 is a novel intestinal integrity marker in patients with alopecia areata: Correlation with the disease severity

Background

The development of alopecia areata is suggested to be influenced by intestinal permeability and gut dysbiosis. Claudin-3, an essential component of tight junctions which may act as an indicator of intestinal barrier integrity.

Aims

The study's objective was to evaluate the plasma concentration level of Claudin-3 in alopecia areata patients and its relationship to the severity of the condition.

Patients and Methods

In this case–control study, 50 alopecia areata patients and 30 healthy age and sex controls were involved. An enzyme-linked immunosorbent assay was used to determine the concentration of claudin-3 in the blood.

Results

Patients with alopecia areata had significantly higher plasma claudin-3 concentrations than healthy controls [median (interquartile range), 7.73 ng/ml (4.49–33.7) vs. 6.14 ng/ml (4.45–15.6), p < 0.005]. Positive relations were found between claudin-3 and SALT score (r = 0.675 & p-value < 0.001).

Conclusions

Claudin-3, a gut permeability biomarker, is elevated in alopecia areata and correlates with disease severity.     

Prevalence and characteristics of patients with undiagnosed HIV infection in an urban emergency department

The Centers for Disease Control and Prevention (CDC) recommends offering HIV testing to persons admitted to emergency departments (EDs). Whether by opt-in or opt-out, many EDs (including our own) have found a seroprevalence of 0.8-1.5% when rapid testing is offered. The true seropositivity rate is unknown. We performed a retrospective chart analysis upon all patients presenting to our ED over a 2-week period in the fall of 2007 who had serum drawn as a part of their emergency care. Demographics and clinical characteristics were linked via de-identified serum, which was sent for HIV testing. Nine hundred fifty nine patients had sera available for rapid HIV testing. One hundred twenty one (13%) samples were reactive via the OraQuick(?) test (OraSure Technologies, Bethlehem, PA), a point of care rapid antibody test. Due to concerns about the appropriateness of sera as substrate for the OraQuick(?) technology, reactive samples were retested via standard enzyme immunoassay (EIA)/Western blot. One hundred twelve analyzable samples were retested-38 were positive and 27 of these were from patients who reported a history of HIV infection. The rate of undiagnosed HIV infection was 1.2% (11/914 potentially analyzable samples). Of all patients with HIV in our ED, 29% of them were presumably unaware of their diagnosis. In conclusion, HIV seroprevalence in our urban ED is high, and a large fraction of the patients appears to be unaware of the infection.     

Fibroma of the tendon sheath around the knee

Fibroma of tendon sheath is an uncommon benign soft tissue tumor, intimately associated with tendons or tendon sheaths, with a predilection for the upper extremity. Fibroma of the tendon sheath around the knee is extremely rare. We report a case of a 51-year-old man who presented a tumor involving the posteromedial aspect of the left knee and which progressed in size for 7 years. Magnetic resonance imaging demonstrated a heterogeneous high-signal intensity in the mass on T1 and T2-weighted images. The tumor was excised en bloc. Macroscopically, it was lobulated and measured 13 cm in its largest diameter. Histology led to the diagnosis of fibroma of the tendon sheath. At 6 years’ follow-up, there was no local recurrence. To the best of our knowledge, the location and the size of this fibroma of the tendon sheath have never been described.