Selective Effect of Adjuvant Arthritis on the Disposition of Propranolol Enantiomers in Rats Detected Using a Stereospecific HPLC Assay

Nonstereospecific studies have indicated that the pharmacokinetics of propranolol (PR) are altered in inflammatory conditions such as arthritis. However, as the kinetics and dynamics of PR are stereoselective, we examined the effect of adjuvant arthritis (AA) on the disposition of the individual enantiomers. A novel normal-phase stereospecific HPLC assay for PR was developed involving chiral derivatization with S-(naphthyl)ethyl isocyanate and fluorescence detection. Oral and iv doses of racemic PR were administered to control and AA rats (n = 6). AA had no significant effect on either clearance or S:R ratio after iv doses. On the other hand, after oral doses, clearance was significantly decreased in AA. Although significant for both enantiomers, this effect was more pronounced on the less active R-enantiomer. The AUC R:S ratio was, therefore, significantly altered (AA, 14 ± 3.0; control, 4.3 ± 1.2). Increased total (S + R) plasma concentrations of PR in AA, possibly due to a reduced intrinsic clearance, therefore, reflect mainly increased concentrations of the less active R-enantiomer.     

Identification and characterization of a DR4-restricted T cell epitope within chlamydia heat shock protein 60

An epitope within the 60 kD Chlamydia trachomatis heat shock protein (hsp) 60, recognized by a HLA-DRB1*0401-restricted T cell clone from a reactive arthritis patient, has been characterized. Stimulatory peptides contained a nine amino acid sequence (residues 38–46) predicted by algorithm to confer strong binding to DRB1*0401, with valine in the P1 position. The overall length of the peptide was critical for efficient recognition; peptides with at least one residue N-terminal to the putative P1 position were markedly more stimulatory than a peptide whose N-terminal is the P1 valine. Optimal responses were seen with 14mer peptides having two to three amino acids N- and C-terminal to the core 9mer. The sequence of the defined epitope is identical in hsp60 from both C. trachomatis and C. pneumoniae. Since the latter is a common respiratory pathogen, patients infected with C. trachomatis may already be primed for responses to hsp60 by prior infection with C. pneumoniae. Such secondary responses are important in the pathogenesis of chlamydia-induced inflammatory diseases such as trachoma. Priming by infection with enteric organisms was considered because of the similarity of the epitope sequence in Escherichia coli hsp60. However, although an E. coli-related peptide was recognized, intact E. coli hsp60 was not, suggesting that the epitope is cryptic in E. coli hsp60. Human hsp60 has six amino acid differences from chlamydial hsp60 in the epitope sequence and was not recognized. Thus cross-reactive recognition of self hsp60 could not be implicated in the pathogenesis of chlamydia-induced reactive arthritis in this patient.     

尼美舒利对佐剂性关节炎大鼠的治疗作用研究

尼美舒利(Nime)0．6、30、15mg·kg^-1对佐剂性关节炎大鼠的原发性和继发性炎症反应均有明显的抑制作用，用药组继发性炎痘反应的全身症状也明显减轻，而Nime对佐剂性关节炎大鼠低下的脾细胞增殖反应和腹腔巨噬细胞产生过高的IL-1活性却无明显影响，提示Nime无明显的免疫作用，该结果表明，Nime对佐剂性关节炎大鼠有明显的治疗作用，这一作用可能与Nime有较强的抗炎作甩有关。     

Involvement of platelet-activating factor and tumour necrosis factor in the pathogenesis of joint inflammation in rabbits.

We have studied the participation of platelet-activating factor (PAF) in antigen-induced arthritis in rabbits, as well as the possible co-operation between PAF and tumour necrosis factor (TNF) in their ability to induce joint inflammation when injected into the knees of healthy rabbits. The administration of two structurally different PAF receptor antagonists, BN52021 and Alprazolam, from 4 h before the intra-articular injection of ovalbumin in preimmunized rabbits, induced an important reduction in the synovial fluid volume, in the amount of cells infiltrating the articular cavity and the synovial membrane, as well as in the prostaglandin E2 (PGE2) concentration. Furthermore, proteoglycans of the articular cartilage, which were found diminished in animals with non-treated arthritis, were well preserved in rabbits treated with PAF antagonists. All the synovial fluids from joints with arthritis had detectable amounts of PAF. The injection of either TNF or PAF into the joints of normal rabbits induced a mild inflammation. When TNF was administered 1 h before PAF, a synergistic response was noted in the synovial fluid volume, in the accumulation of leucocytes, and in the amount of PGE2. The administration of BN50726, a hetrazepine with a potent PAF-receptor antagonist effect, induced a diminution in those parameters. Our results suggest that PAF may be an early and important mediator of joint damage, and that TNF can amplify the inflammatory response induced by PAF. PAF receptor antagonists could play some role in the treatment of inflammatory joint diseases.     

Arthritis in a patient with homozygous familial hypercholesterolemia

Familial hypercholesterolemia is a disorder of lipoprotein metabolism characterized by elevated cholesterol, low-density lipoprotein cholesterol, xanthomas and early onset atherosclerosis. Tendinitis and arthritis have been reported in patients with familial hypercholesterolemia. A report is presented of a 9-year-old girl with an acute arthritic attack who was diagnosed as homozygote familial hypercholesterolemia with hypercholesterolemic arthritis.     

Juvenile Rheumatoid Arthritis: Benefits from Massage Theraphy

Studied children with mild to moderate juvenile rheumatoid arthritiswho were massaged by their parents 15 minutes a day for 30 days(and a control group engaged in relaxation therapy). The children'sanxiety and stress hormone (cortisol) levels were immediatelydecreased by the massage, and over the 30-day period their paindecreased on self-reports, parent reports, and their physician'sassessment of pain (both the incidence and severity) and pain-limitingactivities     

Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease

We have investigated the biological and therapeutic properties of a humanized anti-CD4 MoAb, hlgGl-CD4, in patients with refractory psoriasis and rheumatoid arthritis (RA). hIgGl-CD4 is a modulating, non-depleting MoAb, which induced a first-dose reaction in most patients treated. It provided brief symptomatic relief in both conditions, and psoriasis appeared easier to control with conventional agents after MoAb therapy. At the doses used, hIgGl-CD4 did not synergize therapeutically with the pan-lymphocyte MoAb CAMPATH-1H (C1H) in patients with RA treated sequentially with both agents. There were no serious adverse effects definitely attributable to therapy. Our results are compared with those of other CD4 MoAb studies, and factors influencing the outcome of therapy are discussed.     

Effect of wrist and ulna head position on gliding resistance of the extensor digitorum minimi and extensor digitorum communis III tendons: a cadaver study.

While attrition from sharp bony surfaces is the most common cause of extensor digiti minimi (EDM) tendon rupture, the etiology of other cases of spontaneous EDM tendon rupture is still unknown. Friction within the compartment may play a role, especially with ulna dislocation. The purpose of this study was to compare gliding resistance of the EDM tendon with that of a tendon which rarely ruptures spontaneously, the extensor digitorum communis of the middle finger (EDC III) tendon, under various wrist and ulna head positions. Eight fresh frozen cadavers were used. Gliding resistance between the tendon and its sheath in each compartment was measured in five different wrist positions and three different ulna head positions. Gliding resistance of the EDM tendon (0.13 +/- 0.03 N) was significantly greater than the EDC III tendon (0.09 +/- 0.03 N) (p < 0.05). For the EDM tendon, the gliding resistance in ulnar deviation or pronation was higher than the gliding resistance in neutral, radial deviation, or supination (p < 0.05), and the gliding resistance with ulnar lengthening (over 6 mm) or dorsal ulnar dislocation (over 9 mm) was higher than in neutral ulnar head positioning. For the EDC III tendon, the gliding resistance in ulnar deviation was significantly higher than the gliding resistance in neutral, radial deviation, or supination, or dorsal dislocation with ulnar lengthening (p < 0.05). Wrist ulnar deviation, ulnar dorsal dislocation (over 9 mm), and ulnar lengthening (over 6 mm) increased the gliding resistance of the EDM tendon. In patients at risk for EDM rupture, such as those with rheumatoid arthritis or distal radioulnar joint osteoarthritis, avoiding such positions may be advantageous.     

Arthroscopic treatment of elbowarthritis in athletes

Arthroscopy has a valuable role in the treatment of elbow arthritis in the athletic population. General arthroscopicdebridement techniques used in the treatment of arthritis in other joints are quite valuable. Arthroscopic modifications of open techniques unique to the elbow, such as ulnohumeral arthroplasty, also are useful. As in other joints, the benefits of arthroscopic treatment of elbow arthritis may be temporary. Proper patient selection and attention to technical detail are critical in this population.