General Anesthetics Predicted to Block the GLIC Pore with Micromolar Affinity

Although general anesthetics are known to modulate the activity of ligand-gated ion channels in the Cys-loop superfamily, there is at present neither consensus on the underlying mechanisms, nor predictive models of this modulation. Viable models need to offer quantitative assessment of the relative importance of several identified anesthetic binding sites. However, to date, precise affinity data for individual sites has been challenging to obtain by biophysical means. Here, the likely role of pore block inhibition by the general anesthetics isoflurane and propofol of the prokaryotic pentameric channel GLIC is investigated by molecular simulations. Microscopic affinities are calculated for both single and double occupancy binding of isoflurane and propofol to the GLIC pore. Computations are carried out for an open-pore conformation in which the pore is restrained to crystallographic radius, and a closed-pore conformation that results from unrestrained molecular dynamics equilibration of the structure. The GLIC pore is predicted to be blocked at the micromolar concentrations for which inhibition by isofluorane and propofol is observed experimentally. Calculated affinities suggest that pore block by propofol occurs at signifcantly lower concentrations than those for which inhibition is observed: we argue that this discrepancy may result from binding of propofol to an allosteric site recently identified by X-ray crystallography, which may cause a competing gain-of-function effect. Affinities of isoflurane and propofol to the allosteric site are also calculated, and shown to be 3 mM for isoflurane and for propofol; both anesthetics have a lower affinity for the allosteric site than for the unoccupied pore

Ranging characteristics of the domestic cat (Felis catus) in an urban environment

In many countries, high densities of domestic cats (Felis catus) are found in urban habitats where they have the potential to exert considerable predation pressure on their prey. However, little is known of the ranging behaviour of cats in the UK. Twenty cats in suburban Reading, UK, were fitted with GPS trackers to quantify movement patterns. Cats were monitored during the summer and winter for an average of 6.8 24 h periods per season. Mean daily area ranged (95 % MCP) was 1.94 ha. Including all fixes, mean maximum area ranged was 6.88 ha. These are broadly comparable to those observed in urban areas in other countries. Daily area ranged was not affected by the cat’s sex or the season, but was significantly larger at night than during the day. There was no relationship between area ranged and habitat availability. Taking available habitat into account, cat ranging area contained significantly more garden and other green space than urban habitats. If cats were shown to be negatively affecting prey populations, one mitigation option for consideration in housing developments proposed near important wildlife sites would be to incorporate a ‘buffer zone’ in which cat ownership was not permitted. Absolute maximum daily area ranged by a cat in this study was 33.78 ha. This would correspond to an exclusory limit of approximately 300–400 m to minimise the negative effects of cat predation, but this may need to be larger if cat ranging behaviour is negatively affected by population densit

Graz. Schloßberg.

Blick zum Schloßberg mit Hauptbrück

Use of cataract services in eastern Africa--a study from Tanzania.

PURPOSE: To establish the proportion of patients who are blind or have low vision prior to undergoing cataract surgery at tertiary referral centers in Tanzania. To assess which patient groups presenting for cataract surgery are more likely to be blind or visually impaired. METHODS: Using pre-existing computerized audit systems we gathered data on pre-operative visual status, age, gender and presentation mode (walk-in or outreach) for 3765 patients undergoing 4258 cataract operations at 2 hospitals in Tanzania. Visual status was defined based on vision in the better eye. RESULTS: 32% of operations were performed on blind patients, 37% on patients with low vision and 31% on normally sighted patients. Predictors of blindness at presentation were: female sex (OR 1.15; 95% CI 1.00-1.32); referral from a rural outreach program (OR 1.75; 95% CI 1.51-2.02) and older age (OR 1.02; 95% CI 1.01-1.02). CONCLUSIONS: It is not only the blind who present to cataract services in Tanzania. The demand for surgery amongst patients who or are normally sighted represents a positive move towards prevention, and not only cure of cataract blindness in Tanzania. However, it also highlights the need to target those left blind from cataract in order to deliver services to those most in need. Cataract programs targeting patients in rural areas and older patients are likely to increase the number of blind patients benefiting from cataract services

A prospective study of long term prognosis in young myocardial infarction survivors: the prognostic value of angiography and exercise testing

Objectives: To define the ability of early exercise testing and coronary angiography to predict prognosis in young survivors of myocardial infarction (MI). Methods: 255 consecutive patients (210 men) aged 55 years or less ( mean 48 years) admitted to hospital (1981-85) were eligible. Of these, 150 patients (130 men) who were able to exercise early after MI and underwent coronary angiography within six months constituted the study group and were followed up for up to 15 years. Survival data up to 18 years was obtained for the whole cohort. Results: Survival at a median of 16 years was 52% for the whole cohort, 62% for the study group, and 48% for the excluded group. From nine years onwards survival deteriorated significantly in the study group compared with an age matched background population. Fifteen years after MI, 121 patients (81%) in the study group had had at least one event ( death, MI, revascularisation, cardiac readmission, stroke) leaving 29 (19%) event-free. The number of diseased vessels was the major determinant of time to first event (p = 0.001) and event-free survival (p = 0.04). Exercise duration was also important in the prediction of time to first event (p = 0.003). Death was influenced by a history of prior MI. Conclusion: The favourable initial survival was followed by significant deterioration after nine years. This late attrition is an important treatment target. Furthermore, this study supports risk stratification early after MI combining angiography with non-invasive tools