Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

An exercise-based cardiac rehabilitation programme for AF patients in the NHS: a feasibility study

There is increasing evidence for the role of exercise-based cardiac rehabilitation in the management of patients with atrial fibrillation (AF). However, this intervention has not yet been widely adopted within the National Health Service (NHS).We performed a feasibility study on the utilisation of an established NHS cardiac rehabilitation programme in the management of AF, and examined the effects of this intervention on exercise capacity, weight, and psychological health. We then identified factors that might prevent patients from enrolling on our programme.Patients with symptomatic AF were invited to participate in an established six-week exercise-based cardiac rehabilitation programme, composed of physical activity and education sessions. At the start of the programme, patients were weighed and measured, performed the six-minute walk test (6MWT), completed the Generalised Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire (PHQ-9). Measurements were repeated on completion of the programme.Over two years, 77 patients were invited to join the programme. Twenty-two patients (28.5%) declined participation prior to initial assessment and 22 (28.5%) accepted and attended the initial assessment, but subsequently withdrew from the programme. In total, 33 patients completed the entire programme (63.9 ± 1.7 years, 58% female). On completion, patients covered longer distances during the 6MWT, had lower GAD-7 scores, and lower PHQ-9 scores, compared with their baseline results. Compared with patients that completed the entire programme, those who withdrew from the study had, at baseline, a significantly higher body mass index (BMI), covered a shorter distance during the 6MWT, and had higher PHQ-9 and GAD-7 scores.In conclusion, enrolling patients with AF into an NHS cardiac rehabilitation programme is feasible, with nearly half of those invited completing the programme. In this feasibility study, cardiac rehabilitation resulted in an improved 6MWT, and reduced anxiety and depression levels, in the short term. Severe obesity, higher anxiety and depression levels, and lower initial exercise capacity appear to be barriers to completing exercise-based cardiac rehabilitation. These results warrant further investigation in larger cohorts.Key words: atrial fibrillation, cardiac rehabilitation, National Health Service     

Inhibition and excitation of neck and shoulder muscles during unilateral electrical stimulation of the rat neostriatum

Electrical stimulation of the caudate-putamen (Cd-Pt) in anesthetized adult male rats was used to determine the nature and extent of the control exerted by the Cd-Pt over the following neck and shoulder muscles: the trapezius, biventer cervicis, rectus capitis and scalenus dorsalis. Unilateral Cd-Pt stimulation resulted in a pattern of muscle responses marked by immediate inhibition of ipsilateral spontaneous activity and subsequent excitation of contralateral activity. Lesions of the substantia nigra pars reticulata blocked the excitation in 3 of the 4 muscles, while globus pallidus lesions had equivocal results. However, control ablations of the frontoparietal motor cortex, which blocked excitation in all muscles, and kainic acid lesions of the Cd-Pt, which had no effect on excitation, suggested that the excitation of muscle activity can only be attributed to the stimulation of corticofugal fibers passing through this region (i.e. the Cd-Pt). The inhibition of spontaneous activity does appear to be attributable to stimulation of the Cd-Pt.     

Attitudes about genetic risk of couples undergoing in-vitro fertilization

Many couples undergoing in-vitro fertilization (IVF) are at a higher risk of having a child with a genetic abnormality. In a sample of 55 consecutive couples starting IVF, only 33% had no genetic risk factor. The most common genetic risks were advanced maternal age and possible abnormalities associated with severe male infertility. Despite education on these risks, 71% of couples had no interest in receiving formal genetic counselling. Only 14% of couples at risk would consider using a gamete donor to avoid transmitting a genetic disorder to a child. The triple test to screen for fetal abnormalities was acceptable to 82% of couples, but only 47% planned to have amniocentesis or chorionic villi sampling. Couples were significantly more likely to opt for prenatal testing if they would consider terminating a pregnancy should the fetus have a severe genetic abnormality (P < 0.01). Roman Catholic couples tended to have more conservative attitudes about pregnancy termination. Socio-economic status and whether the infertility factor was male or female were not predictors of a couple's attitudes.      

ALAS, our frailty is the cause … of a new for form of protoporphyria

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload
Whatley et al. (2008)
The American Journal of Human Genetics 83: 408–414     

Multiple interactions between the alpha<Subscript>2C</Subscript>- and beta<Subscript>1</Subscript>-adrenergic receptors influence heart failure survival

Background  

Persistent stimulation of cardiac β₁-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α_2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively) on the risk of death/transplant in heart failure patients.     

TDI技术评价卡维地洛对高血压患者左室舒张功能的影响

目的:应用组织多普勒显像(TDI)技术评价卡维地洛对高血压患者左室舒张功能的影响.方法:对30例高血压给予卡维地洛治疗24周.治疗前、治疗后12周、24周用TDI技术测量左室收缩期二尖瓣环平均舒张早期运动速度(Ea)、舒张晚期运动速度(Aa)及Ea/Aa,并与血流多普勒指标E波速度(E)、A波速度(A)、E/A进行比较,观察降压效果及对左室舒张功能的影响.结果:卡维地洛治疗12周后收缩压(SBP)、舒张压(DBP)、心率(HR)均较治疗前下降(P＜0.05),Ea、Ea/Aa均较治疗前升高(P＜0.05),治疗24周后E、E/A较治疗前升高(P＜0.05),Aa较治疗前降低(P＜0.05),Ea、Ea/Aa有进一步改善的趋势(P＜0.05).结论:TDI技术在评价左室舒张功能方面较二尖瓣血流频谱更敏感;卡维地洛对轻、中度高血压具有良好的降压作用,且能改善患者左室舒张功能.