1. The optical isomers of propranolol have been compared for their f,-blocking and antiarrhythmic activities.2. In blocking the positive inotropic and chronotropic responses to isoprenaline, ( +)-propranolol had less than one hundredth the potency of (-)-propranolol. At dose levels of (+ )-propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram. 3. The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (-)-propranolol. (+ )-Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose. 4. Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea-pigs. 5. The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer.6. Both isomers of propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (-)-propranolol was 0.09+0.02 mg/kg whereas that of (+)-propranolol was 4.2+1.2 mg/kg. At the effective dose level of (+)-propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline.7. Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of ( -)-propranolol was significantly smaller than that of (+ )-propranolol in both species but much higher than that required to produce evidence of ,8-blockade. 8. The implications of these results are discussed.Pronethalol is a specific competitive antagonist of adrenoceptive f8-receptors and the (-) isomer has been shown to be 40 times as active as the (+) isomer

SummaryBackgroundPatients born outside the UK have contributed to a 20% rise in the UK’s tuberculosis incidence since 2000, but their effect on domestic transmission is not known. Here we use whole-genome sequencing to investigate the epidemiology of tuberculosis transmission in an unselected population over 6 years.MethodsWe identified all residents with Oxfordshire postcodes with a Mycobacterium tuberculosis culture or a clinical diagnosis of tuberculosis between Jan 1, 2007, and Dec 31, 2012, using local databases and checking against the national Enhanced Tuberculosis Surveillance database. We used Illumina technology to sequence all available M tuberculosis cultures from identified cases. Sequences were clustered by genetic relatedness and compared retrospectively with contact investigations. The first patient diagnosed in each cluster was defined as the index case, with links to subsequent cases assigned first by use of any epidemiological linkage, then by genetic distance, and then by timing of diagnosis.FindingsAlthough we identified 384 patients with a diagnosis of tuberculosis, country of birth was known for 380 and we sequenced isolates from 247 of 269 cases with culture-confirmed disease. 39 cases were genomically linked within 13 clusters, implying 26 local transmission events. Only 11 of 26 possible transmissions had been previously identified through contact tracing. Of seven genomically confirmed household clusters, five contained additional genomic links to epidemiologically unidentified non-household members. 255 (67%) patients were born in a country with high tuberculosis incidence, conferring a local incidence of 109 cases per 100 000 population per year in Oxfordshire, compared with 3·5 cases per 100 000 per year for those born in low-incidence countries. However, patients born in the low-incidence countries, predominantly UK, were more likely to have pulmonary disease (adjusted odds ratio 1·8 [95% CI 1·2–2·9]; p=0·009), social risk factors (4·4 [2·0–9·4]; p<0·0001), and be part of a local transmission cluster (4·8 [1·6–14·8]; p=0·006).InterpretationAlthough inward migration has contributed to the overall tuberculosis incidence, our findings suggest that most patients born in high-incidence countries reactivate latent infection acquired abroad and are not involved in local onward transmission. Systematic screening of new entrants could further improve tuberculosis control, but it is important that health care remains accessible to all individuals, especially high-risk groups, if tuberculosis control is not to be jeopardised.

Proanthocyanidins and ellagitannins, referred to as "tannins", exist in many plant sources. These compounds interact with proteins due to their numerous hydroxyl groups, which are suitable for hydrophobic associations. It was hypothesized that tannins could bind to the digestive enzymes α-amylase and glucoamylase, thereby inhibiting starch hydrolysis. Slowed starch digestion can theoretically increase satiety by modulating glucose "spiking" and depletion that occurs after carbohydrate-rich meals. Tannins were isolated from extracts of pomegranate, cranberry, grape, and cocoa and these isolates tested for effectiveness to inhibit the activity of α-amylase and glucoamylase in vitro. The compositions of the isolates were confirmed by NMR and LC/MS analysis, and tannin-protein interactions were investigated using relevant enzyme assays and differential scanning calorimetry (DSC). The results demonstrated inhibition of each enzyme by each tannin, but with variation in magnitude. In general, larger and more complex tannins, such as those in pomegranate and cranberry, more effectively inhibited the enzymes than did less polymerized cocoa tannins. Interaction of the tannins with the enzymes was confirmed through calorimetric measurements of changes in enzyme thermal stability.

Relationships among cellular structure, fracturability, and sensory properties in porous, brittle extrudates were investigated. Corn‐based extrudates intentionally processed to exhibit a range of physical structures were characterized in terms of cell size distribution, bulk density, mechanical strength, fracturability, and sensory attributes. These measurements show both mechanical strength, defined by average compressive stress during extended deformation, and fracturability, quantified by fractal and Fourier analyses of stress‐strain functions, increasing with either decreasing mean cell size or increasing bulk density. Fracturability parameters or structural characteristics are furthermore correlated with sensory scores for crunchiness, crispness, hardness and perceived density. These results indicate that cellularity strongly influences the pattern of mechanical failure and that failure characteristics, such as fractal dimension or power spectrum of stress‐strain functions, are reflective of sensory texture.

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The jaggedness of the stress-strain relationship of two kinds of puffed extrudates stored under different humidity conditions was assessed by the power spectrum of the Fast Fourier Transform and the Natural Fractal dimension of normalized compression curves. Both analyses, performed with a micro-computer, provided a consistent measure of jaggedness. The apparent Fractal dimension, obtained using the Blanket algorithm, was the most convenient measure of overall ruggedness since it was expressed by a single number. The power spectrum that resulted from the Fourier transform, however, could be used to identity the length scale of structural features where fracture takes place, and its shape could be more directly related to structural features and textural properties.

Corn-based extrudates that ranged widely in mean cell size and density were produced by varying extrusion moisture and RPM and also by the addition of rice flour, citric acid, tricalcium phosphate, sodium bicarbonate, and gluten. Cell sizes were measured using an Olympus image analysis system and mechanical properties, including breaking stress and plateau stress values achieved during compression, were measured using an Instron. Breaking and plateau stresses were negatively dependent on mean cell size and positively dependent on density in pure corn samples but the form of the relationship was altered by the presence of additives in the extrudates.

Summary1. Chronotropic dose-response curves (non-cumulative) for P-adrenoceptive antagonists were constructed from results in rats anaesthetized with pentobarbitone and depleted of catecholamines by pre-treatment with syrosingopine. 2. Depletion of catecholamines lowered resting heart rate and reduced the threshold to the chronotropic action of isoprenaline by about 50%. Eight /3-adrenoceptive antagonists produced a dose-dependent chronotropic response but the maximum response was in all cases smaller than that obtained with isoprenaline. The order of activity was dichloroisoprenaline>LB 46>practo-lol>INPEA>oxprenolol>pronethalol>alprenolol>I.C.I. 45,763 (Ko 592). Propranolol and sotalol were without significant activity. The duration of the chronotropic response to the antagonists was more prolonged than that to isoprenaline. Propranolol caused a parallel shift to the right of the doseresponse curves for the agonist effects of the antagonists. 3. Estimation of 8-adrenoceptor blocking activity in anaesthetized cats gave an order of activity dissimilar to that found for maximum agonist responses: LB 46 > oxprenolol > alprenolol > propranolol > I.C.I. 45,763 > practolol > dichloroisoprenaline > sotalol > INPEA > pronethalol. 4. Consideration of chemical structure and physico-chemical properties did not explain the differences between the agonist activities of the adrenoceptive antagonists.