Gas-phase and solution studies of three resorcin[4]arene derivatives using electrospray time-of-flight mass spectrometry.

Electrospray ionisation mass spectrometry (ESI-MS) has been used to study the relative gas-phase proton and alkali metal (Li, Na, K and Cs) binding affinities of three different resorcin[4]arenes using the kinetic method. Collision-induced dissociation (CID) was used to study the fragmentation of resorcin[4]arene heterodimer sandwich complexes, allowing the relative binding affinity order to be established. All the alkali metal cations have the same gas-phase binding affinity order with the resorcin[4]arene host molecules. At collision energies of > or = 13eV, one of the [resorcin[4]arene+Metal]+, (Metal = Li, Na, K) ions fragmented through break-up of the resorcin[4]arene, whilst the other host resorcin[4]arene remained intact, causing an apparent change in binding affinity at high collision energy. This effect was not observed with caesium, since all complex ions dissociated readily under CID by displacement of the caesium cation. The binding affinity for the protonated resorcin[4]arenes was found to be different from the alkali metal cation binding affinity because of the higher proton affinity of the nitrogen-containing resorcin[4]arenes. It is shown that resorcin[4]arenes containing an oxazine ring can be converted into a ring-opened derivative via an Eschweiler-CLarke reaction in the presence of formic acid. A second ring-opening process also occurs, including a hydrolysis reaction that results in apparent Losses of 12 mass units from the intact resorcin[4]arene. Both these reactions occur in solution before mass spectrometric investigation and cannot be achieved by CID. This observation was confirmed by inducing the Eschweiter-CLarke reaction in a model benzoxazine compound.

Hertfordshire sarcopenia study: design and methods.

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms. METHODS: One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study. DISCUSSION: The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.

Randomized controlled trial of the efficacy of aerobic exercise in reducing metabolic risk in healthy older people: The Hertfordshire Physical Activity Trial.

BACKGROUND: While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group. METHODS/DESIGN: We aim to recruit 100 participants born between 1931-1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing. DISCUSSION: Given the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN60986572.