Influence of heating and acidification on the flavor of whey protein isolate.

Previous studies have established that whey protein manufacture unit operations influence the flavor of dried whey proteins. Additionally, manufacturers generally instantize whey protein isolate (WPI; ≥ 90% protein) by agglomeration with lecithin to increase solubility and wettability. Whey protein isolate is often subjected to additional postprocessing steps in beverage manufacturing, including acidification and heat treatment. These postprocessing treatments may further influence formation or release of flavors. The objective of the first study was to characterize the effect of 2 processing steps inherent to manufacturing of acidic protein beverages (acidification and heat treatment) on the flavor of non-instant WPI. The second study sought to determine the effect of lecithin agglomeration, a common form of instantized (INST) WPI used in beverage manufacturing, on the flavor of WPI after acidification and heat treatment. In the first experiment, commercial non-instantized (NI) WPI were rehydrated and evaluated as is (control); acidified to pH 3.2; heated to 85°C for 5 min in a benchtop high temperature, short time (HTST) pasteurizer; or acidified to 3.2 and heated to 85°C for 30s (AH-HTST). In the second experiment, INST and NI commercial WPI were subsequently evaluated as control, acidified, heated, or AH-HTST. All samples were evaluated by descriptive sensory analysis, solid-phase microextraction (SPME), and gas chromatography-mass spectrometry. Acidification of NI WPI produced higher concentrations of dimethyl disulfide (DMDS) and sensory detection of potato/brothy flavors, whereas heating increased cooked/sulfur flavors. Acidification and heating increased cardboard, potato/brothy, and malty flavors and produced higher concentrations of aldehydes, ketones, and sulfur compounds. Differences between INST and NI WPI existed before treatment; INST WPI displayed cucumber flavors not present in NI WPI. After acidification, INST WPI were distinguished by higher intensity of cucumber flavor and higher concentrations of E-2-nonenal. No perceivable differences were observed between INST and NI WPI after heating; sulfur and eggy flavors increased in both types of WPI. After treatment, AH-INST-HTST samples were differentiated from AH-NI-HTST by grassy/hay and grainy flavor and increased lipid oxidation products. Further processing of WPI in food applications has negative effects on the flavor contributions of WPI.

Clinical synergy of perindopril and calcium-channel blocker in the prevention of cardiac events and mortality in patients with coronary artery disease. Post hoc analysis of the EUROPA study.

BACKGROUND: The purposes of the study were to determine the effects of addition of perindopril to long-term continuous treatment with calcium-channel blocker (CCB) on cardiac outcomes in the stable coronary artery disease (CAD) population of EUROPA and to explore the presence of synergy between perindopril and CCB in secondary prevention. METHODS: We identified participants receiving CCB at every visit during the 4.2-year follow-up and analyzed the effect of addition of perindopril (n = 1,022 perindopril/CCB vs n = 1,100 placebo/CCB). RESULTS: Addition of perindopril to CCB significantly reduced total mortality by 46% (P < .01 vs placebo) and primary end point (a composite of cardiovascular mortality, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 35% (P < .05 vs placebo). There were 41%, 54%, and 28% reductions in cardiovascular mortality, hospitalization for heart failure, and myocardial infarction, respectively. Comparison of hazard ratios suggests the presence of a clinical synergy between perindopril and CCB, with a greater effect than addition of individual effects. CONCLUSION: Addition of perindopril to CCB in stable CAD patients had a significant supplementary impact on cardiac outcomes and mortality.

Total Ischaemic Burden European Trial (TIBET). Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina. The TIBET Study Group.

OBJECTIVE: To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint. DESIGN: A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average. SETTING: Europe. SUBJECTS: 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery. MAIN OUTCOME: Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure. RESULTS: The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar withdrawal rates in the atenolol and combination therapy groups. CONCLUSION: The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina.

The Total Ischaemic Burden European Trial (TIBET). Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable angina. The TIBET Study Group.

OBJECTIVES: To determine the effects of atenolol, nifedipine and their combination on exercise parameters and ambulatory ischaemic activity in patients with mild chronic stable angina. SETTING: Multicentre, multinational study involving 608 patients from 69 centres in nine countries. DESIGN: Placebo washout followed by double-blind parallel-group study comparing atenolol 50 mg bd, nifedipine SR 20 mg bd, and their combination. Patients underwent maximal exercise testing using either a bicycle (n = 289) or treadmill (n = 319) and 48 h of ambulatory ST segment monitoring outside the hospital environment at the end of the placebo washout period and after 6 weeks of active therapy. RESULTS: Both medications alone and in combination caused significant improvements in exercise parameters and significant reductions in ischaemic activity during daily activities, when compared with placebo. There were, however, no significant differences between groups, for any of the measured ischaemic parameters although combination therapy resulted in a greater fall in resting systolic and diastolic blood pressure than either treatment alone. CONCLUSIONS: In the management of mild chronic stable angina there appears to be little advantage gained from using combination therapy for ischaemia reduction.

Therapeutic implications of dynamic coronary stenosis in patients with single vessel coronary artery disease.

Ten patients with proven single-vessel coronary artery disease and a positive exercise test for ischaemia were investigated to establish the importance and therapeutic implications of dynamic coronary stenosis in such patients. All patients interrupted their anti-anginal therapy and under took serial exercise testing in an attempt to identify variability in the ischaemic threshold. Ergonovine testing was performed in nine patients and all underwent 48 h of ambulatory ST segment monitoring while treatment was discontinued. Patients then entered a randomized double-blind study of atenolol and nifedipine; treadmill exercise testing and 48 h of ambulatory ST segment monitoring were performed at the end of each treatment phase. Six (60%) patients showed evidence of variability in coronary vasomotor tone four of whom developed significant ST segment changes during administration of ergonovine; a further two had greater than 30% variability in time to onset of ischaemia during serial treadmill exercise testing. Atenolol significantly increased the time to ischaemia on exercise testing, both in the group as a whole and in the subgroup with evidence of altered vasomotor tone when compared with no therapy, and led to a non-significant reduction in the frequency and duration of ischaemia during the patients' daily lives. Nifedipine, conversely, did not significantly increase time to ischaemia on exercise testing or reduce the frequency or duration of ambulatory ischaemia in either the whole group or the subgroup. With evidence of altered vasomotor tone when compared to no therapy however it was beneficial in terms of reduction in chest pain and requirement for glyceryl trinitrate during daily life.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of angina pectoris with nifedipine: a double blind comparison of nifedipine and slow-release nifedipine alone and in combination with atenolol.

The relative efficacy of nifedipine and slow-release nifedipine (Adalat Retard) in the treatment of stable exertional angina pectoris was evaluated in a double blind randomised crossover study in eight patients on no concomitant antianginal treatment and in 10 patients who were additionally on atenolol. Patients were assessed by angina diaries and exercise testing. Slow-release nifedipine was as effective as nifedipine in the treatment of these patients, both alone and in combination with atenolol.

Medical treatment of patients with severe exertional and rest angina: double blind comparison of beta blocker, calcium antagonist, and nitrate.

The role of medical treatment of patients who had resting nocturnal angina as well as exertional angina was investigate. The effects of atenolol 100 mg a day, nifedipine 20 mg three times a day, and isosorbide mononitrate 40 mg twice a day were investigated in a double blind, triple dummy randomised study. Nine patients with coronary artery disease, early positive exercise tests, and transient daytime and nocturnal ambulatory ST segment changes were initially assessed off all antianginal medication. They were then treated with each drug for three five day periods. Angina diaries were reviewed and maximal treadmill exercise tests and 48 hour ambulatory ST segment monitoring were performed at the end of each treatment period. Resting and exercise heart rate and blood pressure were significantly lower on atenolol than on either isosorbide mononitrate or nifedipine. The duration of exercise to 1 mm ST segment depression was significantly greater on atenolol than on isosorbide mononitrate. Only one patient had an improvement in exercise tolerance on nifedipine that was greater than the improvement on atenolol; this patient had single vessel disease. The total number and duration of episodes of ST segment change during ambulatory monitoring were significantly lower with atenolol than on either isosorbide mononitrate or nifedipine. Nocturnal ST segment changes were abolished in six patients on atenolol, in six patients on nifedipine, and in five patients on isosorbide mononitrate. When nocturnal ST segment changes occurred, their frequency was reduced with all three drugs. Pain was abolished in four patients on atenolol and pain relief was significantly better on atenolol than on isosorbide mononitrate. There was no significant difference in pain relief between isosorbide mononitrate and nifedipine. Thus beta receptor blockade with atenolol was the most effective means of reducing myocardial ischaemia both during exercise and at rest at night without causing deterioration in any patient. Nocturnal myocardial ischaemia in patients with severe coronary artery disease can be effectively treated with beta receptor antagonists and vasodilators.

Effects of platelet inhibition on myocardial ischaemia.

Ticlopidine, a potent inhibitor of platelet aggregation, was found to have no direct effects on coronary resistance or coronary flow in 5 dogs. To determine whether platelets can be implicated in the pathogenesis of myocardial ischaemia the effects of this drug were studied in 10 patients with proven coronary-artery disease and daily angina pectoris. Each underwent three single-blind treatments: (a) placebo for 2 weeks; (b) ticlopidine 500 mg for 4 weeks; and (c) placebo for 2 weeks. For 4 days after the end of each treatment ambulatory S-T segments were monitored and a record was kept of the reported frequency of chest pain. 4 weeks' treatment with ticlopidine resulted in a significant fall in both the reported frequency of chest pain and the number of episodes of S-T segment depression. This effect was most striking in those episodes of S-T segment depression that occurred without increase in heart rate and in the middle of the night. Thus, although the exact mechanisms remain to be clarified this study suggests that platelets may play an important part in the pathogenesis of myocardial ischaemia.

The use of propranolol and nifedipine in the medical management of angina pectoris.

This study investigates the use of propranolol and nifedipine in the treatment of angina pectoris. The clinical response and the effects on the precordial 16-lead electrocardiogram before and after exercise were studied in 52 patients with frequent angina pectoris. Relief of chest pain and abolition of exercise-induced ST-segment depression was achieved in 16 patients on treatment with propranolol alone (mean dose, 300 mg/d). Of the remaining 36 patients, the precordial area and severity of exercise-induced ST-segment depression were unchanged in 8 patients, of whom 2 reported they were free from chest pain, improved in 10 patients of whom 4 reported they were free of chest pain, and abolished in 14 patients, all of whom were free from chest pain following treatment with both propranolol and nifedipine (mean dose, 50 mg/d). Four patients were unable to tolerate this combination. This study has shown that in patients who do not respond to treatment with propranolol alone the combination of propranolol and nifedipine can be used to control not only anginal pain, but also the precordial electrocardiographic manifestations of ischemia.