Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity

Purpose

Etidocaine (EDC) is a long lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia time and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong the drug release, from liposomes.

Methods

First, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenated soy phosphatidylcholine:cholesterol with 250 mM (NH₄)₂SO₄ - inside gradient - were prepared for the encapsulation of 0.5% EDC. Dynamic light scattering, nanotracking analysis, transmission electron microscopy and electron paramagnetic resonance were used to characterize: nanoparticles size, polydispersity, zeta potential, concentration, morphology and membrane fluidity. Release kinetics and in vitro cytotoxicity tests were also performed.

Results

IGL_EDC showed average diameters of 172.3?±?2.6 nm, low PDI (0.12?±?0.01), mean particle concentration of 6.3?±?0.5?×?10¹²/mL and negative zeta values (?10.2?±?0.4 mV); parameters that remain stable during storage at 4°C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (ca. 24 h), while reducing its toxicity to human fibroblasts.

Conclusion

A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGL_EDC can come to be a tool to reintroduce etidocaine in clinical use.

     

Curcumin supplementation improves oxidative stress and inflammation biomarkers in patients undergoing hemodialysis: a secondary analysis of a randomized controlled trial

International Urology and Nephrology - Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to...     

Photobiomodulation via a cluster device associated with a physical exercise program in the level of pain and muscle strength in middle-aged and older women with knee osteoarthritis: a randomized placebo-controlled trial

Osteoarthritis (OA) is a chronic joint disease that leads to pain and functional incapacity. The aim of the study is to investigate the effects of the incorporation of photobiomodulation (PBM) (via cluster) into a physical exercise program on the level of pain, lower limb muscle strength, and physical capacity, in patients with knee OA. Sixty-two female volunteers with a diagnosis of knee OA were distributed in 4 groups: exercise associated with placebo PBM group, exercise associated with active PBM group, active PBM group, and placebo PBM group. Sixteen sessions of lower limb strength exercises and PBM via cluster (808 nm, 100 mW, 7 points each side, 56 J total) were performed. The level of pain, physical capacity, and lower limb muscle strength were evaluated with the use of the numeric pain rating scale (NPRS), 6-min walking test (6-MWT) and timed up and go (TUG), and maximal voluntary isometric torque (MVIT) before and after the interventions. Both groups presented a significant decrease in the level of pain when compared with the placebo-treated women. Furthermore, the 6-MWT showed that the trained groups (with or without PBM) demonstrated higher values in the distance walked comparing pre and post-treatment values. The same behavior was found for the MVIT load before and after intervention. TUG was higher for all the treated with exercise groups comparing the pre and post-treatment values. Physical exercise and PBM showed analgesic effects. However, PBM did not have any extra effect along with the effects of exercise in improving the distance walked, the TUG, and the muscle strength.

Trial registration: RBR-7t6nzr

     

Biocompatibility of Ricinus communis polymer with addition of calcium carbonate compared to titanium. Experimental study in guinea pigs

Objective

The aim of the present investigation was to determine whether the difference in inflammatory tissue reaction between the Riccinus communis (castor) polymer with calcium carbonate and the titanium implant is statistically significant.

Methods

Thirty-two Cavia porcellus were allocated into four groups of eight animals each. We implanted the two types of materials in the retroperitoneal space of all the animals. They were euthanized at 7, 20, 30 and 40 days after surgery, and an histological study of the samples was conducted.

Results

All implants showed characteristics of chronic inflammation regardless of the material and timepoint of evaluation. There was no statistically significant difference between Pm+CaCO₃ and Ti with regard to the presence of granulation tissue, tissue congestion, histiocytes, lymphocytes, neutrophils, giant cells, and fibrosis (P> 0.05).

Conclusion

The castor oil polymer plus calcium carbonate implant was not statistically different from the titanium implant regarding inflammatory tissue reaction.     

Hospital Costs Associated With Laparoscopic and Open Inguinal Herniorrhaphy

Purpose:

The purpose of this study was to compare the total hospital costs associated with elective laparoscopic and open inguinal herniorrhaphy.

Methods:

A prospectively maintained database was used to identify patients who underwent elective inguinal herniorrhaphy from April 2009 to March 2011. A retrospective review of electronic patient records was performed along with a standardized case-costing analysis using data from the Ontario Case Costing Initiative. The main outcomes were operating room (OR) and total hospital costs.

Results:

Two hundred eleven patients underwent elective unilateral inguinal herniorrhaphy (117 open and 94 laparoscopic), and 33 patients underwent elective bilateral inguinal herniorrhaphy (9 open and 24 laparoscopic). OR and total hospital costs for open unilateral inguinal hernia repair were significantly lower than for the laparoscopic approach (median total cost, $3207.15 vs $3723.66; P < .001). OR and total hospital costs for repair of elective bilateral inguinal hernias were similar between the open and laparoscopic approaches (median total cost, $4574.02 vs $4662.89; P = .827).

Conclusions:

In the setting of a Canadian academic hospital, when considering the repair of an elective unilateral inguinal hernia, the OR and total hospital costs of open surgery were significantly lower than for the laparoscopic techniques. There was no statistical difference between OR and total hospital costs when comparing open surgery and laparoscopic techniques for the repair of bilateral inguinal hernias. Given the perioperative benefits of laparoscopy, further studies incorporating hernia-specific outcomes are necessary to determine the cost-effectiveness of each approach and to define the optimal treatment strategy.     

Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a human CD4⁺ T cell line. Using flow cytometry and fluorescent focus assay, we found that A3.01 cells are susceptible but virtually not permissive to HRSV infection. Dequenching experiments revealed that the fusion process of HRSV in A3.01 cells was nearly abolished in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by RT-qPCR showed that the replication of HRSV in A3.01 cells was considerably reduced. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, using fluorescence in situ hybridization, we found that the inclusion body-associated granules (IBAGs) were almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins colocalized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments were present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4⁺ T cells is virtually unproductive as compared to HEp-2 cells, as a result of defects at several steps of the viral cycle: Fusion, genome replication, formation of inclusion bodies, recruitment of cellular proteins, virus assembly, and budding.     

Performance of Candida albicans germ tube antibodies (CAGTA) and its association with (1 → 3)-β-D-glucan (BDG) for diagnosis of invasive candidiasis (IC)

Invasive candidiasis (IC) plays an important role as severe infection. Elder population, immunocompromised individuals, and intensive care unit (ICU) patients, especially when exposed to major surgery, are the most affected. IC diagnosis and treatment are difficult because of the absence of pathognomonic signs and symptoms. In addition, culture-based examination (gold standard) is known to have low sensitivity and long time to report. All these often lead to unnecessary and costly empirical antifungal therapies, burdened also by the onset of drug resistance and serious side effects for the patient. To partially overcome these problems, in recent years, novel noncultural markers have been investigated with the aim of easily and rapidly achieving an early diagnosis of IC. Such novel markers include the pan-fungal antigen (1?→?3)-β-D-glucan (BDG) and the anti–Candida albicans germ tube antibodies (CAGTAs). We retrospectively analyzed the presence of CAGTA on ?80?°C stored serum samples, where the level of BDG had been previously assessed in a prospective study conducted in the Azienda Ospedaliero–Universitaria Policlinic of Modena (Pini et al. Infection 44:223–233, 2016). In particular, we selected 29 samples from proven IC episodes and 28 from non-IC cases. The 29 IC samples had been diagnosed as infections by C. albicans (n?=?16), C. glabrata (n?=?8), C. parapsilosis (n?=?1), C. pelliculosa (n?=?1), and C. tropicalis (n?=?1), while 2 samples had intrasurgery biopsies positive for yeast (compatible with Candida spp.). The 28 control samples (non-IC) included 9 sera with positive blood cultures [E. faecium (n?=?5), S. pneumoniae (n?=?2), P. aeruginosa?+?A. baumannii (n?=?2)] and 19 negative blood cultures. The CAGTA immunofluorescence assay was performed using 1:40, 1:80, 1:160, and 1:320 dilutions (reference dilution, as indicated by the manufacturer). According to the protocol, the samples were evaluated by the operator-dependent optical reading based on immunofluorescence positive/negative samples. In parallel, with the aim of standardizing the reading, the fluorescence images were captured, and the data were expressed as arbitrary fluorescence units (AFU). Finally, the results were interpreted as positive or negative using a cutoff provided by receiver operating characteristic (ROC) curves (Youden index). The traditional operator-dependent optical reading and the AFU measuring protocol provided comparable information with respect to the processed samples since IC and non-IC sera were correctly identified by the 2 CAGTA reading strategies in most of the cases. Interestingly, the AFU reading enabled a semiquantitative evaluation of the samples and an objective interpretation of the results. Based on the cutoff value, the AFU-based CAGTA procedure demonstrated a sensitivity of 52% and a specificity of 89%, while BDG showed a sensitivity of 90% and a specificity of 75%; the overall accuracy was 70% and 83% for CAGTA and BDG, respectively. The association of the 2 markers greatly increased both sensitivity and accuracy to 97% and 84%, respectively. As expected, when excluding non–C. albicans episodes, the sensitivity of CAGTA increased from 52% to 86%; moreover, with the exclusion of the non–deep-seated episodes, the sensitivity of CAGTA increased to 67% and reached 100% for C. albicans deep-seated candidiasis. Finally, when evaluating the influence of colonization, BDG demonstrated the most drastic decrease in specificity that dropped from 88% in noncolonized to 58% in colonized patients. With the exception of non–C. albicans episodes, CAGTA is a good marker of IC, particularly in the presence of deep-seated candidiasis. The performance of CAGTA greatly increases when used in combination with BDG.     

A universally applicable clinical classification of lymphedema

A simple classification of lymphedema is presented that is based solely on clinical observation. It is suggested that the universal use of such a classification would facilitate the collection of meaningful epidemiologic data and would make possible understandable comparisons of the effectiveness of various treatment modalities.