A liposomal steroid nano-drug for treating systemic lupus erythematosus.

Background: Glucocorticoids have been known for years to be the most effective therapy in systemic lupus erythematosus. Their use, however, is limited by the need for high doses due to their unfavorable pharmacokinetics and biodistribution. We have previously developed a novel liposome-based steroidal (methylprednisolone hemisuccinate (MPS)) nano-drug and demonstrated its specific accumulation in inflamed tissues, as well as its superior therapeutic efficacy over that of free glucocorticoids (non-liposomal) in the autoimmune diseases, including the adjuvant arthritis rat model and the experimental autoimmune encephalomyelitis mouse model.

A Humanized Monoclonal Antibody against Heat Shock Protein 60 Suppresses Murine Arthritis and Colitis and Skews the Cytokine Balance toward an Anti-Inflammatory Response.

We have previously shown that naturally occurring as well as acquired Abs against the Mycobacterium tuberculosis heat shock protein (HSP)65 protect against the induction of murine autoimmune inflammatory arthritis. In the present work, we have studied the anti-inflammatory effect of prozumab, a humanized anti-HSP mAb in murine inflammatory arthritis and colitis, and its effects on cytokine secretion. Prozumab was shown to bind to HSP60, the highly conserved mammalian homolog of the bacterial protein, and it was found to be effective in protecting and suppressing autoimmune arthritis in the models of adjuvant arthritis and collagen-induced arthritis in rats and mice, respectively, as well as in acute hapten-mediated colitis and chronic, spontaneous colitis models.

Glucocorticoids in nano-liposomes administered intravenously and subcutaneously to adjuvant arthritis rats are superior to the free drugs in suppressing arthritis and inflammatory cytokines.

We have previously shown that intravenous (i.v.) treatment with sterically stabilized nano-liposomes (NSSL) actively remote-loaded with the glucocorticoid (GC) methylprednisolone hemisuccinate (NSSL-MPS) or betamethasone hemisuccinate (NSSL-BMS) significantly decreased severity of adjuvant arthritis in Lewis rats (a model of human rheumatoid arthritis) throughout all disease stages.

Prevalence and clinical significance of anticardiolipin, anti-beta2-glycoprotein-1, and anti-heat shock protein-70 autoantibodies in sudden sensorineural hearing loss.

Sudden sensorineural hearing loss (SSNHL) is frequently classified as 'idiopathic' since the causative factor responsible for its onset is not identified in most cases. In the present study, we determined whether SSNHL is clinically associated with serum anti-heat shock protein-70 (anti-HSP70) and antiphospholipids (anti-PLs) autoantibodies and whether these autoantibodies have an impact on the prognosis of SSNHL. Sera from 63 patients with SSNHL were screened prospectively for the presence of anti-HSP70 and anti-PLs autoantibodies by an enzyme-linked immunosorbent assay test.

Amphipathic weak acid glucocorticoid prodrugs remote-loaded into sterically stabilized nanoliposomes evaluated in arthritic rats and in a Beagle dog: a novel approach to treating autoimmune arthritis.

Objective: The use of glucocorticoids (GCs) in rheumatoid arthritis is limited by side effects related to unfavorable pharmacokinetics and biodistribution. Liposomal GC formulations have been studied since the 1970s in an attempt to overcome this obstacle, but none has entered clinical use. We undertook this study to determine whether a novel approach could overcome the limitations that have thus far prevented the clinical use of these formulations: low drug:lipid ratio, low encapsulation efficiency, and lack of controlled release.

Antibodies against the VRT101 laminin epitope correlate with human SLE disease activity and can be removed by extracorporeal immunoadsorption.

Objective: We have previously shown that murine pathogenic lupus autoantibodies bind to VRT101, a 21-mer peptide located at the globular part of the laminin-alpha chain. In this study, we evaluated whether VRT101 also serves as a target for human lupus antibodies, upholding the hypothesis that VRT101 may serve as a potential target in the therapy of lupus.

Methods: Anti-VRT101 and anti-dsDNA reactivity were measured in the serum of lupus patients and compared with that of healthy individuals and patients with other rheumatic disorders.

Treatment with a laminin-derived peptide suppresses lupus nephritis.

The role of DNA as the target for pathogenic lupus autoantibodies in systemic lupus erythematosus is equivocal and renal damage may be due to cross-reactivity of lupus Abs with glomerular components. We have previously shown that lupus autoantibodies bind to the laminin component of the extracellular matrix. In the present work, we have analyzed the fine specificity of the interaction of pathogenic murine lupus autoantibodies with this molecule and the effect of inhibiting their binding to laminin during the course of the disease.

Susceptibility and resistance to experimental adjuvant arthritis.

Autoimmunity is the result of an abnormal immune response against constituents of body tissues. For many years, the study of animal models of human diseases was aimed at defining the factors participating in the autoimmune process. During the past two decades, much of the attention was diverted to another intriguing aspect of animal models: the mechanisms rendering some animal strains autoimmune-susceptible and others resistant.

Resistance to adjuvant arthritis is due to protective antibodies against heat shock protein surface epitopes and the induction of IL-10 secretion.

Adjuvant arthritis (AA) is an experimental model of autoimmune arthritis that can be induced in susceptible strains of rats such as inbred Lewis upon immunization with CFA. AA cannot be induced in resistant strains like Brown-Norway or in Lewis rats after recovery from arthritis. We have previously shown that resistance to AA is due to the presence of natural as well as acquired anti-heat shock protein (HSP) Abs.

Vaporization of melanin in oral tissues and skin with a carbon dioxide laser: a canine study.

Purpose: This study tested the efficacy of carbon dioxide (CO2) laser vaporization in ablating gingival, oral mucosal, and cutaneous melanin in dogs.

Materials And Methods: Three mongrel dogs with pigmentation of the oral mucosa, gingivae, and skin were used. Biopsy specimens from the melanin sites were obtained from all 3 dogs before laser application.

Anti-DNA antibodies cross-reacting with laminin inhibit trophoblast attachment and migration: implications for recurrent pregnancy loss in SLE patients.

Problem: Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with reduced fetal survival, recurrent abortions, and other pregnancy complications. Some of the autoantibodies found in SLE bind to laminins (LNs), which play an important role in the implantation of the fertilized ovum in humans.

Method Of Study: To elucidate the role of these specific autoantibodies, chorionic villous explants from 6 7-week-old human placentas were established as organ cultures on laminin-1 (LN-1), collagen IV (CN-IV) or uncoated culture dishes.

Tumors and tumor-like lesions of the oral cavity and related structures in Israeli children.

The present study comprises a total of 966 biopsies of the oral cavity and related structures obtained from children aged < or =15 years and examined at the Division of Oral Pathology of The Hebrew University. These cases represent 7.15% of the total number of biopsies (13508) during a fifteen-year period (1978-1992).

Down-regulation of surface antigens recognized by systemic lupus erythematosus antibodies on embryonal cells following differentiation and exposure to corticosteroids.

We have previously suggested that anti-DNA antibodies present in systemic lupus erythematosus patients can bind directly to tissues as a result of cross-reactivity with embryonal tissue-based antigens. Here we have analyzed the interaction between polyclonal and monoclonal mouse and human lupus autoantibodies and an embryonal cell line. We report that a murine embryonal stem cell line (ES) expresses a surface antigen which is recognized by mouse and human lupus autoantibodies.

Immunoglobulins from rats that are resistant to adjuvant arthritis suppress the disease in arthritis-susceptible rats.

The therapeutic effect of high doses of polyclonal immunoglobulins has been well established in various B cell-associated autoimmune diseases. In the present work we have examined the effect of low doses of immunoglobulins in adjuvant arthritis, a T cell-associated disease in the Lewis rat. Lewis rats were treated with purified rat immunoglobulins as well as their Fc and F(ab')2 fragments and their protective effect on adjuvant arthritis was evaluated.

The urine of SLE patients contains antibodies that bind to the laminin component of the extracellular matrix.

Direct immunofluorescence of tissues derived from patients affected with SLE demonstrates antibodies bound to the extracellular matrix (ECM). In the present work we have tested whether such antibodies are found in the serum and urine of lupus patients and mice. We found that the urine of patients with active SLE and of MRL/lpr/lpr mice contains antibodies that bind ECM and that a major target for these antibodies is the 200 kDa light chain of laminin which is one of the matrix components.

Oral psoriasis: report of six new cases.

This article presents six cases of oral psoriasis originally diagnosed by means of the histological changes found on biopsies of the oral lesions. Three of the patients presented with oral and skin psoriasis. Of the remaining three, two presented with oral manifestations alone, although their follow-up was short, whilst the third showed delayed dermatological changes.

Ameloblastic fibrodentinoma: report on two new cases.

Brain heterotopia of the tongue is a rare, congenital malformation, probably not embryologically related to encephaloceles or to the so called "nasal gliomas." The progressive growth frequently noted confers to the lesion a tumor-like appearance and can raise a clinical suspicion of some rare neonatal neoplasia. The non-neoplastic nature of the lesion is well established, and the growth may well be due to the fact that heterotopic brain grows as rapidly as normal brain in the infant.

Benign cementoblastoma. A review and five new cases.

This article includes five new cases of benign cementoblastoma. The study includes a review on 66 previously published cases that we consider to be bonafide cases. It is considered that benign cementoblastoma continues to be an infrequent entity that particularly affects young patients under the age of 30.

Lichen planus: exploring its malignant potential.

Almost any area of the mouth may be affected by LP, but the most frequent locations are the cheeks, tongue and gingiva. The eight cases in our study illustrate the proliferative epithelial changes to verrucous or squamous cell carcinoma that can appear in oral LP. We also found a predisposition of LP in women.

Photoacoustic injury and bone healing following 193nm excimer laser ablation.

The argon-fluoride excimer laser was investigated as a cutting-ablating tool for bone surgery. A total of 52 rats were divided into two experimental groups and two control groups. In one experimental group cortical bone defects were made; in another experimental group defects penetrating into the medullary space were performed.