Dairy-Derived and Egg White Proteins in Enhancing Immune System Against COVID-19.

Coronavirus disease (COVID-19) is a global health challenge, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) triggers a plethora of respiratory disturbances and even multiple organs failure that can be fatal. Nutritional intervention is one of the key components toward to a proper management of COVID-19 patients, especially in those requiring medication, and should thus be considered the first-line treatment. Immuno-modulation and -stimulation are currently being explored in COVID-19 management and are gaining interest by food and pharmaceutical industries. Various dietary combinations, bioactive components, nutrients and fortified foods have been reported to modulate inflammation during disease progression. Dietary combinations of dairy-derived products and eggs are gaining an increasing attention given the huge immunomodulatory and anti-inflammatory properties attributed to some of their chemical constituents. Eggs are complex dietary components containing many essential nutrients and bioactive compounds as well as a high-quality proteins. Similarly, yogurts can replenish beneficial bacteria and contains macronutrients capable of stimulating immunity by enhancing cell immunity, reducing oxidative stress, neutralizing inflammation and regulating the intestinal barriers and gut microbiome. Thus, this review highlights the impact of nutritional intervention on COVID-19 management, focusing on the immunomodulatory and inflammatory effects of immune-enhancing nutrients.

Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy.

We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3+/-1.1 mmHg and 3.7+/-0.2 g/kg, respectively), in Group-C0.5 (8.0+/-0.9 mmHg and 3.3+/-0.1 g/kg, respectively) and in Group-C5 (5.5+/-1 mmHg and 3.1+/-0.1 g/kg, respectively) than in Group-V (13.5+/-1.0 mmHg and 3.8+/-0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25+/-3%), in Group-C0.5 (20+/-3%), and in Group-C5 (12+/-1%) than in Group-V (32+/-4%). Furthermore, expressions of transforming growth factor-beta1 and collagen-III mRNA were suppressed in Group-C0.05 (349+/-23% and 395+/-22%, respectively), Group-C0.5 (292+/-81% and 364+/-42%, respectively) and in Group-C5 (204+/-63% and 259+/-33%, respectively) compared with those in Group-V (367+/-26% and 437+/-18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart.

Hemodynamic effects of carvedilol infusion and the contribution of the sympathetic nervous system in rats with heart failure.

We investigated the contribution of the sympathetic nervous system (SNS) in maintaining the blood pressure and in regulating the cardiac function during and after carvedilol administration in rats with heart failure (group F). Left ventricular end-diastolic pressure, percent functional shortening, and rates of intraventricular pressure rise were significantly changed by carvedilol infusion as compared with the basal values in group N (normal rats), but not in group F. The left ventricular end-diastolic pressure was elevated, corresponding to the enhancement of the plasma norepinephrine (NE) concentration caused by carvedilol infusion, in group N. The enhancement of the plasma NE concentration induced by carvedilol administration in group F was higher than that in group N. The value for the maximal hypertensive effect of NE intravenous infusion (Emax) was decreased, and the plasma NE concentration at half-maximal effect (EC50) was increased in group F as compared with the values in group N. These results indicate that the SNS (presynaptic) activity is increased and that the SNS receptor sensitivity in the cardiovascular regulation system is decreased in heart failure.

E-octadec-7-en-5-ynoic acid from the roots of Capparis zeylanica.

A new fatty acid, E-octadec-7-en-5-ynoic acid (1), has been isolated from chloroform extract of the roots of Capparis zeylanica. The structure of this compound was established primarily by 1D and 2D-NMR spectroscopy.

Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis.

The cardioprotective properties of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight days after immunization of pig cardiac myosin, four groups rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end-diastolic pressure (LVEDP), +/- dP/dt, area of myocardial fibrosis, and myocardial mRNA expression of transforming growth factor (TGF)-beta1, collagen-III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and +/- dP/dt was lower in V (14.1 +/- 2.0 mmHg and +2409 +/- 150/-2318 +/- 235 mmHg/sec) than in age-matched normal rats (5.0 +/- 0.6 mmHg and +6173 +/- 191/-7120 +/- 74 mmHg/ sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and +/- dP/dt was increased in a dose-dependent manner (10.8 +/- 1.8 mmHg and +3211 +/- 307/-2928 +/- 390 mmHg/sec in Q0.2, 9.4 +/- 1.5 mmHg and +2871 +/- 270/-2966 +/- 366 mmHg/sec in Q2, and 6.6 +/- 1.5 mmHg, and +3569 +/- 169/-3960 +/- 203 mmHg/sec in Q20). Increased expression levels of TGF-beta1, collagen-III and fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and cardiac function in rats with dilated cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was regressed and myocardial structure returned to nearly normal in animals treated with quinapril.

Comparative effects of angiotensin II receptor blockade (candesartan) with angiotensin-converting enzyme inhibitor (quinapril) in rats with dilated cardiomyopathy.

Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure, but their inhibitory actions on angiotensin I-induced increases in blood pressure in heart failure are not clear. Angiotensin I blocking and cardioprotective properties of the angiotensin II receptor blocker candesartan and the angiotensin-converting enzyme inhibitor quinapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Low-dose candesartan (0.5 mg/kg) showed the same angiotensin I blocking action as high-dose quinapril (20 mg/kg) in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (43/58, 74%) were divided into three groups and given quinapril at 20 mg/kg per day (group Q, n = 14), candesartan at 0.5 mg/kg per day (group C, n = 14) or vehicle alone (group V, n = 15). After oral administration for 1 month, four of 15 (27%) rats in group V and two of 14 (14%) in group C died. None of the animals in group Q died. Although angiotensin II levels of the blood and the left ventricle in group V [367 +/- 26 and 437 +/- 18% versus normal rats (group N)] were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 +/- 32 and 169 +/- 53%, both p < 0.01). The left ventricular end-diastolic pressure and the area of myocardial fibrosis were lower, and the first derivative +/-dP/dt was higher in group Q (7.0 +/- 1.7 mmHg, 9 +/- 3% and +3451+/- 170/-3182 +/- 186 mmHg/s, respectively) than in group V (16.7 +/- 1.3 mmHg, 36 +/- 6% and +2601 +/- 235/-2156 +/- 257 mmHg/s, respectively) and in group C (11.2 +/- 2.0 mmHg, 26 +/- 4% and +3063 +/- 164/-2734 +/- 174 mmHg/s, respectively). Although levels of expression of transforming growth factor beta1 and collagen III mRNA in groupV (367 +/- 26 and 437 +/- 18% versus group N) were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 +/- 32 and 169 +/- 53%, both p < 0.01). These results suggested that although low-dose candesartan can block increases in blood pressure with circulating angiotensin I to the same extent as high-dose quinapril, it does not confer sufficient protection against injury from the renin-angiotensin system in heart failure.

Betaxolol improves the survival rate and changes natriuretic peptide expression in rats with heart failure.

The cardioprotective effects of betaxolol were studied in a rat model with heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups; 0.1 mg/kg betaxolol per day (group 0.1), 1.0 mg/kg betaxolol per day (group 1), 10 mg/kg betaxolol per day (group 10), and vehicle (0.5% methylcellulose, group V) (all groups, n = 13). After oral administration for 1 month, the heart weight, the mRNA expression of atrial natriuretic peptide and brain natriuretic peptide in the left ventricle, the plasma atrial natriuretic peptide concentration, the mean blood pressure, the heart rate, the central venous pressure, the peak left ventricular pressure, the left ventricular end-diastolic pressure and its first derivative +/-dP/dt, and the area of myocardial fibrosis were measured. Betaxolol reduced the heart rate, the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA expression and the atrial natriuretic peptide concentration [group N (normal rats), 367 +/- 4 beats/min, 100%, 100% and 78 +/- 7 pg/ml, respectively; group V, 391 +/- 9 beats/min, 761 +/- 68% versus group N, 317 +/- 42% versus group N and 4374 +/- 312 pg/ml, respectively; group 0.1, 387 +/- 10 beats/min, 621 +/- 78%, 288 +/- 41% and 2875 +/- 331 pg/ml, respectively; group 1, 323 +/- 9 beats/min, 442 +/- 84%, 148 +/- 12% and 884 +/- 51 pg/ml, respectively; and group 10, 312 +/- 8 beats/min, 97 +/- 18%, 92 + 9% and 453 +/- 53 pg/ml, respectively], and increased survival (group V, 62%; group 0.1, 69%; groups N, 1 and 10, 100%). Betaxolol did not significantly alter the heart weight, the hemodynamic parameters or the area of fibrosis. These observations suggest that betaxolol may improve the survival rate by reducing sudden death and changing the atrial natriuretic peptide and brain natriuretic peptide mRNA expression in patients with heart failure.

Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy.

UNLABELLED: Metaiodobenzylguanidine (MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating beta-adrenoceptor-blocking agent, were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. METHODS: Twenty-eight days after immunization, surviving rats (41/55, or 75%) were divided into 2 groups treated with carvedilol, 2 mg/kg/d (group C, n = 19), or vehicle alone (0.5% methylcellulose, group V, n = 22). After oral administration for 2 mo, heart weight, heart rate, left ventricular end-diastolic pressure (LVEDP), and myocardial fibrosis were measured and compared with those in untreated rats (group N, n = 19). Myocardial uptake of (125)I-MIBG (differential absorption ratio) in the left ventricle was measured by autoradiography at 10, 30, or 240 min after tracer injection. RESULTS: Four (18%) of 22 rats in group V died between days 28 and 84 after immunization. None of the rats in group C or N died. Heart weight, heart rate, LVEDP, and area of myocardial fibrosis in group C (1.14 +/- 0.04 g, 345 +/- 16 beats per minute, 7.6 +/- 1.5 mm Hg, and 12% +/- 1%) were significantly lower than those in group V (1.34 +/- 0.04 g, 389 +/- 10 beats per minute, 12.3 +/- 1.3 mm Hg, and 31% +/- 2%). Although the differential absorption ratio was lower at all time points in group V than in group N, uptake after treatment increased in group C, compared with group V, at 10 min (12.5 +/- 1.0 vs. 7.6 +/- 0.8, not significant), 30 min (10.1 +/- 1.1 vs. 6.3 +/- 0.9, not significant), and 240 min (6.5 +/- 0.5 vs. 2.5 +/- 0.2, P < 0.05). The late washout ratio from myocardial radioactivity between 30 and 240 min in group C was lower than that in group V (36% vs. 60%). CONCLUSION: These observations indicated that carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.