Summary Objective To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and ...the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. Methods OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. Results OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. Conclusions Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.
Summary
Bone mineral density (BMD) may be increased due to vertebral compression fractures (VCF). Our study showed trabecular bone scores (TBS) was less affected than BMD by fractured vertebrae. The ...TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.
Introduction
Trabecular bone score (TBS), a noninvasive tool estimating bone microarchitecture, provides complementary information to lumbar spine bone mineral density (BMD). Lumbar spine BMD might be increased due to both degenerative disease and vertebral compression fractures (VCF). Lumbar spine TBS has been confirmed not influenced by osteoarthrosis, but the effects of VCF are still not been well evaluated. This study aimed to investigate whether lumbar spine TBS was affected by fractured vertebrae.
Methods
We studied postmenopausal women and men above 50 years old who underwent DXA between January 1, 2017, and May 31, 2019. By calculating the difference of BMD and TBS between L1 and the mean of L2-3, the study compared the difference of values between the control group and fracture group to determine the effects of fractured vertebrae on BMD and TBS.
Results
A total of 377 participants were enrolled with 202 in the control group (157 females; age: 68.06 ± 6.47 years) and 175 in the fracture group (147 females; age: 71.71 ± 9.44 years). The mean BMD of the L1 vertebrae in the fracture group was significantly higher than that in the control group (
p
< 0.0001). There was no significant difference between the mean differences of TBS between L1 and the means of L2-3 vertebrae in the control group and the most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity.
Conclusion
Lumbar spine TBS, unlike BMD, is less affected by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.
Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical ...properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.
Cell refractive index is an important biophysical parameter, which provides new biological and biomedical insight for disease diagnosis and cell biology.
This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic ...circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.
Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable ...cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023–$28,800 US dollars (USD) in Japan to $14,513–$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.
Background
Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up‐regulation of T helper (Th) 17 cells, and ...down‐regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease.
Methods
Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17‐ and Treg‐related cytokines including IL‐6, IL‐17A, IL‐10, TGF‐β, and mRNA expression levels of RORγt and Foxp3 were tested.
Results
Patients with Kawasaki disease had higher levels of plasma IL‐17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL‐6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL‐6 and IL‐17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL‐10 and IL‐17A.
Conclusion
Kawasaki disease was associated with higher IL‐17A and IL‐6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg‐related FoxP3. IVIG resistance was associated with higher levels of IL‐10 and IL‐17A. Our findings provide further evidence that Kawasaki disease is an autoimmune‐like disease.
We aimed to determine the effect of dementia and Parkinson's disease on one, three and 12-month mortality following surgery for fracture of the hip in elderly patients from an Asian population.
Using ...a random sample of patients taken from the Taiwan National Health Insurance Research Database, this retrospective cohort study analyzed the data on 6626 elderly patients who sustained a fracture of the hip between 1997 and 2012 who had ICD-9 codes within the general range of hip fracture (820.xx). We used Cox regression to estimate the risk of death associated with dementia, Parkinson's disease or both, adjusting for demographic, clinical, treatment, and provider factors.
Among 6626 hip fracture patients, 10.20% had dementia alone, 5.60% had Parkinson's disease alone, and 2.67% had both. Corresponding one-year mortality rates were 15.53%, 11.59%, and 15.82%, compared with 9.22% for those without neurological illness. Adjusted hazard ratio for one-year mortality was 1.45 (95% confidence intervals (CI) 1.17 to 1.79) for those with dementia, and 1.57 (95% CI 1.07 to 2.30) with both dementia and Parkinson's disease versus patients with neither. There was no significant association with death for Parkinson's disease alone. Age, male gender and comorbidities were also associated with a higher risk of mortality.
Dementia, with or without Parkinson's disease, is an independent predictor of mortality following surgery for fractures of the hip. Age, male gender and comorbidities also increase the risk of death. Parkinson's disease alone has no significant effect. Cite this article: Bone Joint J 2018;100-B:1220-6.
Summary Objective To study the effects of oral glucosamine sulfate on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods OA was ...induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee; the left knee was untreated. The OA + glucosamine group received oral glucosamine sulfate (250 mg/kg/day) in a 2-g wafer once a day for 10 consecutive weeks starting at week 5 after ACLT. The OA group was treated as above with 2-g wafers (placebo). The control group of naïve rats received 2-g wafers only. The glucosamine alone group comprised naïve rats receiving glucosamine sulfate only. Nociceptive behavior (mechanical allodynia and weight-bearing distribution of hind paws) during OA development was analyzed pre- and 3, 6, 9, 12, 15, and 18 weeks post-ACLT. Macroscopic and histologic studies were then performed on the cartilage and synovia. Immunohistochemical analysis was performed to examine the effect of glucosamine on expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage chondrocytes. Results OA rats receiving glucosamine showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Glucosamine treatment also suppressed synovitis. Mechanical allodynia and weight-bearing distribution studies showed significant improvement in the OA + glucosamine group as compared to the OA group. Moreover, glucosamine attenuated p38 and c-Jun N-terminal kinase (JNK) but increased extracellular signal-regulated kinase 1/2 (ERK) expression in OA-affected cartilage. Conclusion Our results indicate that treatment with oral glucosamine sulfate in a rat OA model (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cell p38 and JNK and increase of ERK expression.
Background
Exposure to environmental endocrine‐disrupting chemicals (EDCs) is associated with allergy, chronic inflammation, and immunodeficiency. Phthalates, the common EDCs used in plastic ...industry, may act as adjuvants to disrupt immune system and enhance allergy. Plasmacytoid DCs (pDCs) are predominant cells secreting type I interferon (IFN) against infection and are professional antigen‐presenting cells in regulating adaptive immunity. However, the effects of phthalates on the function of pDCs are unknown.
Methods
Circulating pDCs were isolated from healthy subjects, were pretreated with diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP), and were stimulated with Toll‐like receptor (TLR)‐9 agonist CpG. IFN‐α/IFN‐β levels, surface markers, and T‐cell stimulatory function were investigated using ELISA, flow cytometry, and pDC/T‐cell coculture assay. Mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting, and chromatin immunoprecipitation.
Results
Diethylhexyl phthalate and butyl benzyl phthalate suppressed CpG‐induced IFN‐α/IFN‐β expression in pDCs, and the effect was reversed by aryl hydrocarbon receptor (AHR) antagonist. Diethylhexyl phthalate suppressed CpG‐activated mitogen‐activated protein kinase (MAPK)‐MEK1/2‐ERK‐ELK1 and NFκB signaling pathways. Diethylhexyl phthalate suppressed CpG‐induced interferon regulatory factor (IRF)‐7 expression by suppressing histone H3K4 trimethylation at IRF7 gene promoter region through inhibiting translocation of H3K4‐specific trimethyltransferase WDR5 from cytoplasm into nucleus. Butyl benzyl phthalate or diethylhexyl phthalate‐treated pDCs suppressed IFN‐γ but enhanced IL‐13 production by CD4+ T cells.
Conclusion
Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human pDCs via suppressing IFN‐α/IFN‐β expression and modulating the ability to stimulate T‐cell responses.
Summary
Background
Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human ...immunodeficiency virus (HIV) coinfection.
Aim
To evaluate the effectiveness and safety of generic VEL/SOF‐based therapy for HCV infection in patients with or without HIV coinfection in Taiwan.
Methods
Sixty‐nine HIV/HCV‐coinfected and 159 HCV‐monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti‐viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12) were analysed.
Results
The SVR12 was achieved in 67 HIV/HCV‐coinfected patients (97.1%; 95% CI: 90.0%‐99.2%) and in 156 HCV‐monoinfected patients (98.1%; 95% CI: 94.6%‐99.4%) receiving VEL/SOF‐based therapy, respectively. The SVR12 rates were comparable between HIV/HCV‐coinfected and HCV‐monoinfected patients, regardless of pre‐specified baseline characteristics. One hundred twenty‐two (53.5%) and seven (3.1%) patients had baseline resistance‐associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV‐coinfected and HCV‐monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV‐coinfected patients receiving anti‐retroviral therapy containing tenofovir disoproxil fumarate (TDF).
Conclusions
Generic VEL/SOF‐based therapy is well‐tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.
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