Effect of Cornus officinalis glycoside on adjuvant-induced arthritis in rats

The aim of this study was to explore the effect of Cornus officinalis glucosides (COG) on adjuvant-induced arthritis in rats and its mechanism. Seventy-two rats were divided into six groups of normal, model, Dexasone (0.125 mg/kg), high-dose COG (240 mg/kg), mid-dose COG (120 mg/kg), and low-dose COG (60 mg/kg). Rat arthritis was induced by injection of Freund's complete adjuvant in the hind paws. All treatment started from the day the arthritis was induced. The edema degree of the adjuvant injection location was determined on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 20, 23 and the opposite side was observed on days 11, 13, 15, 17, 20, 23 after the injection of adjuvant. All rats were sacrificed on day 24 after the injection of adjuvant for microscopic examination of the ankle, and for the study of the immunological molecular mechanism. The results showed that the COG significantly suppressed both the primary and secondary edema, improved pathological injuries of adjuvant arthritis (AA) rat ankles, significantly suppressed the proliferation of T lymphocytes and DTH reaction. It significantly suppressed IL-1, IL-6 and TNF-αproduction from peritoneal macrophages and PGE2 in plasma. In conclusion, the Cornus officinalis glucosides (COG) is able to prevent and cure the rat adjuvant-induced arthritis, and can suppress the production of pro-inflammatory cytokine IL-1, IL-6, TNF-αand PGE2.     

Effect of β-carotene on the development of adjuvant-induced arthritis and production of interleukin-1 in rats

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 12, pp. 611–613, December 1993     

Inhibition of plasma kallikrein–kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein–kinin system (KKS) was involved in inflammatory processes in kidney disease.

Aim: This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA.

Results: The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527.

Conclusions: These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.     

Therapeutic effect of acetazolamide,an aquaporin 1 inhibitor,on adjuvant-induced arthritis in rats by inhibiting NF-κB signal pathway

Objectives: Previous studies have shown that aquaporin 1 (AQP1) is up-regulated in synovium and cartilage of rheumatoid arthritis (RA) patients and that AQP1 may be involved in joint swelling and synovial inflammation. This study was aimed to investigate the potential therapeutic effect of acetazolamide (AZ, an AQP1 inhibitor) on rat adjuvant-induced arthritis (AIA) and explore its related mechanisms.

Materials and methods: Rat AIA was induced by complete Freund’s adjuvant. The effect of AZ on rat AIA was evaluated by secondary hind paw swelling, arthritis index, TNF-α and IL-1β serum levels and histological examination of ankle joint. Proteoglycans expression and mRNA levels of type-II collagen (COII) and aggrecan in cartilage were measured by alcian blue staining and real-time PCR, respectively. The protein levels of AQP1, IκBα, phospho-IκBα (p-IκBα), NF-κB p65 and phospho-NF-κB p65 (p-NF-κB p65) in synovial tissues were detected by western blot.

Results: AZ treatment could inhibit secondary hind paw swelling and arthritis index, reduce serum levels of TNF-α and IL-1β, and ameliorate pathological changes of ankle joint in AIA rats. AZ increased proteoglycans production and mRNA levels of COII and aggrecan in cartilage tissues. Moreover, AZ decreased AQP1 protein level and suppressed the activation of NF-κB pathway in synovium, indicated by inhibiting the degradation and phosphorylation of IκBα and reducing p-NF-κB p65 protein level.

Conclusions: AZ as an AQP1 inhibitor has a powerful therapeutic effect on rat AIA via inhibiting NF-κB activation, suggesting AQP1 inhibition might be of potential clinical interest in RA treatment.     

Hecogenin exhibits anti-arthritic activity in rats through suppression of pro-inflammatory cytokines in Complete Freund’s adjuvant-induced arthritis

Hecogenin is a steroidal sapogenin isolated from the leaves of Agave genus species that plays an important role in the treatment of a variety of inflammatory diseases. The aim of the present study was to evaluate the anti-arthritic activity of hecogenin in Complete Freund’s adjuvant-induced arthritis in rats. The hecogenin (40?µl of 50?µg/kg, orally) and hecogenin?+?fluticasone (40?µl of 25?µg/kg, each, orally) was tested against Complete Freund’s adjuvant-induced arthritis in rats by evaluating various parameters such as paw volume, arthritic score, joint diameter, spleen weight, thymus weight, haematological and biochemical parameters and pro-inflammatory cytokines. Histopathological and radiological analyzes of ankle joints were also carried out. Treatment of rats with hecogenin and its combination elicited significant reduction in paw edema, arthritic score and joint diameter. Hecogenin and its combination also inhibited joint destruction in histopathological and radiological analyzes of ankle joint. Hecogenin and its combination significantly increased the levels of red blood cells and hemoglobin but decreased the white blood cell count. The anti-arthritic activity was also confirmed with the change in biochemical parameters and myeloperoxidase assay. In the present investigation, hecogenin and its combination prevent destruction of cartilage and protect synovial membrane with improving health status through haematonic properties and down regulation of various cytokines. Hence, hecogenin may be a potential therapeutic candidate for the treatment of rheumatoid arthritis.     

The effect of erythropoietin on endometrial edema during ischemia–reperfusion injury in rats

This experimental study examined the effect of erythropoietin (Epo) in a rat model and particularly in an ischemia–reperfusion protocol. The potential beneficial effect of Epo was studied pathologically using endometrial edema (EE) lesions. Endometrial edema was evaluated 60 min after reperfusion (Groups A and C) and 120 min after reperfusion (Groups B and D) in rats. Epo was administered only in Groups C and D. Epo administration non-significantly increased the EE scores by 0.05 (p = 0.9315). Reperfusion non-significantly increased the EE scores by 0.15 (p = 0.6508). Epo administration and reperfusion together non-significantly increased the EE scores by 0.027 (p = 0.8898). Epo administration, reperfusion, and their interaction reduced the EE scores from significant to non-significant levels. Perhaps a study time longer than 2 h or a higher Epo dose could result in complete resolution of the endometrial edema formed as a result of the ischemia–reperfusion injury in this rat model.     

The effect of TNFα on food intake and central insulin sensitivity in rats

Circulating and tissue levels of the proinflammatory cytokine tumor necrosis factor α (TNFα) are elevated in obesity. TNFα interferes with insulin signaling in many tissues and also plays a causal role in the anorexia that accompanies severe challenges to the immune system. The interactions between TNFα and insulin in the control of eating are less well known. The present study evaluated the role of TNFα in the central nervous system control of food intake by insulin in adult male Long Evans rats. We first determined the ability of several doses of TNFα injected into the 3rd cerebral ventricle (i3vt) to reduce food intake in male rats. Subsequently, we assessed the ability of a subthreshold dose of TNFα to modulate the effect of i3vt insulin on food intake in male rats fed a low-fat chow or a high-fat (HF) diet. TNFα administered i3vt dose-dependently reduced food intake in rats fed a standard low-fat chow diet. Moreover, a low, sub-threshold dose of TNFα diminished the reduction in food intake by insulin in rats maintained on a chow diet, but enhanced insulin action in rats maintained on a HF diet. These data suggest that the interaction of TNFα with central insulin varies with nutritional and/or dietary conditions.     

The pharmacokinetics of ¹²⁴I-rituximab in patients with rheumatoid arthritis

Rheumatoid arthritis is a destructive inflammatory joint disorder. Pre- and mature B-cells, characterized by CD20 antigen expression, play an important role in the inflammatory process. Rituximab, a chimeric monoclonal antibody against the CD20 antigen, has been approved since 2006 for the treatment of patients with rheumatoid arthritis. However, not all patients benefit from this treatment. Persistent activity of the disease has been reported despite treatment with rituximab. Imaging of radiolabeled rituximab can be used to monitor the biodistribution of rituximab, and potentially to predict the efficacy of the treatment. In this study, rituximab was radiolabeled with 12?Iodine for positron emission tomography (PET) imaging. The aim of this study was to investigate the pharmacokinetics and biodistribution of 12?I-rituximab in patients with rheumatoid arthritis, to establish the optimal procedure for PET imaging. Eligible patients received 50 MBq 12?I-rituximab, corresponding to approximately 1.5 mg rituximab. Wholebody PET/CT imaging was performed at 10 min, 24 hrs, and 48 hrs post injection. The total body activity, radioactivity in whole blood, and rituximab serum levels were determined. 12?I-rituximab has favorable pharmacokinetics for targeting of (pathological) B cells and imaging over several days, but only after pre-treatment with unlabeled rituximab. In addition, protection of the thyroid is recommended to prevent uptake of released 12?I.     

The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis

Inflammatory arthritides are chronic diseases characterised by an increase in cardiovascular risk, largely attributable to the synergy between high-grade systemic inflammation and an elevated prevalence of traditional cardiovascular risk factors. Amongst the latter, insulin resistance and type 2 diabetes (T2D) play a key position. Previous studies demonstrated a potential insulin-sensitizing effect of anti-TNF biologic medications. For converse, less is known about the role of newer biologics or small molecules. For this reason, we performed a systematic review of the literature in order to identify the available data on the effect on insulin resistance of non-TNF targeting biologics and small molecules approved for the treatment of inflammatory arthritides. The search strategy initially retrieved 486 records of which only 10 articles were selected for inclusion in the final review. According to the available evidence, some of the newest molecules, in particular tocilizumab and abatacept, may have a role in improving insulin sensitivity; for converse, anakinra-mediated effect on glucose metabolism may exploit different facets of T2D pathophysiology, such as the preservation of beta-cell function. However, the data available on this issue are largely inconsistent and future, adequately designed studies are still needed to clarify the differential impact of novel therapeutics on individual pathophysiological features of T2D and other emerging cardiovascular risk factors.     

Analgesic effect of intrathecally γ-aminobutyric acid transporter-1 inhibitor NO-711 administrating on neuropathic pain in rats

Neuregulin-1 (NRG1) participates in numerous neurodevelopmental processes and plasticity of the brain. Despite this, little is known about its role in Alzheimer's disease (AD). Amyloid β (Aβ) peptide is generally believed to play a critical role in the pathogenesis of AD. The present study examined the effect of synthetic Aβ_1-42 peptides on long-term potentiation (LTP) in the CA1 region of mice hippocampal slices, a cellular model of learning and memory. We found that application of a test dose of Aβ_1-42 (200 nM) significantly inhibited the development of LTP without affecting basal synaptic transmission. Pretreatment with NRG1 effectively prevented Aβ_1-42-induced impairment of LTP, an effect that was dose-dependent. This LTP-restoring action of NRG1 was almost completely abolished by blocking ErbB4, a key NRG1 receptor, suggesting that NRG1 acts through ErbB4 to exert its protective action on LTP. The present study thus provides the first demonstration that NRG1/ErbB4 protects against Aβ-induced hippocampal LTP impairment, suggesting that NRG1 may be a promising candidate for the treatment of early-stage AD.     

Analgesic effect of intrathecally γ-aminobutyric acid transporter-1 inhibitor NO-711 administrating on neuropathic pain in rats

To investigate the analgesic effect of intrathecally administered γ-aminobutyric acid (GABA) transporter-1 inhibitor NO-711 on the sciatic nerve chronic constriction injury (CCI) rats. 5 days after intrathecal catheter placement, neuropathic pain model was established by CCI of sciatic nerve on rats. Withdrawal thresholds for mechanical allodynia and latency for thermal hyperalgesia were measured in all animals. All rats operated upon for CCI displayed decreased withdrawal thresholds for mechanical allodynia and latency for thermal hyperalgesia, which has significant difference compared with sham groups. After intrathecal NO-711 administration, withdrawal thresholds and latency were significantly increased on CCI rats compared with control group after 1 day. The results show that GABA transporter-1 inhibitor could effectively develop analgesic effect in sciatic nerve CCI rats’ model.     

The effect of capsaicin on inducible nitric oxide synthase in puberty and adult rats’ ovaries

The purpose of this study is the in vivo analysis of the changes in iNOS expression in the ovaries of the capsaicin-treated rats in puberty and adult periods. Rats were divided into with two age groups i.e. puberty (42 days old) and adult (70 days old). Each age group was divided into three sub-groups as treated experimental or vehicle, and untreated control. Starting from 21 days up to 42 and 70 days, implementations were as follows: experimental group received a daily subcutaneous injection of capsaicin (1mg/kg body weight); vehicle group received the vehicle solution (10% Tween 80, 10% ethanol, 80% distilled water) in same volume as experimental group, and untreated control group was not subjected to any injections. In ovaries of all groups, iNOS expression was shown in granulosa cells, interstitial cells, theca follicle cells and corpus luteum luteal cells. An immune reaction was observed in pubertal and adult rat ovaries and iNOS was not inactivated with age. The reaction density was reduced in the experimental groups and showed long-term capsaicin implementation in low dosage negatively affects iNOS stimulation in ovaries.     

The effect of stereoisomers of cycloserine on the formation and transformation of free γ-aminobutyric acid in brain tissue

Summary A study was made of the effect produced by the stereoisomers of cycloserine on decarboxylization of glutamic acid and transamination of -aminobutyric acid with -ketoglutaric acid in the homogenates of the rat brain at pH 7.5. As revealed. D.L-cycloserine in a concentration of 10^–3 M depressed the first process by 40% and the second one by 45%. In the same conditions D-cycloserine depressed glutamic acid decarboxylation by 9%; it somewhat activated -aminobutyric acid transamination. A discussion is presented on the possible effect of cycloserine isomers on the content of free -aminobutyric acid in the brain (in vivo) following the administration of isoniazid in large doses.(Presented by Active Member AMN SSSR V. V. Zakusov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 10, pp. 67–69, October, 1962     

The effect of combined treatment with Impella? and landiolol in a swine model of acute myocardial infarction

Cardiogenic shock is associated with a high mortality rate in patients with acute myocardial infarction (AMI). We developed a new treatment approach named heart rest therapy (HRT) for complete revascularization in the early stage of AMI using an ultra-short-acting β-blocker (landiolol) and an Impella(?) left ventricular assist device and verified the effect of this therapy in a swine model. In 18 male pigs, AMI was induced by left anterior descending coronary artery occlusion at the level of the second diagonal branch for 120?min, followed by 240?min of reperfusion. The animals were divided into three groups: group A had no support, group B was supported with the Impella(?), and group C was treated with HRT from 90?min after ischemia to 240?min after reperfusion. Infarct ratio (percentage of the infarct area relative to the area at infarct risk) was significantly reduced in group C (group A 65.38?±?6.07, group B 39.66?±?11.16, group C 21.78?±?7.29), with a significant difference between groups A and B (P?相似文献   

The in vivo immunomodulatory effect of recombinant tumour necrosis factor-alpha in guinea pigs vaccinated with Mycobacterium bovis bacille Calmette-Guérin

A void in understanding primary biliary cirrhosis (PBC) is the absence of appropriate animal models. Our laboratory has studied a murine model of autoimmune cholangitis induced following immunization with 2-octynoic acid (2OA), an antigen identified following extensive quantitative structural activity relationship (QSAR) analysis, using human autoantibodies and three-dimensional analysis of the mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). Mice immunized with 2OA coupled to bovine serum albumin (BSA) develop anti-mitochondrial antibodies (AMAs) of the identical specificity as humans with PBC, and in addition develop inflammatory portal cell infiltrates in liver. However, the natural history of disease is less severe than in humans and does not include fibrosis. Data from human and autoimmune murine models suggest that environmental and/or infectious agents can exacerbate autoimmune reactions, and a model of PBC has been described in which polyinosinic-polycytidylic acid (poly I:C), a viral RNA mimetic and Toll-like receptor 3 (TLR-3) agonist induces low-titre AMAs and in mild portal infiltrates. We took advantage of our established model to determine whether immunization with 2OA-BSA coupled with poly I:C alters the disease process. Indeed, the addition of poly I:C produces a profound exacerbation of autoimmune cholangitis, including a significant increase in CD8(+) infiltrating T cells, as well as a marked increase of proinflammatory cytokines. In addition, mice have evidence of fibrosis. These findings lend support to the concept that besides breakdown of self-tolerance, there is a requirement of a second 'hit' during the breakdown process that leads to disease which more faithfully mimics human PBC.     

Effect of mode and schedule of administration on carcinogenic effect of N-methyl-N′-nitro-N-nitrosoguanidine in rats

Laboratory of Methods of Carcinogen Screening, Research Institute of Carcinogenesis, All-Union Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Trapeznikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 2, pp. 175–176, February, 1990.     

Effect of β-carotene on the plasma membrane lipids in chronically γ-irradiated rats

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 10, pp. 370–374, October, 1993     

Anti-integrin immunotherapy in rheumatoid arthritis: protective effect of anti-α4 antibody in adjuvant arthritis

Conclusions The current treatment of RA does not provide acceptable control of the inflammatory process due to either the onset of adverse effects or the lack of efficacy. RA is a T-cell mediated process, in which activated T cells must migrate through the blood vessels to reach the synovium. Anti-adhesion therapies designed to block the interaction of T cells with activated endothelial cells could be of great interest to control the disease. Flow cytometry analysis, immunohistochemical and functional studies cell adhesion in vitro have shown that the interaction between VLA-4 on T cells and VCAM-1 on endothelial cells could play a relevant role in the onset and perpetuation of RA. Here we show that the treatment with HP2/1, an mAb directed against 4 subunit of VLA-4, prevents adjuvant arthritis in Lewis rats. Data suggest that treatment with anti-4 antibodies could be of value in RA.     

The therapeutic effect of Lamivudine on HBV-DNA in PBMC and its inducement effect against cytokine

AThe purpose of this investigation was to study the therapeutic effect of Lamivudine on HBV DNA in peripheral blood mononuclear cells (PBMC) and serum, and the level of cytokines in serum of the patients with chronic hepatitis B. The patients were divided into two groups (A = 47, B = 34), and treated by Lamivudine, routine medicine, respectively. The levels of HBV-DNA in PBMC and serum and cytokines were all detected before and after treatment. After the treatment of Lamivndine for 36 weeks, the total conversion negative rates of HBV-DNA in PBMC and serum of the patients treated with Lamivudine were 55.32% (26/47) and 61.70% (29/47), respectively. The total negative conversion rates of HBV-DNA in PBMC and serum of the patients treated by routine medicine were 26.47% (9/34) and 32.35% (11/34), respectively. There was significant difference between Lamivudine group and routine medicine group ( P < 0.01). The negative conversion rates of HBeAg in serum of the patients were 46.81% (22/47) and 68.09% (32/47) at the end of 24 weeks and 36 weeks, and were higher than those of routine medicine group ( P < 0.05 and P < 0. 01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST in serum of the patients after being treated by Lamivudine, routine medicine were down-regulated to (30.1±9.6) U/ml, (32.3±10.7) U/ml, 0.9±0.1 and (48.4±10.7) U/ml, (44.7±11.0) U/ml, 1.1±0.2. After the analysis of variance, the high significant difference was obvious between the two groups (P < 0.01). It was due to the high levels of IL-6, IL-8 and TNF-αin chronic hepatitis B which could be down-regulated to (250. 5±33. 3) pg/ml, (153.4±22.2) pg/ml, (232.6±21.2) pg/ml by Lamivudine, which was more obvious than that of routine medicine (P < 0.01). Lamivudine has high therapeutic effect on the treatment of HBV DNA in PBMC and serum and has better therapeutic effect than that of routine therapy. Lamivudine may also have higher down-regulated inflammatory infiltration and secretion in local site caused by chemotactic cytokines and produce promotional effect on the recovery of liver function.