Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery: Preparation, mucoadhesion and pharmacokinetic evaluation.

The present work aimed to develop nanoparticles of tobramycin (TRM) using thiolated chitosan (TCS) in order to improve the mucoadhesion, antibacterial effect and pharmacokinetics. The nanoparticles were evaluated for their compatibility, thermal stability, particle size, zeta potential, mucoadhesion, drug release, kinetics of TRM release, corneal permeation, toxicity and ocular irritation. The thiolation of chitosan was confirmed by 1H NMR and FTIR, which showed peaks at 6.6 ppm and 1230 cm-1, respectively. The nanoparticles had a diameter of 73 nm, a negative zeta potential (-21 mV) and a polydispersity index of 0.15. The optimized formulation, NT8, exhibited the highest values of mucoadhesion (7.8 ± 0.541h), drug loading (87.45 ± 1.309%), entrapment efficiency (92.34 ± 2.671%), TRM release (>90%) and corneal permeation (85.56%). The release pattern of TRM from the developed formulations was fickian diffusion. TRM-loaded nanoparticles showed good antibacterial activity against Pseudomonas aeruginosa. The optimized formulation NT8 (0.1% TRM) greatly increased the AUC(0-∞) (1.5-fold) while significantly reducing the clearance (5-fold) compared to 0.3% TRM. Pharmacokinetic parameters indicated improved ocular retention and bioavailability of TRM loaded nanoparticles. Our study demonstrated that the TRM-loaded nanoparticles had improved mucoadhesion and pharmacokinetics and a suitable candidate for effective treatment of ocular bacterial infections.

Interfacing Coacervates with Membranes: From Artificial Organelles and Hybrid Protocells to Intracellular Delivery.

Compartmentalization is crucial for the functioning of cells. Membranes enclose and protect the cell, regulate the transport of molecules entering and exiting the cell, and organize cellular machinery in subcompartments. In addition, membraneless condensates, or coacervates, offer dynamic compartments that act as biomolecular storage centers, organizational hubs, or reaction crucibles. Emerging evidence shows that phase-separated membraneless bodies in the cell are involved in a wide range of functional interactions with cellular membranes, leading to transmembrane signaling, membrane remodeling, intracellular transport, and vesicle formation. Such functional and dynamic interplay between phase-separated droplets and membranes also offers many potential benefits to artificial cells, as shown by recent studies involving coacervates and liposomes. Depending on the relative sizes and interaction strength between coacervates and membranes, coacervates can serve as artificial membraneless organelles inside liposomes, as templates for membrane assembly and hybrid artificial cell formation, as membrane remodelers for tubulation and possibly division, and finally, as cargo containers for transport and delivery of biomolecules across membranes by endocytosis or direct membrane crossing. Here, recent experimental examples of each of these functions are reviewed and the underlying physicochemical principles and possible future applications are discussed.

Spatial assessment of water quality parameters in Jhelum city (Pakistan).

In this study, we assess the drinking water quality of Jhelum city. Two hundred and ninety-two drinking water samples were randomly collected in the study area. These samples were chemically analyzed for three key toxic (in excess) elements such as pH, total dissolved solids (TDS), and calcium. Geostatistical techniques such as variogram and kriging were used to investigate the spatial variations of these minerals across the city. The spatial structure for each element was found to be anisotropic, and thus, anisotropic variograms were used. The kriging predictions revealed significant concentrations of the above-stated elements at some locations in the study area. While comparing with the World Health Organization, United States Environmental Protection Agency, and Pakistan Environmental Protection Agency standards, the water samples were found to be unsatisfactory for drinking. We conclude that the drinking water in this region is of poor quality and needs proper treatment to make it palatable.

The diagnostic value of single photon-emission computed tomography bone scans combined with CT (SPECT-CT) in diseases of the foot and ankle.

BACKGROUND: A radionuclide bone scan with single photon-emission computed tomography and CT (SPECT-CT) is a new imaging modality which combines highly detailed CT with the functional information from a triple phase radionuclide bone scan. Little has been published about its diagnostic accuracy and usefulness in foot and ankle pathology. The aim of this study is to evaluate whether bone scans with SPECT-CT provide a useful contribution to the management of patients with foot and ankle pain, and whether it results in changes to clinical management. METHODS: A retrospective study involving 50 patients was conducted between March 2010 and April 2011. SPECT-CT was requested in cases where definitive clinical diagnosis could not be achieved after clinical examination and plain radiography. Pathology as highlighted on SPECT-CT was taken as the definitive diagnosis in these patients and was treated accordingly. Patients were subsequently seen in the follow up clinic to evaluate the outcome of their treatment. RESULTS: In 11 patients (22%), the provisional clinical diagnosis matched with the findings of the SPECT-CT and no change in treatment was necessary. In 39 patients (78%) the findings of the SPECT-CT did not correlate exactly with the initial clinical diagnosis and led to a modified treatment plan. The accuracy, sensitivity, specificity, positive predictive and negative predictive value of SPECT-CT in this series was 94%, 95.45%, 83.3%, 97.6% and 71.43% respectively. CONCLUSIONS: SPECT-CT is a useful investigation tool in foot and ankle pathologies. The present study shows a high diagnostic accuracy and we recommend its use in cases with diagnostic uncertainty.

Sterile surgical helmet system in elective total hip and knee arthroplasty.

PURPOSE: To evaluate the sterility of the sterile surgical helmet system (SSHS) during elective total hip and knee arthroplasty in theatres with (n=20) and without (n=20) laminar flow. METHODS: Three surgeons performed 14 total knee arthroplasties (TKAs) and 6 total hip arthroplasties (THAs) in a laminar flow theatre and 15 TKAs and 5 THAs in a non-laminar flow theatre. An SSHS was used in all the procedures. Samples were taken from the hood at 30-minute intervals during surgery. Swabs were then broken into cooked meat broths for cultivation of organisms. The broths were then directly inoculated onto blood agar and fastidious anaerobic agar for culture of aerobic and anaerobic bacteria, respectively. After 24 hours, these plates were reinoculated with broths that had been incubated for 24 hours. Microbial growth was quantified as 0 (none), 1 (mild), 2 (moderate) and 3 (heavy). Bacterial contamination in the 2 groups at 30, 60 and 90 minutes was compared. RESULTS: Respectively in the laminar and non-laminar flow theatres, 0 and 9 of the SSHSs showed bacterial growth after direct inoculation, and 14 and 18 of the SSHSs grew 18 and 24 types of organisms in the swab cultures after 24 hours of incubation. Respectively at 30, 60, and 90 minutes, the degree of contamination from direct incubation was significant, but the degree of contamination on swabs after 24 hours of inoculation was not significant. The mean time-dependent contamination after direct inoculation was 0 for the laminar flow group and 0.5, 0.75, and 1.0 for the non-laminar flow group, whereas the corresponding values after 24 hours of incubation were 1.8, 1.8, and 2.6, and 2, 2.75, and 2.95. Coagulase negative Staphylococcus aureus was the most common organism in both groups. CONCLUSION: 80% of SSHSs used were contaminated intra-operatively. Direct contact with the SSHS should be avoided by the operating team during surgery. Routine changing of gloves in case of contact with the SSHS should be practised.

Autologous transfusion of drain contents in elective primary knee arthroplasty: its value and relevance.

BACKGROUND: Total knee arthroplasty is associated with significant post-operative blood loss often necessitating blood transfusions. Blood transfusions may be associated with transfusion reactions and may transmit human immunodeficiency virus, hepatitis C virus and hepatitis B virus, with devastating consequences. After total knee arthroplasty, transfusion of the contents of an autologous drain is becoming common practice. The aim of our study was to look at the effectiveness of these drains in elective primary total knee arthroplasty. MATERIALS AND METHODS: A prospective study was conducted including 70 non-randomised patients. A normal suction drain was used in 35 patients (group A), whereas in the other 35 patients, a CellTrans™ drain was used (group B). All the operations were performed by four surgeons using a tourniquet with a medial parapatellar approach. Pre- and post-operative haemoglobin concentrations were recorded in both groups. A Student's t-test was applied to determine the statistical significance of the data collected. RESULTS: The average fall in post-operative haemoglobin was 3.66 g/dL (SD 1.46; range, 0.6-7.0) among patients in whom the simple drain was used (group A) and 2.29 g/dL (SD 0.92; range, 0.6-5.9) among those in whom the CellTrans™ drain was used (group B) (p<0.0001). Twenty-five units of allogeneic blood were required in group A compared to four units in group B. The rate of transfusion was 5.7% (2 patients) in the group in which CellTrans™ drain was used and 25.7% (9 patients) in the group in which a simple suction drain was used. DISCUSSION: Total knee arthroplasty is associated with significant post-operative blood loss despite best operative technique. Autologous reinfusion of the contents of a CellTrans™ drain significantly reduces the rate of post-operative blood transfusion. This study indicates that the use of an autologous drain could be recommended as routine practice in primary total knee arthroplasty.

Atraumatic patellar prosthesis dislocation with patellar tendon injury following a total knee arthroplasty: a case report.

INTRODUCTION: Total knee arthroplasty is a well-established procedure with gratifying results. There is no consensus in the literature whether to routinely resurface the patella while performing total knee arthroplasty or not. Although an extremely rare occurrence in clinical practice, patellar prosthesis dislocation is a possible complication resulting from total knee arthroplasty. CASE PRESENTATION: We report a rare case of atraumatic spontaneous dislocation of patellar prosthesis in a 63-year-old Caucasian man of British origin with patellar tendon injury. The patient was treated successfully through a revision of the patellar component and tendon repair. In two years follow-up the patient is asymptomatic with no sign of loosening of his patellar prosthesis. CONCLUSIONS: A thorough understanding of knee biomechanics is imperative in performing total knee arthroplasty in order to achieve a better functional outcome and to prevent early prosthetic failure.