Bioelectrical phase angle values in a clinical sample of ambulatory rehabilitation patients

Background: Phase angle (PhA) is derived from the resistance and reactance measurements obtained from bioelectric impedance analysis (BIA) and is considered indicative of cellular health and membrane integrity. This study measured PhA values of rehabilitation patients and compared them to reference values, measures of functional ability and serum C-reactive protein (CRP) levels to explore their utility as a clinical tool to monitor disease progression and treatment efficacy. Methods: This cross-sectional observational study was conducted on 215 ambulatory rehabilitation patients aged 20 – 94 years. All participants had been hospitalised for a stroke, orthopaedic or other condition resulting in a functional limitation. PhA was derived from BIA analysis and functional ability characterised using the Functional Independence Measure (FIM), timed up and go (TUG) and maximal quadriceps strength (MQS). Serum levels of CRP were also collected. Results: Stroke patients had the highest PhA (5.3°) followed by elective orthopaedic surgery (5.0°) with the other group (4.3°) significantly lower than both previous categories (p < 0.001). Ambulatory rehabilitation patients' PhA values were dependent on age and sex (p < 0.001), lower than published age matched healthy reference values (p ≤ 0.05) and similar to other hospitalised or sick groups, but also higher than values reported in critically ill patients. Patients with CRP values less than 10 mg.L-1 had significantly (p = 0.005) higher mean PhA values. Furthermore, the highest functional status quartiles had significantly higher PhAs (p ≤ 0.04) for the FIM, MQS and TUG measures. Conclusion: The results suggest that the phase angles of rehabilitation patients are between those of healthy individuals and seriously ill patients, thereby supporting claims that PhA is indicative of general health status. Phase angles are a potentially useful indicator of functional status in patients commencing an ambulatory rehabilitation program with a normal hydration status.Simon M. Gunn, Julie A. Halbert, Lynne C. Giles, Jacqueline M. Stepien, Michelle D. Miller and Maria Crott

Rapid scale-up and production of active-loaded PEGylated liposomes

Manufacturing of liposomal nanomedicines (e.g. Doxil®/Caelyx®) is a challenging and slow process based on multiple-vessel and batch processing techniques. As a result, the translation of these nanomedicines from bench to bedside has been limited. Microfluidic-based manufacturing offers the opportunity to address this issue, and de-risk the wider adoption of nanomedicines. Here we demonstrate the applicability of microfluidics for continuous manufacturing of PEGylated liposomes encapsulating ammonium sulfate (250 mM). Doxorubicin was subsequently active-loaded into these pre-formed liposomes. Critical process parameters and material considerations demonstrated to influence the liposomal product attributes included solvent selection and lipid concentration, flow rate ratio, and temperature and duration used for drug loading. However, the total flow rate did not affect the liposome product characteristics, allowing high production speeds to be adopted. The final liposomal product comprised of 80–100 nm vesicles (PDI < 0.2) encapsulating ≥ 90% doxorubicin, with matching release profiles to the innovator product and is stable for at least 6 months. Additionally, vincristine and acridine orange were active-loaded into these PEGylated liposomes (≥ 90% and ~100 nm in size) using the same process. These results demonstrate the ability to produce active-loaded PEGylated liposomes with high encapsulation efficiencies and particle sizes which support tumour targeting

Physical activity and cardiovascular risk factors: effect of advice from an exercise specialist in Australian general practice

OBJECTIVE: To determine whether provision of individualised physical activity advice by an exercise specialist in general practice is effective in modifying physical activity and cardiovascular risk factors in older adults. DESIGN: Randomised controlled trial of individualised physical activity advice, reinforced at three and six months (intervention) versus no advice (control). SETTING: Two general practices in Adelaide, South Australia, 1996. Participants: 299 adults aged 60 years or more who were healthy, sedentary and living in the community. MAIN OUTCOME MEASURES: Changes to physical activity (frequency and duration of walking and vigorous exercise), selected cardiovascular risk factors (blood pressure, body weight, serum lipid levels) and quality of life over 12 months. RESULTS: Self-reported physical activity increased over the 12 months in both groups (P < 0.001). The increase was greater for the intervention than the control group for all measures except time spent walking (P < 0.05). More intervention than control participants increased their intention to exercise (P < 0.001). Serum levels of total and low-density lipoprotein cholesterol and triglycerides fell significantly over the 12 months to a similar extent in the two groups. No other significant changes in cardiovascular risk factors were seen. Quality-of-life scores decreased over the 12 months. The decrease was significantly greater among intervention than control women, but not men, for emotional well-being (P = 0.02), physical well-being (P = 0.04) and social functioning (P = 0.04). DISCUSSION: Provision of general practice-based physical activity advice reinforced three-monthly produced a sustained increase in self-reported physical activity. However, there were no associated changes in clinical measures of cardiovascular risk factors and minimal changes in quality-of-life measures.Julie A Halbert, Christopher A Silagy, Paul M Finucane, Robert T Withers and Phil A Hamdor

The effect of treatment on radiological progression in rheumatoid arthritis: a systematic review of randomized placebo-controlled trials

Haddersfield, U

Effect of muscle glycogen availability on maximal exercise performance

http://www.ncbi.nlm.nih.gov/pubmed/911898

Analyses of Single-Amino-Acid Substitution Mutants of Adenovirus Type 5 E1B-55K Protein

The E1B-55K protein plays an important role during human adenovirus type 5 productive infection. In the early phase of the viral infection, E1B-55K binds to and inactivates the tumor suppressor protein p53, allowing efficient replication of the virus. During the late phase of infection, E1B-55K is required for efficient nucleocytoplasmic transport and translation of late viral mRNAs, as well as for host cell shutoff. In an effort to separate the p53 binding and inactivation function and the late functions of the E1B-55K protein, we have generated 26 single-amino-acid mutations in the E1B-55K protein. These mutants were characterized for their ability to modulate the p53 level, interact with the E4orf6 protein, mediate viral late-gene expression, and support virus replication in human cancer cells. Of the 26 mutants, 24 can mediate p53 degradation as efficiently as the wild-type protein. Two mutants, R240A (ONYX-051) and H260A (ONYX-053), failed to degrade p53 in the infected cells. In vitro binding assays indicated that R240A and H260A bound p53 poorly compared to the wild-type protein. When interaction with another viral protein, E4orf6, was examined, H260A significantly lost its ability to bind E4orf6, while R240A was fully functional in this interaction. Another mutant, T255A, lost the ability to bind E4orf6, but unexpectedly, viral late-gene expression was not affected. This raised the possibility that the interaction between E1B-55K and E4orf6 was not required for efficient viral mRNA transport. Both R240A and H260A have retained, at least partially, the late functions of wild-type E1B-55K, as determined by the expression of viral late proteins, host cell shutoff, and lack of a cold-sensitive phenotype. Virus expressing R240A (ONYX-051) replicated very efficiently in human cancer cells, while virus expressing H260A (ONYX-053) was attenuated compared to wild-type virus dl309 but was more active than ONYX-015. The ability to separate the p53-inactivation activity and the late functions of E1B-55K raises the possibility of generating adenovirus variants that retain the tumor selectivity of ONYX-015 but can replicate more efficiently than ONYX-015 in a broad spectrum of cell types