[Effect of moxibustion on the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor in ankle synovial tissue of rats with adjuvant arthritis].

OBJECTIVE: To observe the effect of moxibustion on the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in ankle synovial tissue of rats with adjuvant arthritis(AA), so as to explore the mechanism of moxibustion in inhibiting synovial angiogenesis and improving joint symptoms of rheumatoid arthritis. METHODS: Sixty healthy male SD rats were randomly divided into normal group, model group, moxibustion group and medication group, with 15 rats in each group. AA rat model was established by subcutaneous injection of Freund's complete adjuvant into the right hind paw. Rats in the moxibustion group were treated with "Zusanli" (ST36), "Guanyuan" (CV4) and "Ashi" point moxibustion, 20 min each time, once a day, for consecutive 3 weeks. Rats in the medication group were given methotrexate (0.35 mg/kg) intragastric administration, twice a week, for consecutive 3 weeks. Foot plantar volume of rats was measured by toe volume mea-suring instrument. HE staining was used to observe the histopathology of ankle synovium. The protein expressions of HIF-1α and VEGF in ankle synovial tissue were detected by immunohistochemistry and Western blot. RESULTS: Compared with the normal group, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly increased (P<0.01) in the model group, the synovial tissue showed obvious hyperplasia and a large number of neovasculogenesis. Following the interventions, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly decreased (P<0.05, P<0.01) in both moxibustion and medication groups in contrast to the model group, and there was no obvious proliferation of synovial tissue, and only a few neovascularization was observed. Compared with the medication group, the foot plantar volume was decreased (P<0.05) in the moxibustion group. CONCLUSION: Moxibustion can improve joint swelling and inhibit synovial angiogenesis in AA rats, and its mechanism may be related to down-regulating of HIF-1α and VEGF protein expressions.

Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats.

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague-Dawley rats underwent acute inflammatory pain by injecting Complete Freund's Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.

Altered sensory innervation and pain hypersensitivity in a model of young painful arthritic joints: short- and long-term effects.

BACKGROUND: Early life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known. Here, we measure pain sensitivity and sensory innervation in a young, juvenile and adult rodent model of arthritic joints and test the consequences of joint inflammation in young animals upon adult arthritic pain and joint innervation. METHODS: Unilateral ankle joint injections of complete Freund's adjuvant (CFA) (6-20 µl) were performed in young, postnatal day (P)8, adolescent (P21) and adult (P40) rats. A separate cohort of animals were injected at P8, and again at P40. Hindpaw mechanical sensitivity was assessed using von Frey monofilaments (vF) for 10 days. Nerve fibres were counted in sections through the ankle joint immunostained for calcitonin gene-related peptide (CGRP) and neurofilament 200 kDa (NF200). RESULTS: Ankle joint CFA injection increased capsular width at all ages. Significant mechanical pain hypersensitivity and increased number of joint CGRP + ve sensory fibres occurred in adolescent and adult, but not young, rats. Despite the lack of acute reaction, joint inflammation at a young age resulted in significantly increased pain hypersensitivity and CGRP+ fibre counts when the rats were re-inflamed as adults. CONCLUSIONS: Joint inflammation increases the sensory nociceptive innervation and induces acute pain hypersensitivity in juvenile and adult, but not in young rats. However, early life joint inflammation 'primes' the joint such that adult inflammatory pain behaviour and nociceptive nerve endings in the joint are significantly increased. Early life joint inflammation may be an important factor in the generation and maintenance of chronic arthritic pain.

Non-target metabolomic analysis reveals the therapeutic effect of Saposhnikovia divaricata decoction on collagen-induced arthritis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (SD), a Chinese crude drug, has long been recognized for therapeutic effect to rheumatoid arthritis (RA). At present, the mechanisms of SD treatment in RA have not been fully understood especially on the perspective of metabolomics. AIM OF THE STUDY: To study the pharmacodynamic effects of Saposhnikovia divaricata decoction on CIA rats, and explore the therapeutic mechanism by metabolomics methods. MATERIALS AND METHODS: Wistar rats were randomly divided into normal group, CIA model group, dexamethasone group and SD decoction groups (10 g crude drug/kg, 5 g crude drug/kg and 2.5 g crude drug/kg of SDD). Body weight, arthritis scores, serum cytokine levels and histopathological parameters of rats were assessed. A metabolomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS) was established to collect the metabolic profiles of rats and explore the metabolic changes that occurred after SDD treatment. RESULTS: SDD showed its protective effect on the affected joints, especially in the middle dosage group of SDD. Eighteen and 13 potential biomarkers for the SDD treatment of CIA rats were identified in the plasma and urine, respectively. SDD could regulate the disturbed metabolic pathways including tryptophan metabolism, glycerophospholipid catabolism, primary bile acid biosynthesis and fatty acid metabolism. CONCLUSIONS: In summary, SDD treatment could effectively alleviate symptoms of RA and regulate metabolic disorders in CIA rats.

Cyclic muscle twitch contraction inhibits immobilization-induced muscle contracture and fibrosis in rats.

We investigated the effects of cyclic muscle twitch contraction caused by neuromuscular electrical stimulation (NMES) on immobilization-induced muscle contracture and fibrosis in rats. Twenty-nine rats were divided into control, immobilization, and immobilization with muscle contraction groups. The ankle joints of the immobilization and muscle contraction rats were fixed in full plantar flexion with a plaster cast for 4 weeks. In the muscle contraction group, cyclic muscle twitch contraction of the soleus muscle was induced using a commercial device (1 Hz, 4 ± 2 mA, 60 min/day, 5 times/week) with the ankle joint immobilized. The dorsiflexion range of ankle joint motion in the muscle contraction group was significantly greater than that in the immobilization group. The expressions of fibrosis-related genes (i.e., hypoxia inducible factor-1α, transforming growth factor-ß1, α-smooth muscle actin, and types I and III collagen) were significantly decreased in the muscle contraction group compared to the immobilization group. The fluorescence intensities of type I and type III collagen in the perimysium and endomysium in the muscle contraction group were significantly decreased compared to the immobilization group. These results suggest that cyclic muscle twitch contraction induced by NMES might alleviate skeletal muscle fibrosis, reducing immobilization-induced muscle contracture.

[Effects of electro-acupuncture on expression of triggering receptor expressed on myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Forty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lß detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot. RESULTS: Compared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lß increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lß decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05). CONCLUSION: EA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.

Anti-arthritic effects of FasL gene transferred intra-articularly by an inducible lentiviral vector containing improved tet-on system.

The objective of this study is to construct and identify an inducible lentiviral vector containing improved tet-on system and FasL gene and observe its effects on pristane-induced arthritis (PIA). FasL gene was amplified from the spleen of Lewis rats by RT-PCR. The tet-on system was improved with insertion of a chicken chromatin insulator (cHS4) element and an rtTA-dependent, tet-responsive element containing modifications of the tetO sequence (TRE-tight1). Pro-apoptosis effect of the vector pTREFasLcHS4V16 on synovial cells was evaluated by flow cytometer in vitro. Anti-arthritis effects of the vector on PIA after intra-articular injection were observed by clinical evaluation and joint histology. Cytokines in synovial tissue were measured by ELISA. The recombinant inducible lentiviral vector pTREFasLcHS4V16 was successfully constructed. The expression response and the pro-apoptosis effects of the vector were doxycycline dose-dependent. The vector injected intra-articularly attenuated the severity of PIA and decreased the level of cytokines in inflamed joints. pTREFasLcHS4V16 with an improved tet-on system can precisely regulate the expression of FasL gene and apoptosis. Anti-arthritis effects were observed after intra-articular injection of the inducible vector.

[The effects of electro-acupuncture on the signaling pathway of TLR/MYD88 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture ( EA) on the related protein expression of the signaling pathway of the toll-like receptor2 (TLR2)/myeloid differentiation factor (MYD) 88 in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Fifty male SD rats were randomly divided into 5 groups: normal group, SMD group, AGA model group, medication group and EA group, 10 rats in each group. SMD group established model by inducing SMD, other groups established AGA model by inducing monosodium urate, except the normal group. Two days before model was established, normal and SMD and AGA model groups were lavaged with normal saline (20 mL/kg), medication group was lavaged with colchicine solution (1 mg/kg), EA (1. 5-2 Hz, D.-D. wave, 9 V, 1-3 mA) was applied to"Sanyinjiao" (SP6),"Jiexi"(ST41) and "kunlun" (BL60) for 20 min, once daily, continuously for 9 days. Then the join sewlling index was observed periodically, the protein expression of TLR2 and MYD88 was determined by immunohistochemistry. RESULTS: Compared to the normal group, the join sewlling of the SMD group in test join increased significantly (P<0. 05) and the protein expression of TLR2 and MYD88 in synovial tissue has not statistically significant (P>0.05), the oin sewlling and protein expression of TLR2 and MYD88 in synovial tissue of model group increased significantly P<0. 05); The medication and EA group compared to the model group, the protein expression of TLR2 and MYD88 in synovial tissue decreased significantly (P <0. 05), the join sewlling in test join decreased significantly P<1. 05); There were not statistically significant between the EA group and the medication group (P>0.05). CONCLUSION: EA can alleviate the symptoms of AGA, which may be related to regulation of the protein expression Y TRI and MYD88 in the TLR/MYD88 signaling pathway.

Tyrosine hydroxylase expression in CD4(+) T cells is associated with joint inflammatory alleviation in collagen type II-induced arthritis.

We have recently reported that CD4(+) T cells synthesize and secrete catecholamines that facilitate a shift of T helper 1 (Th1)/Th2 balance toward Th2 polarization. In this study, we used an animal model of human rheumatoid arthritis, collagen type II-induced arthritis (CIA), to explore relationship between catecholamine production in CD4(+) T cells and Th1-/Th2-mediated joint inflammation. Histopathological observation of ankle joints of CIA mice displayed an evident inflammatory change on day 35 and a major damage to bones on day 55 post-immunization. Expression of Th1-specific transcription factor, T-bet, and cytokines, IL-2 and IFN-γ, and Th2-specific transcription factor, GATA-3, and cytokines, IL-4 and IL-10, was all upregulated on days 35 and 55 post-immunization, but the elevated Th1 response tended to decrease and the enhanced Th2 response tended to increase with the CIA progression. Expression of tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of catecholamines, dramatically increased in ankle joints of CIA mice, although this increase was reduced on day 55 relative to that on day 35 post-immunization. In synovial tissue of CIA ankle joints but not normal joints, CD4-, T-bet-, GATA-3-, and TH-immunoreactive cells were found. Importantly, co-expressed cells with CD4 and TH, T-bet and TH, and GATA-3 and TH were observed in synovial tissue of CIA ankle joints. These results suggest that an increase in catecholamine production occurs in inflamed joints of CIA. The catecholamines are, at least in part, from Th1 and Th2 cells, and they may be related to joint inflammatory alleviation in CIA progression.

Brief report: amelioration of collagen-induced arthritis in mice by lentivirus-mediated silencing of microRNA-223.

OBJECTIVE: MicroRNA (miRNA) plays a role in autoimmune diseases. MiRNA-223 (miR-223) is up-regulated in patients with rheumatoid arthritis (RA) and is involved in osteoclastogenesis, which contributes to erosive disease. The aim of this study was to test the feasibility of using lentiviral vectors expressing the miR-223 target sequence (miR-223T) to suppress miR-223 activity as a therapeutic strategy in a mouse model of collagen-induced arthritis (CIA). METHODS: Levels of miR-223 in the synovial tissue of patients with RA or osteoarthritis (OA), as well as in the ankle joints of mice with CIA, were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Lentiviral vectors expressing miR-223T (LVmiR-223T) or luciferase short hairpin RNA (LVshLuc) as a control vector were injected intraperitoneally into mice with CIA. Treatment responses and disease-related bone mineral density were monitored. Levels of nuclear factor 1A (NF-1A), a direct target of miR-223, and macrophage colony-stimulating factor receptor (M-CSFR), which is critical for osteoclastogenesis, were measured by immunohistochemistry and quantitative RT-PCR. Osteoclasts were assessed by tartrate-resistant acid phosphatase staining. RESULTS: MiR-223 expression was significantly higher in the synovium of RA patients and in the ankle joints of mice with CIA as compared to OA patients and normal mice. LVmiR-223T treatment reduced the arthritis score, histologic score, miR-223 expression, osteoclastogenesis, and bone erosion in mice with CIA. Down-regulation of miR-223 with concomitant increases in NF-1A levels and decreases in M-CSFR levels was detected in the synovium of LVmiR-223T-treated mice. CONCLUSION: This study is the first to demonstrate that lentivirus-mediated silencing of miR-223 can reduce disease severity of experimental arthritis. Furthermore, our results indicate that inhibition of miR-223 activity should be further explored as a therapeutic strategy in RA.

The analgesic and anti-rheumatic effects of Thladiantha dubia fruit crude polysaccharide fraction in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Thladiantha dubia has been used in Chinese manchu nationality folk medicine for treatment of various pains, such as rheumatic pain, lumbocrural pain, and dysmenorrhea. The aim of the present study was to evaluate the anti-rheumatic effect of Thladiantha dubia fruit crude polysaccharide (TF-P) fraction in rats. MATERIALS AND METHODS: TF-P was evaluated in mice for analgesic activity using acetic acid-induced abdominal contractions test and for anti-inflammatory activity using xylene-induced ear oedema model. Moreover, rheumatoid arthritis (RA) was induced by injection of CFA into the subplantar surface of the hind paw of the male Wistar rats. Joint swelling was measured. In order to evaluate the effect of TF-P on disease progression, proinflammatory mediators (TNF-α and IL-2), and antioxidant indicators (SOD, MDA, and NO) were determined in rats induced by CFA. Pathologic changes of RA in rats were also observed under light microscope. RESULTS AND CONCLUSIONS: In the present study, TF-P at the dose of 200mg/kg (according to the clinical traditional dosage) significantly reduced writhings and stretchings induced by the acetic acid in mice. TF-P significantly inhibited xylene-induced ear oedema in mice, compared with control group. TF-P significantly inhibited inoculated and non-inoculated joint swellings in rats induced by CFA. TF-P had no effect of body weight in rats. The histopathological analysis suggested that TF-P obviously alleviated the degree of RA rats. TF-P treated rats preserved a nearly normal histological architecture of the joint. Results of the present study confirm the use of Thladiantha dubia traditionally for the treatment of painful and inflammatory conditions. Those results suggest TF-P has protective and therapeutic effects on RA rats induced by CFA.

Amelioration of rat collagen-induced arthritis through CD4+ T cells apoptosis and synovial interleukin-17 reduction by indoleamine 2,3-dioxygenase gene therapy.

Indoleamine 2,3-dioxygenase (IDO) has been known as an emerging therapeutic target in autoimmunity-related arthritis. The treatment responses of adenoviral vectors encoding IDO (AdIDO) gene therapy in rat collagen-induced arthritis (CIA) were examined in this study. The therapeutic effects on ankle circumference, articular index, and radiographic and histological scores were evaluated in AdIDO-injected ankle joints. We further determined CD4+ T-cell numbers and their apoptotic status, CD68(+) macrophage numbers, kynurenine (a downstream tryptophan metabolite) concentrations, interleukin-17 (IL-17) levels, and retinoic acid-related orphan receptor γt (RORγt) expression in synovial tissues of CIA rats receiving AdIDO treatment. Reduction of ankle circumference, articular index, and radiographic and histological scores were noted in AdIDO-treated ankles, as compared with those receiving injection of control vectors. Furthermore, IDO gene transfer led to decreased infiltrating CD4+ T cells with enhanced apoptosis, reduced CD68+ macrophage numbers, increased kynurenine levels, lower IL-17 concentrations, and decreased RORγt expression within the ankle joints. In addition, such a therapy diminished type II collagen-specific IL-17 production and RORγt expression in CD4+ T cells from draining lymph nodes of CIA rats. Our results demonstrate for the first time that intra-articular delivery of IDO gene ameliorated ankle arthritis of CIA rats by induction of CD4+ T-cell apoptosis and reduction of synovial IL-17 production through the supplement of kynurenine. Taken together, these findings implicate the novel strategy of using IDO gene as a therapeutic approach in treating patients with rheumatoid arthritis.

Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis.

To examine whether grape seed proanthocyanidin extract (GSPE) which is known to act as an antioxidant has therapeutic effect on collagen-induced arthritis (CIA) in mice, an animal model of rheumatoid arthritis. Mice were treated with an intraperitoneal injection of GSPE (10, 50, or 100 mg/kg) or saline. Clinical, histological, and biochemical parameters were assessed. The effects of GSPE on osteoclastogenesis were determined by tartrate-resistant acid phosphatase (TRAP) staining of the inflamed joints and bone-marrow cells cultured with the receptor activator of nuclear factor B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Intracellular levels of hydrogen peroxide were determined using carboxy-dichlorodihydrofluorescein diacetate. GSPE treatment significantly attenuated the severity of CIA in a dose-dependent manner and reduced the histology scores for synovial inflammation, cartilage erosion, bone erosion, and the number of TRAP+ osteoclasts. GSPE treatment significantly reduced the numbers of tumor necrosis factor alpha (TNF-alpha)- or interleukin 17 (IL-17)-producing cells in the synovial tissue and the spontaneous production of TNF-alpha and IL-17 by splenocytes compared with those in the control mice. The serum levels of type-II-collagen-specific IgG2a and plasma levels of 8-isoprostane in the GSPE-treated mice were significantly lower than those in the control mice. GSPE dose-dependently suppressed osteoclastogenesis in vitro. GSPE significantly reduced hydrogen peroxide production by anti-CD3-monoclonal-antibody-stimulated CD4+ splenocytes. These results indicate that intraperitoneal injection of GSPE attenuated CIA in mice. GSPE may be useful in the treatment of rheumatoid arthritis.

[Inhibitiory action of asiaiticoside on collagen-induced arthritis in mice].

The study is to investigate the effect of asiaticoside on collagen-induced arthritis (CIA). The model of CIA mice was prepared and the change of secondary paw swelling and the arthritis scores were observed. In vitro proliferation of spleen cells was examined using MTT assay. The cell-free protein extracts from the arthritic joints and nonarthritic joints were used for the analysis of protein expression of cyclooxygenase-2 (COX-2). And the level of PGE2 in joints was assayed using PGE2 express EIA kit. The tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels in the serum were measured by ELISA. Histopathological examination was performed by hematoxylin-eosin (HE) stain method. Asiaticoside (10, 20 and 40 mg x kg(-1) x d(-1), 22 d, ig) significantly reduced paw swelling, and decreased the arthritis scores. There was a significant reduction in proliferation of spleen cells of CIA mice treated with asiaticoside as compared with that of untreated CIA mice. COX-2, PGE2, TNF-alpha and IL-6 production in CIA mice were inhibited by asiaticoside. Meanwhile, the pathological examination showed that articular cartilage degeneration with synovial hyperplasia and inflammatory cells infiltration in CIA mice was suppressed by asiaticoside. Its active mechanism may be related to inhibiting proliferation of lymphocyte and reduction of expression of COX-2 and inflammatory cytokines.

Effects of electroacupuncture with different frequencies on the glycoconjugate alterations in articular cartilage in the ankle joints of complete Freund's adjuvant-injected rats.

The aim of this study was to investigate the effects of electroacupuncture (EA) on the glycoconjugate (GC) changes in articular cartilage in the ankle of an arthritic model. Arthritis was induced by an intraplantar injection of complete Freund's adjuvant (CFA) into the hindpaw of male Sprague-Dawley rats. Bilateral EA stimulation at 2 Hz, 15 Hz and 120 Hz was applied at those acupoints corresponding to Zusanli and Sanyinjiao in man, using needles for 3-day intervals for 30 days. To determine the presence of arthritis, paw edema was measured by a water displacement plethysmometer. Edema of the hindpaw induced by CFA-injection was strongly inhibited by EA stimulation throughout the experimental period. At 30 days after CFA-injection, GC changes of articular cartilage of the ankle joint were observed using conventional and lectin histochemistry. The CFA-injected rat revealed general reduction of staining abilities and lectin affinities for GC in comparison with normal rats. Significant reductions of neutral and acidic GC were observed in interterritorial matrix and chondrocyte capsules, respectively. All lectin affinities examined except DBA were also decreased in CFA-injected rats compared to normal ones. However, EA-treated rats, showed similar staining patterns and lectin affinities for GC as to normal ones, especially neutral GC in interterritorial matrix and sWGA and RCA-1 affinities in chondrocytes. It is concluded that EA in all frequencies examined, especially 2 Hz, can attenuate inflammatory edema in CFA-injected rats through alleviation of alterations of GC components in articular cartilage.

Use of positron emission tomography with methyl-11C-choline and 2-18F-fluoro-2-deoxy-D-glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium.

OBJECTIVE: To compare positron emission tomography (PET) and magnetic resonance imaging (MRI) in the evaluation of inflammatory proliferation of synovium. METHODS: Ten patients (mean +/- SD age 36 +/- 13 years) with inflammatory joint disease and with clinical signs of inflammation of the joint were studied. A new tracer for cellular proliferation, methyl-(11)C-choline ((11)C-choline), and a widely used tracer for the detection of inflammation and cancer, 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), were applied for PET imaging, and the results were compared with the findings from gadolinium diethylenetriaminepentaacetic acid-enhanced MR images. The uptake of (11)C-choline and (18)F-FDG in the inflamed synovium was measured and expressed as the standardized uptake value (SUV) and the kinetic influx constant (K(i)) obtained from graphic analysis, and these values were compared with quantitative values on MRI. Synovial volumes were measured on the coronal contrast-enhanced T1-weighted MR images using the standard software of the MR imager. RESULTS: All patients showed high accumulation of both (11)C-choline and (18)F-FDG at the site of arthritic changes, where quantification of the tracer uptake was performed. The SUV of (11)C-choline was 1.5 +/- 0.9 gm/ml (mean +/- SD; n = 10) and the SUV of (18)F-FDG was 1.9 +/- 0.9 gm/ml (n = 10) (P = 0.017). The K(i) of (11)C-choline (mean +/- SD 0.048 +/- 0.042 minute(-1)) was 8-fold higher than the K(i) of (18)F-FDG (0.006 +/- 0.003 minute(-1)) (P = 0.009). Both the uptake of (11)C-choline and the uptake of (18)F-FDG correlated highly with the volume of synovium; the highest correlation was observed with the K(i) of (11)C-choline (r = 0.954, P < 0.0001). CONCLUSION: In the use of PET scans,(11)C-choline can be regarded as a promising tracer for quantitative imaging of proliferative arthritis changes. Nevertheless, subsequent prospective studies with larger numbers of patients are necessary to further characterize the relationship between the findings on PET imaging and the clinical and functional measures of inflammation.