Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy

A PEGylated drug delivery system of paclitaxel (PTX), based on glyceryl monooleate (GMO) was prepared by optimizing various parameters to explore its potential in anticancer therapy. The prepared system was characterized through polarized light microscopy, TEM, AFM and SAXS to reveal its liquid crystalline nature. As GMO based LCNPs exhibit high hemolytic toxicity and faster release of entrapped drug (66.2?±?2.5% in 24?h), PEGylation strategy was utilized to increase the hemocompatibility (reduction in hemolysis from 60.3?±?10.2 to 4.4?±?1.3%) and control the release of PTX (43.6?±?3.2% released in 24?h). The cytotoxic potential and cellular uptake was assessed in MCF-7 cell lines. Further, biodistribution studies were carried out in EAT (Ehrlich Ascites tumor) bearing mice using (99m)Tc-(Technetium radionuclide) labeled formulations and an enhanced circulation time and tumor accumulation (14 and 8 times, respectively) were observed with PEGylated carriers over plain ones, at 24?h. Finally, tumor growth inhibition experiment was performed and after 15 days, control group exhibited 15 times enhancement in tumor volume, while plain and PEGylated systems exhibited only 8 and 4 times enhancement, respectively, as compared to initial tumor volume. The results suggest that PEGylation enhances the hemocompatibility and efficacy of GMO based system that may serve as an efficient i.v. delivery vehicle for paclitaxel.     

Multidetector computed tomography of spinal trauma: a pictorial review

Spinal trauma is 1 of the major causes of disability that commonly affects young adults, and radiologists play a crucial role in the evaluation of acutely traumatized patients. With the advent of multidetector computed tomography (MDCT), the algorithm of imaging of spinal trauma has changed dramatically and MDCT is now established as the imaging modality of choice for the diagnosis of spinal trauma. The appearance on MDCT of the spinal injury depends on the mechanism of the injury, which also determines the stability of the injury. This pictorial essay describes the MDCT appearances, mechanism, and stability of commonly encountered traumatic spinal injuries.     

After early release of tourniquet in total knee arthroplasty,should it be reinflated or kept deflated? A randomized trial

Purpose

This study was undertaken to determine the efficacy of reinflation of the tourniquet after its early release in TKA compared to early release alone, in terms of surgical field visualization and operative time. We also questioned whether tourniquet reinflation after its early release is safe, with respect to post-operative blood loss, post-operative pain and other tourniquet-related complications.

Methods

Two hundred and six patients undergoing TKA were randomly allocated to either the early release (deflation) group (n = 105) or reinflation after early release (reinflation) group (n = 101). Efficacy was measured in terms of surgical field visualization, specifically the number of wound clearances, and operative time. Safety outcomes were drained volume, decline in haemoglobin on post-operative days 2 and 5, the frequency of transfusion, knee and thigh pain visual analog scale, local wound complications, tourniquet site complications and other complications, including infection, deep vein thrombosis and pulmonary embolism.

Results

Surgical field visualization was better in the reinflation group; however, the operative time did not differ between the two groups. There were no differences between the two groups in post-operative blood loss, decline in haemoglobin on days 2 and 5, transfusion rate, pain level, local complications and other complications.

Conclusion

Reinflation of tourniquet is a safe alternative to its early release after deflation in that it improves surgical field visualization during TKA.

Level of evidence

Therapeutic study, Level I.

     

Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties

Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll‐like receptor 5–deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross‐sectional geometry, implicating impaired bone tissue material properties. Small differences in whole‐bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole‐bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.     

Skin substitutes with noncultured autologous skin cell suspension heal porcine full-thickness wounds in a one-stage procedure

Clinical application of skin substitute is typically a two-stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split-thickness skin graft (STSG). This two-stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one-stage procedure by combining bioengineered collagen-chondroitin-6-sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full-thickness wound healing model was evaluated. Twelve full-thickness excisional wounds on the backs of pigs received one of six different treatments: empty; ASCS; DS1 with or without ASCS; DS2 with or without ASCS. The ASCS was prepared using a point-of-care device and was seeded onto the bottom side of DS1, DS2, and empty wounds at 80 000 cells/cm². Wound measurements and photographs were taken on days 0, 9, 14, 21, 28, 35, and 42 post-wounding. Histological analysis was performed on samples obtained on days 9, 14, 28, and 42. Wounds in the empty group or with ASCS alone showed increased wound contraction, fibrosis, and myofibroblast density compared with other treatment groups. The addition of ASCS to DS1 or DS2 resulted in a marked increase in re-epithelialisation of wounds at 14 days, from 15 ± 11% to 71 ± 20% (DS1 vs DS1 + ASCS) or 28 ± 14% to 77 ± 26 (DS2 vs DS2 + ASCS) despite different mechanisms of tissue regeneration employed by the DS used. These results suggest that this approach may be a viable one-stage treatment in clinical practice.