SERPINB3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by inducing a more tolerogenic immune phenotype

Objective: To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis. Methods: 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 \u3bcg/0.1 mL or 15 \u3bcg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria ( 65100 mg/dl). Two additional mice groups were provided by including 20 MRL/lpr mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/lpr mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated. Results: Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/lpr mice treated with SERPINB3, compared to untreated control mice. Conclusions: SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype

Multiparticle production in the model with antishadowing

We discuss the role of absorbtion and antishadowing in particle production. We reproduce power-like energy behavior of the mean multiplicity in the model with antishadowing and discuss physical implications of such behavior for the hadron structure.Comment: 11 pages, 3 figures, extended version of the talk at the XXXII International Symposium on Multiparticle Dynamics September 7-13, 2002 Alushta, Crimea, Ukrain

Transgenic chloroplasts are efficient sites for high-yield production of the vaccinia virus envelope protein A27L in plant cells.

Orthopoxviruses (OPVs) have recently received increasing attention because of their potential use in bioterrorism and the occurrence of zoonotic OPV outbreaks, highlighting the need for the development of safe and cost-effective vaccines against smallpox and related viruses. In this respect, the production of subunit protein-based vaccines in transgenic plants is an attractive approach. For this purpose, the A27L immunogenic protein of vaccinia virus was expressed in tobacco using stable transformation of the nuclear or plastid genome. The vaccinia virus protein was expressed in the stroma of transplastomic plants in soluble form and accumulated to about 18% of total soluble protein (equivalent to approximately 1.7 mg/g fresh weight). This level of A27L accumulation was 500-fold higher than that in nuclear transformed plants, and did not decline during leaf development. Transplastomic plants showed a partial reduction in growth and were chlorotic, but reached maturity and set fertile seeds. Analysis by immunofluorescence microscopy indicated altered chlorophyll distribution. Chloroplast-synthesized A27L formed oligomers, suggesting correct folding and quaternary structure, and was recognized by serum from a patient recently infected by a zoonotic OPV. Taken together, these results demonstrate that chloroplasts are an attractive production vehicle for the expression of OPV subunit vaccines

Scaling violations: Connections between elastic and inelastic hadron scattering in a geometrical approach

Starting from a short range expansion of the inelastic overlap function, capable of describing quite well the elastic pp and $\bar{p}p$ scattering data, we obtain extensions to the inelastic channel, through unitarity and an impact parameter approach. Based on geometrical arguments we infer some characteristics of the elementary hadronic process and this allows an excellent description of the inclusive multiplicity distributions in $pp$ and $\bar{p}p$ collisions. With this approach we quantitatively correlate the violations of both geometrical and KNO scaling in an analytical way. The physical picture from both channels is that the geometrical evolution of the hadronic constituents is principally reponsible for the energy dependence of the physical quantities rather than the dynamical (elementary) interaction itself.Comment: 16 pages, aps-revtex, 11 figure

S7A:7 Administration of serpinb3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by an immunomodulatory effect

Background Abnormal apoptosis and clearance of cellular debris concur to development of systemic lupus erythematosus (SLE). SERPINS (serin-protease inhibitors) are ancient molecules regulating immune homeostasis. SERPINB3 modulates apoptosis and is hypoexpressed on SLE B cells. Aim To explore the effects of SERPINB3 administration in murine lupus models, focusing on glomerulonephritis. Methods NZB/W F1 and MRL/lpr mice were used. 40 NZB/W F1 mice were divided into 4 groups of 10 mice each and intraperitoneally injected twice a week starting before occurrence of proteinuria traces (group 1 and 2, prophylactic approach) or after development of proteinuria 30 mg/dl (group 3 and 4, therapeutic approach) with hrSERPINB3 (7.5 µg/0.1 mL prophylactic approach, or 15 µg/0.1 mL therapeutic approach) or PBS (0.1 mL). 20 MRL/lpr mice were injected with hrSERPINB3 (group 5, n=10) or PBS (group 6, n=10) with a prophylactic approach. We assessed time of occurrence and titers of anti-dsDNA and anti-C1q antibodies by ELISA; proteinuria and serum creatinine; overall- and proteinuria-free survival. Six NZB/W F1 mice were sacrificed at week 27, while 10 MRL/lpr mice at week 13 and another 10 at 16/18 weeks for histological kidneys comparison. Flow-cytometry was performed on MRL/lpr splenocytes. Non parametric tests were performed for statistics; proteinuria-free ( Results Levels of autoantibodies were significantly decreased and delayed in group 1 vs group 2, group 3 vs group 4, and group 5 vs group 6 (p Conclusions Administration of SERPINB3 significantly improves disease and delays the onset of severe glomerulonephritis in lupus-prone mice. SERPINB3 may influence immune-cell function through immunoregulatory effects involving promotion of Treg

Techniques for pneumocephalus and brain shift reduction in DBS surgery: a review of the literature

Deep brain stimulation has become an established therapeutic choice to manage the symptoms of medically refractory Parkinson’s disease. Its efficacy is highly dependent on the accuracy of electrodes’ positioning in the correct anatomical target. During DBS procedure, the opening of the dura mater induces the displacement of neural structures. This effect mainly depends on the loss of the physiological negative intracranial pressure, air inflow, and loss of cerebrospinal fluid. Several studies concentrated on correcting surgical techniques for DBS electrodes’ positioning in order to reduce pneumocephalus which may result in therapeutic failure. The authors focused in particular on reducing the brain air window and maintaining the pressure gradient between intra- and extracranial compartments. A significant reduction of pneumocephalus and brain shift was obtained by excluding the opening of the subarachnoid space, by covering the dura mater opening with tissue sealant and by reducing the intracranial pressure in general anesthesia. Smaller burr hole diameters were not statistically relevant for reducing air inflow and displacement of anatomical targets. The review of the literature showed that conserving a physiological intra-extracranial pressure gradient plays a fundamental role in avoiding pneumocephalus and consequent displacement of brain structures, which improves surgical accuracy and DBS long-term results