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ID PMID Title PublicationDate abstract
25148796 New angle of view on the role of rho/rho kinase pathway in human diseases. 2014 Dec Rho-kinase is an effector molecule of RhoA, a monomeric GTP-binding protein, and causes Ca2+ sensitization through inactivation of myosin phosphatase. The major physiological functions of Rho/Rho-kinase cascade include contraction, proliferation and migration in cells.There are some excellent reviews about Rho/Rho-kinase signal pathway, most of which focus on the specific proteins of the pathway including some upstream regulators and its final effects. But few articles cover signal pathways that can activate the signaling concerned, and/or the pathways that Rho/Rho-kinase can exactly activate. This review hence highlights the two questions after a profound survey of published literatures. Rho/Rho-kinase can exert positive feedback with just another kinase/signal transducers and activator of transcription, receptor tyrosine kinase signal pathways, even reactive oxygen species, which seem to comprise certain signal loops. The authors also presume, accordingly, that the positive feedback suggests a possible reason for exacerbation of some kind of inflammatory diseases including asthma, rheumatoid arthritis, multiple sclerosis, atherosclerosis, etc. This essay, therefore, provides a new angle of view for the therapy of these kinds of diseases.
25068998 Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retin 2015 BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area. METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness. RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area. CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.
25068679 IgG4-related disease: a rheumatologist's perspective. 2014 Sep OBJECTIVES: Given that the clinical features of several IgG4-related diseases (IgG4-RD) can mimic those of autoimmune disorders, the aim of this study was to find possible distinguishing characteristics that would help us identify such cases from the pool of patients in a rheumatology clinic. METHODS: From our clinic's medical records, we identified patients who fulfilled the recently published diagnostic criteria for IgG4-RD. We recorded their presenting features, co-morbid conditions, laboratory, radiologic and histologic findings as well as their treatment and outcome. RESULTS: We identified 11 cases of IgG4-RD: 4 cases of IgG4-related autoimmune pancreatitis (AIP), 5 cases of IgG4-related retroperitoneal fibrosis (RPF)/ periaortitis, 2 cases of IgG4-related sialadenitis and one of IgG4-related interstitial nephritis. 5 out of the 11 patients had been diagnosed with an autoimmune disease, namely rheumatoid arthritis (RA), Sjogren's syndrome (SS) and antiphospholipid syndrome (APS). 3 out of 11 patients were subsequently diagnosed with neoplastic disorders. All patients with IgG4-related AIP had raised CRP levels at presentation. Presenting features of RPF/periaortitis patients were constitutional symptoms, abnormal renal function, hypertension and back pain. Patients with IgG4-related sialadenitis had clinical features mimicking SS. The majority of patients had a favourable response to steroids. CONCLUSIONS: We present common IgG4-RD presentations in the setting of a rheumatology clinic. Increased awareness may avoid delay in diagnosis.
25003637 Formation of cartilage and synovial tissue by human gingival stem cells. 2014 Dec 1 Human gingival stem cells (HGSCs) can be easily isolated and manipulated in culture to investigate their multipotency. Osteogenic differentiation of bone-marrow-derived mesenchymal stem/stromal cells has been well documented. HGSCs derive from neural crests, however, and their differentiation capacity has not been fully established. The aim of the present report was to investigate whether HGSCs can be induced to differentiate to osteoblasts and chondrocytes. HGSCs were cultured either in a classical monolayer culture or in three-dimensional floating micromass pellet cultures in specific differentiation media. HGSC differentiation to osteogenic and chondrogenic lineages was determined by protein and gene expression analyses, and also by specific staining of cells and tissue pellets. HGSCs cultured in osteogenic differentiation medium showed induction of Runx2, alkaline phosphatase (ALPL), and osterix expression, and subsequently formed mineralized nodules consistent with osteogenic differentiation. Interestingly, HGSC micromass cultures maintained in chondrogenic differentiation medium showed SOX9-dependent differentiation to both chondrocyte and synoviocyte lineages. Chondrocytes at different stages of differentiation were identified by gene expression profiles and by histochemical and immunohistochemical staining. In 3-week-old cultures, peripheral cells in the micromass cultures organized in layers of cuboidal cells with villous structures facing the medium. These cells were strongly positive for cadherin-11, a marker of synoviocytes. In summary, the findings indicate that HGSCs have the capacity to differentiate to osteogenic, chondrogenic, and synoviocyte lineages. Therefore, HGSCs could serve as an alternative source for stem cell therapies in regenerative medicine for patients with cartilage and joint destructions, such as observed in rheumatoid arthritis.
25000839 The problem of pain in old age. 2013 The elderly are more susceptible to feeling pain than young people. Pain is described as a complex, subjective feeling causing significant limitation of physical, psychical and social functioning. In the literature, there are many classifications of pain. Considering the duration, pain may be divided into acute and chronic. Acute pain does not depend on age and lasts less than three months whereas chronic pain is more frequent with the elderly and lasts more than three months. It can be divided into nociceptive and neuropathic pain. Involutional changes progressing in the organism of an old person, combined with numerous chronic diseases occurring in old age, cause approx. 85% of the elderly to suffer from pain. Among the diseases with concurring pain, the first are diseases of the locomotor system and include: osteoporosis, osteoarthritis, and rheumatoid arthritis. Moreover, pain is an intrinsic part of malignant cancer, neuralgia shingles, and diabetic neuropathy. Pain also conceals depression and the depression intensifies the feeling of pain. Due to frequent cognitive disorders and depression, the measurement of pain in the elderly is difficult, it thus requires vast experience. To assess the pain intensity, subjective scales are used, e.g. verbal scale, score scale. To assess the qualitative and quantitative scales the following questionnaires are used: McGill-Melzak Pain Questionnaire and the Pain Assessment Form. Significant for pain assessment with people diagnosed with dementia are objective pain symptoms, namely: worsening appetite, gnashing teeth, grimaces. Pain treatment should be multimodal and include usage of both pharmacological and non-pharmacological methods. Pharmacology is the basis for pain treatment in people of old age, which should be used in the least invasive way, starting with small dosages. The pain-relieving medicine of first choice is paracetamol. In the pharmacological treatment of old people there are also non-opioid pain relieving medicine, opioids and supportive medicine. Among non-pharmacological treatments are rehabilitation and psychological therapy. In pain treatment, awareness among the elderly, their families and carers, and medical staff that the pain is not an attribute of old age; thus, it can be correctly diagnosed and treated.
24883332 JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. 2014 Janus kinase (JAK) pathways are key mediators in the immunopathogenesis of psoriasis. Psoriasis treatment has evolved with the advent of targeted therapies, which inhibit specific components of the psoriasis proinflammatory cascade. JAK inhibitors have been studied in early phase trials for psoriasis patients, and the data are promising for these agents as potential treatment options. Tofacitinib, an oral or topically administered JAK1 and JAK3 inhibitor, and ruxolitinib, a topical JAK1 and JAK2 inhibitor, have been most extensively studied in psoriasis, and both improved clinical symptoms of psoriasis. Additional JAK1 or JAK3 inhibitors are being studied in clinical trials. In phase III trials for rheumatoid arthritis, tofacitinib was efficacious in patients with inadequate responses to tumor necrosis factor inhibitors, methotrexate monotherapy, or disease-modifying antirheumatic drugs. The results of phase III trials are pending for these therapies in psoriasis, and these agents may represent important alternatives for patients with inadequate responses to currently available agents. Further investigations with long-term clinical trials are necessary to verify their utility in psoriasis treatment and assess their safety in this patient population.
24795433 Restoring the balance: immunotherapeutic combinations for autoimmune disease. 2014 May Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state.
24785098 Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging an 2014 Oct Skeletal muscle is the most abundant body tissue accounting for many physiological functions. However, muscle mass and functions are not routinely assessed. Sarcopenia is defined as skeletal muscle loss and dysfunction in aging and chronic diseases. Inactivity, inflammation, age-related factors, anorexia and unbalanced nutrition affect changes in skeletal muscle. Mechanisms are difficult to distinguish in individual subjects due to the multifactorial character of the condition. Sarcopenia includes both muscle loss and dysfunction which induce contractile impairment and metabolic and endocrine abnormalities, affecting whole-body metabolism and immune/inflammatory response. There are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases. Appetite regulation and physical activity affect energy balance and changes in body fat mass. Appetite regulation by inflammatory mediators is poorly understood. In some patients, inflammation induces anorexia and fat loss in combination with sarcopenia. In others, appetite is maintained, despite activation of systemic inflammation, leading to sarcopenia with normal or increased BMI. Inactivity contributes to sarcopenia and increased fat tissue in aging and diseases. At the end of the metabolic trajectories, cachexia and sarcopenic obesity are paradigms of the two patient categories. Pre-cachexia and cachexia are observed in patients with cancer, chronic heart failure or liver cirrhosis. Sarcopenic obesity and sarcopenia with normal/increased BMI are observed in rheumatoid arthritis, breast cancer patients with adjuvant chemotherapy and in most of patients with COPD or chronic kidney disease. In these conditions, sarcopenia is a powerful prognostic factor for morbidity and mortality, independent of BMI.
24618929 Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development 2014 May It has recently been appreciated that atherosclerosis is predominantly an inflammatory process. Atherosclerosis begins with a fatty streak, which is made up almost entirely of monocyte-derived macrophages. The development of an atheroma continues as T-cells, mast cells, and other inflammatory cells are recruited to the intima. This collection of inflammatory cells promotes smooth muscle cell replication and extracellular matrix elaboration, thereby increasing the lesion size. Various studies have highlighted that interleukin-6 (IL-6) is an upstream inflammatory cytokine that plays a central role in propagating the downstream inflammatory response responsible for atherosclerosis. IL-6 release is stimulated by acute infections, chronic inflammatory conditions, obesity, and physiologic stress. The high level of IL-6 found in such conditions has a myriad of functions, including hepatic synthesis of acute-phase reactants, activation of endothelial cells, increased coagulation, activation of the hypothalamic-pituitary-adrenal axis, and promotion of lymphocyte proliferation and differentiation. Considering the importance of IL-6 in the development of coronary artery disease, targeting its actions could prove to be beneficial. Individuals with a variant in the IL-6 receptor that impairs classic IL-6 signaling were found to have a decreased risk for coronary heart disease. Tocilizumab is a monoclonal antibody that targets the IL-6 receptor and has been show to alleviate symptoms in patients with rheumatoid arthritis, a disease largely driven by the proinflammatory actions of IL-6. Therefore, further studies are needed to determine the role of tocilizumab and other IL-6 receptor blockers in decreasing the inflammatory response key in the development of atherosclerosis.
24585776 Emerging roles for platelets as immune and inflammatory cells. 2014 May 1 Despite their small size and anucleate status, platelets have diverse roles in vascular biology. Not only are platelets the cellular mediator of thrombosis, but platelets are also immune cells that initiate and accelerate many vascular inflammatory conditions. Platelets are linked to the pathogenesis of inflammatory diseases such as atherosclerosis, malaria infection, transplant rejection, and rheumatoid arthritis. In some contexts, platelet immune functions are protective, whereas in others platelets contribute to adverse inflammatory outcomes. In this review, we will discuss platelet and platelet-derived mediator interactions with the innate and acquired arms of the immune system and platelet-vessel wall interactions that drive inflammatory disease. There have been many recent publications indicating both important protective and adverse roles for platelets in infectious disease. Because of this new accumulating data, and the fact that infectious disease continues to be a leading cause of death globally, we will also focus on new and emerging concepts related to platelet immune and inflammatory functions in the context of infectious disease.
24574735 Helicobacter pylori and autoimmune disease: cause or bystander. 2014 Jan 21 Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.
24450300 Significance of sugar chain recognition by galectins and its involvement in disease-associ 2014 May Galectins are β-galactoside-binding lectins that participate in a wide range of biological processes. Galectins are distributed both inside and outside cells and are believed to have roles in both intra- and extracellular milieus. One of the well-recognized functions of galectins is stabilization of glycoproteins on the cell surface, thereby promoting stable signal transduction and transport of substances such as glucose. Glycoprotein-associated diseases, including congenital disorder of glycosylation (CDG, previously called carbohydrate-deficient glycoprotein syndrome), comprise a disease family established only in the last decade. Although numerous in vitro glycobiology studies have been performed, including investigation of glycan-galectin interactions and of galectin action in cultured cells, a few in vivo studies have investigated molecular mechanisms of galectin actions in animal models. Both in vitro and in vivo studies are needed in order to better determine the biological significance of sugar chain recognition. Hitherto, some reports have focused on the role of impaired sugar chain recognition and galectin function in the development of diverse diseases, including rheumatoid arthritis, diabetes mellitus, colitis, and cancer. We recently focused on the function of galectins in immunity and embryogenesis, and in this review we summarize the diseases related to disorders of sugar chain-galectin interaction and discuss the role of galectins as potential risk factors for some congenital and acquired diseases. These diseases are disorders of immunity, metabolism, and cell differentiation. This approach to understanding the significance of sugar chain recognition by galectins may open up a new field into the nature of glycoprotein-related diseases, including CDG.
24406424 Cancer risk in amyloidosis patients in Sweden with novel findings on non-Hodgkin lymphoma 2014 Feb BACKGROUND: Systemic amyloidoses include immunoglobulin light chain (AL) amyloidosis, serum amyloid (AA)-related amyloidosis and senile systemic amyloidosis (SSA). AL amyloidosis is associated with myeloma, and we showed recently that transthyretin-related hereditary amyloidosis was related to non-Hodgkin lymphoma (NHL). In SSA, amyloids constitute wild-type transthyretin. We wanted to analyze cancer risks in amyloidosis, particularly in SSA. PATIENTS AND METHODS: Nonhereditary amyloidosis patients were identified from the Swedish Hospital Discharge and Outpatients Registers from years 1997 through 2010. Their cancer risk was assessed based on the Swedish Cancer Registry using standardized incidence ratio (SIR) between amyloidosis patients and the remaining population. To gain information about amyloidosis subtypes, we used the Swedish Prescribed Drug Register from years 2005 through 2010 to find out the specific medication prescribed. RESULTS: Among 1400 identified amyloidosis patients, cancer risk was increased for myeloma, NHL and squamous cell skin cancer. Myeloma and skin cancers were diagnosed 7-8 years earlier than in the population, whereas NHL was diagnosed in elderly patients. The SIR was 204 for myeloma in patients who received AL amyloidosis medication, and it was 17.22 in patients receiving rheumatoid arthritis medication, suggesting AA amyloidosis. In remaining patients, including SSA, NHL risk was 14.78, including lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia (51.41) and diffuse large B-cell lymphoma (18.69). In these patients, endometrial cancer (7.04) and cancer of unknown primary site (6.56) were also increased. CONCLUSIONS: SSA is likely to be a main cause of NHL in the elderly population. The present findings suggest a novel mechanism for amyloidosis-related cancer, highlighting the role of chronic stimulation by amyloid.
27170875 A Device for Local or Remote Monitoring of Hand Rehabilitation Sessions for Rheumatic Pati 2014 Current clinical practice suggests that recovering the hand functionality lost or reduced by injuries, interventions and chronic diseases requires, beyond pharmacological treatments, a kinesiotherapic intervention. This form of rehabilitation consists of physical exercises adapted to the specific pathology. Its effectiveness is strongly dependent on the patient's adhesion to such a program. In this paper we present a novel device with remote monitoring capabilities expressly conceived for the needs of rheumatic patients. It comprises several sensorized tools and can be used either in an outpatient clinic for hand functional evaluation, connected to a PC, or afforded to the patient for home kinesiotherapic sessions. In the latter case, the device guides the patient in the rehabilitation session, transmitting the relevant statistics about his performance to a TCP/IP server exploiting a GSM/GPRS connection for deferred analysis. An approved clinical trial has been set up in Italy, involving 10 patients with Rheumatoid Arthritis and 10 with Systemic Sclerosis, enrolled for 12 weeks in a home rehabilitation program with the proposed device. Their evaluation has been performed with traditional methods but also with the proposed device. Subjective (hand algofunctional Dreiser's index) and objective (ROM, strength, dexterity) parameters showed a sustained improvement throughout the follow-up. The obtained results proved that the device is an effective and safe tool for assessing hand disability and monitoring kinesiotherapy exercise, portending the potential exploitability of such a methodology in clinical practice.
24358898 Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies. 2013 Red blood cells (RBCs) from a rhesus D (RhD)-positive fetus that reach the bloodstream of an RhD-negative pregnant woman during birth can induce a pathogenic antibody (Ab) response against the RhD-positive RBCs, leading to fetal hemolytic disease in subsequent pregnancies. To prevent a pathogenic immune reaction, the RhD-negative mother receives serum immunoglobulin G (IgG) containing polyclonal RhD-specific IgG Abs that is purified from healthy RhD-negative men immunized with RhD-positive RBCs. However, the protective mechanism of these polyclonal RhD-specific IgG Abs is unclear. It has become increasingly clear that the effector function of IgG Abs is regulated by the glycan pattern linked to the Fc region of IgG Abs. Non-fucosylated (afucosylated) IgG Abs have a higher affinity for activating Fc gamma receptors, and thus induce a stronger Ab-dependent cellular cytotoxicity (ADCC) reaction than do fucosylated IgG Abs. Agalactosylated and asialylated, autoantigen-specific serum IgG Abs correlate with pro-inflammatory immune responses and disease activity in patients with rheumatoid arthritis. In contrast, galactosylated and sialylated IgG Abs are immunosuppressive and inhibit in form of immune complexes (ICs) dendritic cell (DC) maturation and pro-inflammatory T and B cell immune responses in an antigen-specific manner. However, the galactosylation and sialylation levels of the protective polyclonal RhD-specific IgG Abs are unknown. Here, we purified RhD-specific IgG Abs from the approved commercial product Rhophylac® (CSL Behring) and found that these RhD-specific IgG Abs were even more galactosylated and sialylated than the total Rhophylac® IgG Abs. This result suggests that these galactosylated and sialylated polyclonal RhD-specific IgG Abs are immunosuppressive and induce tolerance against RhD, which would be in strong contrast to a low fucosylated, low galactosylated and low sialylated monoclonal RhD-specific IgG Ab developed to prevent fetal hemolytic disease that has recently passed a clinical phase II study.
24157344 HSA nanocapsules functionalized with monoclonal antibodies for targeted drug delivery. 2013 Dec 15 The chronic autoimmune disorder rheumatoid arthritis (RA) affects millions of adults and children every year. Chronically activated macrophages secreting enzymes and inflammatory cytokines play a key role in RA. Distinctive marker molecules on the macrophage surface could be used to design a targeted drug delivery device for the treatment of RA without affecting healthy cells and tissues. Here, different methods for covalent attachment of antibodies (mAb) recognizing MHC class II molecules found on macrophages onto human serum albumin (HSA) nanocapsules were compared. HSA nanocapsules were prepared with a hydrodynamic diameter of 500.7 ± 9.4 nm and a narrow size distribution as indicated by a polydispersity index (PDI) of 0.255 ± 0.024. This was achieved by using a sonochemical process avoiding toxic cross linking agents and emulsifiers. Covalent binding of mAb on the surface of HSA nanocapsules was realized using polyethyleneglycol (PEG)3000 as spacer molecule. The presence of mAb was confirmed by confocal laser scanning microscopy (CLSM) and enzyme-linked immunosorbent assay (ELISA). Specific binding of mAb-HSA nanocapsules to MHC class II molecules on antigen-presenting cells was demonstrated by flow cytometry analysis.
24035226 Protection of H9c2 rat cardiomyoblasts against oxidative insults by total paeony glucoside 2013 Dec 15 Total paeony glucosides (TPG) extracted from the roots of Radix Paeoniae Rubrae, have been approved for the therapy of rheumatoid arthritis by the State Food and Drug Administration. We previously demonstrated the myocardial protective effects of TPG in both isoprenaline-induced myocardial ischemia rat and acute myocardial infarction rat. However, the underlying mechanism of TPG effect in cardiomyocytes remains to be investigated. The aims of this study were to elucidate the effect of TPG on the activities of antioxidant defense targets and the bioenergetic system in rat cardiomyocytes. The changes of viability, antioxidant defense system activities, protein contents, and mitochondrial functions in tert-butyl hydroperoxide challenged H9c2 rat cardiomyoblasts were evaluated. The results suggest that TPG ameliorated cardiomyoblast dysfunction by preserving antioxidant defense and bioenergetic system.
23919335 Experience with low-dose rituximab in off-label indications at two tertiary hospitals. 2013 Aug BACKGROUND: Rituximab is a monoclonal antibody directed against B cells and is increasingly used to treat a variety of autoimmune conditions. Most published evidence reporting the successful use of rituximab in off-label indications has empirically used a high-dose regimen (either 375 mg/m(2) weekly for 4 weeks, or 1000 mg × 2), which is the approved course of treatment for lymphoma and rheumatoid arthritis patients. AIMS: The aims of this report are to review the indications, outcomes and adverse events of low-dose (500 mg twice, given 1-2 weeks apart), off-label use of rituximab in our institutions, and to review the available evidence. METHODS: We performed a retrospective audit of the off-label use of low-dose rituximab at two university teaching, tertiary referral hospitals, from mid-2008 until the end of 2011. RESULTS: Off-label rituximab was given to 52 patients (53 indications) across a heterogeneous group of autoimmune conditions. Outcomes were known for 46 conditions (affecting 45 patients), and of these, complete responses were observed in 16 (35%) conditions and a further 19 (41%) had a partial response. There was no response to rituximab in 11 (24%) patients. There were eight significant adverse events, mostly related to infectious complications. CONCLUSION: This case series suggests that low-dose courses of rituximab can be used off-label to treat several severe and/or refractory immunological disorders with a reasonable safety profile; however, further trials are required in many off-label indications.
23876501 Zein-based oral drug delivery system targeting activated macrophages. 2013 Sep 15 Reactive oxygen species (ROS) play an important role in the pathogenesis of rheumatoid arthritis (RA). ROS such as hydrogen peroxide and superoxide are overproduced by activated macrophages in RA. As scavengers of ROS, enzymatic proteins such as catalase and superoxide dismutase (SOD) have a great therapeutic potential; however, in vivo application is limited especially when they are orally administered. Although, the oral route is the most convenient for drug administration, therapeutic proteins are easily degraded in vivo by the harsh conditions of gastrointestinal (GI) tract. Here, we introduce a novel drug delivery system composed of zein, a plant storage protein derived from maize. We demonstrate that zein nanoparticles can protect therapeutic proteins, catalase and SOD, from the harsh conditions of GI tract. Folate-conjugated catalase or SOD in zein nanoparticles can target the activated macrophages and scavenge the ROS generated by macrophages in vitro. This novel drug delivery system will be applicable to other orally administered treatments based on the protective property in the harsh conditions of GI tract.
23789210 Content analysis of systematic reviews on effectiveness of traditional Chinese medicine. 2013 Apr OBJECTIVE: To evaluate evidence for the efficacy of Traditional Chinese Medicine (TCM) in systematic reviews. METHODS: Chinese (TCM Periodical Literature Database, Chinese Biological Medicine database, Chinese Medical Current Contents, China Hospital Knowledge Database journal fulltext database, Virtual Machining and Inspection System, and Wanfang) and English (Cochrane Database of Systematic Reviews, PubMed and Embase) databases were searched. RESULTS: Three thousand, nine hundred and fifty-five articles were initially identified, 606 of which met the inclusion criteria, including 251 in English (83 from the Cochrane Database) and 355 in Chinese. The number of articles published each year increased between 1989 and 2009, Cardiocerebrovascular disease was the most studied target disease. Intervention measures included TCM preparations (177 articles), acupuncture (133 articles) and combinations of TCM and Western Medicine (38 articles). Control measures included positive medical (177 articles), basic treatment (100 articles), placebo (219 articles), and blank and mutual (107 articles). All articles included at least one reference; the greatest number was 268. Six of 10 articles with high quality references demonstrated curative effectsagainst target diseases including upper respiratory tract infection, dementia and depression. Interventions that were not recommended were tripterygium for rheumatoid arthritis and TCM syndrome differentiation for pediatric nocturia. In 10.4% of the studies, the authors concluded that the intervention had a curative effect. The assessors agreed with the authors' conclusions in 88.32% of cases, but rejected 8.94% (54 articles). CONCLUSION: 1) Training in systematic review methods, including topic selection, study design, methods and technology, should be improved. 2) Upper respiratory tract infection, dementia and depression may become the predominant diseases treated by TCM, and the corresponding interventions could be developed into practical applications. 3) Use of non-recommended interventions should be controlled, and there should be more research on side effects.