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Biomedical subjects

G V Skúladóttir

Publications and source records attributed to G V Skúladóttir.

7 recordsLinked to original sources

Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions.

Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection.

Amino Acid Sequence↗

Inotropic response of rat heart papillary muscle to alpha 1- and beta-adrenoceptor stimulation in relation to dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) and age.

The effect of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) and age on inotropic responses of heart papillary muscle to alpha 1-or beta-adrenoceptor stimulation was examined in young (4 months), middle-aged (12 months) and senescent (27 months) male Wistar rats. From the age of two months the rats were fed a diet containing 2% or 12% of fat by weight varying in PUFA type: a) standard low-fat n-6 PUFA diet, b) high-fat n-6 PUFA diet or c) high-fat n-3 PUFA diet. The inotropic responses to alpha 1-adrenoceptor stimulation with phenylephrine were triphasic (positive, negative, then positive). Young, high-fat n-3 PUFA-fed rats exhibited significantly lower negative and higher positive responses to phenylephrine stimulation, and higher positive responses to isoprenaline stimulation than young, high-fat n-6 PUFA-fed rats. On the other hand, no such dietary-related difference was found between young rats fed a high-fat n-3 PUFA diet and a standard low-fat n-6 PUFA diet. The young high-fat n-6 PUFA-fed rats exhibited inotropic responses similar to those of the middle-aged and senescent rats within the three dietary groups. The time to peak force and the time of half relaxation did not differ within dietary and age groups. The findings indicate that dietary n-6 PUFA-rich supplementation at a young age induces changes resembling the effects of age, as evidenced by decreasing cardiac responses to adrenoceptor agonists, such as phenylephrine or isoprenaline.

Adrenergic alpha-Agonists↗

Effects of ageing and adrenergic stimulation on alpha 1- and beta-adrenoceptors and phospholipid fatty acids in rat heart.

The purpose of this study was to examine the influence of ageing on the alterations in binding characteristics of adrenoceptors and membrane phospholipid fatty acids in rat heart following repeated administration of epinephrine. The maximal number of binding sites (Bmax) and dissociation constant (Kd) of [3H]prazosin and [3H]dihydroalprenolol binding to alpha 1- and beta-adrenoceptors, respectively, changed significantly during ageing. The downregulation of alpha 1- and beta-adrenoceptors after repeated epinephrine administration for one week, did not differ with age, but the response of the affinity (1/Kd) of both alpha 1- and beta-adrenoceptors to epinephrine treatment was age dependent. In 3-month-old rats the affinity of alpha 1-adrenoceptors was decreased after epinephrine treatment but the affinity of beta-adrenoceptors was unchanged. In 10- and 23-month-old rats the affinity of beta-adrenoceptors decreased after epinephrine treatment but the affinity of alpha 1-adrenoceptors did not change. During ageing the linoleic acid (18:2(n-6)) level decreased in phosphatidylcholine and the arachidonic acid (20:4(n-6)) level increased in phosphatidylcholine and phosphatidylethanolamine. After epinephrine administration the 18:2(n-6) level decreased and the docosahexaenoic acid (22:6(n-3)) level increased in phosphatidylcholine and phosphatidylethanolamine and those changes were not age dependent. The 20:4(n-6) level increased in phosphatidylcholine after epinephrine administration, but that increase was smaller in old than in young rats. The results show that both ageing and epinephrine administration simultaneously modify the fatty acid composition of membrane phospholipids and the binding properties of alpha 1- and beta-adrenoceptors in rat heart.

Adrenergic alpha-1 Receptor Agonists↗

Plasma fatty acids and lipids in two separate, but genetically comparable, Icelandic populations.

Levels of serum lipids and lipoproteins, and the fatty acid composition of plasma phospholipids, were measured in two genetically comparable, but widely separated, populations. The 1975 mortality rates for ischemic heart disease were significantly higher in one of these populations, the Manitoban residents of pure Icelandic descent, than in the other, a rural population from Northeastern Iceland. Two study populations, Icelanders and Icelandic-Canadians, were drawn from these larger populations. The study populations were matched for age and sex and divided into three age groups, 20-39, 40-59, and 60-69 years. In comparison to the Icelandic-Canadians, the Icelanders exhibited significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, but lower triglyceride levels. Their plasma phospholipids contained significantly lower levels of saturated fatty acids (SFA), monounsaturated fatty acids, and n-6 polyunsaturated fatty acids (PUFA); but their n-3 PUFA levels were three times as high. It was additionally found that fatty acid composition of plasma phospholipids differed among Icelanders of different ages. SFA levels were significantly lower, and n-6 PUFA levels significantly higher, in the 20-39 year group than in the 60-69 year group, possibly due to different dietary fat consumption patterns between generations. No corresponding age-related difference in the fatty acid composition of plasma phospholipids was found in the Icelandic-Canadian study population. As the Icelandic and Icelandic-Canadian groups are assumed to be genetically similar, the biochemical differences between them are evidently due to environmental, probably dietary, differences. The findings indicate that n-3 PUFA may be cardioprotective in the context of an otherwise atherogenic diet.

Adult↗

Effects of dietary oils and methyl ethyl ketone peroxide on in vivo lipid peroxidation and antioxidants in rat heart and liver.

Weanling male Sprague-Dawley rats were fed diets for four weeks which differed in their content of n-6 (corn oil; CO) and n-3 fatty acids (fish oil; FO), but were similar in their content of saturated and monounsaturated fatty acids and vitamin E. At the end of the four-week feeding period, each dietary group was subdivided into two groups. One group received a single placebo injection of alpha-tocopherol-stripped corn oil (TSCO); the other group received a single injection of the free radical generator; methyl ethyl ketone peroxide (MEKP), in TSCO. Twenty-four hours after injection, the effect of dietary oil and MEKP treatment on endogenous lipid peroxide (LPO) production (measured as methylene blue formed by the "Determiner LPO" assay), glutathione (GSH) and vitamin E content, and fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in heart and liver from unfasted animals were measured. FO-fed rats had significantly heavier hearts and livers, increased levels of n-3 fatty acids in membrane phospholipids, and higher liver LPO levels than CO-fed rats. MEKP treatment resulted in significantly lower body weights and liver GSH levels. The data indicate that dietary n-3 fatty acids increase lipid peroxidation in liver somewhat more than in heart. The study also demonstrates that the effect of induced oxidative stress due to a single dose of MEKP on lipid peroxide formation and antioxidant status in tissues from unfasted animals was independent of the dietary oils.

Animals↗

Polyunsaturated fatty acids in heart muscle and alpha 1-adrenoceptor binding properties.

Modifications of membrane phospholipids and binding characteristics of adrenoceptors by hydrocortisone and epinephrine were examined in sarcolemmal preparation from rat heart muscle. The influence of hydrocortisone and epinephrine on the fatty acid composition of membrane phospholipids and the affinity (1/Kd) and number of binding sites (Bmax) of alpha 1- and beta-adrenoceptors was studied in male Wistar rats treated daily for 7 days with the hormones. The alpha 1- and beta-adrenoceptors were characterized by using the antagonist ligands [3H]prazosin and [3H]dihydroalprenolol, respectively. Administration of the hormones altered significantly the composition of fatty acids, decreased linoleic acid (18: 2(n-6)) level of both phosphatidylcholine and phosphatidylethanolamine, and increased arachidonic acid (20: 4(n-6)) level of phosphatidylcholine and docosahexaenoic acid (22: 6(n-3)) level in both phosphatidylcholine and phosphatidylethanolamine. The binding sites of alpha 1-adrenoceptors were of high affinity in the control group. Following administration of the hormones Kd of alpha 1-adrenoceptors increased markedly. The number of alpha 1-adrenoceptors binding sites did not change significantly due to the hormones. In contrast, while the hormone treatments did not alter the affinity of the beta-adrenoceptors the number of binding sites were significantly decreased by the hormones. The results indicate that the decrease in affinity of alpha 1-adrenoceptors and the down-regulation of beta-adrenoceptors is accompanied by alteration in percentage fatty acid compositions of phosphatidylethanolamine and phosphatidylcholine in cardiac muscle.

Animals↗

Influence of dietary cod liver oil on fatty acid composition of plasma lipids in human male subjects after myocardial infarction.

A randomized crossover study was carried out to investigate the fatty acid profile and concentrations of plasma lipids in male patients with myocardial infarction (MI) who supplemented their diet with 20 ml cod liver oil daily for 6 weeks. Subjects were divided into two groups, A and B. Group A received cod liver oil daily for 6 weeks after hospital discharge, but none for the subsequent 6 weeks. Group B did not start taking cod liver oil until 6 weeks after hospital discharge, and they then took cod liver oil for 6 weeks. Diet, medication or smoking habits were kept as constant as possible during the study. During the period of cod liver oil intake, eicosapentaenoic acid (20:5 (n-3), EPA) and docosahexaenoic acid (22:6 (n-3), DHA) increased significantly in phospholipids (PL), triglycerides (TG) and cholesterol esters (CE), whereas linoleic acid (18:2 (n-6), LA), dihomo-gamma-linolenic acid (20:3 (n-6), DHGLA) and arachidonic acid (20:4 (n-6), AA) were significantly decreased in phospholipids. The plasma level of TG was significantly decreased during the cod liver oil intake. Total cholesterol, high density lipoprotein (HDL) cholesterol, and levels of apolipoproteins A1 and B were not affected by cod liver oil in these MI patients.

Apolipoproteins↗