An analysis of injury rates after the seasonal change in rugby league.

OBJECTIVES: To determine whether the increase in the incidence of injury found for the first summer season in which rugby league (RL) was played in the UK was repeated in subsequent summer seasons. DESIGN: A retrospective and prospective cohort study design. SETTING AND PARTICIPANTS: Injuries were recorded from all players who took part in 141 games over 3 summer seasons (1997 to 1999) for 1 professional team. These were compared against rates from previously collected data for 3 earlier winter and 1 summer season. ASSESSMENT OF RISK FACTORS: For each injury it was recorded in which season it occurred; how many games or training sessions, if any, were subsequently missed; the type, site and severity of injury. MAIN OUTCOME MEASURES: Injuries were reported as rate per 1000 hours, also broken down into severity according to the number of games missed and whether subsequent training sessions were missed. RESULTS: A sustained increase in injury incidence has been found comparing summer RL over RL played in the winter. There was an increase in injury rates for all sites and types, but not all reached significance. CONCLUSIONS: Data collected over 6 seasons indicate a higher risk of sustaining an injury playing summer RL, but the cause may be related to a combination of factors. These may include the ground or weather conditions associated with summer rugby, player characteristics or changes in the game itself and future research needs to investigate these further.     

The flickery block of ATP-dependent potassium channels of skeletal muscle by internal 4-aminopyridine

We have examined the effects of 4-aminopyridine (4-AP) on single ATP-dependent potassium channels in patches excised from frog skeletal muscle. 4-AP applied to the internal face of the membrane caused a flickery block. We could not detect any flickery block when 10 mM 4-AP was applied to the external surface of the membrane. The reduction in mean unitary current by internal 4-AP was consistent with 11 binding with a K _d of 3.3 mM at 0 mV. The block was voltage-dependent, increasing with depolarization with an effective valency of 0.57. Rate constants for blocking and unblocking by 4-AP were obtained by fitting functions to the distribution of current amplitudes. Both rate constants were voltage-dependent. At 0 mV they were 17 mM^–1 ms^–1 and 61 ms^–1. Simulation of the block using these rate constants produced a flickery block very similar to that observed experimentally.     

Modulation of hERG potassium currents in HEK-293 cells by protein kinase C. Evidence for direct phosphorylation of pore forming subunits

The human ether-a-go-go related gene (hERG) potassium channel is expressed in a variety of tissues including the heart, neurons and some cancer cells. hERG channels are modulated by several intracellular signalling pathways and these provide important mechanisms for regulating cellular excitability. In this study, we investigated muscarinic modulation of hERG currents and direct phosphorylation of channel subunits expressed in HEK-293 cells at physiologically relevant temperatures by protein kinase C (PKC). Activation of G_αq/11-coupled M₃-muscarinic receptors with methacholine, reduced current amplitudes at all potentials with minor effects on the voltage dependence of activation and inactivation. The response to methacholine was insensitive to intracellular BAPTA, but was attenuated by either acute inhibition of PKC with 300 n m bisindolylmaleimide-1 (bis-1) or chronic down-regulation of PKC isoforms by 24 h pretreatment of cells with phorbol 12-myristate 13-acetate (PMA). Stimulation of PKC with 1-oleoyl 2-acetylglycerol (OAG), an analogue of diacylglycerol (DAG), mimicked the actions of muscarinic receptor stimulation. Direct phosphorylation of hERG was measured by [³²P]orthophosphate labelling of immunoprecipitated protein with an anti-hERG antibody. Basal phosphorylation was high in unstimulated cells and further increased by OAG. The OAG dependent increase was abolished by bis-1 and down-regulation of PKC, but basal levels of phosphorylation were unchanged. Deletion of the amino-terminus of hERG prevented both the modulation of channel activity and the increase of phosphorylation by OAG. Our results are consistent with calcium and/or DAG sensitive isotypes of PKC modulating hERG currents through a mechanism that involves direct phosphorylation of sites on the amino terminus of hERG.     

Cannabinoid CB1 receptors fail to cause relaxation, but couple via Gi/Go to the inhibition of adenylyl cyclase in carotid artery smooth muscle.

1. The aim of the current study was to characterize which cannabinoid receptors, if any, are present on rat carotid artery smooth muscle. Additionally, the effects of cannabinoids on carotid artery tone, on cyclic AMP accumulation and on forskolin-induced relaxation were examined in the same tissue. 2. Stimulation of carotid arteries with forskolin (10 microM) significantly increased cyclic AMP accumulation, an effect that was inhibited in a concentration-dependent manner by the cannabinoid receptor agonist, methanandamide. 3. Similar inhibition was seen with the CB1 agonist HU-210 but this inhibition was not mimicked by the CB2 agonist, WIN 55,2212-2. 4. The inhibitory effect of methanandamide on cyclic AMP accumulation was prevented by incubation of the arteries with pertussis toxin and was significantly reduced by LY320135, a selective CB1 antagonist, but not by SR 144528, a CB2-selective antagonist. 5. Methanandamide failed to relax carotid arteries pre-contracted with phenylephrine, but inhibited forskolin-induced relaxation of these arteries. This functional inhibition of relaxation by methanandamide was inhibited by CB1-selective (LY320135 and SR 141716A), but not a CB2-selective antagonist (SR 144528). 6. These data demonstrate the presence of functional G protein-linked cannabinoid receptors of the CB1 subtype in the rat carotid artery, but show that these receptors inhibit cyclic AMP accumulation rather than cause relaxation.     

Direct block of native and cloned (Kir2.1) inward rectifier K+ channels by chloroethylclonidine.

1. We have investigated the inhibition of inwardly rectifying potassium channels by the alpha-adrenergic agonist/antagonist chloroethylclonidine (CEC). We used two preparations; two-electrode voltage-clamp of rat isolated flexor digitorum brevis muscle and whole-cell patch-clamp of cell lines transfected with Kir2.1 (IRK1). 2. In skeletal muscle and at a membrane potential of -50 mV, chloroethylclonidine (CEC), an agonist at alpha2-adrenergic receptors and an antagonist at alpha1x-receptors, was found to inhibit the inward rectifier current with a Ki of 30 microM. 3. The inhibition of skeletal muscle inward rectifier current by CEC was not mimicked by clonidine, adrenaline or noradrenaline and was not sensitive to high concentrations of alpha1-(prazosin) or alpha2-(rauwolscine) antagonists. 4. The degree of current inhibition by CEC was found to vary with the membrane potential (approximately 70% block at -50 mV c.f. approximately 10% block at -190 mV). The kinetics of this voltage dependence were further investigated using recombinant inward rectifier K+ channels (Kir2.1) expressed in the MEL cell line. Using a two pulse protocol, we calculated the time constant for block to be approximately 8 s at 0 mV, and the rate of unblock was described by the relationship tau=exp((Vm+149)/22) s. 5. This block was effective when CEC was applied to either the inside or the outside of patch clamped cells, but ineffective when a polyamine binding site (aspartate 172) was mutated to asparagine. 6. The data suggest that the clonidine-like imidazoline compound, CEC, inhibits inward rectifier K+ channels independently of alpha-receptors by directly blocking the channel pore, possibly at an intracellular polyamine binding site.     

Prevalence and factors associated with anthropometric failure,vitamin A and iron deficiency among adolescents in a Nigerian urban community

BackgroundUnder nutrition is a problem of severe magnitude in low income countries like Nigeria. Adolescent school children might also be vulnerable. The dearth of data hinders planning of school health and nutrition programmes for school children.ObjectiveTo determine the prevalence of stunting, thinness; vitamin A and iron deficiencies among adolescent students in Nsukka urban, Nigeria and to determine factors that are associated with these nutritional problems.MethodsA total of 400 participants were randomly selected from 717 students aged 12 – 18 years in 3 randomly selected secondary schools. Questionnaires, anthropometric measurements, and blood analyses were the data collection methods employed.ResultsThe prevalence of stunting was 33.3% and thinness 31.0%. Neither overweight nor obesity was observed. While 64.0% were anaemic; 44.0% had vitamin A deficiency (VAD). A total of 48.0% had both anaemia and stunting, 42% had VAD + thinness; while 40% had anaemia + VAD. Household income was a predictor of vitamin A status. Children from medium/high income households had higher odds of having VAD than those from low income households (AOR=0.14; 95% CI=0.031, 0.607; P=0.009). Household income (AOR=0.12; 95% CI=0.021, 0.671; P=0.016), and age (AOR=0.09; 95% CI=0.014, 0.587; P=0.012) were independent determinants of height-for-age status.ConclusionAmong urban adolescent students in Nigeria, stunting, thinness, anaemia and VAD were problems of public health significance. Age and household monthly income played major roles.