Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of diverse autoantibodies with various systemic organ involvements. In patients with SLE, autoantibodies, such as antinuclear antibody (ANA) and anti-dsDNA antibody, play an important role not only in diagnosing the disease, but also representing the pathogenesis of the disease. ANA is the main screening tool in diagnosis and serum complement levels and anti-dsDNA antibody level are closely related to the disease activities. Nevertheless, exceptionally, some patients represent with negative ANA and/or anti-dsDNA antibody leading to diffi-culties in diagnosing the disease. Here, we report a case of 37-year old female SLE patient with negative ANA, negative anti-dsDNA antibody, and positive anti-Ro/SSA antibody, which manifested with nephrotic syndrome.
Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) are reported to be increased in various inflammatory diseases, but there clinical significance in adult onset still disease (AOSD) remains unclear.
Objectives
The aim of the present study was to evaluate NLR and PLR as a inflammatory marker in AOSD.
Methods
The medical records of 23 AOSD patients and age, sex-matched 25 healthy individuals were retrospectively reviewed. NLR, PLR between AOSD patients and healthy controls were compared, and correlation between these indexes and clinical characteristics were analyzed. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or metabolic disorder.
Results
The NLR and PLR were found to be significantly higher in AOSD patients when compared to the healthy control (NLR: 10.67± 6.73 vs 2.05±1.07, p<0.001, PLR: 255.78±107.22 vs 128.10 ±42.60, p<0.001). The NLR and PLR were decreased significantly after treatment (4.67±3.22, 196.84±78.54). NLR was positively correlated with erythrocyte sedimentation rate (ESR)(r=0.612, p<0.001), C-reaction protein (CRP)(r=0.597, p<0.001) and ferritin (r=0.552, p<0.001). PLR was positively correlated with ESR (r=0.648, p<0.001), CRP (r=0.536, p<0.001) except ferritin (r=0.33, p=0.025).
Conclusions
NLR, PLR, together with other serum inflammatory markers, were proving as significant clinical tools which could be used as biomarkers for inflammatory response of disease activity in AOSD patients.
Postherpetic neuralgia (PHN) is a disease entity defined as persistent pain after the acute pain of herpes zoster gradually resolves. It is associated with impaired daily activities, resulting in reduced quality of life. General epidemiological data on PHN is necessary for the effective management. However, data on the epidemiology of PHN in Korea is lacking. The aim of this study was to evaluate the epidemiological features of PHN in the general population.We used population-based medical data for 51,448,491 subscribers to the Health Insurance Service in the year of 2013 to analyze of PHN epidemiology in Korea, such as the incidence, regional distribution, seasonal variation, and healthcare resource utilization. Total number of patients and medical cost on PHN were analyzed from 2009 to 2013.Findings indicate that the incidence of PHN in Korea was 2.5 per 1000 person-years, which was strongly correlated with age and sex. There were no differences in seasonal variation or regional distribution. The medical cost increased steadily over the study period. When admitted to general hospitals, patients with PHN were mainly managed in the dermatology and anesthesiology departments.The incidence and prevalence rates of PHN in Koreans appear to be considerably higher compared to those in western populations, while the sex and age predisposition was similar. Considering that the pain associated with PHN can have a marked impact on a patient's quality of life resulting in a medicosocial economic burden, anesthesiology physicians have an important role in primary care in Korea. Future research on the cost-effectiveness of the management of PHN is needed.
Tacrolimus is a T cell specific, anti-inflammatory agent that has been used as a therapeutic agent for rheumatoid arthritis (RA). IL-1b- and thapsigargin (TG)-induced endoplasmic reticulum (ER) stress modulates the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis.
Objectives
This study was aimed at defining the effect of tacrolimus on endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation and to elucidate the underlying mechanisms.
Methods
Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β, TG, or TAC. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. Collagen-induced arthritis (CIA) was induced by immunization of female Lewis rats with an emulsion of bovine type II collagen and incomplete Freund9s adjuvant. Lesions of bone and cartilage were assessed on the basis of histological changes in the knee joint and radiographic analysis of the hind paw. Tacrolimus at doses of 3.2 mg/kg or its placebo formulation was orally administered to rats for 28 days from the day after immunization. We examined the histopathological changes of osteolysis and the expression of specific ER stress-mediated inflammatory signaling pathway biomarkers (IRE1α, GRP78/Bip, c-Fos, and NF-κB). In addition, pro-inflammatory cytokines and osteoclastogenic molecules (RANKL, and M-CSF) were assessed in the knee and ankle joints in the CIA mouse model.
Results
In vitro, IL-1b- and thapsigargin (TG)-induced endoplasmic reticulum stress modulates the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis. In the mouse model, tacrolimus administration resulted in a dramatic amelioration of osteolysis and significant reduction in ER stress intensity. Simultaneously, tacrolimus lessened inflammatory cell infiltration, reduced the capability of osteoclastogenesis, and reduced the inflammatory response by reducing the levels of IRE1α, GRP78/Bip, c-Fos, and NF-κB.
Conclusions
These findings suggest that tacrolimus has the potential to inhibit the progression of joint damage by inhibiting endoplasmic reticulum stress as well as anti-inflammatory effects in established RA.
Rebamipide is an antiulcer drug that protects gastric epithelial cells, improves gastric defense mechanisms by increasing gastric mucus, increases prostaglandin production, and reduces free oxygen radicals. Interestingly, recent research has demonstrated that rebamipide acts as an oxygen radical scavenger and also exhibits anti-inflammatory activity.
Objectives
We determined the effects of rebamipide on the production of proinflammatory mediators, including MMPs, COX-2, and PGE2, and signaling pathway produced by rheumatoid arthritis synovial fibroblasts (RASFs) and the proliferation of these cells after stimulation with IL-1β.
Methods
The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1β with/without rebamipide. The expression of MMPs, tissue inhibitor of metalloproteinase-1 (TIMP-1), COXs, members of the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, including p-ERK, p-p38, p-JNK, and nuclear factor-kappaB (NF-κB), and the production of PGE2 were examined by western blotting or semi-quantitative RT-PCR and ELISA.
Results
Rebamipide inhibited IL-1β–induced RASF proliferation. The inhibitory effects of rebamipide were significantly enhanced in a dose-dependent manner. IL-1β enhanced the expression of MMP-1 and MMP-3, but not that of TIMP-1, in RASFs, as per the results of mRNA expression. The expression of MMP-1 and MMP-3 were significantly inhibited by treatment with rebamipide at 48 h. IL-1β phosphorylated the intracellular NK-κB and MAPKs including ERK, p-38, and JNK. Rebamipide significantly inhibited IL-1β–induced NF-κB and intracellular JNK activation, but it did not inhibit the activation of ERK and p-38.
Conclusions
To the best of our knowledge, this is the first study to report that repamipide can inhibit the IL-1β-induced proliferation of RASFs via the inhibition of IL-1β-induced activation of NF-κB and phosphorylation of the JNK pathway. These findings suggest that rebamipide may be beneficial for the treatment of patients with RA.
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are potent inhibitors of cholesterol biosynthesis. They have been reported to have anti-inflammatory and/or immunomodulatory as well as prophylactic and therapeutic effects in collagen-induced arthritis models. Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome.
Objectives
This study was designed to define the effect of statins on IL-1β-induced osteoclastogenesis and to elucidate the underlying mechanisms.
Methods
Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the above effects of atorvastatin on osteoclastogenesis were investigated using RT-PCR and immunoblotting for osteoclast specific molecules.
Results
Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of NFATc1 mRNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-κB and blocks the activation of c-JUN N-terminal kinase, extracellular signal-regulated kinase, and p38, thus implicating the NF-κB and MAPK pathway in this process.
Conclusions
These results indicate that atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases
Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) are reported to be increased in various inflammatory diseases, but there clinical significance in systemic sclerosis (SSc) remains unclear
Objectives
The aim of the study is to evaluate usefulness of neutrophil to lymphocyte ratio in diagnosis of systemic sclerosis and in prediction of lung involvement such as pulmonary fibrosis.
Methods
The medical records of 88 SSc patients and 50 healthy controls were retrospectively reviewed. NLR, PLR between SSc patients and healthy controls were compared, and correlation between these indexes and lung involvement were analyzed. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or metabolic disorder.
Results
The NLR and PLR were found to be significantly higher in SSc patients when compared to the healthy control (NLR: 3.95±6.59 vs 2.00±1.07, p<0.01, PLR: 163.87±101.12 vs 126.33 ±42.31, p<0.05). SSc patients with lung involvement had higher NLR and PLR levels than those without lung involvement (p<0.01, p<0.05). NLR was negatively correlated with forced vital capacity (FVC)(r=-0.341, p<0.01) but not diffusing capacity for carbon monoxide (DLCO). Receiver-operating characteristics analysis (ROC) of NLR to predict lung involvement in SSc showed that the area under the curve (AUC) was 0.763. The cut-off NLR value for prediction of lung involvement was determined as 2.59. (sensitivity, 0.700;specificity, 0.729; p<0.01)
Conclusions
NLR may be a promising marker that reflects lung involvement in patients with SSc and values greater than 2.59 were useful in prediction of lung involvement.
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