Comparison of Long-Term Biocompability of PVDF and PP Meshes

ABSTRACT

Background: Abdominal hernia repair is the most frequently performed operation in surgery. Mesh repair in hernia surgery has become an integral component. Although meshes made of PVDF are already in clinical use, so far no data of long-term biocompability are available. Methods: In this study a PVDF mesh was compared to a polypropylene mesh with regard to its long-term biocompatibility. A total of 28 rats were randomized to two groups. Mesh material was implanted subcutaneously; animals were euthanized seven days and six months postoperatively. The quantity of inflammatory tissue response was characterized by measuring the diameter of the foreign body granuloma. Furthermore quality of cellular immune response (T-lymphocytes, macrophages, and neutrophils), and inflammation (COX-2) was analyzed by immunohistochemistry. Furthermore the collagen type I/III ratio was determined. Results: Macrophages, T-lymphocytes, neutrophiles, and COX-2 declined significantly up to six months postoperatively in comparison to day 7 for both PVDF and PP meshes, and in both groups the collagen ratio increased significantly in the course of time. PVDF meshes showed a foreign body granuloma size significantly reduced compared to PP (7 days: 20 ± 2 μm vs. 27 ± 2 μm; 6 months 15 ± 2 μm vs. 22 ± 3 μm; p < .001). However no significant differences were found analyzing cellular response six months postoperatively. Conclusions: Our current data suggest that even in the long-term course after six months and despite a higher effective surface of the PVDF samples it showed a smaller foreign body granuloma than with PP whereas the cellular response was similar.     

Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP_139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.     

Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (¹H, ²³Na, ¹³C) was instrumental in delineating the components of the matrix. We identified the root cause to be an acid base reaction occurring in the DP, whereby sodium ion in sodium stearyl fumarate (SSF) is replaced by proton leading to SSF form conversion. We also identified commercially available SSF to be a hydrate that can dehydrate to an anhydrous form upon heating. In general, the same techniques can be used to investigate interactions of any multi component solid dosage forms.     

喘可治注射液联合布地奈德福莫特罗治疗慢性阻塞性肺疾病的疗效观察

摘 要 目的： 观察喘可治注射液联合布地奈德福莫特罗治疗慢性阻塞性肺疾病(COPD) 的疗效。方法: 120例COPD患者随机分为2组,观察组予布地奈德福莫特罗吸入同时肌注喘可治注射液,对照组单纯给予布地奈德福莫特罗吸入。治疗28 d,比较两组FEV₁%预计值、FEV₁ /FVC、6 min 步行距离(6MWD)等肺功能指标变化和急性加重次数,同时观察治疗期间两组药物不良反应的发生情况。结果: 治疗后2组肺功能和 6 MWD均较前改善;观察组比对照组FEV1%预计值改善更明显[（59.7±12.1) %和(49.8±11.3)%,P<0.05],至少有1次急性加重的患者数明显减少( 35%和62%,P＜0.01) ,并且两组的药品不良反应发生率差异无统计学意义。结论:喘可治注射液联合布地奈德福莫特罗比单用布地奈德福莫特罗能更好地改善COPD患者的肺功能,减少急性加重次数,不会增加药品的不良反应发生率。     

Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.     

Effectiveness of Delayed-release Dimethyl Fumarate on Clinical and Patient-reported Outcomes in Patients With Relapsing Multiple Sclerosis Switching From Glatiramer Acetate: RESPOND,a Prospective Observational Study

Purpose

The goal of this study was to evaluate clinical outcomes and patient-reported outcomes (PROs) over 12 months in patients with relapsing multiple sclerosis (RMS) who switched from glatiramer acetate (GA) to delayed-release dimethyl fumarate (DMF) 240 mg BID after suboptimal response to GA in real-world clinical practice.

Aclidinium bromide and formoterol fumarate for the maintenance treatment of chronic obstructive pulmonary disease

ABSTRACT

Introduction: Treatment options for COPD have evolved rapidly in the last decade and inhaled bronchodilators have largely supplanted the use of oral bronchodilators because of their increased efficacy and excellent safety with topical delivery to the lung. Recently added to the therapeutic armamentarium are fixed-dose combinations (FDC) of two long acting bronchodilators. LAMAs (long acting muscarinic antagonists) and LABAs (long acting beta agonists) are the main classes available and use different pathways to effectively produce bronchial smooth muscle relaxation.

Areas covered: The most recent inhaled FDC LAMA/LABA to come to market is Aclidinium Bromide and Formoterol Fumarate. We searched databases of PubMed, Cochrane Library, and manufacturers’ websites and retrieved all the randomized-controlled trials (RCTs) conducted with these drugs up to September 2019.

Expert opinion: It is likely that FDCs will become the core of our COPD pharmacotherapy for all but the mildest COPD patients. These individual drugs have excellent efficacy and safety records for the maintenance treatment of COPD. Studies have demonstrated that twice daily treatment with aclidinium/formoterol resulted in significant improvement in lung function and an improved exercise tolerance when compared to placebo. Adverse effects are within the range of what is seen with other LAMA/LABA combinations.     

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ² test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log₁₀ IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log₁₀ IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.     

Surface roughness enhances upward migration of bacteria on polymer fibers above liquid cultures

Monofilament polypropylene (PP) fibers, very similar to fibers that have been used as monofilament tailstrings of interuterinc contraceptive devices, were suspended vertically in bacterial liquid monocultures so that a portion of a fiber extended above the liquid surface. In some cases these highly oriented, cold drawn fibers were abraded prior to insertion in the cultures in order to produce surface roughness characterized by axial channels and protruding microfibrils that partially peeled from the fiber surface thereby forming the channels. Extent of migration on a fiber was assessed by aseptically cutting it into small segments, followed by culturing each segment on agar containing growth medium. Such assessment of the PP fibers after 48 h of incubation in the cultures revealed upward migration of Eschericia coli, Pseudomonas aeruginosa, and Staphylococcus aureus over significantly longer distances on the pre-roughened fibers than on those not so pre-treated. Mean measured distances of migration during 48 h were: for E. coli 2.7 ± 0.6 mm on roughened fibers (n = 16) and 0.4±0.7 mm on fibers not roughened (n = 17); for S. aureus 9.0±4.3 mm on roughened fibers (n = 13) and 0.2± 0.3 mm on fibers not roughened (n = 14); for P. aeruginosa 8.5± 3.7 mm on roughened fibers (n = 26) and 0.2± 0.5 mm on fibers not roughened (n = 5). Although no statistically significant (95% confidence level) difference could be discerned between the migration distances of S. aureus and P. aeruginosa, each of these species migrated a greater distance on the PP than did E. coli. The migrations observed are attributed predominantly to wicking of the liquid cultures upward in the axial grooves developed on the surface of the PP by the eruption and peeling of microfibrils from the surface. Surface tension of the growth medium was significantly lower than that of water and its contact angle on PP was less than 90 deg, thereby indicating a tendency to wet the PP. Bacterial growth in the medium further reduced its contact angle on PP, thereby indicating an even greater tendency to wet PP after such growth.