Prostaglandin E2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts

Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E(2) (PGE(2)) acts on a set of E-prostanoid (EP) receptors that activate multiple signal transduction pathways leading to downstream responses. We investigated the modulation by PGE(2) of VEGF release by human lung fibroblasts. Human lung fibroblasts were cultured until reaching 90% confluence in tissue culture plates, after which the culture media were changed to serum-free Dulbecco's modified Eagle's medium, with or without PGE(2), and with specific agonists or antagonists for each EP receptor. After 2 days, culture media were assayed for VEGF by ELISA. The results demonstrated that PGE(2) and the EP2 agonist ONO-AE1-259-01 significantly stimulated the release of VEGF in a concentration-dependent manner. Agonists for other EP receptors did not stimulate the release of VEGF. The stimulatory effect of PGE(2) was blocked by the EP2 antagonist AH6809, but was not blocked by antagonists for other EP receptors. The protein kinase-A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE(2). The increased release of VEGF induced by PGE(2) was accompanied by a transient increase in the concentration of VEGF mRNA. These findings demonstrate that PGE(2) can modulate the release of VEGF by human lung fibroblasts through its actions in the EP2 receptor/PKA pathway. This activity may contribute to the maintenance of pulmonary microvasculature in the alveolar wall.     

A transmission electron microscopy study of the diversity of Candida albicans cells induced by Euphorbia hirta L. leaf extract in vitro

Objective

To determine the major changes in the microstructure of Candida albicans (C. albicans) after treatment with Euphorbia hirta (E. hirta) L. leaf extract.

Methods

Transmission electron microscopy was used to study the ultrastructural changes caused by E. hirta extract on C. albicans cells at various exposure time.

Results

It was found that the main abnormalities were the alterations in morphology, lysis and complete collapse of the yeast cells after 36 h of exposure to the extract. Whereas the control cultures showed a typical morphology of Candida with a uniform central density, typically structured nucleus, and a cytoplasm with several elements of endomembrane system and enveloped by a regular, intact cell wall.

Conclusions

The significant antifungal activity shown by this methanol extract of E. hirta L. suggests its potential against infections caused by C. albicans. The extract may be developed as an anticandidal agent.     

Use of transcutaneous electrical nerve stimulation for chronic pruritus

Pruritus is a distressing symptom in many dermatological as well as systemic conditions, and it is sometimes very chronic and relapsing. Transcutaneous electrical nerve stimulation (TENS) is an inexpensive form of analgesia that could also ameliorate itching. This study aimed to evaluate TENS efficacy in patients with pruritus due to some types of chronic eczema, and in patients with chronic hepatic disease. Ten patients with atopic dermatitis (AD), 20 patients with lichen simplex chronicus (LSC), and 16 patients with chronic liver disease having chronic distressing pruritus received three sessions of TENS weekly for 12 sessions, and the effect on the visual analogue scale (VAS) scores was recorded after 2 weeks of therapy, at treatment end, and after an additional month for follow up. There was a statistically significant decline in the mean VAS score for studied groups at weeks 2 and 4 of therapy compared to baseline, but the improvement was more significant in patients with AD, and LSC (p < 0.001 for both) than in those with chronic liver disease (p < 0.01) who also showed an early re‐elevation of VAS score on follow up. TENS therapy holds promise as a palliative, alternative, safe and inexpensive treatment for patients with some chronic pruritic conditions.     

Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo

Background  The pathogenetic mechanisms in vitiligo have not been clarified completely. One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. The active and stable phases of vitiligo are defined as the progression or appearance of new lesions in the last 3 months and the absence of new lesions or progression in the last 6 months, respectively.
Methods  We examined the levels of malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase in the tissues of 10 patients with active vitiligo, 10 patients with stable vitiligo, and 20 matched healthy controls.
Results  The results revealed that the levels of superoxide dismutase, glutathione peroxidase, and malondialdehyde in tissues were increased significantly in patients with active vitiligo relative to those in patients with stable vitiligo and matched controls; however, the levels of catalase in tissues were decreased significantly in patients with active vitiligo relative to those in patients with stable vitiligo and matched controls.
Conclusions  Our study shows that oxidative stress is involved in the pathophysiology of both active and stable vitiligo, but an increased imbalance of antioxidants is observed in the tissues of patients with active vitiligo.     

Analyzing the Mechanism of Zinc Oxide Nanowires Bending and Bundling Induced by Electron Beam under Scanning Electron Microscope Using Numerical and Simulation Analysis

The bending effect of self-catalyst zinc oxide nanowires on a photoconducting behavior has been investigated by in-situ scanning electron microscope method and interpreted by analytical modeling. Zinc oxide NWs tend to incline due to geometric instability and because of the piezoelectric properties, which was confirmed by scanning electron microscope images. A cantilever bending model adequately describes the bending and bundling events, which are linked to the electrostatic interaction between nanowires. The light absorption of zinc oxide nanowires in the visible and near infrared bands has been modelled using the finite difference time domain method. The influence of the density of nanowires (25%, 50%, 75%) and the integration of plasmonic nanoparticles distributed on the seed layer (with varied radii) on the light absorption of zinc oxide nanowires was studied using simulation analysis. We have shown that the geometry of zinc oxide nanowires in terms of length, separation distance, and surface charge density affects the process of zinc oxide nanowires bending and bundling and that absorption will be maximized by integrating Au plasmonic nanoparticles with a radius of 10 nm.     

Beneficial effect of polyclonal immunoglobulins from malaria-infected BALB/c mice on the lupus-like syndrome of (NZB × NZW)F1 mice

We previously reported that infection of BALB/c mice with the parasite Plasmodium chabaudi induces high production of natural autoantibodies. Here we demonstrate that such an infection of lupus-prone (NZB × NZW)F1 (B/W) mice retards the development of their autoimmune disease. Survival and disease hallmarks (high-grade proteinuria and IgG anti-DNA antibodies) were delayed for 6 months when parasite inoculation was given at either 3 or 7 months of age, i.e. before or after the onset of the clinical symptoms. Similar beneficial effects, although less pronounced, were obtained when mice were treated with a total of 800 m?g of IgG (P-IgG) or IgM (P-IgM) or 300 m?g of cryoglobulin preparations isolated from P. chabaudi-infected BALB/c mice while similarly prepared fractions from uninfected mice had little effect. Compared to these fractions, P-IgG and P-IgM contained higher levels of natural antibodies bearing the D23 idiotype characteristic of polyreactive natural autoantibodies with enhanced activity against Fab and Fc fragments of IgG. In surviving mice, the level of anti-DNA antibodies, particularly those of IgG1 isotype, were significantly decreased. Flow cytometric analysis of various T cell subsets showed that the number of cells expressing γδ T cell receptor (TcR) antigens which did not vary with age was not modified after P-IgG or P-IgM treatment. In contrast, the number of T cells expressing Vβ8.1,2, Vβ10 and Vβ14 TcR antigens, which increased with age, were significantly reduced. Taken together, these results indicate that parasite infection of mice induces the synthesis of populations of IgM and IgG natural autoantibodies with immunoregulatory properties and that these antibodies attempt, at least transitorily, to rescue a natural autoantibody network that is deficient in B/W mice.     

Opsonic Antibodies to the Surface M Protein of Group A Streptococci in Pooled Normal Immunoglobulins (IVIG): Potential Impact on the Clinical Efficacy of IVIG Therapy for Severe Invasive Group A Streptococcal Infections

The surface M protein of group A streptococci (GAS) is one of the major virulence factors for this pathogen. Antibodies to the M protein can facilitate opsonophagocytosis by phagocytic cells present in human blood. We investigated whether pooled normal immunoglobulin G (IVIG) contains antibodies that can opsonize and enhance the phagocytosis of type M1 strains of GAS and whether the levels of these antibodies vary for different IVIG preparations. We focused on the presence of anti-M1 antibodies because the M1T1 serotype accounts for the majority of recent invasive GAS clinical isolates in our surveillance studies. The level of anti-M1 antibodies in three commercial IVIG preparations was determined by enzyme-linked immunosorbent assay (ELISA), and the opsonic activity of these antibodies was determined by neutrophil-mediated opsonophagocytosis of a representative M1T1 isolate. High levels of opsonic anti-M1 antibodies were found in all IVIG preparations tested, and there was a good correlation between ELISA titers and opsonophagocytic activity. However, there was no significant difference in the levels of opsonic anti-M1 antibodies among the various IVIG preparations or lots tested. Adsorption of IVIG with M1T1 bacteria removed the anti-M1 opsonic activity, while the level of anti-M3 opsonophagocytosis was unchanged. Plasma was obtained from seven patients with streptococcal toxic shock syndrome who received IVIG therapy, and the level of anti-M1 antibodies was assessed before and after IVIG administration. A significant increase in the level of type M1-specific antibodies was found in the plasma of all patients who received IVIG therapy (P < 0.006). The results reveal another potential mechanism by which IVIG can ameliorate severe invasive group A streptococcal infections.     

Improved success of myoblast transplantation in mdx mice by blocking the myostatin signal

BACKGROUND.: Duchenne muscular dystrophy (DMD) is caused by a dystrophin gene mutation. Transplantation of normal myoblasts results in long-term restoration of dystrophin. However, the success of this approach is compromised by the limited time of regeneration following muscle damage. Myostatin is known to be responsible for limiting skeletal muscle regeneration. Our purpose is to verify whether blocking the myostatin signal in mdx host mice or in normal myoblasts transplanted in mdx host mice would increase the extent of muscle repair and thus allow the formation of more dystrophin-positive fibers. METHODS.: Transgenic mdx mice carrying a dominant negative form of myostatin receptor (dnActRIIB) were used to test the fiber resistance to damage and to act as a host for normal myoblast transplantation. Myoblasts obtained from nondystrophic transgenic mice carrying the dominant negative myostatin receptor were also transplanted in nontransgenic mdx mice. RESULTS.: Transgenic mdx mice carrying the dnActRIIB gene have bigger muscles than mdx mice with the normal gene of ActRIIB. Their fiber resistance to exercise-induced damage was also greatly improved. Moreover, the success of normal myoblast transplantation was significantly enhanced in mdx/dnActRIIB mice. Finally, nondystrophic dnActRIIB myoblasts formed more abundant and bigger dystrophin positive fibers when transplanted in mdx mice. CONCLUSIONS.: Blocking the myostatin signal in mdx mice allowed the size of muscle fibers to increase, the fiber resistance to damage induced by exercise to increase, and the success of normal myoblast transplantation to improve. The transplantation in mdx mice of dnActRIIB myoblasts formed more abundant and larger dystrophin positive fibers.