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ID PMID Title PublicationDate abstract
22035481 Narrowed indications improve outcomes for hip resurfacing arthroplasty. 2011 Hip resurfacing arthroplasty has had excellent clinical outcomes from multiple centers. However, controversy exists regarding the most appropriate patient selection criteria. Many proponents of hip resurfacing believe that narrowing the patient indications with strict inclusion and exclusion criteria may lead to improved outcomes and decreased complication rates. The purpose of this study was to review the results of resurfacing performed by an experienced surgeon to determine if implant survival and complication rates were different between subgroups of patients with different demographic factors. MATERIALS AND METHODS: We evaluated 311 patients who had a hip resurfacing arthroplasty performed after the initial learning curve and who had a minimum follow-up of 5 years (mean, 93 months). These patients were compared to a group of 93 patients (96 hips) who underwent resurfacings, with newer selection criteria based on the findings of the first cohort. RESULTS: Overall, there were 10 failures in the first patient cohort (97% survivorship), compared to no failures in the second cohort. Higher revision rates were associated with patients who had osteonecrosis or rheumatoid arthritis. Patients who had femoral component sizes larger than 50 millimeters had lower revision rates. There were no revisions in patients who were under 50 years of age, had head sizes greater than 50 millimeters, and who had a primary diagnosis of osteoarthritis. DISCUSSION: After evaluating our initial experience after the learning curve, the ideal patient selection criteria was determined to be young males who have femoral head sizes greater than 50 millimeters. The early results are encouraging in that, although resurfacing may not be appropriate for all patients, it can provide predictable, excellent survivorship in these patients.
22042416 [Inflammatory bowel disease and lymphoproliferative disorders]. 2011 Oct 25 The risk of lymphoproliferative disorders (LPDs) has been reported to be increased in autoimmune diseases and chronic inflammatory diseases. Similar with other chronic inflammatory diseases such as rheumatoid arthritis, there is a concern about the risk of LPDs in patients with inflammatory bowel disease (IBD). Generally, in IBD patients, the risk of LPDs appears to be similar with or very slightly higher, compared to the general population. The association of therapeutic agents with the risk of LPDs is difficult to evaluate due to multiple other potentially involved factors and co-treatment with other agents. To date, data show that thiopurine is associated with a moderately increased risk of LPDs in patients with IBD. Evidence regarding the risk of LPDs in IBD patients using methotrexate is not sufficient, but the risk of LPDs seems low. The responsibility of anti-TNF-a agents on the risk of LPDs is difficult to determine, because most of IBD patients receiving anti-TNF-a agents are co-treated with thiopurines. Attention should be given to the high risk of hepatosplenic T-cell lymphoma in young male patients treated with anti-TNF-a agents together with thiopurines. The risk and benefit of immunosuppressive therapy for IBD should be carefully evaluated and individualized considering the risk of LPDs.
22011638 Vitamin D levels and potential impact in systemic sclerosis. 2011 Nov Vitamin D is essential not only for calcium and bone metabolism, but it also may exert other biological activities, including immunomodulation through the expression of vitamin D receptor in antigen-presenting cells and activated T cells. Evidence from animal models and human prospective studies of rheumatoid arthritis, multiple sclerosis, type I diabetes, and systemic lupus erythematosus, indeed suggested an important role for vitamin D as a modifiable environmental factor in autoimmune diseases. In systemic sclerosis (SSc), this role has not been completely dissected, although recent studies clearly evidenced a high prevalence of vitamin D deficiency. Moreover, some degree of association between vitamin D deficiency and disease activity or phenotype characteristics has also been observed. Vitamin D deficiency in SSc may be related to several factors: insufficient sun exposure due to disability and skin fibrosis, insufficient intake because of gut involvement and malabsorption. Although it is advisable to regularly check vitamin D status in these patients, there is no consensus about which vitamin D supplementation regimen might be sufficient to modulate immunological homeostasis, and possibly reduce disease activity or severity, thus further prospective studies are needed. Moreover, novel vitamin D analogues with more pronounced immune modulatory effect and lower activity on calcium metabolism are in the pipeline, and might represent a great innovative opportunity for the treatment of vitamin D deficiency in such autoimmune disorders.
21958147 Clinical significance and antibiotic susceptibilities of nontuberculous mycobacteria from 2011 Sep AIM: To describe the clinical significance and antibiotic susceptibilities of nontuberculous mycobacteria (NTM) isolated from patients in Crete, Greece between January 2000 and December 2009. PATIENTS & METHODS: NTM identification was performed using conventional bacteriological methods and confirmed by molecular characterization with commercially available assays. Rare and novel species were identified by sequencing of the 16SrRNA and of the hsp65 genes. Antibiotic susceptibility testing was performed by E-test. Rapidly growing (RGM) and slowly growing (SGM) NTM were tested against 14 antimicrobials, including nine common ones, except for Mycobacterium avium and Mycobacterium intracellulare (MAC) complex isolates that were tested only against azithromycin, clarithromycin, linezolid and moxifloxacin. RESULTS: During the study period, 290 positive samples for NTM were recovered from 207 patients. Among the positive samples, 150 were identified as SGM and 57 as RGM. Overall, 50 patients met American Thoracic Society criteria for disease due to NTM, 42 by SGM and eight by RGM. Risk factors in patients with NTM disease were underlying lung diseases, mainly chronic obstructive pulmonary disease and asthma, smoking, rheumatoid arthritis, AIDS, alcohol or drug abuse, malignancies and bronchiectasis. The most common disease-causing species were the MAC complex (n = 25) followed by Mycobacterium kansasii (n = 10). Amikacin was the most active drug for RGM with 100% susceptibility. Macrolides were very active against isolates of the MAC complex, while tigecycline had excellent activity in vitro against RGM. M. kansasii was the most susceptible NTM species in vitro. CONCLUSION: Our study is the first to describe the clinical significance, risk factors and susceptibility patterns of NTM isolates in a Greek population.
21915882 Possible association of lower rate of postherpetic neuralgia in patients on anti-tumor nec 2011 Nov Recently, a study of patients with rheumatoid arthritis who developed herpes zoster while taking a tumor necrosis factor (TNF)-α inhibitor reported a decreased incidence of postherpetic neuralgia. The objective of this study was to investigate whether patients on TNF-α inhibitors who developed herpes zoster have a lower incidence of subsequent development of postherpetic neuralgia. A retrospective review of herpes zoster patients on TNF-α inhibitors (infliximab, etanercept, or adalimumab) was conducted in 12 dermatology clinics. Medical records of such patients were reviewed thoroughly to confirm herpes zoster and TNF-α inhibitors and any subsequent development of postherpetic neuralgia (pain score ≥ 3 out of 10 after 90 days of shingles onset) was noted. A total of 206 cases were reviewed, of which only 2 cases (<1%) developed postherpetic neuralgia, a considerably lower incidence rate than noted in the literature. Increasing age is a known risk factor in the development of postherpetic neuralgia. However, of the 58 (28.1%) cases ≥ 70 years of age, only 1 patient (1.7%) developed neuralgia compared to approximately 50% of patients who develop postherpetic neuralgia in this age group as reported in the literature. Treatment with TNF-α inhibitors may be associated with a lower incidence of postherpetic neuralgia but further prospective large-scale studies are needed to confirm this data.
21881303 [Mass spectrometry-based quantitative analysis and biomarker discovery]. 2011 Mass spectrometry-based quantitative analysis and biomarker discovery using metabolomics approach represent one of the major platforms in clinical fields including for the prognosis or diagnosis, assessment of severity and response to therapy in a number of clinical disease states as well as therapeutic drug monitoring (TDM). This review first summarizes our mass spectrometry-based research strategy and some results on relationship between cysteinyl leukotriene (cysLT), thromboxane (TX), 12-hydroxyeicosatetraenoic acid (12-HETE) and other metabolites of arachidonic acid and diseases such as atopic dermatitis, rheumatoid arthritis and diabetes mellitus. For the purpose of evaluating the role of these metabolites of arachidonic acid in disease status, we have developed sensitive determination methods with simple solid-phase extraction and applied in clinical settings. In addition to these endogenous compounds, using mass spectrometry, we have developed actually applicable quantitative methods for TDM. Representative example was a method of TDM for sirolimus, one of the immunosuppressant agents for a recipient of organ transplant, which requires rigorous monitoring of blood level. As we recognized great potential in mass spectrometry during these researches, we have become interested in metabolomics as the non-targeted analysis of metabolites. Now, established strategy for the metabolomics investigation applies to samples from cells, animals and humans to separate groups based on altered patterns of metabolites in biological fluids and to identify metabolites as potential biomarkers discriminating groups. We would be honored if our research using mass spectrometry would contribute to provide useful information in the field of medical pharmacy.
21785178 The role of omega-3 fatty acids contained in olive oil on chronic inflammation. 2011 Apr Nowadays, people have been eating lots of unhealthy dietary excesses, that make them have chronic inflammatory diseases or known as chronic diseases. Countless millions of people worldwide can not help eating selectively massive quantities of unhealthy foods, until they become sick, often mortality. The omega-6 fatty acids account for the majority of PUFA (Poly Unsaturated Fatty Acids) in the food supply. They are the pre-dominant PUFA in all diets, especially the western diets, which produce pro-inflammatory metabolic products. The persistent antigenic or cytotoxic effects will lead to chronic inflammation. Olive tree is native to the Mediterranean basin and parts of Asia Minor. Its compression-extracted oil from the fruit has a wide range of therapeutic and culinary applications. It had been used as aphrodisiacs, emollients, laxatives, nutritives, sedatives, and tonics. In the later part of the 20th century, several studies had revealed that the olives in the Mediteranian diet is linked to a reduced incidence of degenerative diseases. It is one of phytomedicine which has omega-3 fatty acid as its constituent, may inhibit inflammation composing chronic inflammatory process in many chronic diseases, such as coronary artery disease, rheumatoid arthritis, hypertension, and even cancer.
21732672 Hematopoietic stem cell gene therapy as a treatment for autoimmune diseases. 2011 Oct 3 A key function of the immune system is to protect us from foreign pathogens such as viruses, bacteria, fungi and multicellular parasites. However, it is also important in many other aspects of human health such as cancer surveillance, tissue transplantation, allergy and autoimmune disease. Autoimmunity can be defined as a chronic immune response that targets self-antigens leading to tissue pathology and clinical disease. Autoimmune diseases, as a group of diseases that include type 1 diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus, have no effective cures, and treatment is often based on long-term broad-spectrum immunosuppressive regimes. While a number of strategies aimed at providing disease specific treatments are being explored, one avenue of study involves the use of hematopoietic stem cells to promote tolerance. In this manuscript, we will review the literature in this area but in particular examine the relatively new experimental field of gene therapy and hematopoietic stem cell transplantation as a molecular therapeutic strategy to combat autoimmune disease.
21597375 Biological treatments and connective tissue disease associated interstitial lung disease. 2011 Sep PURPOSE OF REVIEW: There is no specific therapy for interstitial lung disease associated with connective tissue diseases (CTDs-ILD), a potentially fatal condition for some of these patients. This article reviews currently available information on the effects on CTDs-ILD of biological treatments that are increasingly used with considerable success in various systemic diseases. RECENT FINDINGS: A beneficial effect of antitumor necrosis factor (TNF) agents on CTDs-ILD has been described in sporadic patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). However, and despite the fact that there was no clear evidence of pulmonary toxicity of these agents in randomized-controlled trials comprising thousands of patients with RA and spondylarthropathies, new onset or exacerbation of preexisting ILD with high mortality rates has so far been observed in 144 RA patients following anti-TNF treatment in clinical practice. Likewise, administration of the B-cell depleting anti-CD20 antibody rituximab was beneficial for ILD in SSc patients but associated with new-onset ILD in isolated patients with RA and SLE. Pertinent information on other biological treatments is currently lacking. SUMMARY: Data on the therapeutic role of biological agents in CTDs-ILD is preliminary and controversial. Although preexisting ILD is not a contraindication for these agents, until more information is available their administration should be stopped when new pulmonary symptoms occur.
21574146 [Current diagnostic procedure on neuroendocrine differentiation of prostate cancer]. 2011 Apr Chromogranin A (CgA) is considered as a major specific neuroendocrine tumor marker. It belongs to the secretogranin family, which is present in the gastrointestinal tract, respiratory system, endocrine glands and in a group of endocrine cells such us pancreas and thyroid. Serum levels of CgA could reflect the neuroendocrine activity and could be used when evaluating advance prostate carcinoma. Moreover, there are also several factors that may increase the serum level of CgA: treatment with proton-pump inhibitors or H2-receptor blockers, chronic atrophic gastritis, rheumatoid arthritis, liver and renal failure. Another method to evaluate NE differentiation is scintigraphy with the 111In-labeled somatostatin analogue (DTPA-D-Phe)-octrotide, (Octreoscan). This method takes advantage of the overexpression of type II somatostatin receptors on the cell surface of NE tumors. With this technique the presence of NE differentiation can be detected both at the primary (prostate) and the metastatic sites. A more specific system to detect NE cell activity is obtained by analyzing CgA gene expression in prostate tissue by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).
21354470 New insights into the role of mast cells in autoimmunity: evidence for a common mechanism 2012 Jan Mast cells are classically considered innate immune cells that act as first responders in many microbial infections and have long been appreciated as potent contributors to allergic reactions. However, recent advances in the realm of autoimmunity have made it clear that these cells are also involved in the pathogenic responses that exacerbate disease. In the murine models of multiple sclerosis, rheumatoid arthritis and bullous pemphigoid, both the pathogenic role of mast cells and some of their mechanisms of action are shared. Similar to their role in infection and a subset of allergic responses, mast cells are required for the efficient recruitment of neutrophils to sites of inflammation. Although this mast cell-dependent neutrophil response is protective in infection settings, it is postulated that neutrophils promote local vascular permeability and facilitate the entry of inflammatory cells that enhance tissue destruction at target sites. However, there is still much to learn. There is little information regarding mechanisms of mast cell activation in disease. Nor is it known how many mast cell-derived mediators are relevant and whether interactions with other cells are implicated in these diseases including T cells, B cells and astrocytes. Here we review the current state of knowledge about mast cells in autoimmune disease. We also discuss findings regarding newly discovered mast cell actions and factors that modulate mast cell function. We speculate that much of this new information will ultimately contribute to a greater understanding of the full range of mast cell actions in autoimmunity. This article is part of a Special Issue entitled: Mast cells in inflammation.
21248363 Dissecting the role of the S1P/S1PR axis in health and disease. 2011 Jul Sphingosine-1-phosphate (S1P) is a pleiotropic sphingophospholipid generated from the phosphorylation of sphingosine by sphingosine kinases (SPHKs). S1P has been experimentally demonstrated to modulate an array of cellular processes such as cell proliferation, cell survival, cell invasion, vascular maturation, and angiogenesis by binding with any of the five known G-protein-coupled sphingosine 1 phosphate receptors (S1P1-5) on the cell surface in an autocrine as well as a paracrine manner. Recent studies have shown that the S1P receptors (S1PRs) and SPHKs are the key targets for modulating the pathophysiological consequences of various debilitating diseases, such as cancer, sepsis, rheumatoid arthritis, ulcerative colitis, and other related illnesses. In this article, we recapitulate these novel discoveries relative to the S1P/S1PR axis, necessary for the proper maintenance of health, as well as the induction of tumorigenic, angiogenic, and inflammatory stimuli that are vital for the development of various diseases, and the novel therapeutic tools to modulate these responses in oral biology and medicine.
21247219 Mammalian target of rapamycin (mTOR) inhibitors: potential uses and a review of haematolog 2011 Feb 1 Mammalian target of rapamycin (mTOR) inhibitors (mTORis) constitute a relatively new category of immunosuppressive and antineoplastic drugs. These share a unique mechanism of action that is focused on the inhibition of the mTOR. Their clinical applications have recently expanded significantly to cover a wide spectrum of immune and non-immune-mediated disorders, including, apart from solid organ transplantation, various solid organ and haematological malignancies, rheumatological and auto-immune diseases such as rheumatoid arthritis, systemic lupus erythematosus, fibrotic conditions, e.g. pulmonary and hepatic fibrosis, and even metabolic problems such as diabetes mellitus and obesity. The most challenging and frequent adverse effects of the mTORis are the haematological ones, especially anaemia, leukopenia and thrombocytopenia. A unique characteristic of mTORi-induced anaemia is concurrent marked microcytosis. Recently, mechanisms have been proposed to explain the microcytic appearance of this anaemia; these include globin production defect, erythropoietin resistance, chronic inflammation, dysregulation of cellular iron metabolism and hepcidin-mediated iron homeostasis interference. As the differential diagnosis of microcytic anaemia includes pure iron deficiency, functional iron deficiency and haemoglobinopathies, characterization of the anaemia requires significant investigation, time and costs. Therefore, understanding of the likely interaction between mTORis and patients is valuable in clinical practice. Moreover, this could expand the drugs' therapeutic applications to other disorders, and suggest novel targets for further research.
21158933 MIF: a key player in cutaneous biology and wound healing. 2011 Jan Owing to its implication in a range of pathological conditions, including asthma, rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and cancer, the pleiotropic cytokine macrophage migration inhibitory factor (MIF) has been the subject of intensive recent investigation. In the field of dermatology, MIF is believed to be a detrimental factor in diseases such as systemic sclerosis, atopic dermatitis, psoriasis, eczema and UV radiation damage. However, its contribution to other aspects of cutaneous biology is currently unclear. Although its expression in intact skin is well characterized, little is known about MIF's role in cutaneous homoeostasis. However, recent data do identify MIF as a key player in the immune privilege of hair follicles. Similarly, although MIF is rapidly released and its local expression significantly induced upon wounding, its primary role in the ensuing repair process remains a source of contention. MIF has been identified as being a key effector of the beneficial effects of estrogen on wound repair, yet studies employing Mif null mice, recombinant MIF, and neutralizing anti-MIF antibodies have failed to provide a consensus as to whether it benefits or inhibits healing. In fact MIF appears to be able to exert both positive and negative effects, with the cell-specific relevancy of MIF in wound healing still unclear. Thus, if MIF and/or its downstream targets are to be therapeutically useful in the context of cutaneous repair, more needs to be done to establish the nature and mechanism of action of MIF and its receptors in healing wounds.
21094154 A comparison of restriction fragment length polymorphism, tetra primer amplification refra 2011 Feb 20 BACKGROUND: From the wide range of methods currently available for genotyping, we wished to identify a quick, reliable and affordable approach for routine use in our laboratory for LTA+252 C>T SNP screening. METHODS: We set up and compared three genotyping methods for SNP detection: restriction fragment length polymorphism (RFLP), tetra primer amplification refractory mutation system PCR (TPAP) and unlabeled probe melting analysis (UPMA). The SNP model used was LTA+252 C>T, a cytokine gene polymorphism that has been associated with response to treatment in rheumatoid arthritis. The study was performed using 46 samples from healthy Caucasian volunteers. RESULTS: Allele and genotype distribution was similar to that previously described in the same population. All three genotyping methods showed good reproducibility and are suitable for a medium scale throughput molecular platform. UPMA was the most cost effective, reliable and safe method since it required the shortest technician time, could be performed in a single closed tube and involved automatic data analysis. CONCLUSION: This work is the first to compare these three genotyping techniques and provides evidence for UPMA being the method of choice for LTA+252 C>T SNP genotyping.
21029209 Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients. 2011 Jul BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ-specific autoimmune disease was described in case reports. OBJECTIVES: To evaluate the presence of a broad spectrum of organ-specific and non-organ-specific autoantibodies other than anti-desmoglein antibodies in pemphigus patients. PATIENTS AND METHODS: Serum samples were obtained from 105 pemphigus foliaceus (PF) patients, 51 pemphigus vulgaris (PV) patients and 50 controls. Both indirect immunofluorescence assay and ELISA were used to assess the presence of autoantibodies related to connective tissue diseases, autoimmune hepatitis, vasculitis, rheumatoid arthritis, coeliac disease, diabetes and thyroiditis. RESULTS: Significant difference was observed between the three groups for anti-thyroglobulin antibodies in the pemphigus foliaceus group (18% vs. 4%, P=0.03). A significantly higher occurrence of IgM anti-cardiolipin (P=0.03), IgG anti-reticulin (P=0.01) and IgG anti-gliadin antibodies (P=0.008) were observed in the PV group. Cases with more than four autoantibodies were frequently positives for both anti-desmoglein 1 and anti-desmoglein 3. CONCLUSION: Autoantibodies other than anti-desmoglein antibodies are not rare in pemphigus patients. Clinical and serological follow-up of pemphigus patients with positive autoantibodies are needed to clarify their impact in disease evolution.
20725943 Long-term complications, extraintestinal manifestations, and mortality in adult Crohn's di 2011 Jan BACKGROUND: Crohn's disease (CD) is a chronic, progressive, destructive disease. Numerous intestinal and extraintestinal complications and manifestations can occur during its clinical course. This literature review summarizes our current knowledge of the long-term complications, extraintestinal complications, and mortality in CD in adults as reported in population-based studies that include long-term follow-up results. METHODS: A literature search of English and non-English language publications listed in the electronic databases of Medline (source PubMed, 1935 to July, 2009). RESULTS: The relative risk of incident fractures is increased in CD patients by ≈30%-40%. These patients have also have a 3-fold increased risk of deep venous thrombosis and pulmonary embolism. A variety of extraintestinal manifestations (primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, erythema nodosum) and diseases (asthma, bronchitis, pericarditis, psoriasis, rheumatoid arthritis, and multiple sclerosis) are associated with CD. The risks of colorectal and small bowel cancers relative to the general population are 1.4-1.9 and 21.1-27.1, respectively. A slightly increased risk of lymphoma, irrespective of medication use, has been reported in a recent meta-analysis of population-based studies. Overall mortality is slightly increased in CD, with a standardized mortality ratio of 1.4. CONCLUSIONS: CD is frequently associated with disease complications and extraintestinal conditions. Whether the impact of changing treatment paradigms with increased use of immunosuppressives and biologic agents can reduce disease complications and associated conditions is unknown.
20551624 Coupling vascular and myocardial inflammatory injury into a common phenotype of cardiovasc 2011 The rising epidemic of cardiovascular (CV) disease is fuelled by obesity, hypertension and diabetes and, independently and cumulatively, by an aging population. Extensive research identified immunoinflammatory mechanisms as key drivers in the initiation and progression of the disease, from early asymptomatic stages of vascular and myocardial injury leading to the clinically manifest dysfunction and remodeling in advanced stages. Underlying processes include endothelial dysfunction and extracellular matrix restructuration leading to increased vascular stiffness, as well as myocardial remodeling with dilatation and wall thinning. In this, overproduction of tumor necrosis factor-α, amongst others, contributes to generalized CV injury and dysfunction. Moreover, recent insights into the involvement of innate and adaptive immunity in atherosclerosis have shed light on many interesting parallels with chronic systemic inflammatory conditions, such as rheumatoid arthritis, with aggravated inflammation-induced vascular and myocardial injury. Besides, chronologic age has been identified as a potent, independent risk for reduced CV capacity and a plethora of heart diseases, with other modifiable risk factors acting as accelerators. We discuss the available evidence and propose that characterization of inflammatory CV responses might reveal a distinctive CV inflammatory phenotype. A comprehensive noninvasive bio-signature, comprising immunomic biomarkers and integrated noninvasive imaging, may serve as a potential tool in the early diagnosis and prognostication of CV risk.
23472357 [DING proteins, their biochemical and structural properties, and their ability to inhibit 2012 Mar DING proteins comprise an intriguing phosphate-binding protein family present in all animal phyla. Five different DING representatives have been described in humans. Eukaryotic DING proteins are mostly involved in cellular processes such as cell cycle regulation, and also in pathological process such as rheumatoid arthritis and kidney stone formation. Although these proteins are ubiquitous in eukaryotes, no relevant locus or ORF has yet been found in sequenced genomes. This lack of sequence information has considerably hampered functional and structural studies of these proteins, and has required the use of novel and original techniques such as ab initio protein sequencing based on a combination of X-ray crystallography and mass spectrometry. Sub-Angstrom structural resolution has elucidated the molecular binding mechanism of phosphate ions by these high-affinity proteins. Immunohistochemical studies show that these proteins are present in a wide variety of mouse tissues. Some DING proteins, particularly human phosphate binding protein (HPBP), can inhibit HIV replication. This inhibition takes place at the transcriptional step, which is not targeted by any current antiretroviral drug. Initial studies suggest that HPBP warrants animal testing. This recent discovery opens new possibilities for the treatment of HIV infection.
23344621 Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells. 2012 Jan 24 Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-α (TNFα) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells.