Severity Of Joint Injury Research Articles

Baicalin alleviates collagen‑induced arthritis and suppresses TLR2/MYD88/NF‑κB p65 signaling in rats and HFLS‑RAs.

Baicalin is a flavonoid isolated from the root of Scutellaria baicalensis with anti-inflammatory, antioxidant and antiapoptotic pharmacological properties. However, the therapeutic effect of baicalin on rheumatoid arthritis (RA) is not completely understood. The present study aimed to explore the therapeutic potential and mechanisms underlying baicalin in collagen-induced arthritis (CIA) model rats. CIA was induced in male SD rats. The hind paw thickness and severity of joint injury were monitored to assess the onset of arthritis. At 28 days after the initial immunization, different doses of baicalin were administered once daily via oral gavage for 40 days. The radiologic and pathological alterations were examined using X-ray, and hematoxylin and eosin staining, respectively. ELISA was employed to measure the serum levels of proinflammatory cytokines. Reverse transcription-quantitative PCR and western blotting were conducted to determine the expression of toll-like receptor (TLR)2, myeloid differentiation factor 88 (MYD88) and NF-κB p65. Baicalin treatment noticeably alleviated radiographic and histologic abnormalities in the hind paw joints of CIA model rats in a dose-dependent manner. The serum levels of proinflammatory cytokines were significantly decreased in baicalin-treated CIA model rats compared with vehicle-treated CIA model rats. The mRNA expression levels of TLR2 and MYD88, as well as the protein expression levels of TLR2, MYD88 and NF-κB p65 were significantly decreased by baicalin treatment in the synovial tissue of CIA model rats and human RA fibroblast-like synoviocytes. The results suggested that baicalin may exert a beneficial effect on CIA, which may be mediated by inhibiting the TLR2/MYD88/NF-κB signaling pathway.

Chronically administered nicotine attenuates bradykinin-induced plasma extravasation and aggravates arthritis-induced joint injury in the rat

We recently showed that acute administration of nicotine in the rat decreases bradykinin-induced plasma extravasation and that adrenal medullary-derived epinephrine, acting at a β 2-adrenergic receptor, mediates the nicotine effect. Since agents which decrease bradykinin-induced plasma extravasation have been associated with increased joint injury in a rat model of chronic inflammation (experimental arthritis induced by subcutaneous injection of Mycobacterium butyricum) we examined the effect of chronic nicotine on both plasma extravasation and the severity of joint injury. In normal rats, bradykinin-induced plasma extravasation was decreased after nicotine administered both by repeated injection (10 −2mg/kg, s.c., once per h for 4 h) and by continuous long-term infusion (subcutaneous mini-osmotic pump; 1.5 × 10 −3mg/kgper h for 30 days). Nicotine-induced inhibition of bradykinin-induced plasma extravasation did not show tachyphylaxis. In rats with arthritis, chronic administration of nicotine also produced a decrease in bradykinin-induced plasma extravasation. This effect of chronic nicotine in the arthritic rats was antagonized by co-administration of hexamethonium (a nicotinic receptor antagonist), by surgical removal of the adrenal medulla, or by co-administration of ICI-118,551 (a β 2-adrenoceptor antagonist). Chronic administration of nicotine decreased the latency to the onset of arthritis and, in a dose-dependent manner, led to an increase in the radiographic joint injury score. In summary, both acute and chronic administration of nicotine decrease bradykinin-induced plasma extravasation, at least in part, via an action at nicotinic receptors on adrenal medullary cells, presumably by releasing epinephrine to act on β 2-adrenoceptors located on terminals of sympathetic postganglionic neurons in the joint. The mechanisms derived may contribute to the increase in severity of arthritis found in cigarette smokers.

Double-blind Comparison of Diclofenac Potassium, Ibuprofen and Placebo in the Treatment of Ankle Sprains

In a double-blind, placebo-controlled comparative study in 60 patients with ankle sprains suffering from moderate to severe inflammation and tenderness, the efficacy and tolerability of 150 mg/day diclofenac potassium given for 7 days was superior to that of 1.2 g/day ibuprofen which was, in turn, superior to placebo. Efficacy was assessed by volumetric evaluation of inflammation of the injured ankle, tenderness on finger pressure, pain on movement and the severity of the joint injury. Patients used visual analogue scales to assess severity of pain at rest and on walking before and during treatment. Diclofenac potassium was significantly superior (P less than 0.02) to ibuprofen for all measures of efficacy (except severity of joint injury) and ibuprofen was consistently superior to placebo. No serious adverse effects were reported. In conclusion, diclofenac potassium has been demonstrated to be effective in the treatment of acute ankle sprains and it had a rapid onset of action and good tolerability.

Beta 2-adrenergic mechanisms in experimental arthritis.

We have studied (i) the contribution of specific adrenergic receptors to the proinflammatory effects of the sympathetic nervous system in experimental arthritis and (ii) the phases of the disease during which the sympathetic nervous system influences joint injury. Severity of joint injury was measured radiographically 28 days after induction of adjuvant arthritis in control rats and in rats treated with a variety of sympatholytic agents at various times during the course of the disease. Rats treated with a nonspecific catecholamine depletor (reserpine) or a beta-adrenergic receptor antagonist (propranolol) had a delayed onset and significantly less severe joint injury than saline-treated controls when treatment began prior to injection of the adjuvant and continued to day 28 after the injection. When administered over the same treatment period, neither nonselective (phenoxybenzamine) nor selective [prazosin (alpha 1) and yohimbine (alpha 2)] alpha-adrenergic receptor antagonists affected the onset or severity of joint injury. Metoprolol, a beta 1 antagonist, was also without effect. In contrast, two beta 2 antagonists (butoxamine and ICI 118,551) significantly retarded disease onset and reduced the severity of joint injury. When reserpine or butoxamine treatment was initiated after the onset of clinically apparent arthritis, it was still possible to favorably influence the course of the disease. These data indicate an important contribution of the beta 2-adrenergic receptor to joint injury in experimental arthritis.