Whole-body & muscle responses to aerobic exercise training and withdrawal in ageing & COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V′(O(2))(peak)), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy young (HY), healthy older (HO) and COPD volunteers to whole-body exercise. METHODS: HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before and after 8 weeks of AET (65% V′(O(2))(peak)) and after 4 weeks of exercise withdrawal. V′(O(2))(peak), muscle maximal mitochondrial ATP production rate (MAPR), mitochondrial content, mitochondrial DNA (mtDNA) copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points. RESULTS: Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean±sd) was greater in HY (804±67) than in HO (631±69; p=0.041). AET increased V′(O(2))(peak) in HO (17%; p=0.002) and HY (21%; p<0.001), but not COPD (p=0.603). Muscle MAPR for palmitate increased with training in HO (57%; p=0.041) and HY (56%; p=0.003), and decreased with exercise withdrawal in HO (−45%; p=0.036) and HY (−30%; p=0.016), but was unchanged in COPD (p=0.594). mtDNA copy number increased with AET in HY (66%; p=0.001), but not HO (p=0.081) or COPD (p=0.132). The observed changes in muscle mRNA abundance were similar in all groups after AET and exercise withdrawal. CONCLUSIONS: Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All groups showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD

In vivo knee kinematics of ACL-deficient patients after unicompartmental knee arthroplasty

Introduction: In cases where a patient has arthritis in the medial side of their knee and has anterior cruciate ligament deficiency (ACLD), an operating surgeon has three options; (1) perform unicompartmental knee arthroplasty (UKA-ACLD), (2) perform unicompartmental knee arthroplasty and also reconstruct the ACL (UKA-ACLR), or (3) perform total knee arthroplasty (TKA-ACLD) which would require sacrificing the ACL even if it were present and functioning. Performing UKA in patients with a deficient ACL is normally avoided because there is evidence that it may increase the risk of tibial loosening [1]; however, in certain cases, upon patient request, the operation has been performed in our centre. A recent study examined these UKA-ACLD patients and found no evidence of loosening, and equivalent patient recorded outcomes to patients with an intact ACL (UKR-ACLI) [2]. The purpose of this study was to examine a subset of this cohort of UKA-ACLD patients in terms of their knee kinematics and compare to historical data controls (UKA-ACLI, UKA-ACLR, and TKA-ALCD). Methods: Six patients with seven ACL-deficient knees who had undergone mobile unicompartmental knee arthroplasty were examined. The study was approved by the Bristol Research Ethics Committee in January 2013, reference 13/SC/008. All of the primary operations had been performed between February 2004 and February 2012. For the fluoroscopic analysis, each patient was instructed to perform a step-up exercise, followed by a weight-bearing deep knee bend and fluoroscopy images were recorded as each exercise was performed. A calibration grid was imaged after each exercise to enable any image distortion to be removed. For each video frame (each video had ~50 frames) the patellar tendon angle (PTA) and the knee flexion angle (KFA) was manually measured using a custom software developed using MATLAB (MathWorks Ltd.). The results of the kinematic analysis were compared to previous work by Pandit et al. on UKA-ACLR knees [3], UKA-ACLI knees [3], and TKA-ACLD knees [4]. Non-parametric Mann-Whitney-U tests were used to examine significance between PTA results, and a Standard t-Test was used to examine difference in the cohorts. Results: The cohort for the UKA-ACLD group were significantly older than the UKA-ACLR and UKA-ACLI cohorts studied by Pandit et al. and had approximately double the mean time to follow up (Table 1), but no statistical difference was found between the ages of the UKA-ACLD and the TKA-ACLD groups. For the UKA-ACLD patients the PTA reduced with increasing KFA in the same manner previously observed in the UKA-ACLI and UKA-ACLR patients; however, the PTA was significantly reduced overall (Figure 1).Discussion: Previous studies have demonstrated that UKA-ACLI and UKA-ACLR knees are not significantly different to a normal knee in terms of the kinematics. The PTA of the UKA-ACLD knees throughout flexion was significantly lower compared with the UKA-ACLI and UKA-ACLR knees, indicating the UKA-ACLD knees have abnormal kinematics. The reduced PTA indicates that the tibia is more anteriorly positioned relative to the femur throughout flexion, this is likely to be due to the ACL not being present, or able, to resist anterior tibial translation. The PTA reduces throughout flexion, which shows that the knee is functioning more normally than the TKA-ACLD knee and may reflect the work by Boissoneault et al. that UKA-ACLD patients can have good outcome. However, the more posterior loading of the tibial tray may explain the increased likelihood of component loosening reported by Goodfellow et al. [1], although further work is required to confirm whether this is the case. In light of this data, it appears that in cases where a patient is ACL-deficient and has medial compartment arthritis, out of all the options examined in this study unicompartmental knee arthroplasty combined with ACL reconstruction will result in the most normal knee kinematics. Significance: Although ACLD knees that have undergone UKA appear to do well in many cases [2] the results presented here demonstrate significantly different knee kinematics in UKA-ACLD patients, and show that the tibia is more anteriorly positioned. The reduction of PTA with flexion is promising and indicates more normal knee kinematics than a TKA-ACLD knee, but this study shows UKA combined with ACL reconstruction to be the better option for ACLD knees, although this may not be justified in low-demand elderly patients. Acknowledgments: The authors would like to thank the ARUK for funding this project, Josie Cowell at the Nuffield Orthopaedic Centre for all her help with the fluoroscopy and all the patients who participated. References: [1] Goodfellow JW et al. J Bone Joint Surg [Br] (1988) 70-B: p692-701. [2] Boissoneault A et al. Knee Surg Sports Traumatol Arthrosc. (2012) DOI 10.1007/s00167-012-2101-8. Epub ahead of print [3] Pandit H et al. The Knee (2008) p101-106.[4] Pandit H et al. JBJS (2005) 87-B, p940-94

An overview of recent patents on nanosuspension

Pharmaceutical scientists involved in drug discovery and drug development are facing serious problems with newer poorly water soluble drugs with respect to their dissolution and bioavailability. Reducing the particle size of active pharmaceutical ingredient has been an efficient and reliable method for improving the bioavailability of insoluble drugs. Nanosuspension has emerged as an efficient and promising strategy for delivery of insoluble drugs due to its unique advantages such as ease of modification, process flexibility, targeting capabilities, altered pharmacokinetic profile leading to safety and efficacy. These unique features of nanosuspension have enabled its use in various dosage forms, including specialized delivery systems such as oral, parenteral, peroral, ocular and pulmonary routes. Currently, efforts are being directed to extend their applications in site-specific drug delivery. Large numbers of products based on nanosuspension are in the market and few are under clinical trials. The commercialization potential of nanosuspension based formulation for oral route is well established and products for other routes will enter the market within short span. Among the various techniques available, only wet milling technique has been successfully used for commercial production of nanosuspension. Nanosuspension based patents have extensive potential of reaching faster in the market as compared to other nanotechnology based formulations. This review covers various aspects of techniques of preparation, route of administration and commercialization of nanosuspension with main focus on the recent patents granted in the field

Safety and Efficacy of Vacuum-Assisted Breast Biopsies under Ultrasound and Stereotactic Guidance

Purpose To evaluate the safety and efficacy of vacuum-assisted breast biopsy (VABB) under ultrasound and stereotactic guidance

Society of Chest Imaging and Interventions Consensus Guidelines for the Interventional Radiology Management of Hemoptysis

The recommendations from the Society of Chest Imaging and Interventions expert group comprehensively cover all the aspects of management of hemoptysis, highlighting the role of diagnostic and interventional radiology. The diversity existing in etiopathology, imaging findings, and management of hemoptysis has been addressed. The management algorithm recommends the options for effective treatment while minimizing the chances of recurrence, based on the best evidence available and opinion from the experts