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Biomedical subjects

S R Davis

Publications and source records attributed to S R Davis.

At least 127 records · Page 7Linked to original sources

Mammary blood flow and regulation of substrate supply for milk synthesis.

In ruminants, mammary supply of substrate varies with rate of mammary blood flow and concentrations of blood substrates. Blood concentrations of most mammary substrates, except acetate and tryptophan, do not vary greatly with feed intake, short term. Fasting reduces mammary blood flow, whereas milking and injection of growth hormone or thyroxine increase flow. It is proposed that the fraction of cardiac output that perfuses the udder of lactating ruminants plays a role in regulation of nutrient partitioning between milk and body tissues. In fed animals this fraction is 15 to 16% of cardiac output, which declines on fasting to 8 to 9% and increases slightly following growth hormone treatment to 17.6%. Following realimentation of fasted cows or goats, mammary blood flow takes several hours to return to normal. Investigation of the mechanism of this response, in terms of the ability of the animal to recognize its nutritional status and partition nutrients accordingly, should prove fruitful to understanding causes of variations of milk production in response to feed quantity and quality. Several substrates show increased mammary arteriovenous difference with increasing blood concentrations. This may reflect differing ratios of blood flow:milk yield. The steep gradient of concentration of substrates across the mammary epithelial cell membrane suggests that a major impediment to substrate supply for milk synthesis is the rate of substrate transport across the membrane.

3-Hydroxybutyric Acid↗

Induction of lactation in nonpregnant cows by estradiol-17 beta and progesterone from an intravaginal sponge.

An intravaginal sponge impregnated with 500 mg estradiol-17 beta and 1000 mg progesterone to induce lactation in nonpregnant dairy cattle was investigated. Sponge retention (greater than 95%) was achieved by its attachment to a nylon collar. Treatment with the sponge for 10 days resulted in lactogenesis in 25% of treated cows compared with an 89% success rate when an adjunct injection of dexamethasone esters (20 mg intramuscular) was given on day 6 or a 96% success rate when reserpine injections (2.5 mg intramuscular) were given on days 6, 8, and 10 10 after sponge insertion. Milking was begun 12 days after sponge insertion (2 days after removal). Peak milk yield was unaffected by adjunct treatments but was greater in spring (mean 11.5 kg/day) than in autumn treated cows (mean 3 and 6 kg/day) in 2 yr of trials. Concentration of estradiol-17 beta in plasma rose rapidly after sponge insertion to a peak similar to that in cows in late pregnancy. Measurement of estradiol-17 beta concentration in milk indicated less, even at first milking than in commercially distributed pasteurized milk. Milk fat and protein content were higher in milk from induced lactations compared with that from normally calving cows on the same day.

Animals↗

Protein metabolism in growing lambs given fresh ryegrass (Lolium perenne)--clover (Trifolium repens) pasture ad lib. 2. Endocrine changes, glucose production, and their relationship to protein deposition and the partition of absorbed nutrients.

1. Glucose metabolism and changes in the concentrations of several hormones in jugular plasma were measured in growing lambs fed on fresh pasture ad lib. One group of lambs acted as control while the second received a continuous abomasal infusion supplying 44 g sodium caseinate+0.5 g L-methionine/d. 2. Hormone concentrations were determined by radioimmunoassay procedures and glucose irreversible loss measured from continuous infusion of D-[U-14C]glucose. 3. Protein infusion increased plasma concentrations of insulin, glucagon and thyroxine (T4), depressed those of growth hormone, prolactin and somatostatin and had no effect on triiodothyronine (T3) concentrations. Cortisol concentrations also tended to be slightly higher in the plasma of protein-infused lambs. 4. Increases in herbage intake within the ad lib, range were associated with increases in plasma insulin and glucagon concentrations and decreases in growth hormone concentration, and it is suggested that these effects could be mediated in part by the accompanying increases in protein absorption from the intestines. The T4:T3 value also decreased with increasing herbage intake, and it is suggested this was due to conversion of T4 to T3. 5. After correction by covariance to equal herbage intake, rates of irreversible glucose loss for control and protein-infused lambs were 9.2 and 10.0 mg/min per kg body-weight 0.75. It was calculated that respectively 0.12 and 0.19 of the total glucose production in control and protein-infused lambs could be accounted for by net synthesis from protein. 6. It was concluded that changes in the circulating concentration of several hormones in protein-infused compared with control lambs were likely to have been implicated in protein deposition forming a greater proportion of energy retention in the infused lambs (0.41 v. 0.27).

Animal Feed↗

Protein synthesis in tissues of growing lambs.

1. The fractional rate of protein synthesis (FSR) in tissues of nine growing lambs (4-5 months of age) was estimated following continuous infusion of L-[4,5-3H]leucine for a period of 7 h. Minimum and upper estimates of FSR were obtained assuming that the specific radioactivity (SRA) of leucine in blood plasma and tissue homogenate respectively defined that of leucyl tRNA. 2. Mean upper estimates of tissue protein FSR (/d) were skin 0.35, longissimus dorsi muscle 0.05 biceps femoris muscle 0.04, liver 0.54, rumen 0.79, cardiac muscle 0.09. Minimum estimates of tissue protein FSR ranged from 0.03 (muscle) to 0.15 (liver). 3. Plasma leucine flux was closely related to body protein content and dietary leucine absorption (r 0.94). 4. The rate of whole-body protein synthesis (WBS) derived from plasma leucine flux corrected for oxidation and localized recycling of leucine into protein was similar to that calculated from the sum of daily protein synthesis in individual tissues using the upper estimate of FSR, i.e. 610 g/d v. 581 g/d. 5. The estimate of WBS derived from plasma leucine flux directly (241 g/d) was similar to that calculated from the sum of minimum estimates of daily protein synthesis in individual tissues (214 g/d). 6. The ratio, intracellular leucine SRA:plasma leucine SRA tended to increase with increasing dietary leucine absorption in all tissues although these factors were only significantly correlated (P less than 0.05) in cardiac muscle, skin and rumen. Such relationships suggest an increased exchange of plasma leucine with intracellular leucine with increased food intake. 7. It was estimated that the energy cost of protein synthesis accounted for approximately 42% of daily heat production.

Animals↗

Relative importance of pre-partum and post-partum factors in the control of milk yield in the guinea-pig.

Examination of data pertaining to milk yield and litter growth rate of guinea-pigs at peak lactation showed that milk yield increased with increasing number of pups carried by the dam during pregnancy and also with increasing maternal weight. There was a significant linear correlation (P less than 0.05) of mammary gland weight (expressed per unit of maternal body weight) with litter size. Increasing litter size, within 18 h of parturition, from 1 pup to 5 pups did not elicit a response in milk yield. Decreasing litter size from 5 pups to 1 pup reduced milk yield to the level expected of a monotocous dam. Data are presented showing the ability of the guinea-pig pup to survive from birth without access to milk and the inadequacy of milk supply to meet litter requirements when the litter size is more than 2 pups. The mechanisms controlling lactation in the guinea-pig are discussed in relation to data obtained in other species.

Animals↗

Amino acid uptake by the mammary gland of the lactating ewe.

(1) The arterio-venous difference technique, previously used to measure mammary substrate uptake with cows and goats, was used to measure amino acid uptake by the mammary gland of the lactating Merino ewe. Possession of a single large superficial epigastric vein by the Merino ewe makes the Merino breed the most suitable for this type of study. (2) A method was developed enabling hourly measurement of milk yield without causing undue stress. Milk yield was essentially constant over a 7-8 h period. (3) Mammary extraction of most non-essential amino acids was low relative to output in milk protein and showed a greater variability with time than that found for the essential amino acids. There was a significant mammary extraction of ornithine and citrulline, neither amino acid being found in ovine milk protein. (4) Of the essential amino acids valine, isoleucine, leucine and arginine were taken up in excess of their requirement for milk protein synthesis. (5) On the basis of the extent of mammary extraction, methionine, lysine and leucine were first-, second- and third-limiting to the rate of milk protein synthesis. (6) Despite fluctuations in arterial amino acid concentrations the arterio-venous differences of the essential amino acids were relatively constant over a 7-8 h period. (7) The pattern of mammary amino acid uptake in the ewe is contrasted with that found in similar studies carried out with the lactating cow and goat.

Amino Acids↗

Mammary glucose uptake in the lactating ewe and the use of methionine arterio-venous difference for the calculation of mammary blood flow.

(1) The validity of using the arterio-venous concentration difference of methionine to calculate mammary blood flow in the ewe, on the basis of the Fick principle, is discussed. (2) Calculation of mammary blood flow in the lactating Merino ewe indicated that blood flow per unit weight of tissue and the ratio of blood flow : milk yield were approximately twice that found in the lactating cow and goat. (3) Calculated mammary blood flow in Merino ewes was used in conjunction with glucose arterio-venous difference to determine mammary glucose uptake. Glucose uptake per unit weight of tissue in the ewe was almost double that found in the cow and goat. The ratio of mammary glucose uptake to lactose output was also higher in the ewe than that found in the cow and goat. The utilization of glucose by the mammary gland of the ewe is discussed in relation to the possible greater requirement for NADPH and glycerol for milk fat synthesis in this species.

Animals↗

Metabolism of L-(U-14C)valine, L-(U-14C)leucine, L-(U-14C)histidine and L-(U-14C) phenylalanine by the isolated perfused lactating guinea-pig mammary gland.

1. The incorporation of L-[U-14C]leucine, L[U-14C]histidine and L-[U-14C]phenylalanine into casein secreted during perfusion of isolated guinea-pig mammary glands was demonstrated. 2. The extent of incorporation of label into casein residues was consistent with their being derived from free amino acids of the perfusate plasma. 3. The mean transit time of the amino acids from perfusate into secreted casein was approx. 100 min. 4. Whereas radioactive histidine and phenylalanine were incorporated solely into milk protein, radioactivity from [U-14C]valine was also transferred to CO2 and to an unidentified plasma component, and from [U-14C]leucine to plasma glutamic acid. 5. Evidence from experiments with [U-14C]phenylalanine suggests that, as in rats, but in contrast with ruminant species, guinea-pig mammary tissue does not possess phenyl alanine hydroxylase activity. 6. The results are discussed in relation to the possible role of essential amino acid catabolism in the control of milk-protein synthesis.

Amino Acids, Essential↗

Acetate utilization by the isolated perfused guinea-pig mammary gland.

Acetate uptake by isolated perfused guinea-pig mammary glands was approximately 1.0 mg g-1 h-1 when perfusate acetate concentrations were in the physiological range (5-11 mg/100 ml plasma). At perfusate concentrations below this range (mean 3.62 mg/100 ml plasma) the uptake was not significantly different, but in one experiment in which the mean acetate concentration was 14.5 mg/100 ml plasma the uptake was markedly elevated. Radioactivity from Na (1-14C) acetate was incorporated into CO2 and milk and tissue fat, being largely present in C16 and C18 fatty acids. The guinea-pig is atypical of non-ruminants and similar to ruminants in respect of the blood concentration and mammary utilization acetate.

Acetates↗

The therapeutic use of androgens in women.

Androgens have significant and varied actions in women and there is now acknowledgment that women may experience symptoms secondary to androgen deficiency. There is also substantial evidence that prudent androgen replacement can be effective in relieving both the physical and psychological symptoms of androgen insufficiency, and is indicated for clinically affected women. Testosterone replacement for women is now available in a variety of formulations. It appears to be safe, with the caveat that doses are restricted to the 'therapeutic' window for androgen replacement in women, such that the beneficial effects on wellbeing and quality of life are achieved without incurring undesirable virilizing side effects. The predominant symptom of women with androgen deficiency is loss of sexual desire. This is not limited to women experiencing a surgical menopause but may also be a feature of women who have either undergone premature or natural menopause. There is increasing interest in other uses of androgen replacement in women that include premenopausal iatrogenic androgen deficiency states, glucocorticosteroid-induced bone loss, management of wasting syndromes and possibly premenopausal bone loss, premenopausal loss of libido and the treatment of the premenstrual syndrome.

Aging↗

Testosterone influences libido and well being in women.

There is increasing awareness of the significant and varied actions of endogenous androgens in women, and acknowledgement that women might experience symptoms secondary to androgen deficiency. There is also substantial evidence that prudent testosterone replacement is effective in relieving both the physical and psychological symptoms of androgen insufficiency in clinically affected women. However, our understanding of the actions of testosterone in women is incomplete, with no consensus as to what constitutes either biochemical or clinical testosterone deficiency. The focus of the limited research into testosterone replacement has been on sexuality, primarily sexual desire. However, the influence of testosterone on mood and well being also requires further exploration.

Androgens↗

Acute administration of conjugated equine oestrogen does not improve exercise-induced myocardial ischaemia in men with coronary artery disease.

BACKGROUND: The parenteral administration of oestradiol acutely protects against exercise-induced myocardial ischaemia in women, but whether this effect is sex-specific is not known. AIMS: The effects of acutely administered conjugated equine oestrogen on exercise-induced myocardial ischaemia in men with established coronary heart disease were investigated in a randomized, placebo-controlled, double-blind cross-over trial. METHODS: Twenty men, aged 62 +/- 11.6 years, with reproducible exercise-induced myocardial ischaemia were treated with either intravenous conjugated equine oestrogen (25 mg) or saline prior to undergoing an exercise stress test. Primary end-points were total exercise time and time to 1 mm ST-segment depression. RESULTS: All participants completed the protocol. Total exercise time exceeded the baseline value in 17 of the 20 men following saline, and in 17 of the 20 men following oestrogen pretreatment. Time to 1 mm ST-segment depression exceeded the baseline value in 14 of the 19 men following saline, and following oestrogen administration, exceeded baseline in 13 of the 19 men. There was no significant difference between the two treatments in either time to 1 mm ST-segment depression or total exercise time. A period effect was apparent for total exercise time (P = 0.05) but not for time to ST-segment depression. CONCLUSION: Acute parenteral oestrogen therapy did not increase total exercise time or time to the onset of electrocardiographic changes of ischaemia in men with chronic stable coronary artery disease. These findings contrast the favourable effects of oestrogen in women in comparable studies and indicate a sex specificity for the acute cardiovascular effects of oestrogen.

Adult↗