Hylan G-F 20: Review of its Safety and Efficacy in the Management of Joint Pain in Osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease that is a clinically and economically important disease. The increased prevalence of OA with aging, coupled to the demographics of aging populations, make OA a high priority health care problem. Viscosupplementation (VS) is a well-established treatment option in knee OA that is included in the professional guidelines for treatment of this joint disease, and could potentially provide a useful alternative in treating such patients with painful OA. Theoretically VS is an approach that should apply to all synovial joints. OBJECTIVES: The aim of this review is to assess the efficacy and safety of viscosupplementation with Hylan GF-20 (Synvisc(®)) in the management of joint pain in osteoarthritis. METHODS: THE FOLLOWING DATABASES WERE SEARCHED: Medline, Database of Abstract on Reviews and Effectiveness, Cochrane Database of Systematic Reviews. Furthermore, the lists of references of retrieved publications were manually checked for additional references. The search terms Review, Viscosupplementation, Osteoarthritis, Hyaluronic acid, Hyaluronan, Sodium Hyaluronate, Hylan GF-20, Synvisc, intra-articular injection were used to identify all studies relating to the use of Synvisc(®) viscosupplementation therapy in OA. RESULTS: Hylan GF-20 is a safe and effective treatment for decreasing pain and improving function in patients suffering from knee and hip OA but new evidences are emerging for its use in other joints

Intra-articular administrations of Jonexa® in patients with symptomatic osteoarthritis of the hip. Data from a monocentric cohort study

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Long-Term Safety of Anti-TNF Adalimumab in HBc Antibody-Positive Psoriatic Arthritis Patients: A Retrospective Case Series of 8 Patients

Immunosuppressive drugs commonly used in the treatment of psoriatic arthritis make patients more susceptible to viral, bacterial, and fungal infections because of their mechanism of action. They not only increase the risk of new infections but also act altering the natural course of preexisting infections. While numerous data regarding the reactivation of tuberculosis infection are available in the literature, poor information about the risk of reactivation or exacerbation of hepatitis viruses B and C infections during treatment with biologics has been reported. Furthermore, reported series with biological therapy included short periods of followup, and therefore, they are not adequate to verify the risk of reactivation in the long-term treatment. Our study evaluated patients with a history of hepatitis B and psoriatic arthritis treated with adalimumab and monitored up to six years. During the observation period, treatment was effective and well tolerated in all patients, and liver function tests and viral load levels remained unchanged

Water and air ozone treatment as an alternative sanitizing technology

Aims. We investigated the effectiveness of ozone (aqueous and gaseous) treatment as an alternative sanitizing technology to common conventional disinfectants in reducing the microbial contamination of both water and air. Methods. Ozone was added for 20 minutes to a well-defined volume of water and air by the system named "Ozonomatic®". The effectiveness of ozonation was determined by counting CFU/m3 or ml of bacteria present in samples of air or water collected before (T0) and after (T1) the addition of ozone and comparing the microbial load of different bacteria present in ozonized and non-ozonized samples. Results. When the ozonisation equipment was located at 30 cm from the surface of the water in the bath tub in which the bacteria investigated were inoculated, the treatment was able to reduce the total microbial load present in the aerosol by 70.4% at a temperature of 36°C for 48 hours. Conversely, at 22°C for 5 days, only a modest decrease (9.1%) was observed. Escherichia coli and Pseudomonas aeruginosa were completely eliminated. A 93.9% reduction was observed for Staphylococcus aureus, followed by Streptococcus faecalis (25.9%). The addition of ozone to water was able to almost eliminate Staphylococcus aureus (98.9% reduction) and also to exert a strong impact on Legionella pneumophila (87.5% reduction). Streptococcus faecalis and Pseudomonas aeruginosa showed a decrease of 64.2% and 57.4%, respectively. Conversely, only a 26.4% reduction was observed for the bacterium Escherichia coli. This study showed that the addition of ozone in the air exerted a modest reduction on microbial load at 36°C, whereas no effect was observed at 22°C. Conclusions. Aqueous and gaseous ozone treatments were effective against microbial contaminants, reducing the CFU of the microorganisms studied. These results confirm the efficacy of the ozone disinfection treatment of both water and air; particularly, it constitutes an extremely promising alternative, allowing the possibility to reuse contaminated water

A Planck-scale axion and SU(2) Yang-Mills dynamics: Present acceleration and the fate of the photon

From the time of CMB decoupling onwards we investigate cosmological evolution subject to a strongly interacting SU(2) gauge theory of Yang-Mills scale $\Lambda\sim 10^{-4}$ eV (masquerading as the $U(1)_{Y}$ factor of the SM at present). The viability of this postulate is discussed in view of cosmological and (astro)particle physics bounds. The gauge theory is coupled to a spatially homogeneous and ultra-light (Planck-scale) axion field. As first pointed out by Frieman et al., such an axion is a viable candidate for quintessence, i.e. dynamical dark energy, being associated with today's cosmological acceleration. A prediction of an upper limit $\Delta t_{m_\gamma=0}$ for the duration of the epoch stretching from the present to the point where the photon starts to be Meissner massive is obtained: $\Delta t_{m_\gamma=0}\sim 2.2$ billion years.Comment: v3: consequences of an error in evolution equation for coupling rectified, only a minimal change in physics results, two refs. adde

Confining strings in SU(N) gauge theories

We calculate the string tensions of $k$-strings in SU($N$) gauge theories in both 3 and 4 dimensions. In D=3+1, we find that the ratio of the $k=2$ string tension to the $k = 1$ fundamental string tension is consistent, at the $2 \sigma$ level, with both the M(-theory)QCD-inspired conjecture and with `Casimir scaling'. In D=2+1 we see a definite deviation from the MQCD formula, as well as a much smaller but still significant deviation from Casimir scaling. We find that in both D=2+1 and D=3+1 the high temperature spatial $k$-string tensions also satisfy approximate Casimir scaling. We point out that approximate Casimir scaling arises naturally if the cross-section of the flux tube is nearly independent of the flux carried, and that this will occur in an effective dual superconducting description, if we are in the deep-London limit. We estimate, numerically, the intrinsic width of $k$-strings in D=2+1 and indeed find little variation with $k$. In addition to the stable $k$-strings we investigate some ofthe unstable strings, finding in D=2+1 that they satisfy (approximate) Casimir scaling. We also investigate the basic assumption that confining flux tubes are described by an effective string theory at large distances. We estimate the coefficient of the universal L\"uscher correction from periodic strings that are longer than 1 fermi, and find $c_L=0.98(4)$ in D=3+1 and $c_L=0.558(19)$ in D=2+1. These values are within $2 \sigma$ of the simple bosonic string values and are inconsistent with other simple effective string theories.Comment: 57 pages, 11 figures. Errors on fits reduced by altering the analysis to a standard one. Conclusions unchanged; note addedchanged. Some typos correcte

Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression

: Sickle cell disease and β-thalassemia affect the production of the adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in adult life (i.e., the hereditary persistence of fetal hemoglobin). Mutations clustering ~200 nucleotides upstream of the HBG transcriptional start sites either reduce binding of the LRF repressor or recruit the KLF1 activator. Here, we use base editing to generate a variety of mutations in the -200 region of the HBG promoters, including potent combinations of four to eight γ-globin-inducing mutations. Editing of patient hematopoietic stem/progenitor cells is safe, leads to fetal hemoglobin reactivation and rescues the pathological phenotype. Creation of a KLF1 activator binding site is the most potent strategy - even in long-term repopulating hematopoietic stem/progenitor cells. Compared with a Cas9-nuclease approach, base editing avoids the generation of insertions, deletions and large genomic rearrangements and results in higher γ-globin levels. Our results demonstrate that base editing of HBG promoters is a safe, universal strategy for treating β-hemoglobinopathies

Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to ets binding sites

The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21-22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (K(d) approximately 10(-7) M) at 37 degrees C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction