The Physical Inactivity Matrix: Lessons from the classification of physical inactivity interventions

Physical inactivity (PI), a leading modifiable cause of disease and injury, is endemic in industrialised nations. Although considerable research has been undertaken in this field, we lack a system to synthesise the research literature to inform policy and identify research needs. The aims of this study were to (1) develop a system to classify physical inactivity intervention studies, (2) examine the distribution of PI interventions published in the peer-reviewed health literature using the system, and (3) consider implications for future research. We developed the Physical Inactivity Matrix (PIM), with 12 intervention points, created by the intersection of two dimensions: the intervention target (individual, physical environment and social/cultural environment) and the activity focus (transport, work/school, leisure and consumer). A formal search of the health research literature identified 529 eligible studies and each was classified into one of the 12 cells of the PIM. Most studies were categorised as: individual-leisure (68%), individual-work/school (12%) or social/cultural environment-leisure (13%). Only 4% targeted the physical environment. The findings of this initial application of the PIM support the call for greater investment in policies, interventions and research that focus on the relationship between the environment and PI, and transportation in particular. There would be merit in establishing the inter-rater reliability of the PIM and applying it to a wider variety of studies, including those published in the transportation and urban planning literatures. The PIM could be a useful tool for monitoring trends in research directions and funding levels over time and across countries.     

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.     

Detection of liver fibrosis with magnetic cross-relaxation

The utility of MRI using magnetization transfer (MT) enhanced pulse sequences to diagnose hepatic cirrhosis in a rat model was investigated. Hepatic T₁ was measured with and without MT off-resonance RF pulses in 17 treated and six control rats. The livers were evaluated histologically, and the hydroxyproline content quantitatively measured. We did not find a statistically significant linear correlation between the MR relaxation times and the degree of tissue injury. However, the MR measurements performed with MT were superior to those without differentiating the treated and control groups. Specifically, the T₁ times were 695 ±76 ms for the treated group, versus 748 ± 61 ms in the controls; P= 0.095. The T_1sat times were also lower in the treated group, with statistical significance: 367 ± 51 ms versus 421 ± 38 ms, P = 0.016. Finally, the change in the relaxation rates (the inverse of the relaxation times) with and without saturation were 1.31 ± 0.22 s^?1 (treated group) versus 1.05 ± 0.12 s^?1 (controls), which differed significantly, P= 0.001.     

The therapeutic antibodies market to 2008.

The therapeutic biologics market is currently dominated by recombinant protein products. However, many of these products are mature, and growth of the biologics market will increasingly rely on the expansion of the therapeutic monoclonal antibody sector. Successive technology waves have driven the growth of the monoclonal antibody sector, which is currently dominated by chimeric antibodies. Chimeric products, led by Remicade and Rituxan, will continue to drive market share through to 2008. However, over the forecast period, humanized and fully human monoclonal antibodies, together with technologies such as Fabs and conjugated antibodies, will play an increasingly important role, driving monoclonal antibody market growth at a forecast compound annual growth rate of 20.9%, to reach $16.7 billion by 2008. In terms of therapeutic focus, the monoclonal antibody market is heavily focused on oncology and arthritis, immune and inflammatory disorders, and products within these therapeutic areas are set to continue to be the key growth drivers over the forecast period. Underlying the growth of the market is the evolution of the monoclonal antibody company business model, set to transition towards the highly successful innovator model.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

Besprechungen

Ohne Zusammenfassung