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Biomedical subjects

J P Robin

Publications and source records attributed to J P Robin.

At least 37 records · Page 2Linked to original sources

Early changes in plasma hormones and metabolites during fasting in king penguin chicks.

Chicks of the king penguin (Aptenodytes patagonica) can tolerate a fast of 4-6 months during the subantarctic winter. The aim of this work was to study their initial response to food deprivation. Nine chicks were starved for 18 days. Two phases of starvation were defined according to changes in the specific daily loss in body mass: it decreased by 92% in phase I (6.6 +/- 0.3 days) and remained steady and low in phase II. Phase I was marked by a large decline in protein utilization, indicated by decreases in plasma levels of alanine (58%), uric acid (89%) and urea (76%) together with a decrease in circulating corticosterone (60%) and thyroxine (75%). In phase I, plasma insulin concentration decreased (61%) in some birds, but did not change in others; plasma pancreatic glucagon was stable whereas gut-glucagon decreased by 75%. Free fatty acids and beta-hydroxybutyrate concentrations gradually rose during the fast to 5 to 6 times pre-fast levels. Glycemia remained unchanged. Phase II was characterized by no change in plasma concentrations of protein-derived metabolites and by no or little change in circulating hormone levels. From comparison with previous data, we conclude that there are similar early adjustments to food deprivation in king penguin chick, rat and man: (1) a decrease in resting metabolic rate, (2) a decrease in protein utilization, and (3) mobilization of fat stores. The key adaptations to long-term fasting in these species are therefore effectiveness in protein sparing and ability to prolong this situation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Protein and lipid utilization during long-term fasting in emperor penguins.

The body mass of male emperor penguins is approximately 38 kg at the beginning of the 4-mo winter fast connected with breeding, and it is an estimated approximately 18 kg in leanest birds at time of spontaneous refeeding. For a 38- to 18-kg range, we investigated the changes in the rate of body mass loss, body composition, and plasma concentrations of uric acid and urea. After the first few days (phase I) a steady state (phase II) was reached in the proportions of the energy derived from proteins and lipids with proteins accounting for a constant 4%, and the remaining 96% being from lipids. The same proportions were maintained until body mass had decreased to 24 kg. Below this value the proportion of energy derived from proteins increased progressively (phase III), being 14 times higher at 18 kg than during phase II. Rate of body mass loss and plasma uric acid and urea concentrations closely reflected the changes in protein utilization: being at a low and steady value throughout phase II and increasing during phase III. Emperor penguins also fast during the spring, but for periods of only 2-3 wk. We found a 2.5 times higher value for rate of body mass loss, uric acid, and urea during spring phase II, suggesting lower effectiveness in protein sparing at that time. It may be attributed to the lower initial lipid reserves of spring birds. Would these findings be generalized to the wide variety of birds and mammals that spontaneously fast under natural conditions?(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Fasting in king penguin. I. Hormonal and metabolic changes during breeding.

During long-term fasting in birds and mammals, protein utilization initially decreases (phase I), is thereafter maintained at a low value (phase II), and then further increases (phase III). To delineate hormonal and biochemical changes responsible for these modifications, the effect of food deprivation for 50 days was studied in 6 male king penguins captured at the beginning of their natural breeding fast. During phase II, both rate of mass loss and plasma uric acid concentration remained at low levels, whereas plasma beta-hydroxybutyrate concentration increased. In phase III there was by contrast a 2.5-fold increase in the rate of mass loss, an eightfold increase in plasma uric acid, and an 80% drop in plasma beta-hydroxybutyrate. Plasma corticosterone was low and steady in phase II and increased three times in phase III. During the overall fast, there were no significant variations in plasma insulin, but there was a fourfold increase in plasma glucagon and a decrease in plasma thyroxine and triiodothyronine. These findings suggest that protein sparing (phase II) requires low levels of corticosterone, insulin, and thyroid hormones, whereas the further increase in protein utilization (phase III) is due to an increase in plasma corticosterone. The high plasma glucagon concentration in phase III is presumably responsible for a transient increase in plasma glucose observed at this stage; such increase in glucagon could enhance gluconeogenesis from amino acids.

Aldosterone↗

[Augmentation of nitrogen efficiency and hyperphagia associated with refeeding after prolonged fast in the domestic goose].

The domestic goose is hyperphagic after a fast resulting in a 40% decrease in body mass (a decrease similar to that during breeding anorexia). Food intake is maximum on the 8th day of refeeding. As it is then an average of 2.5 times higher than before the fast, food intake may thus reach the value during forced-feeding for "foie gras". Since nitrogen assimilation rate also increases 2.5 times, nitrogen fixation is increased 6.8 times, suggesting a high level of protein synthesis.

Animals↗

Uric acid and urea in relation to protein catabolism in long-term fasting geese.

Five ganders were subjected to an experimental fast comparable to that which spontaneously occurs during breeding in domestic geese, and during migration and breeding in various wild birds. Plasma uric acid and urea concentrations, and their excretion as a proportion of total nitrogen excretion, were studied in relation to daily change in body mass per unit body mass, mg/mdt. This variable has previously been found to reflect changes in protein catabolism over the three phases of fast: I, dm/mdt and protein utilization both decrease; II, they are maintained at a low value; and III, they increase. In the fed state, daily total nitrogen excretion was 5 gN X 24 h-1; uric acid, ammonia and urea accounted for 51, 15 and 5% respectively. The high remaining proportion of excreted nitrogen (29%), after subtraction of uric acid-N, ammonia-N and urea-N to total nitrogen, accords with the literature. During fasting, the changes in daily excretion of uric acid, urea, ammonia and total nitrogen followed a pattern essentially similar to that for dm/mdt. Uric acid accounted for a progressively increasing fraction of total nitrogen, up to 76% at the end of phase III, while urea remained at a constant 5%. Plasma concentrations of both uric acid and urea followed similar trends during the fast, in particular both increasing during phase III, i.e. when there was a rise in nitrogen excretion. This suggests they could be used as an index in field investigations, to determine whether birds which naturally fast in connection with specific activities have entered into the situation where proteins are no longer spared.

Ammonia↗

Evidence that mammalian lignans show endogenous digitalis-like activities.

Enterolactone, a lignan that has been identified in biological samples from man and several mammals, shares with ascorbic acid and cardiac glycosides a gamma-butyrolactone. It displaces 3H-ouabain from its binding sites on cardiac digitalis receptor and inhibits, dose dependently, the Na+, K+-ATPase activity of human and guinea-pig heart. The time dependence of this inhibition resembles that of dihydroouabain, a cardiac glycoside in which the lactone ring does not contain conjugated double bonds. The active concentrations of enterolactone as inhibitor of Na+,K+-ATPase are in the 10(-4) M range and, at those concentrations, the cross-reactivity with antidigoxin antibodies is low. Lignans may contribute to the putative digitalis-like activity found in tissues, blood and urine of several mammals including man.

4-Butyrolactone↗

Ambient temperature and ketone body plasma concentration in fasting geese.

The effect on ketonemia of alternate exposure to ambient temperatures (Ta) of 25 and 5 degrees C was investigated in fasting geese. Three experimental birds were compared to three controls continuously exposed to 25 degrees C Ta while fasting. During the first 9 days of fasting, when both groups were exposed to 25 degrees C, plasma concentration of beta-hydroxybutyrate (beta-OHB) increased similarly in both, from 0.10 +/- 0.02 to 6.62 +/- 0.71 mmol X L-1. It later plateaued at 8-9 mmol X L-1 in the control birds. When the experimental birds were exposed to 5 degrees C Ta between the 9th and 15th day of the fast, it increased further during the first 24 h but thereafter decreased of 57%, from 8.62 +/- 1.56 to 3.73 +/- 1.24 mmol X L-1. This decrease was reversed within the 6 days of return to 25 degrees C Ta. In both groups, plasma acetoacetate (AcAc) concentration remained very low during the fast: 51 +/- 1 mumol X L-1. This reversible cold-induced effect on ketonemia may be used for investigating the possible role of ketone bodies in protein sparing during fasting.

3-Hydroxybutyric Acid↗

Inhibition of the erythrocyte Na+, K+-pump by mammalian lignans.

Several mammalian lignans, particularly enterolactone, 3-oxy-methyl enterolactone and prestegane B are able to inhibit Na+, K+-pump activity in human red cells with IC50 of about 1 mM. The inhibition of Na+, K+-pump activity by mammalian lignans have the following properties: the IC50 for ouabain remains unchanged suggesting a noncompetitive inhibition. The apparent affinity for internal Na+ and maximal rate of cation translocation are both diminished. The above inhibition of the Na+, K+-pump was obtained at doses 2-3 orders of magnitude higher than those required for ouabain. However we cannot exclude that a glycosyl- (and/or butenolide)-derivative of enterolactone could be one endogenous ouabain-like factor.

Cross Reactions↗

Endogenous lignans--a potential endogenous digitalis.

Lignans are natural products formed by oxidative dimerization of monomeric phenols. A few were recently discovered in human and animal urine, semen and blood plasma but their role has never been assessed. We investigated the actions of mammalian lignans obtained by total synthesis or extracted from the urine of pregnant women, on the Na+K+-pump in human red cells. Some of the tested lignans (enterolactone, prestegane B and 3-O-methylenterolactone) inhibited the Na+K+-pump activity with IC50 ranging from 5 to 9 X 10(-4) mol/l. The IC50 for ouabain (7 X 10(-7) mol/l) was not modified by addition of lignans suggesting a non-competitive inhibition.

4-Butyrolactone↗

[Mammalian lignans: possible involvement in endogenous digitalis activity].

Lignans are natural products, some of which were recently discovered in animal urines, semen and blood plasma. We investigated the actions of animal lignans obtained by total synthesis or extracted from urines of pregnant women on Na+, K+-ATPase in human red cells and human and guinea-pig heart cell membranes. Some of the tested lignans (enterolactone, prestegane B and 3-O-methyl enterolactone) inhibited Na+, K+-pump activity in human red cells with IC50 ranging from 5 to 9 X 10(-4) M. The IC50 for ouabain (7 X 10(-7) M) was not modified by addition of lignans. Enterolactone inhibited Na+, K+-ATPase activity in human and guinea pig heart membranes. It also displaced [3H]-ouabain binding from human heart with IC50 = 1.5 X 10(-4) M. The apparent dissociation rate constants (kd) of [3H]-ouabain were not different in presence of digoxin or enterolactone. Enterolactone exhibited a poor cross reactivity against antidigoxin antibodies. The aglycones of the lignans studied here were slight inhibitors of the Na+, K+-ATPase. However, we cannot exclude that a glycosyl- (and/or butenolide-) derivative of enterolactone could be one "endogenous ouabain-like" factor.

Animals↗

[Acquired angioneurotic edema caused by acquired deficiency of C1 esterase inhibitor disclosing lymphoproliferative syndrome. Apropos of a case, review of the literature].

One case of acquired angio-neurotic oedema is described and discussed with the other cases recorded in literature since Caldwell's one in 1972. This entity is characterized by: --the late onset of angio-oedema but its presence only in about half cases, --a complement deficiency resulting from the lack of C1-esterase inhibitor, --the absence of familial identical cases, --the great frequency of associated illnesses overall lympho-proliferative diseases, --the therapeutic response to either etiologic treatment of the associated disease or to the symptomatic effect of drugs used in hereditary angio-neurotic oedema.

Aged↗

Structure--antitubulin activity relationship in steganacin congeners and analogues. Inhibition of tubulin polymerization in vitro by (+/-)-isodeoxypodophyllotoxin.

A new series of 23 synthetic analogues of the naturally occurring antitumor lignan steganacin was tested for the inhibition of microtubule assembly in vitro. Interestingly, (+/-)-isopicrostegane (I50 = 5 microM) was found to be almost as active as (+/-)-steganacin(I50 = 3.5 microM). On the other hand, racemic isodeoxypodophyllotoxin has an inhibiting activity of microtubule assembly comparable to that of (-)-podophyllotoxin, whereas (-)-isodeoxypodophyllotoxin is totally inactive.

Colchicine↗

Two-dimensional electrophoresis of the total polypeptides in ripe red grape berries.

The total polypeptide composition of mature grape berries was analyzed by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis (isoelectric focusing in the first dimension followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension), followed by Coomassie Blue and nitrate silver staining, respectively. Adapted methods for total protein preparation of grapes and for two-dimensional gel electrophoretic separation of polypeptides are presented. The grape patterns presented up to 52 fractions with Mrs ranging from 15,000 to 110,000. The polypeptides displayed pIs from 4.6 to 7.3. A group of spots from Mr 28,000 to 83,000 and with a pI from 4.6 to 5.4 was strongly silver stained. The Mr 28,000 spot, pI 4.6, was revealed to be a complex of four fractions. Reproducible separations were obtained with the different carrier ampholyte mixtures tested.

Electrophoresis, Gel, Two-Dimensional↗

Neoisostegane, a new bisbenzocyclooctadiene lignan lactone from Steganotaenia araliacea.

Neoisostegane, the first naturally occurring steganin without a functional group at C-5, was isolated from two different collections of Steganotaenia araliacea. The structure of neoisostegane, which contained five aromatic methoxyl groups rather than the more usual three methoxyls and one methylenedioxy moiety, was elucidated by comparison of the pmr coupling constants with those of synthetic steganes and by selective decoupling experiments. The structure was confirmed by cmr data, by preparation of a derivative having five aromatic methoxyl moieties from stegane, which was compared spectroscopically to neoisostegane, and by thermal isomerization experiments.

Antineoplastic Agents, Phytogenic↗

[Preparation, stereochemical study and evaluation of the antileukemic activity of glucoside derivatives of (-)-steganol].

The optically active lignan (-)-steganol was prepared from natural (-)-steganacin by selective deacetylation and was transformed, via a three-step sequence, into the corresponding 4', 6'-O-ethylidene- and thenylidene-beta-D-glucopyranosides, 3b and 3c, respectively, which are the analogues, in the steganol series, of the podophyllotoxin derived, and clinically useful, anticancer drugs, VP16-213 and VM26. Formation of the dimeric compound distegyl ether as a minor by-product was established. Complete elucidation of all the asymmetric centres was performed with the help of high resolution 1H-nmr studies at 400 MHz, COSY experiment at 500 MHz and X-ray analysis. Contrary to the podophyllotoxin series, the glycosylation of (-)-steganol occurred with retention of configuration, and all the synthesized compounds, including distegyl ether, exhibited the starting natural R configuration at C-5.

Animals↗

Milking strategy in subantarctic fur seals Arctocephalus tropicalis breeding on Amsterdam Island: evidence from changes in milk composition.

Milk composition was investigated throughout the 10-mo pup-rearing period in subantarctic fur seals (Arctocephalus tropicalis) breeding on Amsterdam Island. The mean milk composition was 42.8% +/- 5.7% lipid, 12.1% +/- 1.5% protein, and 42.6% +/- 7.3% water. Subantarctic fur seals breeding on Amsterdam Island produced one of the richest milks ever reported in otariids (20.4 +/- 2.9 kJ/g), with lipid content contributing 85% of total gross energy. The high lipid levels measured in the milk of subantarctic fur seals breeding on Amsterdam Island is consistent (i) with the relatively long time lactating females spend at sea, due to the relatively poor local trophic conditions near the colony that necessitate that they travel long distances to reach the foraging grounds, and (ii) with the consequently short time mothers spend with their pups ashore. Milk composition changed according to the time mothers were fasting ashore: milk produced during the first 2 d spent ashore, when more than 80% of milk transfer occurred, had higher levels of lipids, proteins, and gross energy than milk produced later during the visit ashore, suggesting that the pups were fed with two types of milk during a suckling period. Throughout the year, mothers in good condition produced milk of higher lipid content than others, suggesting that individual foraging skills contribute to enhance milk quality. Milk lipid and gross energy content varied with pup age, according to quadratic relationships, increasing during the earlier stages of lactation before reaching asymptotic values when pups were 180 d old. The stage of lactation appears to be a better predictor of milk lipid content than the duration of the preceding foraging trip, suggesting that either changes in the nutritional requirements of the pup and/or seasonal changes in trophic conditions act on milk composition. These changes in milk quality may also be related to changes in maternal care; lactating subantarctic fur seals apparently reallocate their body reserves toward gestation rather than lactation at the end of the pup-rearing period.

Animals↗