Effects of CRL 41034 on the adrenergic neuroeffector interaction in the canine saphenous vein

Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.     

Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations

Summary— Oxidative modifications of low density lipoproteins (LDL) are now recognised as one of the major processes in atherogenesis. Various drugs, as well as a number of natural products, have been proposed to inhibit such processes. Among the naturally-occurring constituents of plants which appear to possess antioxidant activity are polyphenolic compounds such as flavonoids. The aqueous extract of Vaccinium myrtillus is rich in such molecules. In this report, we describe the in vitro antioxidative potential of this extract on human LDL. The copper-induced oxidative modification of these lipoproteins was assessed using 1) measurement of oxidative resistance as determined by the lag-phase preceding conjugated diene formation; 2) quantification of the amount of lipoperoxides and thiobarbituric acid-reactive substances generated, and measurement of the modification in the net negative electrical charge of the lipoproteins, over a 7-hour time course experiment. Trace amounts of V myrtillus extract (15 to 20 μg/mL) induce statistically significant changes in the oxidation behaviour of LDL, which include 1) prolongation of the lag-phase of conjugated diene production ( P < 0.01); 2) reduction in the formation of lipoperoxides and of thiobarbituric acid-reactive substances up to 7 hours and especially between 1 and 5 hours ( P < 0.01); and 3) inhibition of modification in the net negative charge of LDL. These results demonstrate that V myrtillus extract exerts potent protective action on LDL particles during in vitro copper-mediated oxidation. Calculation of IC₅₀ values indicates that, on a molar basis, this extract may indeed be more potent than either ascorbic acid or butylated hydroxytoluene in the protection of LDL particles from oxidative stress.     

Design and evaluation protocol of "FATaintPHAT", a computer-tailored intervention to prevent excessive weight gain in adolescents

Background  

Computer tailoring may be a promising technique for prevention of overweight in adolescents. However, very few well-developed, evidence-based computer-tailored interventions are available for this target group. We developed and evaluated a computer-tailored intervention for adolescents targeting energy balance-related behaviours: i.e. consumption of snacks, sugar-sweetened beverages, fruit, vegetables, and fibre, physical activity, and sedentary behaviours. This paper describes the planned development of a school-based computer-tailored intervention aimed at improving energy balance-related behaviours in order to prevent excessive weight gain in adolescents, and the protocol for evaluating this intervention.     

Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction

Summary— Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H₂O₂. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0***) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24–96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 ± 0.80 (T0***) to 4.57 ± 1.24 (peak), and decreased to 2.96 ± 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.7 ± 7.5 hours. The iron increased significantly from 0.67 ± 0.34 (T0) to 1.15 ± 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 ± 0.28 UI/L at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, TO vs T48: NS). The mean time of the peak was observed at 9.4 ± 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.     

The febrile stress of routine vaccination does not increase central apnoea in normal infants

Abstract We tested the hypothesis that the febrile stress of routine vaccination would increase central apnoea in normal infants. Twenty-one normal infants had continuous overnight breathing and temperature recorded at home, before and after 58 routine vaccination episodes. Central apnoea, of at least 5 sec duration, was detected by computer algorithm and confirmed by human inspection. The longest recorded apnoea was 16 sec ( n = 1) during 3629 h of sleep. Overnight rectal temperature increased after vaccination (median 0.52°C, 95% CI 0.40, 0.65). Apnoea density reduced on 46/53 vaccination nights (median -29%, 95% CI -20, -37) followed by an increase on subsequent nights (median +10%, 95% CI +1%, +21%). Overall, apnoea density was similar during the 3 nights preceding and 4 nights following vaccination (median +1%, 95% CI +9,-6). The febrile stress of routine vaccination did not increase central apnoea in normal infants.     

Dual energy X-ray absorptiometry of the hand and wrist–a possible technique to assess skeletal maturation: methodology and data in normal youths

Ninety five normal Caucasian subjects (51F, 44 M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA™) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 ± 0.007 g/cm to 0.365 ± 0.035 g/cm in females and 0.425 ± 0.040 g/cm in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1–5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively ( r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age ( r > 0.85).     

Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics

The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-merrcaptobenzoate-arginine-glycine-aspartate -2-mercaptoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular diehroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.     

Evaluation of coronary artery disease by an improved method of exercise electrocardiography: the ST segment/heart rate slope

Analysis of the rate-related change in exercise-induced ST segment depression, the ST/HR slope, has been shown to significantly improve the accuracy of the exercise ECG for the identification of patients with coronary artery disease and for the recognition of patients with stable angina pectoris who have anatomically or functionally severe coronary artery obstruction. This method, in effect, normalizes the extent of ST segment depression for heart rate, which serves as an index of exercise-induced augmentation of myocardial oxygen demand. While preserving the specificity of the exercise ECG at greater than 90%, an ST/HR slope value of 1.1 microV/bpm as an upper limit of normal improved exercise test sensitivity from 57% to 91% in patients with stable angina who were examined using standard Bruce protocols and three monitoring leads. In addition, an ST/HR slope value of 6.0 microV/bpm was found to partition patients with and without three-vessel coronary artery disease with a sensitivity of 78%, specificity of 97%, positive predictive value of 93%, and overall test accuracy of 90%. No other criteria based on standard ECG interpretation performed as well as the ST/HR slope for the recognition of three-vessel disease in these patients. Further, patients with high ST/HR slopes who did not have three-vessel coronary disease could be shown to have functionally severe two-vessel disease by radionuclide cineangiography. These data suggest that the ST/HR slope can improve the evaluation and management of patients with possible coronary disease. Additional improvement in ST/HR slope accuracy and applicability is likely to result from modification of exercise protocols to reduce heart rate increments between stages, an increase in monitoring leads to include CM5, and computer analysis of the ST segment depression.