Important Chinese herbal remedies

This review presents seven examples of effective drugs derived from the ancient Chinese therapeutics. They are artemisinin (qinghaosu) and its derivatives for malaria, henbane drugs for microcirculatory and other disturbances, tetrahydropalmatine as a dopamine receptor antagonist, yuanhuacine and yuanhuadine for abortion, trichosanthin for abortion, moles, and choriocarcinoma, indirubin for leukemia, and Tripterygium plants for autoimmune and various other diseases.     

Metabolic syndrome and a course of osteoarthrosis

AIM: To compare osteoarthritis (OA) course in patients with metabolic syndrome (MS) and those free of MS. MATERIAL AND METHODS: The presence and completeness of MS according to 2005 criteria were studied in 1350 OA patients (mean age 52.65 +/- 11.31 years). Most of the patients were women (74%) and persons over 45 years of age (80%). RESULTS: MS was detected in 82.3% examinees with OA. MS was complete in 62.56%. MS-free OA was separately comorbid with arterial hypertension, obesity and diabetes mellitus. OA patients with MS had earlier clinical symptoms of OA, its longer duration, prevalence of generalized disease, more frequent development of knee joint synovitis and periarthritis, more intensive pain in the joints. OA patients with MS were more frequently affected with cardiovascular, gastrointestinal, renal and thyroid diseases, diabetes mellitus and complications of these diseases. This resulted in 2.5 times greater nosological load on the patients. 20% patients with OA were declared invalid, most of them (266, 90.17%) had MS. CONCLUSION: Relationship of OA symptoms with metabolic factors may point to participation of the latter in the development and progression of OA.     

Cross-reactivity of highly purified okadaic acid (OA), synthetic, spiroketal East sphere of OA and ciguatoxin.

This study presents data from the cross-reactivity analysis of purified ciguatoxin (CTX), okadaic acid (OA), and the East sphere or Fragment B-C of OA with their homologous antibodies, monoclonal antibodies to ciguatoxin (MAb-CTX) and okadaic acid (MAb-OA). The test system used was the stick enzyme immunoassay. MAb-CTX gave peak titers of 1.5ng, 10ng and 50ng respectively for CTX, East sphere and OA. Competitive inhibition analysis showed that 4ng purified CTX blocked completely MAb-CTX reaction with crude CTX, OA and East sphere of OA blocked at similar concentrations (approximately 50ng). The activity with MAb-OA in the homologous system with OA and East sphere was insignificant. This may be attributable to the improper concentrations used. The cross-reactivity between MAb-CTX with OA and its Fragment B-C may cause difficulty in the test system in its application to assess toxic fish due to ciguatoxin.     

Structure of osteoarthrosis diseases and the problem of concomitant diseases

AIM: To study pattern of osteoarthrosis (OA) morbidity, OA age and gender characteristics; to analyse affection of the para-articular tissues in gonarthrosis (GA), GA concomitant diseases in outpatient settings. MATERIAL AND METHODS: OA detection and concomitant diseases were studied in the outpatient department with computer informative system. ICD (10 revision) was used in classification. Results. OA morbidity was 6.2%. Male to female ratio was 1:2.6. Incidence rate of paraarticular tissue lesions in exacerbation of GA rose 2.5 times. In GA patients concomitant diseases were registered 1.7 times more frequently than in other outpatients, while obesity, hypertension, ischemic heart disease occurred 2 times more frequently. CONCLUSION: OA as disease of accumulation was confirmed in older patients. Old age conditioned more frequent concomitant diseases. This determines polymorbidity of clinical manifestations and requires an individual approach to the patients.     

SDF-1/CXCR4信号通路在骨性关节炎病理进程中的作用

背景：骨性关节炎的发病机制错综复杂,其预防与治疗是当今医学界的难题之一,与其相关的信号通路的研究已成为国内外研究的热点,其靶向治疗有望成为攻克骨性关节炎的关键。目的：总结SDF-1/CXCR4信号通路在诸多疾病尤其是在骨性关节炎发病中的作用,为骨性关节炎的靶向治疗提供科学依据。方法：应用计算机检索PubMed和CBM数据库中2008-09/2010-07发表的相关文献。以主题检索为主要检索方法,结合限定检索等方法,以＂SDF-1/CXCR4信号通路、骨性关节炎＂和＂SDF-1/CXC4 signaling pathway,osteoarthritis＂为中英文检索词,选择与骨性关节炎SDF-1/CXCR4信号通路有关的文献,排除内容陈旧、重复的文章。结果与结论：共检索到2147篇文章,按纳入和排除标准对文献进行筛选,保留32篇文章进行综述。目前,SDF-1/CXCR4信号通路在诸多疾病的发生发展过程中具有重要作用,已成为目前世界医学的研究热点之一。有研究表明,SDF-1/CXCR4信号通路可能在骨性关节炎的发病中具有重要作用,而对该信号通路的干预可能成为预防与治疗骨性关节炎的靶点,有望成为今后骨性关节炎防治方面研究的热点。     

膝关节病变的超声检查

通过对24例正常人、18例骨性关节炎（OA）及14例类风湿性关节炎（RA）患者双侧膝关节的超声探查发现：（1）OA及RA组髌上囊积液的比例分别为41．7％及64．3％；（2）RA组髌上囊的平均滑膜厚度明显大于正常组及OA组；（3）两个病变组膝关节股骨内髁处软骨厚度较正常组相比明显变薄，并有不同程度的超声异常表现；（4）OA组膝关节股骨内髁处软骨及软骨下骨质破坏的比例显著高于外髁，而RA组则无此现象。结果提示二维超声检查在膝关节病变的诊断及鉴别诊断方面具有良好的临床应用价值。     

Role of nitric oxide in Parkinson's disease

As a signal molecule, nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of vascular, respiratory, immune, muscular, and nervous systems. NO and its derivatives are also involved in the pathogenic processes in various types of diseases including, but not limited to, neurodegenerative disorders. Although the molecular mechanisms of how NO contributes to diseases are not completely understood, studies have shown that NO may cause neuronal injury and death by mediation of excitotoxicity, damage of DNA, and/or modification of proteins. Understanding the pathogenic mechanisms of NO and its role in Parkinson's disease (PD) and other neurodegenerative diseases may help to develop novel neuroprotective therapies for these diseases.     

Alteration of tryptophan metabolism in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis

Tryptophan, its metabolites and related enzyme activity in synovial fluid, blood and urine in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were measured. The levels of tryptophan, kynurenine and anthranilic acid in the synovial fluid higher in RA were than in OA, whereas the xanthurenic acid level was equal in RA and OA. Indoleamine 2, 3-dioxygenase activity in the synovial membrane was higher in RA than in OA. 5-Hydroxytryptamine (5-HT) levels in the synovial fluid and the blood and the 5-hydroxyindole acetic acid (5-HIAA) level in the synovial fluid were essentially the same for both diseases. However, the 5-HIAA level in the serum of RA patients was higher than in those with OA, and the 5-HIAA level in the urine of RA patients was lower than in those with OA. In addition, monoamine oxidase-A and B activity in the synovial fluid of RA patients was decreased than in those with OA. These findings suggest that metabolism of tryptophan is altered in patients with RA.     

Long-term effects of structum administration (according to data from multicenter trial)

AIM: To evaluate duration of a clinical response to the drug structum in patients with osteoarthrosis (OA) of the knee and hip joints as well as structum effects on OA course and that of concomitant diseases. MATERIAL AND METHODS: The duration of a clinical response to structum after the end of the treatment and its effect on OA and concominant diseases course were studied for 12 months in 9 centers participating in the study of the drug efficacy and tolerance in patients with gon- and coxarthrosis in an open multicenter randomized controlled 6-month trial. Out of 555 patients with OA of the knee and hip joints enrolled in the first study, the examination covered 373 patients: 159 patients of the test group treated for 6 months with structum and 214 controls. By basic clinical parameters the groups were similar. Clinical examination was made after structum treatment and 12 months later and included assessment of the number of exacerbations, hospitalizations, outpatient consultations, days of temporary disability for OA, pain in the joints while walking and at rest by the visual scale, Leken's functional index, x-ray pictures of the joints, administration of nonsteroidal anti-inflammatory drugs (NSAID), exacerbations of concomitant diseases (gastrointestinal diseases, arterial hypertension, ischemic heart disease). RESULTS: An overall functional Leken's index in patients with gon- and coxarthrosis given structum 12 months after the treatment did not reach the initial values as well as pain and daily need in NSAID. Structum effect in patients with knee joint OA persisted for 4.6 months, in hip joint OA--4.1 months; in patients with stage I-II the effect lasted longer than in stage III (5.2 and 4.6 months vs 4.17 and 3.24 months, respectively. Even short-term therapy with structum reduced the number of further exacerbations, hospitalizations and visits to their doctor. 12 months after structum therapy the effect persisted in 40% patients. Frequency of exacerbations of the concomitant diseases was less than in patients on continuous NSAID. CONCLUSION: Structum is a highly effective drug against OA as it acts long, reduces frequency of exacerbations, hospitalizations, visits to the doctor, duration of disability, NSAID requirement and improves the course of some concomitant diseases.     

Is osteoarthritis an infection-associated disease and a target for chemotherapy?

The treatment of osteoarthritis (OA) continues to be a challenge, and current treatment modalities are disappointing. New approaches in therapy may be developed as a result of evidence of the involvement of inflammatory cytokines in the progression of OA. Cotrimoxazole (sulfamethoxazole/trimethoprim) was noted to have anti-inflammatory properties and has been used in the therapy of several autoimmune diseases. Analyzing our own and world experience, we propose that OA and degenerative joint and spine disease might be infection-associated diseases and a target for sulfamethoxazole/trimethoprim therapy.     

Co-Stimulatory Effects of Misoprostol and Diclofenac on Glycosaminoglycan Synthesis in Human Cartilage Explants and Their Therapeutic Relevance

Misoprostol, a prostaglandin E(1) analog, is currently available to manage ulcer disease, being used predominantly in the prophylaxis of nonsteroidal anti-inflammatory drug (NSAID)-induced ulceration, a serious side effect of anti-inflammatory therapy in arthritis. The protective effects of misoprostol have now also been shown to extend to cartilage in a series of experiment using an ex vivo system employing normal human and osteoarthritis (OA) cartilage. Misoprostol reproducibly reverses inhibition of proteoglycan synthesis induced by interleukin-1 and certain NSAIDs, and also stimulates synthesis in OA cartilage. The article reviews these findings and also presents the results obtained in a study of 20 OA cartilages in which synergy was demonstrated between misoprostol (at 50 ng/ml) and diclofenac (0.3 &mgr;g/ml) in preventing proteoglycan synthesis. Diclofenac on its own is unusual amongst NSAIDs in exerting virtually no deleterious effect on cartilage. The synergy with misoprostol is of clinical interest in view of the recent introduction of a misoprostol/diclofenac combination product (Arthrotec), the intention of which was to provide antiinflammatory efficacy with a reduced incidence of GI damage. The implications of these cartilage experiments is that such a combination may also offer improvements in the management of the arthritic process in OA, and methods whereby this would be assessed clinically are discussed.     

Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: a review

Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects approximately 1% of the population worldwide, and unlike OA, generally involves many joints because of the systemic nature of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs of choice for the symptomatic treatment of both OA and RA. Because of the risks associated with the use of NSAIDs and other limitations, the use of alternative therapies, such as acupuncture and medicinal herbs, is on the rise and according to reports approximately 60-90% of dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine (CAM). This paper reviews the efficacy of some of the common herbs that have a history of human use and their anti-inflammatory or antiarthritic properties have been evaluated in animal models of inflammatory arthritis, in studies employing well defined and widely accepted in vitro models that use human chondrocytes/cartilage explants or in clinical trials. Available data suggests that the extracts of most of these herbs or compounds derived from them may provide a safe and effective adjunctive therapeutic approach for the treatment of OA and RA. This, in turn, argues for trials to establish efficacy and optimum dosage of these compounds for treating human inflammatory and degenerative joint diseases.     

Protein oxidation markers in the serum and synovial fluid of psoriatic arthritis patients

The role of oxidative stress has been studied in rheumatoid arthritis (RA) and other inflammatory joint diseases to some extent, but its importance in psoriatic arthritis (PsA) has rarely been investigated. The aim of this study was to analyze the levels of protein oxidation markers, sulfhydryl (SH) and carbonyl (CO) groups, in the synovial fluid (SF) and serum of PsA patients and compare them with the findings in RA and osteoarthritis (OA) patients. A total of 49 subjects with a knee-joint effusion including 16 PsA, 18 RA, and 15 OA patients were studied. In all patients, the levels of SH groups measured in the serum and SF inversely correlated with the number of white blood cells (WBC) (P<0.05) and the percentage of polymorphonuclear leukocytes (PMN) (P<0.01) in SF. Serum SH levels inversely correlated with serum erythrocyte sedimentation rate (ESR) (P<0.02) and C-reactive protein (CRP) (P<0.05) values. The SH levels in SF were significantly lower in patients affected by PsA and RA compared to OA cases (P<0.02). The serum SH levels in PsA were lower than OA (P<0.001) and higher than RA patients (P<0.05). The serum and synovial levels of CO groups in PsA, RA, and OA patients were similar. Our study provides novel evidence on the involvement of protein oxidation in PsA and confirms the important role of oxidative stress in the pathogenesis of RA. These data suggest that antioxidant agents can potentially be a useful addition to the conventional therapy in the management of these diseases.     

Osteoarthritis: a review

In 1994, the Centers for Disease Control and Prevention reported that by the year 2020, arthritis will have the largest increase in numbers of new patients of any disease in the United States. The term arthritis refers to many diseases, the most common of which is osteoarthritis (OA). OA affects at least 16 million Americans, most of whom are older than 60 years. The disease is usually defined using radiologic criteria. More than 80% of people older than 75 years are symptomatic of OA. Considering cost of diagnosis, therapy (nonpharmacologic, pharmacologic, and surgical), side effects of therapy, and lost productivity, it is one of the more expensive and debilitating diseases in the United States. Given the large numbers of patients and the expense of the disease, it is not surprising that the diagnosis and care of patients with OA have come under scrutiny. The following article will provide some background on the disease and discuss management approaches that view the patient as a whole.     

Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis

OBJECTIVES: The metabolism of cells in inflammatory and noninflammatory arthritic joint diseases is subject to complex environmental controls. The aim of the present study was to investigate the total antioxidant capacity (TAC), levels of lipid peroxidation (LPO), and antioxidant enzyme activities in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). DESIGN AND METHODS: Plasma levels of TAC, malondialdehyde (MDA), the activities of some erythrocyte antioxidant enzymes, as well as erythrocyte sedimentation rates (ESR) were estimated in patients with RA and OA and compared with controls. RESULTS: The plasma TAC levels were significantly lower in the RA group than the OA and control group (P < 0.05). Plasma MDA concentrations were significantly higher in patients with RA than those with OA and healthy subjects (P < 0.05). Erythrocyte GSH-Px and CAT activities were found to be significantly lower in patients with RA than those with OA and healthy subjects (P < 0.05, P < 0.05, respectively). However, there were no significant differences in erythrocyte SOD activities between the groups (P > 0.05). ESR were significantly higher in RA patients than in healthy subjects and patients with OA (P < 0.01). Moreover, there were significant negative correlations between TAC vs. MDA, ESR vs. TAC, and a positive correlation between ESR vs. MDA in the RA group (r = -0.398, P < 0.05; r = -0.422, P < 0.05; r = 0.530, P < 0.05, respectively). CONCLUSIONS: Our results demonstrated that levels of LPO are increased in patients with RA compared to patients with OA. In addition, plasma TAC levels are decreased in RA due to its inflammatory character. We conclude that detecting plasma TAC levels with this novel method may be used as a routine and rapid test to verify the levels of oxidative stress in RA. Furthermore, correlating TAC and LPO levels with acute phase reactants such as ESR may give some clues about disease activity in RA.     

Pain and rheumatology: An overview of the problem

Actually pain is a very important health problem, affecting the majority of people, leading to a significant worsening of patients quality of life and being responsible for a large amount of both medical resources’ expenses and indirect costs. Between the different causes of pain, rheumatic conditions are predominant; in fact diseases such as osteoarthritis (OA), rheumatoid arthritis (RA), fibromyalgia (FM) and extra-articular rheumatisms (EARs) are not only frequently observed, but are also invariably associated with pain occurrence. According to the wide range of rheumatic diseases described, pain expression is complex and not univocal, being influenced not only by the underlying disease, but also by other factors. Generally, 3 rhythms of pain presentation are described in rheumatic conditions: the “inflammatory” rhythm, characteristic of chronic arthritis, the “mechanic” one, characteristic of degenerative joint’s diseases such as OA, and the “fibromyalgic” one, described in patients affected by FM; however also a true “neuropathic” pain may be present in these patients. This classification may be useful in the initial screening of the diseases potentially underlying to a painful syndrome, and in the follow-up of patients once established the diagnosis. With this paper we describe the different aspect and the burden of pain in different rheumatic diseases.     

Immune responses against replication-deficient adenovirus inhibit ovalbumin-specific allergic reactions in mice

Replication-deficient adenovirus vector (Ad) is one of the most efficient gene transfer vehicles for human gene therapy. However, Ad is antigenic, known to evoke prominent inflammatory responses in vivo, and there are concerns that using Ad in patients with immune-mediated disorders (allergy and autoimmune diseases) may affect the status of the diseases. To evaluate this concept in a manner close to clinical scenarios, a mouse model of airway eosinophilic inflammation was developed by administering intraperitoneal injections and inhalations of chicken ovalbumin (OA), with Ad administered intranasally 5 days after the OA sensitization. The administration of Ad resulted in a significant suppression of eosinophil counts in peripheral blood as well as in the bronchoalveolar lavage fluid (BALF), and a decrease in OA-specific IgE. The decrease in the number of eosinophils in BALF was associated with a marked upregulation of interferon gamma (IFN-gamma) expression. In contrast, the Ad-specific, delayed-type hypersensitivity response and efficacy of reporter gene expression mediated by Ad were only marginally affected in animals sensitized with OA. Together, these data support the idea that Ad administration in patients with Th2-mediated immune disorders does not exacerbate the parameters of ongoing inflammations or gene transfer efficiency, and with its ability to induce prominent type 1 immune response to the antigen in vivo, Ad could potentially be used as an efficient adjuvant to control immune disorders where Th2 cell-mediated mechanisms are involved.     

Prevalence of Co-existing Autoimmune Disease in Rheumatoid Arthritis: A Cross-Sectional Study

Introduction

Many autoimmune diseases, including rheumatoid arthritis (RA), share common mechanisms; however, population-based studies of the magnitude of multiple autoimmune diseases in patients with RA have not been performed.

Methods

We conducted a cross-sectional study using a US administrative healthcare thcare claims database to screen for prevalence of multiple autoimmune diseases in patients with RA and osteoarthritis (OA). Each patient diagnosed with RA between January 1, 2006 and September 30, 2014 was age- and sex-matched with five patients with OA. The prevalence of 37 pre-specified autoimmune diseases during the 24-month period before and after RA or OA diagnosis was compared.

Results

Overall, 286,601 patients with RA and 992,838 matched patients (from 1,421,624 records) with OA were evaluated. During the baseline period, at least one and more than one autoimmune diseases were identified in 24.3% and 6.0% of patients with RA compared with 10.5% and 1.4% of patients with OA, respectively. Highest prevalence rates for patients with RA were for systemic lupus erythematosus (3.8% versus 0.7% for OA) and psoriatic arthritis (3.2% versus 0.4%). Highest odds ratios (ORs) comparing RA with OA were for the prevalence of ankylosing spondylitis (OR 8.0; 95% CI 7.6, 8.5) and psoriatic arthritis (OR 7.8; 95% CI 7.6, 8.1).

Conclusion

Patients with RA have more concurrent autoimmune diseases than patients with OA. These data suggest that the interrelationship between RA and other autoimmune diseases, and outcomes associated with the occurrence of multiple autoimmune diseases, may play an important role in disease understanding, management, and treatment decisions.

Funding

Bristol-Myers Squibb.

     

Piperazine derivatives with central pharmacological activity used as therapeutic tools

Medicinal chemistry is a science applied to the search and discovery of new therapeutic agents for the treatment of various diseases. Therefore, promising structures have been identified; one of these structures is the piperazine moiety, a cyclic molecule containing two nitrogen atoms in positions 1 and 4 as well as four carbon atoms. Many piperazine derivatives have central pharmacological activity that mainly involves the activation of the monoamine pathway. Thus, piperazine derivatives have been the subject of research for many central therapeutic applications, including antipsychotic, antidepressant and anxiolytic applications. Benzylpiperazine is the prototype of piperazine derivatives; this substance is the main component of recreational drugs, partly due to its stimulant and euphoric effects. This paper describes some piperazine derivatives used therapeutically as antipsychotic (clozapine), antidepressant (vortioxetine) and anxiolytic (buspirone) drugs.     

Silencing of miR-101 Prevents Cartilage Degradation by Regulating Extracellular Matrix–related Genes in a Rat Model of Osteoarthritis

Osteoarthritis (OA) is a common, degenerative joint disease characterized by articular cartilage degradation. Currently, clinical trials based on microRNA therapy have been performed to treat various diseases. However, no treatment has been found for arthritis. This study investigated the functions of miR-101 in cartilage degradation in vivo and evaluated the feasibility of using miR-101 as a therapeutic agent for OA. Mono-iodoacetate-induced arthritis (MIA) rats were used as an animal model of OA. miR-101 mimic or miR-101 inhibitor was injected into the rats'' knees to evaluate its effects on cartilage degradation. Cartilage degradation aggravated at 14 days after the injection of miR-101 mimic. By contrast, miR-101 silencing reduced cartilage degradation. Moreover, the administration of miR-101 mimic is sufficient to cause cartilage degradation in the normal cartilage of rats. By contrast, miR-101 inhibitor could prevent this change. Microarray and qPCR were used to investigate the different expressed genes after injecting miR-101 mimic and miR-101 inhibitor in the rats'' articular cartilage. Several cartilage degradation-related genes were selected and validated to function in cartilage degradation with miR-101. Our results demonstrated the therapeutic effect of miR-101 inhibition on cartilage degradation in MIA rats by regulating several cartilage degradation–related genes.