This product is isolated and purified from the root bark of Morus alba L.
Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.
628.2±55.0 °C at 760 mmHg
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Personal Projective Equipment
For Reference Standard and R&D, Not for Human Use Directly.
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To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.
Interventional time-series analysis.
Ontario, Canada, from 2003 to 2014.
Ontario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014.
Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario’s Narcotics Safety and Awareness Act (NSAA; November 2011).
Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions.
Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59).
Although the Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain led to a decline in opioid prescribing rates among ODB beneficiaries these guidelines and subsequent Ontario legislation did not result in a significant change in rates of opioid-related hospitalizations. Given the prevalence of high dose opioid prescribing in this population, this suggests that improved strategies and programs for the safe prescribing of long-acting opioids are needed.
High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study
Luke Spooner,1 Kimberly Fernandes,2 Diana Martins,2 David Juurlink,2,3 Muhammad Mamdani,2,4,5,6,7 J. Michael Paterson,2,5,8 Samantha Singh,2 and Tara Gomes2,5,6,7,*Dena L. Schanzer, Editor
Intervertebral disc (IVD) disorders are often accompanied by painful inflammatory and immunopathological processes. Nucleus pulposus (NP) cells play a pivotal role in maintenance of IVD by organizing the expression of anabolic, catabolic, anti-catabolic and inflammatory cytokines. Human NP cells have been targeted by gene therapeutic approaches using lentiviral or adenoviral systems that could be critical due to genome incorporation or immunological side effects. Adeno-associated viruses (AAVs), which do not express any viral gene and are not linked with any known disease in humans, are attractive gene delivery vectors. However, their lack of specific tissue tropism and preexisting immune response are main problems for therapeutic applications. Heretofore, AAVs have not been studied in human IVD research. Therefore, we attempted to identify NP cell specific AAV serotype by targeting human NP cells with different self-complementary AAV (scAAV) serotypes.
Identification and characterization of the proper serotype is crucial to establish less immunogenic and safer gene therapeutic approaches of IVD disorders.
Preoperative magnetic resonance imaging (MRI) was used for grading of IVD degeneration. NP cells were isolated, cultured with low-glucose and transduced with green fluorescent protein (GFP) packing scAAV serotypes (scAAV1-8) in a dose-dependent manner. scAAV titers were determined by quantitative polymerase chain reaction (qPCR). Transduction efficiencies were determined by fluorescence microscopy and fluorescence-activated cell sorting within 48 days of post-transduction. The 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine NP cell viability. Three-dimensional (3D) cell culture and enzyme-linked immunosorbant assay (ELISA) were performed to examine the expression levels of inflammatory, catabolic and matrix proteins in NP cells.
scAAV6, scAAV2 and scAAV3 showed high and prolonged transgene GFP expressions with transdution efficiencies of 98.6 %, 91.5 % and 89.6 % respectively (p ≤ 0.002). Unlike scAAV6, the serotypes scAAV2 and scAAV3 declined the viability of NP cells by about 25 % and 10 % respectively (p ≤ 0.001). Moreover, scAAV6 did not affect the expression of the inflammatory, catabolic and matrix proteins.
As original primary research evaluating AAVs in degenerative human IVDs, this study identified scAAV6 as a proper serotype for high, stable and non-immunogenic target gene expression in human NP cells. The data could be very important to design efficient and safer gene therapeutic approaches of IVD disorders.
Intervertebral disc disorders, Inflammatory and catabolic cytokines, Nucleus pulposus cells, Nucleus pulposus cell specific adeno-associated virus, Targeted gene therapy, Maintenance of intervertebral disc matrix
Identification and characterization of human nucleus pulposus cell specific serotypes of adeno-associated virus for gene therapeutic approaches of intervertebral disc disorders
Demissew S. Merncorresponding author and Claudius Thome
The genome of the multihost bacteriophage ΦK64-1, capable of infecting Klebsiella capsular types K1, K11, K21, K25, K30, K35, K64, and K69, as well as new capsular types KN4 and KN5, was analyzed and revealed that 11 genes (S1-1, S1-2, S1-3, S2-1, S2-2, S2-3, S2-4, S2-5, S2-6, S2-7, and S2-8) encode proteins with amino acid sequence similarity to tail fibers/spikes or lyases. S2-5 previously was shown to encode a K64 capsule depolymerase (K64dep). Specific capsule-degrading activities of an additional eight putative capsule depolymerases (S2-4 against K1, S1-1 against K11, S1-3 against K21, S2-2 against K25, S2-6 against K30/K69, S2-3 against K35, S1-2 against KN4, and S2-1 against KN5) was demonstrated by expression and purification of the recombinant proteins. Consistent with the capsular type-specific depolymerization activity of these gene products, phage mutants of S1-2, S2-2, S2-3, or S2-6 lost infectivity for KN4, K25, K35, or K30/K69, respectively, indicating that capsule depolymerase is crucial for infecting specific hosts. In conclusion, we identified nine functional capsule depolymerase-encoding genes in a bacteriophage and correlated activities of the gene products to all ten hosts of this phage, providing an example of type-specific host infection mechanisms in a multihost bacteriophage.
IMPORTANCE We currently identified eight novel capsule depolymerases in a multihost Klebsiella bacteriophage and correlated the activities of the gene products to all hosts of this phage, providing an example of carriage of multiple depolymerases in a phage with a wide capsular type host spectrum. Moreover, we also established a recombineering system for modification of Klebsiella bacteriophage genomes and demonstrated the importance of capsule depolymerase for infecting specific hosts. Based on the powerful tool for modification of phage genome, further studies can be conducted to improve the understanding of mechanistic details of Klebsiella phage infection. Furthermore, the newly identified capsule depolymerases will be of great value for applications in capsular typing.
Klebsiella, bacteriophage, capsular type, capsule depolymerase, multiple host
Klebsiella Phage ΦK64-1 Encodes Multiple Depolymerases for Multiple Host Capsular Types
Yi-Jiun Pan,a Tzu-Lung Lin,b Ching-Ching Chen,b Yun-Ting Tsai,b Yi-Hsiang Cheng,b Yi-Yin Chen,b Pei-Fang Hsieh,b Yi-Tsung Lin,c and Jin-Town Wangcorresponding authorb,d
2017 Mar 15;