International journal of tissue reactions最新文献

We examined the effect of a nonsteroidal anti-inflammatory drug (NSAID), piroxicam, on apoptosis and matrix metalloproteinase 2 (MMP-2) activity compared with diclofenac and dexamethasone. The fibrosarcoma (WEHI-164) cell line was used to assess tolerability, MMP-2 activity and apoptosis. Piroxicam, dexamethasone and diclofenac were used at concentrations of 10-200 microg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymography. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. The results of this study show that piroxicam is able to diminish MMP-2 activity and induce apoptosis under in vitro conditions. Piroxicam also showed high tolerability compared with diclofenac and dexamethasone. In conclusion, piroxicam is able to induce apoptosis and suppress MMP-2 activity.

The aim of this study was to evaluate the joint count for affected joints and involvement distribution in erosive osteoarthritis (EOA) versus nodal osteoarthritis (NOA) of the hands in patients matched for sex, age, and disease duration. After recruitment of 101 consecutive outpatients affected with EOA, 101 patients affected by NOA were selected and matched for age, sex, and disease duration. Joint count for distal interphalangeal (DIP), proximal interphalangeal (PIP), and first carpo-metacarpal (CMC-1) joints, presenting Kellgren and Lawrence grade 2-4 OA, was performed. In our study, the number of affected joints was higher in NOA, with significant differences for some articular districts, especially in PIP joints of the fourth finger, and DIP joints of the second, third and fourth fingers.

alpha-Linked galactooligosaccharide (alpha-GOS) has been reported to change the composition of enteric microflora. In the present study, the antiarthritic effect of alpha-GOS was evaluated by employing adjuvant-induced arthritis (AIA) in Wistar rats and type II collagen-induced arthritis (CIA) in DBA/1J mice. The animals were given alpha-GOS orally. This substance had beneficial effects on both clinical signs, such as erythema and swelling of the limbs, and histopathological findings in the hind paw joints in a dose-dependent manner. alpha-GOS reduced the plasma nitrite/nitrate (NOx) level in rats with AIA. In the cell culture system employing peritoneal macrophages from rats with AIA, alpha-GOS enhanced interleukin-1 production without lipopolysaccharide stimulation in a dose-dependent manner, suggesting that alpha-GOS stimulates peritoneal macrophages through modulation of enteric microflora. Since alpha-GOS modulates the composition of the enteric microflora, the antiarthritic effects of alpha-GOS could be partly attributable to its immunomodulating activity. Thus, alpha-GOS is a potential functional food for the treatment of human rheumatoid arthritis.

We report on successful induction of remission in a patient with necrotizing crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasm antibodies by primary use of the anti-tumor necrosis factor (TNF)-alpha chimeric monoclonal antibody infliximab in combination with corticosteroids only. The standard treatment containing cyclophosphamide has reduced the former high mortality from systemic vasculitides. However, the toxicity of this alkylating agent limits its long-term use. As TNF-alpha has been shown to play a central pathogenic role in vasculitis as well as in crescentic glomerulonephritis, anti-TNF-alpha treatment in combination with cyclophosphamide has been found to be effective in therapy-resistant vasculitis. Previous reports on TNF-alpha-blocking therapies without additional cyclophosphamide did not include patients with active and severe crescentic glomerulonephritis. As our patient refused cyclophosphamide, he was given four infusions of infliximab (4 mg/kg on weeks 0, 2, 6 and 10) and methylprednisolone pulses (1 g on days 1-3), followed by daily oral prednisolone (starting with 2 mg/kg and tapering down to 5 mg daily within 3 months). After 12 weeks, control biopsy demonstrated lack of active glomerular inflammation while initially reduced renal function (creatinine 271 versus 172 mol/l, clearance 26 versus 62 ml/min) and proteinuria (2.4 versus 1.0 g/d) improved. Under remission maintenance therapy with azathioprine and prednisolone, the patient showed no relapses during a 1-year follow-up. Finally we demonstrate that there might be patients with crescentic glomerulonephritis who do not require therapy with alkylating substances and that less toxic agents such as the TNF-alpha-blocking monoclonal antibody infliximab could play a role in future primary treatment of crescentic glomerulonephritis.

Recent studies of our newly developed synthetic collagen-like hexapeptide have shown that it enhances cultured cell adhesion and differentiation and improves the morphology of ex vivo skin. Consequently, we were interested in further investigating the effects of the collagen-like peptide on the skin. We performed different immunostaining studies on ex vivo human skin samples treated with the collagen-like peptide at 1% in time course studies. Our research also included comparative studies with vitamin C (often used as a positive control for enhancing collagen synthesis). The results showed that application of the collagen-like peptide to the skin enhanced synthesis of many extracellular matrix (ECM) molecules and that this effect was observed very early in some ECM molecules such as laminin 5, collagen 111, and collagen IV The expression of the other molecules was increased after different times of application of the collagen-like peptide. Interestingly, comparative studies with vitamin C showed that the synthesis response of some ECM molecules such as laminin 5, collagen 111 and collagen IV was more rapid after the administration of the collagen-like peptide than through vitamin C administration. Our results also revealed that after a longer treatment period, both active ingredients stimulated ECM molecule synthesis to a similar degree, with the exception of some molecules that remained superiorafterpeptide administration, such as collagen IV and beta 1 integrin. These histological studies demonstrate the remarkable and rapid effect of the collagen-like peptide on stimulating ECM molecule synthesis and suggest wide application for the peptide in antiaging and photoaging skin care products.

This randomized, investigator-masked study compared the remanence on the nail surface of commercially available antimycotic nail lacquers containing amorolfine, ciclopirox and tioconazole. The lacquers, to which a coloring agent was added, were applied randomly to the left and right thumbnails and great toenails of 10 healthy volunteers. Volunteers were asked to wash their hands under standardized conditions at 30, 60 and 90 min after product application and to take at least one shower during the study. Photographs were taken immediately after drug application and at 30, 60 and 90 min, i.e., immediately after each hand washing, and then at 8 and 24 h. Photographs of treated toenails were taken at 0, 8 and 24 h. Photographic image analysis allowed automatic calculation of the proportion of nail surface remaining covered by the different nail lacquers over time and after washing. In addition, clinical visual assessment was made to determine the degree of the nail surface covered by the nail lacquers over time. It was demonstrated that at 24 h after product application, remanence of amorolfine nail lacquer on the thumbnails was significantly higher than that of ciclopirox (p < 0.05) and that of tioconazole on the thumb- and toenails at each time point up to 8 h after product application (all p < 0.05). Clinical observation showed that 30 min after application, the tioconazole nail lacquer had still had not completely dried. Amorolfine nail lacquer was shown to be more resistant than ciclopirox and tioconazole nail lacquers to chemical trauma from soaps and to mechanical aggressions from the immediate nail environment.

Hochu-ekki-to is one of Kampo formulas containing Astragalus root, liquorice, jujube, ginseng, white Atractylodes rhizome, fresh ginger and Chinese angelica root. This formula has been identified as an effective drug to improve the function of digestive systems and to strengthen defensive systems against many kinds of infections. We examined serum IgE levels and eosinophils before and after the administration of Hochu-ekki-to in patients with recalcitrant atopic dermatitis. The increased numbers of eosinophils was statistically decreased after 3 months' use of this formula. Serum IgE levels showed a tendency to decrease after the administration of this substance.

In this double-blind clinical study, we evaluated the effect of our newly developed synthetic collagen-like hexapeptide on wrinkles. Twenty healthy women volunteers, aged 40 to 62 years old, participated in the study Volunteers applied either a gel formula containing 3% of the collagen-like peptide and 1% of a booster molecule that stimulates general cell metabolism with no specific effect on wrinkles, or a placebo gel, on the eye zone area twice a day for 4 weeks. Control visits were performed at the beginning and the end of the study. Skin wrinkles were evaluated clinically and by silicon replica analysis followed by statistical treatment using the matched-pairs Student's t-test. The results showed that application of the collagen-like peptide on the skin significantly reduced the total surface of wrinkles and this effect was observed in 75% of the replicas. Similarly, the decrease in number and average depth of wrinkles was also significant and was observed in 65% and 75% of the replicas, respectively. The effect of the collagen-like peptide on reducing the total and average length of wrinkles was also remarkable. This effect was statistically highly significant (p < 0.003) and was observed in 75% to 80% of the replicas. Moreover these results were supported by volunteer questionnaires and clinical observation. The results demonstrate that the collagen-like peptide acts deeply and intensely on wrinkles; these properties are of great interest in the field of antiaging skin care research.

The structure of lymphatic capillaries (LC) of the synovial membrane (SM) from patients with rheumatoid arthritis and juvenile idiopathic arthritis obtained by synovectomy was investigated by transmission electron microscopy. This method allows comparison of the structure of the same vessel under light and electron microscope and clear differentiation between lymphatic and blood capillaries and venules. Synovial LC were localized in the subintimal connective tissue of the SM in the vicinity of venules. The shape of some LC was irregular, suggesting edema of the interstitium. Lymphatic endothelium has extremely attenuated cytoplasm with the exception of the perinuclear region. Many nuclei of endothelial cells had distinct nucleoli. The basal lamina was discontinuous. The walls of LC showed close connection with the interstitium represented by anchoring filaments that were attached to the endothelial cells and to the surrounding connective tissue. In some LC connective tissue appeared to be disconnected from endothelium and gaps between their walls and the interstitium were seen. Mononuclear cells were accumulated adjacent to some LC. Specialized interendothelial junctions (endothelial microvalves) were observed in the LC walls. Their structure and function in the migration of cells and debris from synovial interstitium into LC lumina in rheumatoid arthritic synovium deserves further investigation. In the lumina of some of the LC lymphocytes, monocytes, macrophages, cell debris and enlarged endothelium were observed. Accumulation of such material may cause obstruction of tiny LC. We suggest that reported alterations of the fine synovial lymphatic vessels can contribute to the progression of the inflammatory process to chronicity.

Radiotherapy continues to cause skin disorders. In this article, with the aid of our human skin model maintained in ex vivo survival conditions for 15 days, we describe the modifications caused by irradiation and their modulation by a trolamine-containing emulsion (Biafine). Normal human skin fragments were maintained in organ culture. One ionizing radiation session with 5 Gy was applied. Skin parameters were evaluated 24 h after the radiation session and were compared with a nonirradiated skin fragment: vascular modifications (histology), edema, epithelial proliferation, interleukin (IL)-1alpha and IL-6. Another series of skin fragments was maintained in survival conditions for 15 days after the radiation session to evaluate collagen neosynthesis by fibroblasts and any vascular changes (CD34). After irradiation the basal cell proliferation was reduced by approximately 50%. Extensive vasodilation occurred with altered capillary permeability accompanied by decreased CD34 transmembrane protein expression. Collagen synthesis and IL-1 secretion were increased. Biafine significantly reduced capillary alterations, restored CD34 expression as well as epithelial cell proliferation and significantly decreased collagen synthesis and IL-1 expression. With this ex vivo human skin model we confirmed the main modifications induced by radiotherapy as previously described in animal models: decreased basal cell proliferation and endothelial cell alterations and increased collagen synthesis by fibroblasts, probably under the influence of IL-1. The effect of Biafine emulsion on these histological and biochemical parameters may support its clinical efficacy.