The Use of Laser Therapy for Patients with Fibromyalgia: A Critical Literary Review.

The management of pain - despite many anaesthetic drugs - remains to be an urgent task. If the goal is to achieve permanent pain relief - and not to temporarily mask the pain (masking pathology) - then this goal can only be achieved by treating pain with physiotherapeutic methods, the most universal and effective of which, is low level laser therapy (LLLT). The treatment methods vary fundamentally in the case of neuropathic (nonspecific, primary) pain, which includes pain with the localization of the trigger points (TP) and nociceptive (specific, secondary), which includes all types of pain resulting from trauma, inflammation, etc. When treating patients with fibromyalgia (FM), a comprehensive approach is required, using different methods of laser therapy and guided by well-known rules. These rules include setting all the correct parameters of the laser exposure (wavelength, operating mode, power, exposure, etc), limiting exposure and power to optimal values and limiting the total time of the procedure and the number of procedures per course.

Addition of αGal HyperAcute™ technology to recombinant avian influenza vaccines induces strong low-dose antibody responses.

Highly pathogenic avian influenza represents a severe public health threat. Over the last decade, the demand for highly efficacious vaccines against avian influenza viruses has grown, especially after the 2013 H7N9 outbreak in China that resulted in over 600 human cases with over 200 deaths. Currently, there are several H5N1 and H7N9 influenza vaccines in clinical trials, all of which employ traditional oil-in-water adjuvants due to the poor immunogenicity of avian influenza virus antigens. In this study, we developed potent recombinant avian influenza vaccine candidates using HyperAcute™ Technology, which takes advantage of naturally-acquired anti-αGal immunity in humans. We successfully generated αGal-positive recombinant protein and virus-like particle vaccine candidates of H5N1 and H7N9 influenza strains using either biological or our novel CarboLink chemical αGal modification techniques. Strikingly, two doses of 100 ng αGal-modified vaccine, with no traditional adjuvant, was able to induce a much stronger humoral response in αGT BALB/c knockout mice (the only experimental system readily available for testing αGal in vivo) than unmodified vaccines even at 10-fold higher dose (1000 ng/dose). Our data strongly suggest that αGal modification significantly enhances the humoral immunogenicity of the recombinant influenza vaccine candidates. Use of αGal HyperAcute™ technology allows significant dose-sparing while retaining desired immunogenicity. Our success in the development of highly potent H5N1 and H7N9 vaccine candidates demonstrated the potential of αGal HyperAcute™ technology for the development of vaccines against other infectious diseases.

Co-expression of alpha(1,3)galactosyltransferase and Bacillus thuringiensis PIPLC enhances hyperacute rejection of tumor cells.

The use of alpha(1,3)galactosyltransferase (alphaGT) as a method of inducing hyperacute rejection of tumors has been gaining interest recently. However, the approach is based in part on the sensitivity of each tumor line to the effects of complement lysis. Tumors expressing complement resistance factors such as membrane cofactor (CD46), decay accelerating factor (CD55) and protectin (CD59) have been shown to be more resistant to complement mediated lysis. Anchored to the membrane by a glycosylphosphoinositol moiety (GPI-anchored), CD55 and CD59 can be cleaved by Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (PIPLC). Complement resistant A549 human lung carcinoma cells were engineered to express both the murine alphaGT gene and the B. thuringiensis PIPLC gene to alleviate complement resistance and enhance alphagal-mediated cancer killing. The PIPLC native signal sequence was replaced with the human epidermal growth factor signal sequence, EGFssPIPLC, to induce secretion from A549. Expression of EGFssPIPLC resulted in complete removal of CD55 and CD59 while sparing the non-GPI-anchored CD46. Results demonstrated that A549 cells transduced with two recombinant retroviral vectors carrying the alphaGT and EGFssPIPLC genes expressed high levels of alphagal epitope and exhibited a 5-fold increase in sensitivity to anti-alphagal mediated complement lysis.

Expression of the Protein with Molecular Weight 104-110 kDa by Normal and Malignant Human B Lymphoid Cells.

In this paper we present the results of the distribution of a cell surface protein with molecular weight 104-110 kDa (p104-110) detected by monoclonal antibody made in our laboratory. The protein is expressed by a number of cell lines belonging to B lymphoid cells, but not to the other blood cell lineages. In healthy donors the expression of p104-110 is restricted to a minor population of human peripheral blood mononuclear cells shared by both CD20(+) and CD20(-) subpopulation. No expression of p104-110 has been found on resting and activated T cells as well as on monocytes and polymorphonuclear cells. FACS analysis of mononuclear cells derived from normal human bone marrow has revealed the presence of p104-110 on committed CD34(-); CD38(+) mononuclear cell subset that composes only the minor part of mature CD20(+) B cells being mostly CD20 negative. Furthermore, CD19(+)CD5(+)CD20(-) malignant cells derived from the patients with chronic lymphoid leukemia express p104-110 at high level. Similarly, it has been shown that some patients with malignant non-Hodgkin's lymphomas can have the increased contents of CD20(+) cells bearing that surface antigen. Possible associations of p104-110 expression on human B lymphoid cells with their differentiation and activation are discussed.