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Elevated serum concentrations of beta-glucuronide metabolites and 4-oxoretinol in lactating sows after treatment with vitamin A: a model for evaluating supplementation in lactating women.

BACKGROUND: The effects of large doses of preformed vitamin A, such as those provided in supplementation programs for the prevention of deficiency, on total serum vitamin A have been inadequately investigated. OBJECTIVE: This study characterized the time course of serum vitamin A metabolites in lactating sows after single high doses of retinyl ester. DESIGN: Lactating sows were fitted with jugular catheters and subsequently fed either 1.05 or 2.1 mmol retinyl ester (n = 6/group) or a corn oil vehicle (n = 3). Blood was collected at baseline and at intervals to 48 h and analyzed by gradient HPLC for retinol, retinyl esters, and metabolites. RESULTS: The mean (+/-SD) total serum vitamin A concentration peaked at 1 h (3.69 +/- 4.0 mumol/L) and 2 h (7.70 +/- 6.8 mumol/L) in the low- and high-dose groups, respectively (P < 0.05). Retinyl esters accounted for most of the serum vitamin A in both groups at peak time points. Mean serum retinol concentrations changed little and accounted for most of the serum vitamin A at baseline (94% and 97% for the low- and high-dose groups, respectively) but for only 22% and 14% at peak times for the low- and high-dose groups, respectively. Postdosage increases were observed for total vitamin A and retinyl esters, 4-oxoretinol, retinoyl beta-glucuronide, and retinyl beta-glucuronide but not for retinoic acid. CONCLUSIONS: Serum retinol concentration remains relatively static after a large dose of preformed vitamin A and therefore is not an appropriate measure of intervention efficacy. The increases in beta-glucuronide metabolites and 4-oxoretinol suggest a preventive role against a rise in retinoic acid and retinol.

Animals↗

Parenteral administration of progestin Nestorone to lactating cynomolgus monkeys: an ideal hormonal contraceptive at lactation?

Nestorone (NES) progestin is highly effective for contraception following parenteral administration, but ineffective after oral ingestion due to rapid first-pass metabolism. Thus, NES might be ideal for lactational contraception; possible NES in milk should be metabolized by the nursing infant. We evaluated the distribution of NES, its endocrine effects and infant weight gain in five cynomolgus monkeys and their nursing infants. Nestorone implants, releasing approximately 40 microg NES/day in vitro, were placed s.c. in the mothers 3-4 months following delivery, where they remained in situ for 4 weeks. Sampling (blood daily from the mother; milk and blood from the infant at 3 day intervals) was initiated at 2 weeks prior to insertion, and continued for 2 weeks following removal of the implant. NES, oestradiol, progesterone and prolactin were measured by radioimmunoassays and the infants were weighed weekly. The (mean +/- SD) maternal serum and milk concentrations of NES were 337 +/- 90 and 586 +/- 301 pmol/l during the use of the implants. The ratio of milk/serum NES was 1.68 +/- 0.12 (mean +/- SE), and the serum and milk concentrations were significantly correlated (r = 0. 75, P < 0.001). NES was not detectable (<13 pmol/l) in any infant serum samples. Concentrations of prolactin (mean +/- SD) were 41.1 +/- 32, 26.7 +/- 7.6 and 26.3 +/- 9.5 ng/ml before, during and after the use of the implants respectively. The (mean +/- SE) infant weight increased from 643 +/- 54 g 1 week prior to insertion to 713 +/- 54 g 1 week following removal. These data confirm that NES in milk is rapidly metabolized by the suckling infant. Therefore, NES appears to be an ideal hormonal contraceptive for use during lactation.

Animals↗

One cycle of reproduction consisting of pregnancy, lactation or no lactation, and recovery: effects on fat pad cellularity in ad libitum-fed and food-restricted rats.

Groups of nine ad libitum-fed and food-restricted Osborne-Mendel rats, weighing between 200 and 220 g at mating, were killed on day 21 of pregnancy, day 21 of lactation and day 21 of a postweaning recovery period. Food-restricted rats were fed 70% of the mean daily ad libitum intake. Groups of nine ad libitum-fed animals, not permitted to suckle their young, were also killed on day 21 and day 42 postpartum. Groups of nine nonpregnant rats of comparable body weight on day 0 were killed on day 0, day 21, day 43 and day 64 of the experiment to serve as age and growth controls. At the time of death, subscapular, parametrial and retroperitoneal fat pads were dissected, weighed and sampled for determination of fat cell size and fat cell number. At 21 days postpartum, animals that had gone through pregnancy but did not lactate exhibited increased fat pad weight and significantly increased fat cell number in the parametrial and retroperitoneal depots although not in the subscapular depot. This increase in fat cell number was still evident 42 days postpartum and may predispose these animals to subsequent obesity.

Adipose Tissue↗

Inhibition of constitutive protein secretion from lactating mouse mammary epithelial cells by FIL (feedback inhibitor of lactation), a secreted milk protein.

The effect of a protein feedback inhibitor of lactation (FIL) on casein synthesis and secretion was examined using isolated acini from lactating mouse mammary gland. As previously found, FIL partially inhibited protein synthesis but produced an additional inhibition of constitutive casein secretion. The inhibition of synthesis and secretion showed similar dose-dependency and the inhibition was fully reversible. Constitutive secretion of pre-formed protein was inhibited by FIL in a pulse-chase protocol, indicating that the inhibitor regulated protein secretion by reducing protein movement through the secretory pathway independently of any initial inhibition of synthesis. Regulated exocytosis was not inhibited since casein release due to elevation of cytosolic Ca2+ concentration by the ionophore ionomycin was unaffected. Brefeldin A, which is known to block ER-to-Golgi transport, also inhibited both protein synthesis and secretion in mammary cells. The action of FIL on synthesis and secretion and previously described actions on casein degradation would be consistent with a block at an early stage in the secretory pathway. In support of this idea FIL treatment was found to result in vesiculation and swelling of the endoplasmic reticulum. These data provide evidence for a novel control of a constitutive secretory pathway by a physiological extracellular regulatory protein.

Animals↗

Enhancing effects of myristyl lactate and lauryl lactate on percutaneous absorption of indomethacin in rats.

The enhancing effects of myristyl lactate (ML) and lauryl lactate (LL) on the percutaneous absorption of indomethacin (ID) from test solutions in propylene glycol (PG) were investigated in rats. ID absorption was observed to be markedly enhanced by the addition of ML or LL to PG as compared with the control (PG alone). The marked enhancing effects were observed at concentrations greater than 3% ML and 3% LL in PG. In particular, the maximal enhancement of percutaneous absorption of ID was achieved at 5% ML and LL. To elucidate the mode of action of ML as an enhancer, the percutaneous absorption of ID through the skin pretreated with ML alone was investigated. It was suggested that ML acts on the stratum corneum to produce its effect.

Administration, Topical↗

Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, VI. Nucleotide sequences of lactate dehydrogenase genes from the thermophilic bacteria Bacillus stearothermophilus, B. caldolyticus and B. caldotenax.

Based on the previously determined amino-acid sequence of lactate dehydrogenase from B. stearothermophilus, an oligonucleotide probe was synthesized and used to clone the structural genes for lactate dehydrogenase from B. stearothermophilus, B. caldolyticus and B. caldotenax. The nucleotide sequences of the entire LDH genes from these three thermophilic bacilli were determined by the method of Maxam and Gilbert. The nucleotide sequence of the LDH gene from B. stearothermophilus is exactly identical to the one published recently; it agrees with the experimentally determined amino-acid sequence except at three positions. The amino-acid homologies among these thermophilic enzymes are 90% or more. The LDH genes are efficiently expressed in E. coli.

Amino Acid Sequence↗

Influence of age of ewe and photoperiod on the intervals between parturition and first oestrus in lactating and non-lactating ewes at different nutritional levels.

A total of 131 2- to 6-year-old Mutton Merino ewes in two experiments were maintained in pens during the post-partum period and were exposed either to an artificial photoperiod of decreasing daylength, or to the naturally increasing photoperiod. After lambing in July, the ewes either were deprived of their lambs or they reared one lamb for 40 days. In both groups, the ewes were fed at one of four nutritional levels until the first post-partum oestrus had been recorded. The proportion of ewes showing first oestrus within 90 days of lambing was 44% for those subjected to the artificial photoperiod compared with 67% for those exposed to the natural photoperiod. First oestrus in the ewes which showed first oestrus more than 90 days after lambing was less delayed in those exposed to the artificial photoperiod. Nutritional level had no effect on the time of resumption of oestrus. In the natural photoperiod, 67% of lactating ewes and 68% of non-lactating ewes showed oestrus in 56.3 and 42.1 days, respectively, and a similar effect was observed in those exposed to the artificial photoperiod. In the natural photoperiod, 33% of 2-year-old, 53% of 3-year-old and 84% of mature ewes showed first oestrus within 90 days of lambing. It was concluded that, in most periods of the year, many ewes of this breed can be remated within 2 to 3 months of lambing and may thus be able to lamb three times in 2 years.

Aging↗

Cardiorespiratory and lactate responses to a 1-hour submaximal running at the lactate threshold.

Cardiorespiratory and blood lactate (La) responses to prolonged submaximal running at an intensity relative to lactate threshold (LT) were examined in 15 recreational runners, aged 19 to 32. In test 1 where treadmill speed was progressively incremented by 10-20m/min until exhaustion, oxygen uptake at the LT (VO2 @ LT: 2.34 +/- 0.331/min or 41.6 +/- 5.7 ml/kg/min) and VO2max (3.58 +/- 0.341/min or 63.6 +/- 5.5 ml/kg/min) were measured. In test 2, the subject was required to run on the treadmill for 1 hour at a fixed velocity (Vt) which corresponded to his Vt @ LT. As expected, mean VO2 ranged during the 1-h submaximal running from 2.31 +/- 0.411/min or 63.0 +/- 7.8% VO2max at min 10-20 to 2.52 +/- 0.351/min or 69.2 +/- 6.2% VO2max at min 50-60, both of which were close to VO2 @ LT (65.2 +/- 4.4% VO2max). The slight decrease in blood La was found from min 20 to min 60, and this was accompanied by a parallel decline in respiratory exchange ratio. Shifts in the energy substrate toward a reliance on fat oxidation may occur during the course of 1-h running at Vt @t LT. The small oxygen debt observed after the 1-h running may confirm the assumption that prolonged running at Vt at LT would be performed in an almost fully aerobic steady state. We conclude that prolonged running at Vt @ LT may possibly maximize health-related benefits in the healthy adult.

Adult↗

Feeding oleamide to lactating Jersey cows 1. Effects on lactation performance and milk fatty acid composition.

Oleamide was previously reported to resist ruminal biohydrogenation and elevate milk oleic acid concentration when fed to lactating Holstein cows. To determine if Jersey cows responded similarly to oleamide, four lactating Jersey cows (mean 417 kg of body weight and 64 days in milk) were fed four diets in a 4x4 Latin square with 2-wk periods. Diets were total mixed ration containing 47% corn silage and 53% concentrate (dry matter basis) and were supplemented with no added fat (control), or with 3.5% added fat from either higholeic canola oil, a commercial source of oleamide, or oleamide synthesized from oleic acid and urea. The canola oil supplement had no effect on milk yield or composition. Compared to canola oil, the oleamide supplements reduced milk yield, dry matter intake, and milk fat and protein contents. Milk oleic acid concentration increased from 17.4% of total fatty acids for the control diet to 22.1% for the canola oil diet. Both oleamides further increased milk oleic acid to 30.0 and 27.1% of total fatty acids for the commercial and synthesized oleamides, respectively. Milk palmitic acid was reduced and stearic acid was increased by all fat supplements but more so by the oleamides than by the canola oil. Consistent with previous reports that fatty acyl amides resist ruminal biohydrogenation, feeding oleamide to Jersey cows in this study increased milk oleic acid concentration but had negative effects on feed intake and milk yield.

Animal Feed↗

Type of cottonseed and level of gossypol in diets of lactating dairy cows: effects on lactation performance and plasma gossypol.

Objectives were to determine the effects of feeding whole linted Upland (WUP) and cracked Pima cottonseed (BUPCP) to lactating cows on plasma gossypol concentrations and lactation performance. Holstein cows (n = 813) from three commercial dairies were assigned to one of two diets starting at 13+/-11 d in milk (DIM) for a 170-d experimental period. Cottonseed was included at 10% of the diet dry matter, and treatments consisted of replacing WUP with a 1:2 blend of BUPCP. Blood was collected from all cows at 61 and 91 DIM and from a subset of 56 cows on one dairy at 10, 33, 61, 91, 120, and 152 DIM. Intakes of free gossypol increased 32% in cows receiving the BUPCP diet, and concentrations of total gossypol (TG), as well as the proportion of TG as minus (-) isomer in plasma, were higher for cows fed BUPCP than WUP. Plasma TG increased linearly with increasing DIM, but cows fed the BUPCP, especially multiparous cows, had a higher increase in plasma TG over time. Yields of milk and milk components did not differ between the two treatments, although, yields of milk and milk components were greater in cows with higher plasma TG. Replacement of WUP cottonseed with BUPCP cottonseed increased plasma gossypol, but dry matter intake and yields of milk and milk components were not affected.

Animal Feed↗

Metabolic and lactational responses during recombinant bovine tumor necrosis factor-alpha treatment in lactating cows.

This study examined the effects of recombinant bovine tumor necrosis factor-alpha (rbTNF) administration on metabolic and hormonal responses and lactational performance in dairy cows. Twelve lactating Holstein cows were injected subcutaneously with rbTNF (2.5 microg per kg per d) or saline (3 ml per head per d) at 1200 h daily for 7 d (d 0-6) and used in a crossover design. The rbTNF treatment induced increases in plasma haptoglobin, nonesterified fatty acid, cortisol, and growth hormone levels compared with the control levels. The rbTNF-treated cows had lower triiodothyronine and insulin-like growth factor-1 concentrations than control cows. In a somatoliberin challenge on d 6, the somatotropin response to somatoliberin (0.25 microg/kg) was smaller in the rbTNF group than in the control. The rbTNF treatment also produced increases of the nitrite plus nitrate concentration in plasma and milk during the period between d 1 and 7. Milk yield was reduced by rbTNF administration from d 1 to 8. The percentage of milk fat was increased on d 1-7 by rbTNF treatment, but milk protein content in the rbTNF group was decreased on d 5 and 7 as compared with that in the control group. These results support the possibility that tumor necrosis factor-alpha is responsible for the changes in hormone secretion, milk production and composition, and inflammatory parameters observed during coliform mastitis.

Animals↗

Hormonal and lactational responses to growth hormone-releasing hormone treatment in lactating Japanese Black cows.

Ten multiparous lactating Japanese Black cows (beef breed) were used to evaluate the effects of bovine growth hormone-releasing hormone (GHRH) analog on milk yield and profiles of plasma hormones and metabolites. The cows received 2 consecutive 21-d treatments (a daily s.c. injection of 3-mg GHRH analog or saline) in a 2 (group) x 2 (period) Latin square crossover design. The 5 cows in group A received GHRH analog during period 1 (from d 22 to 42 postpartum) and saline during period 2 (from d 57 to 77 postpartum), and those in group B received saline and GHRH analog during periods 1 and 2, respectively. Mean milk yield decreased in saline treated compared with that during the 1-wk period before treatment 7.4 and 19.1% during periods 1 (group B) and 2 (group A), respectively. Treatment with GHRH analog increased milk yield 17.4% (period 1, group A) and 6.3% (period 2, group B). Treatment with GHRH analog induced higher basal plasma concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin, and glucose compared with saline-treated cows. In glucose challenge, the GHRH analog-treated beef cows had greater insulin secretion than the saline-treated beef cows. In insulin challenge, however, there were no significant differences in the areas surrounded by hypothetical lines of basal glucose concentrations and glucose response curves between GHRH analog- and saline-treated cows. These results demonstrate that GHRH analog treatment facilitates endogenous GH secretion in lactating Japanese Black cows, leading to increases in milk yield and plasma concentrations of IGF-1, insulin, and glucose.

Animals↗

The effects of varying gossypol intake from whole cottonseed and cottonseed meal on lactation and blood parameters in lactating dairy cows.

Effects of varying amounts of gossypol from whole Upland cottonseed (WCS) and cottonseed meal (CSM) were evaluated in 40 midlactation Holstein cows. After 14 d of pretreatment, cows were assigned to 1 of the 5 treatments for 84 d: control (no gossypol), 931 mg/kg total gossypol (TG) and 850 mg/kg free gossypol (FG) from WCS (moderate TG and high FG); 924 mg/kg TG and 91 mg/kg FG from CSM (moderate TG and low FG), 945 mg/kg TG and 479 mg/kg FG with equal amounts of TG from WCS and CSM (moderate TG and FG), or 1894 mg/kg TG and 960 mg/kg FG with equal amounts of TG from WCS and CSM (high TG and FG). Concentrations of plasma gossypol (PG) and its isomers were directly proportional to FG intake. Concentrations of PG reached a plateau after 28 d on treatment, and they were highest in cows receiving a diet with high TG and FG. Erythrocyte fragility differed among treatments and increased with increasing FG intake. Plasma gossypol returned to negligible concentrations 28 d after withdrawal of cottonseed products from the high TG and FG diet. Serum vitamin A was similar among treatments, but vitamin E increased with increasing FG intake. Serum enzymes were generally unaffected by treatments, but urea N increased in diets higher in TG and FG. Intake of dry matter was higher for the diet high in TG and FG than for the control diet, but was similar for other treatments. Cows receiving the high TG and FG diet produced more milk and 3.5% fat-corrected milk, with no changes in milk composition. Feeding a diet containing 1894 mg/kg TG and 960 mg/kg FG for 84 d increased PG concentrations and erythrocyte fragility and resulted in minor changes in blood metabolites and enzymes, but no detrimental effect on lactation performance was observed. Indicators of liver, kidney, and muscle cell viability suggest that the higher amounts of gossypol consumed in this study had only minor effects on those tissues in lactating dairy cows.

Animal Nutritional Physiological Phenomena↗

Varying protein content and nitrogen solubility for pluriparous, lactating Holstein cows: digestive performance during early lactation.

Thirty-four pluriparous Holstein cows were used to examine effects of crude protein (15.3 vs. 13.6%, dry matter basis) and nitrogen solubility (39.7 vs. 47.9%) on digestibility, energy and protein balances, and related traits during early lactation. Cows were assigned randomly at parturition to treatments in a 2 X 2 factorial arrangement; measurements were during wk 6, 10, and 14 postpartum. Diets were protein supplements (varying in protein content and nitrogen solubility), low-protein concentrate, corn silage treated with urea at ensiling, and wilted grass silage fed individually for ad libitum intake. Reducing nitrogen solubility of diet improved energy intake and productive energy factors but resulted in no significant increase of milk yield or body tissue balances, although body fat balance tended to be higher for low-solubility diets. There was no effect on overall partition of nitrogen in the body. Digestibility of carbohydrates and protein was higher for 15.3 than for 13.6% crude protein diets, resulting in higher total digestible nutrients and digestible and metabolizable energy of dry matter. Raising crude protein in the ration decreased milk yield of cows in early lactation but generally increased body tissue balances. Concentrations of rumen ammonia and blood urea nitrogen were not influenced by nitrogen solubility; increasing dietary protein increased concentrations of both, although not enough to increase consumption of free water. Best digestive efficiency was for animals fed the ration of medium crude protein and low nitrogen solubility.

Ammonia↗

Effect of prolactin infusion on lactation, glucose kinetics, and pancreatic hormones in lactating goats.

To determine lactational and glucogenic responses to increased prolactin concentrations, five lactating dairy goats were used in a crossover design. Prolactin at .85 mg/h or placebo was infused on each of 8 consecutive d via jugular catheter for 14 h initiated 30 min after the a.m. milking. To examine the effect of treatments on glucose metabolism, goats were given a single isotope injection of [6-3H]glucose 2 h after initiation of treatment infusion on the final day of the treatment period. Milk yield and milk protein percentage were not affected by prolactin infusion; however, milk fat and SNF percentage were significantly decreased. No differences in dry matter intake and digestibility of the diet were observed. Prolactin increased plasma prolactin and decreased plasma glucagon concentrations, but did not affect plasma insulin or glucose concentrations. Although glucose pool size per kilogram of BW was significantly lower in the prolactin-treated group than in the control group, no difference in glucose turnover rate was observed.

Animals↗

Effect of increased postmilking prolactin concentrations on lactation, plasma metabolites, and pancreatic hormones in lactating goats.

Six lactating dairy goats were utilized in a replicated 3 x 3 Latin square design to examine the effect of increased postmilking prolactin concentrations on lactational performance. Thirty minutes after each milking, either placebo or pituitary-derived ovine prolactin at 2 mg/h or 4 mg/h was infused via jugular cannula for 2 h. Goats were housed in a controlled environment at 19 degrees C and a cycle of 16 h light and 8 h dark. Mean plasma prolactin concentrations after milking were increased 100 and 180% for 2 and 4 mg/h prolactin infusion, respectively. Milk yield was slightly but significantly increased by 2 mg/h prolactin infusion compared with placebo and 4 mg/h prolactin infusion. However, milk composition and yields of milk components were not influenced by treatments. No differences in dry matter intake, digestibility of the diet, or N retention were observed. Circulating concentrations of glucose, nonesterified fatty acids, insulin, and glucagon were not altered.

Animals↗

Multi-farm use of bovine somatotropin for two consecutive lactations and its effects on lactational performance, health, and reproduction.

In a two-lactation study, 352 Holstein cows (124 primiparous) from six commercial dairy herds were assigned to daily injections of bST. Dosages were 0 (control), 5.15, 10.3, or 16.5 mg/d of bST; injections began 28 to 35 d postpartum. During yr 1, FCM production increased linearly as bST dose increased for primiparous and multiparous cows. However, FCM production for primiparous cows that were retained for yr 2 was not increased by bST, and the increase in FCM for multiparous cows was only 67% of that observed during yr 1 for doses of 10.3 and 16.5 mg/d. Milk SCC were not increased with the use of bST during either lactation. Days to conception of multiparous cows during yr 1 tended to increase linearly with increasing dose. Multiparous cows administered bST during yr 2 tended to have a lower conception rate than control cows (71 vs. 87%, respectively). Body condition was decreased linearly by bST dose at the end of yr 1 and 2. Prior to receiving bST during yr 2, bST-treated cows regained less body condition than control cows. Number of health disorders at parturition and assisted births of cows that received bST during yr 1 were unaffected by previous treatment. General health, ratio of single to multiple births, and BW gain of calves was similar among treatments.

Animals↗