OBJECTIVE: To investigate the efficacy and safety of oral bovine type II collagen (C II) in the treatment of rheumatoid arthritis (RA). METHODS: Forty-five patients with active RA were enrolled and randomized to receive placebo or oral C II for 3 months. Efficacy parameters were assessed monthly. Cumulative response rates (percentages of patients meeting the criteria for response at anytime during the study) were analyzed utilizing 3 set of composite criteria : Paulus criteria, ACR criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: The C II-treated group (n=25) showed significant higher response rate by the Paulus criteria compared to placebo group (n=20, p=0.04), and MHAQ scores between baseline and 3 months of treatment were also significantly decreased in the C II-treated group (p<0.05). However, there were no significant differences in tender and swollen joint count, and physician and patient global scores between C II-treated and placebo groups. Only one patient treated with C II had a urticaria 1 week after administration, but no serious side effects were found in the two groups. Patients treated with C II (n=15) showed the decreased levels of circulating IgG antibodies to bovine C II 3 months after treatment (p=0.02), whereas significant changes of IgG antibodies to C II were not found in placebo group (n=12). CONCLUSION: Oral administration of C II was safe and effective for the treatment of rheumatoid arthritis. The finding that serum IgG antibodies to bovine C II was decreased in patients who treated with C II suggest that autoimmune response to C II could be decreased by repetitive administration of C II.
Administration, Oral ; Antibodies ; Arthritis, Rheumatoid* ; Autoimmunity ; Collagen Type II* ; Humans ; Immunoglobulin G ; Joints ; Urticaria

We have investigated whether oral administration of ovalbumin (OVA) could prevent active systemic anaphylaxis to the antigen. Oral tolerance was induced by a single feecfing with 40 mg OVA before, but not after, sensitization characterized by diminished OVA-specific IgE and IgG responses. Feeding 15 mg OVA suppressed anaphylaxis and antibody responses to a lesser extent. Spleen cells from tolerant donors were incapable of transferring the tolerance to naive recipients. Pretreatment of cyclophosphamide (100 mg/kg) 2 days before OVA feeding did not restore the tolerance. Furthermore, in vitro cell mixing studies showed that the proliferation of spleen cells from OVA- sensitized donors was not inhibited by the addition of spleen cells from tolerant donors, arguing against the role of suppressor cells. Anergy was demonstrated by the ability to reverse the tolerant state after culturing tolerant cells in the presence of IL-2. These findings indicate that only a high-dose (40 mg) feeding OVA was found to be effective in inducing tolerance in this experimental system, and demonstrate anergy as the mechanism underlying oral tolerance to systemic anaphylaxis.
Administration, Oral ; Anaphylaxis* ; Antibody Formation ; Cyclophosphamide ; Humans ; Immunoglobulin E ; Immunoglobulin G ; Interleukin-2 ; Ovalbumin ; Ovum ; Spleen ; Tissue Donors

Canine Subcorneal pustular dermatosis (CSPD) represents a sterile, superficial, pustular skin disease of unknown cause but may be a variant of pemphigus foliaceus. A 7-year-old, intact female, mixed dog presented with 3-month history of pruritic multiple pustules and crusts. Direct smears from intact pustules revealed numerous nondegenerate neutrophils, some acantholytic cells, and bacterial culture was negative. Histologic examination of lesional skin showed subcorneal pustules filled with neutrophils and acantholytic cells. The direct immunofluorescence tests stained with IgG, IgA, IgM, C3 were negative. Oral administration of dapsone (1 mg/kg/q8h) was initiated and it was reduced to 1 mg/kg/q12h with good control of the lesions.
Administration, Oral ; Animals ; Dapsone ; Dogs ; Female ; Fluorescent Antibody Technique, Direct ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Neutrophils ; Pemphigus ; Skin ; Skin Diseases ; Skin Diseases, Vesiculobullous

In this study, a self-designed powder needleless injection system was compared with subcutaneous injection using a needle and syringe to deliver tetanus toxoid (TT) into mice to elicit immunity. First of all, factors influencing the prepartion of TT into powder by being absorbed on aluminium hydroxide were investigated and the micromeritic characters of Al (OH)3-TT powder were observed with optical microscope and laser particle analyzer. The results showed that salt concentration and absorption time had an enhancive effect on drug loading, but the pH value and temperature did not influence the absorption reaction obviously. The absorption reaction was optimized with sodium chloride concentration of 0.4 mol x L(-1) and lasting for 10 min. The average diameter of Al(OH)3-TT powder prepared with conditions optimized above was (60.6 +/- 4.4) microm. The immunization effect of TT was determined through enzyme-linked immunosorbent assay (ELISA) of the concentration of IgG antibody elicited by TT. With delivery of Al(OH)3-TT (of 30 microg TT) by powder needleless injection to mice, the IgG antibody concentration were (6.19 +/- 0.52) and (10.70 +/- 0.78) U x L(-1) after immunization of 4 and 8 weeks, respectively, while the values were (4.25 +/- 0.58) and (7.48 +/- 0.57) U x L(-1) by subcutaneous injection (of 20 microg TT) using a needle and syringe. The results suggested that the self-designed powder needleless injection of Al(OH)3-TT was comparable to subcutaneous injection with a good immunity.
Adjuvants, Immunologic ; administration & dosage ; Aluminum Hydroxide ; administration & dosage ; Animals ; Drug Compounding ; Female ; Immunoglobulin G ; blood ; Injections, Jet ; Male ; Mice ; Particle Size ; Powders ; Tetanus Toxoid ; administration & dosage ; immunology

OBJECTIVETo synthesize the complex fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) for labeling IgG and investigate the in vitro stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG and its biodistribution in mice.

METHODSfac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) was synthesized and its radiochemical purity determined using polyamide membrane chromatography. IgG was directly labeled with fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) and the labeling ratio was determined using chromatography. The stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG in human serum albumin and normal saline was evaluated. ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was injected via the tail vein into 9 mice at the dose of 3.7×10⁴ Bq/100 µl, and SPECT image was obtained at 2, 4 and 12 h after the injection. The mice were sacrificed at these time points to measure the radioactivity and calculate the %ID/g in each organ.

RESULTSFac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) had a radiochemical purity of 82.48% and remained stable in vitro at room temperature within 4 h. The labeling ratio of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was 57.04% with a radiochemical purity exceeding 90%. In the solution of human serum albumin, the labeled IgG maintained a stable radiochemical purity, but in normal saline, its radiochemical purity was lowered to 20% at 24 h. After injection in mice, the labeled IgG was deposited mainly in the liver, spleen, kidneys, and the blood pool showed a sustained radioactivity.

CONCLUSION⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG prepared in this study has good stability in vitro and in vivo in 24 h and shows a biodistribution pattern similar to that of IgG protein in vivo. The intermediate fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) can meet the experimental requirement for labeling monoclonal antibodies and polypeptides.

Animals ; Immunoglobulin G ; administration & dosage ; metabolism ; Mice ; Mice, Inbred Strains ; Organotechnetium Compounds ; pharmacokinetics ; Radiopharmaceuticals ; pharmacokinetics ; Tissue Distribution

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract diseases in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV yet. The attachment glycoprotein (G) of RSV is a potentially important target for protective antiviral immune responses. Recombinant baculovirus has been recently emerged as a new vaccine vector, since it has intrinsic immunostimulatory properties and good bio-safety profile. METHODS: We have constructed a recombinant baculovirus-based RSV vaccine, Bac-RSV/G, displaying G glycoprotein, and evaluated immunogenicity and protective efficacy by intranasal immunization of BALB/c mice with Bac-RSV/G. RESULTS: Bac-RSV/G efficiently provides protective immunity against RSV challenge. Strong serum IgG and mucosal IgA responses were induced by intranasal immunization with Bac-RSV/G. In addition to humoral immunity, G-specific Th17- as well as Th1-type T-cell responses were detected in the lungs of Bac-RSV/G-immune mice upon RSV challenge. Neither lung eosinophilia nor vaccine-induced weight loss was observed upon Bac-RSV/G immunization and subsequent RSV infection. CONCLUSION: Our data demonstrate that intranasal administration of baculovirus-based Bac-RSV/G vaccine is efficient for the induction of protection against RSV and represents a promising prophylactic vaccination regimen.
Administration, Intranasal ; Animals ; Baculoviridae ; Eosinophilia ; Glycoproteins ; Immunity, Humoral ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Lung ; Mice ; Respiratory Syncytial Viruses ; Respiratory Tract Diseases ; T-Lymphocytes ; Vaccination ; Weight Loss

Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and-mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infection has been initiated, which is hardly achievable through parenteral immunization. Given that effective delivery of vaccine materials into immune inductive sites is prerequisite for effective oral mucosal vaccination, M cell-targeting strategy is crucial in successful vaccination since M cells are main gateway for luminal antigen influx into mucosal lymphoid tissue. Here, we applied previously identified M cell-targeting ligand Co1 to VP1 of FMDV in order to test the possible oral mucosal vaccination against FMDV infection. M cell-targeting ligand Co1-conjugated VP1 interacted efficiently with M cells of Peyer's patch. In addition, oral administration of ligand-conjugated VP1 enhanced the induction of VP1-specific IgG and IgA responses in systemic and mucosal compartments, respectively, in comparison with those from oral administration of VP1 alone. In addition, the enhanced VP1-specific immune response was found to be due to antigen-specific Th2-type cytokine production. Collectively, it is suggested that the M cell-targeting strategy could be applied to develop efficient oral mucosal vaccine against FMDV infection.
Administration, Oral ; Animals ; Foot-and-Mouth Disease ; Foot-and-Mouth Disease Virus ; Imidazoles ; Immunity, Mucosal ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Lymphoid Tissue ; Nitro Compounds ; Phenobarbital ; Vaccination

Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.
Adenoviridae* ; Administration, Mucosal ; Animals ; Antibodies ; Head* ; Hemagglutinins* ; Immunization* ; Immunoglobulin A ; Immunoglobulin G ; Influenza Vaccines ; Influenza, Human* ; Membrane Glycoproteins ; Mice* ; Mortality ; Orthomyxoviridae* ; Respiratory Tract Infections ; Seasons ; Vaccination ; Viruses

Herpes zoster, an inflammatory human disease caused by varicella zoster virus, is characterized by papulovesicular lesions along the distribution of a sensory nerve. We experienced a herpes zoster in 23 day old premature infant. The papules were distributed on his skin corresponding to the dermatomes innervated by the left Th3-Th4. The diagnosis of herpes zoster was made with dermatomal distribution of typical skin lesions, pathologic findings of eosinophilic intranuclear body and multinucleated giant cells in skin lesion (biopsy specimen). Detection of VZV specific IgG and IgM in the sera of patient was carried out. He was successfully treated with topical and intravenous administration of acyclovir. We report this case with a review of related literatures.
Acyclovir ; Administration, Intravenous ; Diagnosis ; Eosinophils ; Giant Cells ; Herpes Zoster* ; Herpesvirus 3, Human ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Infant, Newborn ; Infant, Premature* ; Skin

PURPOSE: To report a case of a patient with cytomegalovirus (CMV) retinitis who was treated with oral valganciclovir. CASE SUMMARY: A 34-year-old man who had undergone anti-cancer chemotherapy for Non-Hodgkin lymphoma was referred to the ophthalmologic oncology clinic because of decreased vision in both eyes. Fundus examination showed white, opaque, and granular retinal lesions in both eyes, and a serologic test showed a positive response to CMV antibody IgG and a negative response to CMV antibody IgM. The patient received induction therapy with intravenous ganciclovir and maintenance therapy with oral valganciclovir 900 mg once daily. CMV retinitis reactivated 4 weeks after maintenance therapy was discontinued. At that point, the patient received induction therapy with oral valganciclovir 900 mg twice daily for 3 weeks and maintenance therapy with 900 mg once daily for 5 weeks. The retinal lesion disappeared and did not recur after oral administration of valganciclovir. The patient discontinued valganciclovir after 5 weeks of maintenance therapy, and CMV retinitis did not reactivate during 6 months of follow-up. CONCLUSIONS: Oral valganciclovir was clinically effective in the treatment of CMV retinitis in a patient who was treated with anti-cancer chemotherapy for non-Hodgkin lymphoma.
Administration, Oral ; Adult ; Cytomegalovirus ; Cytomegalovirus Retinitis ; Eye ; Follow-Up Studies ; Ganciclovir ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Lymphoma, Non-Hodgkin ; Retinaldehyde ; Retinitis ; Serologic Tests ; Vision, Ocular