Effects of cold-damp and hot-damp environment on VEGF and IL-1 expression in joint cartilage cells in adjuvant arthritis in rats.

OBJECTIVE: To study the effects of environmental factors on the degree of injury and expression of vascular endothelial growth factor (VEGF) and interleukin-1 (IL-1) in cartilage cells of the joint in a rat model of adjuvant arthritis (AA). METHODS: SD rats aged 10 months were randomly divided into 4 groups that varied by temperature and humidity housing conditions and induction of AA: a control group, a model group, a cold-damp group, and a hot-damp group. All groups except the control group were induced with AA. After 4 w, VEGF and IL-1 expression in cartilage cells of ankle joints of hind limbs were observed. RESULTS: Mean area, optical density, and numbers of VEGF- and IL-1-positive cells in the model group, the cold-damp group, and the hot-damp group were significantly higher than that of the control group (all P < 0.05). Optical density and positive cell numbers in the cold-damp group and the hot-damp group were significantly higher than that of the model group (all P < 0.05). Optical density and positive cell numbers in the hot-damp group were significantly higher than that of the cold-damp group. Bone in the hot-damp and cold-damp groups was severely injured. CONCLUSION: Environmental factors such as high humidity combined with either high or low temperature increase the severity of damage and expression of VEGF and IL-1 in cartilage cells of joints in rats induced with AA.

Assessment of clinical effect of therapy combining disease with syndrome on rheumatoid arthritis.

OBJECTIVE: To observe the effectiveness and safety of a therapy combining disease with syndrome on rheumatoid arthritis. METHODS: Eighty patients with rheumatoid arthritis belonging to syndrome of damp-heat obstruction were randomly divided into a treatment group and a control group according to stratified blocked randomization method. Forty cases in the control group orally took Loxoprofen Sodium Tablet and Leifumite Tablet and the other 40 cases in the treatment group orally took a Chinese medicine for 12 weeks as a course of treatment. ACR therapeutic effect was used as the standard for evaluating the total therapeutic effect. RESULTS: After 12 weeks of treatment, there was a statistical difference (P < 0.01) in the improvement of VAS score, morning stiffness time, number of swelling joints, index of swelling joints, number of joints with tenderness, index of joints with tenderness, average grip strength of both hands, DSA28 score, HAQ, patient's assessment, physician's assessment, ESR, CRP and RF in both groups. The improvement of morning stiffness time, number of swelling joints, index of swelling joints, grip strength, HAQ and patient's assessment in the treatment group was much better than that in the control groups with statistical difference (P < 0.05). ACR20, ACR50 and ACR70 was 27.5% (11/40), 37.5% (15/40) and 22.5% (9/40) respectively in the treatment group and 40% (16/40), 27.5% (11/42) and 10.0% (4/40) respectively in the control group with statistical difference (P < 0.05) in the superiority of the treatment group over the control group. The incidence of adverse reaction in the control group was higher than that in the treatment group (P < 0.05). CONCLUSION: Definite therapeutic effect and high safety can be achieved in using the therapy combining disease with syndrome to treat rheumatoid arthritis belonging to syndrome of damp-heat obstruction.

Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats.

OBJECTIVE: To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats. METHODS: Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1ß, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) ß were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. RESULTS: MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1ß and TGF-ß levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05). CONCLUSIONS: NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.

[Role of hypothalamic orexin in drug addiction].

Hypothalamus is considered as an important brain region regulating natural rewards. Orexin, a neuropeptide specifically expressed in hypothalamus, arrests investigators much attention for its function in drug rewards. Orexin neurons in different brain regions exert different roles in regulating reward and motivation in the addiction research: orexin neurons in perifornical area (PFA) and dorsomedial hypothalamus (DMH) are mainly concerned with activating stress system, while orexin neurons in lateral hypothalamus participate in mediating reward-related behavior through activating brain circuitry involved in reward learning. The orexin system may therefore represent a target for preventing relapse to drug seeking during protracted abstinence. And targeting orexin receptors may provide new therapeutic strategies to treat addiction.

Corticosterone combined with intramedial prefrontal cortex infusion of SCH 23390 impairs the strong fear response in high-fear-reactivity rats.

Accumulating evidence suggests that stress-dose corticosteroids impair fear memory in animals and humans. Corticosteroid treatment after critical illness is seen as a potential psychotropic medication by which to prevent posttraumatic stress disorder. However, individual difference in the responsiveness to stress (i.e., stress reactivity) is a factor that modulates the efficacy of corticosteroids. To understand the contribution of fear reactivity to the effect of post-stress corticosterone, male Sprague-Dawley rats were subjected to classical tone-cued fear conditioning and separated into high and low reactivity (HR and LR, respectively) responder groups based on their levels of freezing during conditioning. The HR rats showed significantly higher fear responses than the LR rats during conditioning as assessed by freezing behavior. At two intervals, 30 min and 48 hr later, the HR rats still displayed more pronounced conditioned responses to cued stimuli compared with the LR rats. Moreover, in contrast to the LR rats, the enhanced fear response in the HR rats was difficult to attenuate by post-training high-dose corticosterone. These results suggest that fear reactivity results in stronger fear memory, and that it is difficult to disrupt this strong fear memory in the HR phenotype using monotherapy. However, the strong fear memory in the HR rats was impaired by concurrent intramedial prefrontal cortex infusion of a high dose of the dopamine D1 receptor antagonist SCH 23390 and systemic administration of corticosterone. SCH 23390 and corticosterone alone did not decrease freezing levels in the HR rats. The fear impairment induced by SCH 23390 combined with corticosterone was not attributable to the effect of these drugs on locomotor activity. This effect was not found with administration of the D2 antagonist eticlopride combined with corticosterone. Our findings demonstrate that the conditioned fear memory in individuals with high stress reactivity is difficult to disrupt using monotherapy, but that combined pharmacotherapy may be useful for treating intervention-resistant fear.

Calcification of bilateral ureters: a novel association with systemic lupus erythematosus.

A 16-year-old female patient with systemic lupus erythematosus (SLE) presented with abdominal pain and oliguria, after one month of hospital treatment with methylprednisolone and cyclophosphamide. Computed tomography of the abdomen revealed the calcification of bilateral superior segmental ureteral wall. Computed tomography urography revealed stenosis of bilateral ureters. This calcification may be associated with lupus-induced inflammatory reaction of ureteral endomembrane. By receiving the ureteral catheters, her abdominal pain and oliguria had been completely resolved. After discharge, she underwent the surgery of cutaneous ureterostomy in the local hospital. During two years follow-up, her condition is stable without any symptom of the urinary system.