PubMed Health⌕ Search

Biomedical subjects

A B Moore

Publications and source records attributed to A B Moore.

At least 19 recordsLinked to original sources
PubMed1999

Kinetic and inhibition studies on substrate channelling in the bifunctional enzyme catalysing C-terminal amidation.

A series of experiments has been conducted to investigate the possibility that substrate channelling might occur in the bifunctional forms of enzymes carrying out C-terminal amidation, a post-translational modification essential to the biological activity of many neuropeptides. C-terminal amidation entails sequential action by peptidylglycine mono-oxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate lyase (PGL, EC 4.3.2.5), with the mono-oxygenase catalysing conversion of a glycine-extended pro-peptide into the corresponding alpha-hydroxyglycine derivative, which is then converted by the lyase into amidated peptide plus glyoxylate. Since the mono-oxygenase and lyase reactions exhibit tandem reaction stereospecificities, channelling of the alpha-hydroxy intermediate might occur, as is the case for some other multifunctional enzymes. Selective inhibition of the mono-oxygenase domain by competitive ester inhibitors, as well as mechanism-based mono-oxygenase inactivation by the novel olefinic inhibitor 5-acetamido-4-oxo-6-phenylhex-2-enoate (N-acetylphenylalanyl acrylate), has little to no effect on the kinetic parameters of the lyase domain of the AE from Xenopus laevis. Similarly, inhibition of the lyase domain by the potent dioxo inhibitor 2,4-dioxo-5-acetamido-6-phenylhexanoate has little effect on the activity of the monooxygenase domain in the bifunctional enzyme. A series of experiments on intermediate accumulation and conversion were also carried out, along with kinetic investigations of the reactivities of the monofunctional and bifunctional forms of PAM and PGL towards substrates and inhibitors. Taken together, the results demonstrate the kinetic independence of the mono-oxygenase and lyase domains, and provide no evidence for substrate channelling between these domains in the bifunctional amidating enzyme.

Acrylates↗
PubMed1999

A demonstration of classical conditioning of the human eyeblink to an olfactory stimulus.

While acquisition of the eyeblink conditioned response to a variety of stimuli has been widely studied, it has yet to be established that humans will demonstrate a conditioned response to an olfactory stimulus. In this study we present data to show that humans will demonstrate a classically conditioned eyeblink response to an olfactory stimulus. Ten participants were tested in a delay conditioning procedure with an olfactory stimulus presented in a heated, humidified stream of air via an olfactometer, allowing the precise control over stimulus duration necessary for delay conditioning. Trials on which odor alone was presented were administered to four additional participants. Establishing that humans will demonstrate an eyeblink conditioned response to an olfactory stimulus will allow further exploration of the pathways involved in classical conditioning and associative learning, as well as an analysis of conditioning pathways across sensory modalities.

Adult↗
PubMed1998

Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.

OBJECTIVE AND DESIGN: 1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain. MATERIALS AND METHODS: The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin. RESULTS: CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity. CONCLUSIONS: CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.

Acetates↗
PubMed1998

Influence of insulin on follicular development and the intrafollicular insulin-like growth factor I (IGF-I) system in sows after weaning.

Twenty-four crossbred primiparous sows were used to investigate the influence of insulin administration after weaning on the intrafollicular insulin-like growth factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1 (n = 4). The number and diameters of ovarian follicles were recorded, and fluid was aspirated from the 20 largest follicles for determination of oestradiol and IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins (IGFBPs) by western ligand blotting. The walls of the follicles were collected for mRNA analysis by RNase protection assay or granulosa cells were collected for estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the number of follicles available on day 5 compared with saline-treated animals (19.8 versus 17.8). The concentration of oestradiol in follicular fluid from large (7-10 mm) follicles on days 3 and 5 was reduced (treatment by size class interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular concentrations of IGF-I at days 3 and 5 after weaning (treatment by day interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass 30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in saline-treated animals but decreased fourfold in insulin-treated sows from day 3 to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a manner consistent with slowing follicular growth and possibly allowed more follicles to become available for ovulation.

Animals↗
PubMed1998

Comparative effects of insulin and porcine somatotropin on postweaning follicular development in primiparous sows.

We compared the effects of exogenous insulin and porcine ST (pST) on follicular development after weaning. Crossbred primiparous sows received saline (1.5 mL i.m.; n = 9), insulin (.4 IU/kg BW s.c.; Eli Lilly Lente Iletin II; n = 10), or pST (40 microg/kg BW i.m.; n = 10) from d 1 to 5 after weaning (d 0). Ovaries were collected, the diameter of each follicle > or = 2 mm was measured, and fluid from the 20 largest follicles was assessed for IGF-I, IGF binding proteins (IGFBP), estradiol, progesterone, and testosterone. The total number (27.7, 25.3, and 29.1 for saline, insulin, and pST, respectively; SEM = 3.2) and average diameter (4.7, 5.2, and 5.5 mm for saline, insulin, and pST treatments, respectively; SEM = .3 mm) of ovarian follicles were not affected by insulin or pST treatment. The pST and insulin increased follicular fluid estradiol and testosterone in medium and large follicles compared to fluid from saline-treated sows, but the increase was greater for insulin than for pST treatment (treatment x size interaction, P < .01). Similarly, progesterone concentrations in follicular fluid were higher in medium and large follicles after insulin treatment, and pST treatment induced higher progesterone concentrations in small follicles and increasingly lower concentrations of progesterone in medium and large follicles (treatment x size interaction, P < .0007) compared to saline treatment. Follicular fluid IGF-I was greater (treatment x health interaction, P < .0001) in atretic and nonatretic follicles from pST-treated sows than in those from insulin- and saline-treated sows. Follicular fluid IGFBP-2 (tendency, P < .07) and IGFBP, possibly representing IGFBP-5 (30 kDa) and IGFBP-4 (22 kDa), were higher in atretic follicles than in nonatretic follicles (P < .05), whereas IGFBP-3 was not influenced by health status. The 30- and 22-kDa IGFBP were also influenced by treatment, increasing due to pST compared with saline or insulin treatments (P < .008). Follicular fluid IGFBP-2 and IGFBP-3 were not influenced by treatment. In conclusion, pST and insulin positively influenced follicular steroidogenesis and possibly follicular development, although through different mechanisms.

Animals↗
PubMed1997

Pyruvate-extended amino acid derivatives as highly potent inhibitors of carboxyl-terminal peptide amidation.

Carboxyl-terminal amidation, a required post-translational modification for the bioactivation of many neuropeptides, entails sequential enzymatic action by peptidylglycine monooxygenase (PAM, EC 1.14.17.3) and peptidylamidoglycolate lyase (PGL, EC 4.3.2.5). The monooxygenase, PAM, first catalyzes conversion of a glycine-extended pro-peptide to the corresponding alpha-hydroxyglycine derivative, and the lyase, PGL, then catalyzes breakdown of this alpha-hydroxyglycine derivative to the amidated peptide plus glyoxylate. We now introduce the first potent inhibitors for peptidylamidoglycolate lyase. These inhibitors, which can be viewed as pyruvate-extended N-acetyl amino acids, constitute a novel class of compounds. They were designed to resemble likely transient species along the reaction pathway of PGL catalysis. A general synthetic procedure for preparation of pyruvate-extended N-acetyl amino acids or peptides is described. Since these compounds possess the 2,4-dioxo-carboxylate moiety, their solution tautomerization was investigated using both NMR and high performance liquid chromatography analyses. The results establish that freshly prepared solutions of N-Ac-Phe-pyruvate consist predominantly of the enol tautomer, which then slowly tautomerizes to the diketo form when left standing for several days in an aqueous medium; upon acidification, formation of the hydrate tautomer occurs. Kinetic experiments established that these novel compounds are highly potent, pure competitive inhibitors of PGL. Kinetic experiments with the ascorbate-dependent copper monooxygenases, PAM and dopamine-beta-monooxygenase, established that these compounds also bind competitively with respect to ascorbate; however, pyruvate-extended N-acyl-amino acid derivatives possessing hydrophobic side chains are much more potent inhibitors of PGL than of PAM. Selective targeting of N-Ac-Phe-pyruvate so as to inhibit the lyase, but not the monooxygenase, domain was demonstrated with the bifunctional amidating enzyme of Xenopus laevis. The availability of potent inhibitors of PGL should facilitate studies regarding the possible biological role of alpha-hydroxyglycine-extended peptides.

Amides↗
PubMed1997

Amidative peptide processing and vascular function.

Substance P (SP), an amidated peptide present in many sensory nerves, is known to affect cardiovascular function, and exogenously supplied SP has been shown to activate nitric oxide synthase (NOS) in endothelial cells. We now report that SP-Gly, the glycine-extended biosynthetic precursor of SP (which is enzymatically processed to the mature amidated SP), causes relaxation of rat aortic strips with an efficacy and potency comparable to that of SP itself. Pretreatment of the aortic strips with 4-phenyl-3-butenoic acid (PBA), an irreversible amidating enzyme inactivator, results in marked inhibition of the vasodilation activity induced by SP-Gly but not of that induced by SP itself. Isolated endothelial cell basal NOS activity is also decreased by pretreatment with PBA, with no evidence of cell death or direct action of PBA on NOS activity. Both bifunctional and monofunctional forms of amidating enzymes are present in endothelial cells, as evidenced by affinity chromatography and Western blot analysis. These results provide evidence for a link between amidative peptide processing, NOS activation in endothelial cells, and vasodilation and suggest that a product of amidative processing provides intrinsic basal activation of NOS in endothelial cells.

Amino Acid Sequence↗
PubMed1997

Influence of exogenous insulin before breeding on conception rate and litter size of sows.

We conducted two experiments on commercial farms to evaluate the effect of insulin administered to primiparous sows before postweaning estrus on subsequent reproductive performance. On the day after weaning in Exp. 1, 138 crossbred primiparous sows were assigned to receive saline or insulin (.4 IU/kg BW) once daily at the time of feeding for four consecutive days. Treatment did not affect interval from weaning to estrus (5.1 +/- .2 d) or percentage in estrus by 7 d after weaning (92.6%). Farrowing rate at second parity was increased by insulin (76.7 and 92.3% for saline and insulin treatments, respectively; P < .01). Litter sizes at second parity were not affected by insulin treatment. Experiment 2 was conducted on a different commercial farm using 491 primiparous crossbred sows. They were treated similarly to those in Exp. 1 with saline or insulin after weaning, except that treatment duration of 2 d of saline or insulin was included. Treatment did not affect the interval from weaning to estrus (overall, 9.2 +/- .5 d), percentage in estrus by 7 d after weaning (79.1%) or farrowing rate (90.2%). However, the number of total pigs born in the second litter for sows mated within 7 d after weaning was increased (P < .05) by one pig in sows treated with insulin for 4 d (10.3 +/- .3 pigs) compared with 2 d (9.1 +/- .3) and with saline (2 d and 4 d grouped together: 9.3 +/- .1). Third-parity litter size was not adversely affected by treatments applied before the second litter. In conclusion, manipulation with a metabolic hormone such as insulin may improve postweaning fertility by affecting aspects of ovarian follicle development or pregnancy establishment.

Analysis of Variance↗
PubMed1997

Antiinflammatory and analgesic activity of an inhibitor of neuropeptide amidation.

4-Phenyl-3-butenoic acid (PBA) has been shown in vitro to be a turnover-dependent inactivator of peptidylglycine alpha-monooxygenase (PAM), the rate-limiting enzyme involved in the formation of amidated neuropeptides from their glycine-extended precursors. In the studies reported herein, we have shown that PBA produces a dose-dependent (50-500 mg/kg s.c.) inhibition of serum PAM activity in normal rats without affecting peptidylamidoglycolate lyase activity. Because amidated neuropeptides such as substance P and calcitonin gene-related peptide are involved in acute inflammation, we evaluated the effects of PBA on carrageenan-induced inflammation in rats. The acute administration of PBA (s.c. or i.p.) produced a dose-related inhibition of edema with maximum inhibition (67%) observed at 2 hr postphlogistic agent. In addition, the continuous administration of PBA to animals over a 7-day period using osmotic pumps not only inhibited hind paw swelling induced by carrageenan but also inhibited serum PAM activity and reduced tissue levels of substance P in hind paws. These results demonstrate for the first time a correlation between the antiinflammatory activity produced by an inhibitor of peptide amidation with its ability to inhibit serum PAM activity and lower endogenous tissue levels of substance P. Moreover, these results confirm our contention that PAM is an excellent pharmacological target for controlling the acute inflammatory response. We also demonstrate the ability of PBA to inhibit phenyl-p-quinone and acetylcholine-induced writhing in mice without affecting the spinally mediated tail immersion assay in rats. Because this analgesic effect was extremely rapid (within 15 min), PBA may be producing this effect by a mechanism other than peptide amidation.

Amidine-Lyases↗
PubMed1996

Depressed luteinizing hormone response to estradiol in vivo and gonadotropin-releasing hormone in vitro in experimentally diabetic swine.

The influence of the acute withdrawal of insulin therapy in streptozocin-diabetic female swine was examined for changes in 1) the in vivo pulsatile secretion of luteinizing hormone (LH), 2) the preovulatory-like gonadotropin patterns after exogenous estradiol, and 3) the in vitro LH secretion by cultured pituitary cells. In Experiment 1, ovariectomized diabetic pigs (n = 4) were maintained with insulin therapy until 4 d before estradiol benzoate (EB; 7 micrograms/kg body weight; subcutaneous) was administered. Four normal ovariectomized pigs, matched for age and weight, served as controls. The diabetic state was confirmed by the measurement of glucose and insulin concentrations during a glucose tolerance test. Pulsatile LH secretion was not influenced by experimental diabetes mellitus. However, the expected surge in LH was not induced by EB in diabetic gilts. In contrast, three of four normal gilts had a preovulatory-type surge in LH. Concentrations of follicle-stimulating hormone in serum were not affected by diabetes mellitus. Estradiol concentrations in serum after ER were influenced by diabetes mellitus (treatment by time interaction; P < 0.001). In individual estradiol profiles, maximum concentrations were similar (104 +/- 10.4 and 91 +/- 12.0 ng/ml for normal and diabetic pigs, respectively), but the interval to maximum concentration was delayed in diabetic pigs (27.5 vs. 9.0 h; SE = 3.0; P < 0.05). However, the duration of standing estrus (2.2 +/- .3 d) and the interval from EB to estrus (3.6 +/- 0.3 d) were not influenced by diabetes mellitus. In Experiment 2, LH secretion by cultured cells and residual cellular LH content were greater in the pituitaries of normal than diabetic pigs (P < 0.05), and only cells from normal pigs responded to gonadotropin-releasing hormone (GnRH), with increased production of LH (P < 0.05). In conclusion, diabetes mellitus did not affect pulsatile LH secretion but did lower the ability of exogenous estradiol to stimulate a surge in vivo and of GnRH to increase LH in vitro, suggesting that the pituitary response to estradiol and GnRH is more severely affected by diabetes than is the GnRH pulse generator.

Animals↗
PubMed1996

Depletion of insulin in streptozocin-induced-diabetic pigs alters estradiol, insulin-like growth factor (IGF)-I and IGF binding proteins in cultured ovarian follicles.

The objectives were to investigate whether insulin-dependent diabetes mellitus disrupts production of estradiol and activity of the insulin-like growth factor (IGF)-I system in individual ovarian follicles during the preovulatory period of the estrous cycle. Diabetes mellitus was induced with streptozocin (150 mg/kg) in seven cyclic gilts at 180 +/- 5 days of age. On Day 12 of the estrous cycle, insulin replacement therapy was withdrawn from three gilts and continued in four; four gilts served as normal controls. After ovary removal on Day 18, all follicles > or = 3 mm diameter were dissected free and cultured for 6 h in the presence of 280 ng testosterone for assessment of estradiol and IGF-I production and binding protein activity. Treatments did not affect corpora lutea number (15.4 +/- 0.8) or serum estradiol (5.8 +/- 0.8 pg/ml) on Day 18. There were no differences for any measure of follicular development between normal and insulin-treated diabetic gilts. Untreated diabetic gilts, compared to normal and insulin-treated diabetic gilts, had fewer total visible follicles (22.7 vs. 61.3 and 63.3; SEM = 8; p < 0.01) and reduced follicular diameter (3.4 vs. 4.4 and 4.2 mm; SEM = 0.3; p < 0.0001), respectively. Untreated diabetic gilts had a greater percentage of macroscopically atretic follicles than normal and insulin-treated diabetic gilts (75% vs. 47% and 36%; SEM = 10; p < 0.05). Untreated diabetes mellitus lowered estradiol (p < 0.01); however, effects of treatment on estradiol production were not significant when diameter was part of statistical models. When contents of IGF-I in follicular fluid and conditioned medium were summed after 6 h of culture, untreated diabetic pigs had lower IGF-I at all follicle diameters than pigs in the other treatments (p < 0.05). IGF binding protein (BP) activity was affected by diabetes mellitus, with untreated diabetic pigs having greater IGFBP-1 activity in medium and with both diabetic groups having greater IGFBP-2 activity in follicular fluid (p < 0.05). Activity of IGFBP-1 predominated in conditioned medium, and IGFBP-2 activity predominated in follicular fluid. IGFBP-3 was decreased in follicular fluid of atretic follicles and in medium of atretic follicles in all except the insulin-treated diabetic gilts; in these gilts it was increased in atretic follicles (treatment by atresia interaction; p < 0.05). In conclusion, estradiol was most related to size of the follicle; however, lowering of IGF-I regardless of follicle diameter and alterations in IGFBP activity suggest that diabetes affects IGF-I and its binding proteins differently from estradiol production. These alterations may explain reduced follicular growth and increased follicular atresia in diabetic pigs.

Animals↗
PubMed1993

Effects of exogenous porcine somatotropin on the carcass composition, hormonal and metabolic profiles, lipogenic capacity, and binding of insulin to erythrocyte receptors of fast- versus slow-growing swine.

Twenty barrows were designated as fast-growing (FG) and their littermates designated as slow-growing (SG) based on birth, weaning, and 56-d weight. Half of each group received 70 micrograms of porcine somatotropin (pST)/kg BW daily beginning at 40 kg BW. At 60 and 105 kg BW, blood was collected every .5 h for 12 h beginning 1 h before pST injection, fat biopsies were taken for in vitro lipogenic activity, and insulin erythrocytes were isolated for receptor binding. Swine treated with pST had elevated ADG (.95 vs .88 kg/d; P < .1) and reduced days to slaughter (61 vs 67; P < .1). The pST-treated pigs had less average backfat (2.73 vs 3.96 cm; P < .01), larger longissimus muscle areas (32.3 vs 28.2 cm2; P < .05), and a higher percentage of muscle (56.3 vs 50.3%; P < .01) than control pigs. Exogenous pST increased protein (17.4 vs 13.2%; P < .05) and decreased fat (22.9 vs 37.1%; P < .05). The FG pigs had higher ADG (.98 vs .86 kg/d; P < .01) and required fewer days to slaughter (57 vs 71; P < .01) than SG pigs. Administration of pST increased (P < .01) average pST levels (1.7 vs 14.0 ng/mL) in FG and SG pigs at 60 kg BW. At 105 kg BW, pST was higher (P < .01) in pST-FG than in pST-SG swine (46.0 vs 19.3 ng/mL) but was not different between FG and SG control swine (1.9 vs 1.8 ng/mL). Administration of pST increased concentrations of IGF-I (510.0 vs 160.0 ng/mL) and nonesterified fatty acids (182 vs 109 muEq/L, P < .01) in FG and SG swine. Over sample periods and growth rates, pST reduced (P < .05) CO2 production and lipid synthesis (.345 and 1.85 vs .575 and 2.71 mumol of glucose incorporated.g-1.2 h-1). At 60 kg BW, FG swine had less (P < .01) CO2 production and lipid synthesis (.299 and 1.83 vs .921 and 3.61 mumol.g-1.2 h-1) than did SG swine. Exogenous pST increased (P < .05) binding to insulin erythrocyte receptors (7.25 vs 6.34%).

Adipose Tissue↗
PubMed1993

Estrous and endocrine responses of lactating Holsteins to forced ventilation during summer.

Fourteen lactating and cycling Holsteins in each of two summers were assigned randomly to pens in a free-stall barn either with or without overhead fans to study the effect of fan cooling on certain endocrine and behavioral responses during the estrous cycle. After an adjustment period of 8 d in the first summer and 21 d in the second summer, jugular cannulas were inserted, and 25 mg of PGF2 alpha were injected. After injection, blood samples were collected frequently for 84 h in the first summer and 88 h in the second summer, followed by collection three times weekly for 3 wk thereafter each summer. Rectal temperatures were lower in the group cooled by fans than in the control group each summer. Luteal progesterone secretion tended to be greater in the fan group each summer; area under the luteal phase curve was significantly higher than for controls during the second summer. There was tendency for more preovulatory surges of LH and higher estrous responses rates in the fan group during the second summer. Thus, fan cooling of lactating dairy cows for several weeks before anticipated breeding provides potential for more efficient reproductive performance during the summer.

Animals↗
PubMed1993

Preemployment urine substance screening. One-year experience of a large hospital system.

Alcohol and drug abuse is estimated to cost our nation more than $160 billion per year in lost productivity, health care costs and crime. Preemployment screening for substances of abuse has become a standard in some industries, including the health care industry. Samaritan Health Services of Phoenix, Arizona, a large health care provider (11,244 employees) began preemployment drug screening and for-cause substance abuse testing March 1, 1991. This paper presents 1-year's statistics for that provider, including problems peculiar to the health care industry, eg, forensic testing stipulation agreements from professional boards. Problems are addressed including the ease of obtaining prescription medications by health care workers ("curbstone consultations") and dealing with a professional population knowledgeable about prescription drug use. It was this corporation's experience that preemployment drug screening can be performed without great hardship to a large health care provider.

Arizona↗
PubMed1991

Effects of exogenous insulin and body condition on metabolic hormones and gonadotropin-induced follicular development in prepuberal gilts.

To determine influences of insulin and body condition on follicular growth, prepuberal gilts (n = 16) treated with pregnant mare's serum gonadotropin (PMSG) were used in a 2 X 2 factorial experiment with main effects of insulin (0 or .4 IU/kg every 12 h beginning at 1800 on the day before PMSG) and backfat depth (moderate, 25 +/- .8; high, 32 +/- .7 mm; P less than .0001). Body weights were similar. Blood sampling was at 6-h intervals for analyses of LH, FSH, growth hormone (GH), glucagon, cortisol, insulin, insulin-like growth factor-I (IGF-I), plasma urea nitrogen (PUN), nonesterified fatty acids (NEFA), testosterone, estradiol-17 beta, and progesterone. Ovaries were removed 75 h after PMSG treatment, and visible small (less than or equal to 3 mm), medium (4 to 6 mm), large (greater than or equal to 7 mm), and macroscopically atretic follicles were counted. Administration of insulin increased IGF-I in fluid of medium follicles (108.8 vs 60.7 ng/ml; SEM = 13.3; P less than .05). Neither insulin nor fatness affected hCG binding by granulosa cells (12.5 +/- 1.6 ng/10(6) cells) or numbers of large (16.7 +/- 2.6) and medium (10.4 +/- 2.3) follicles. However, insulin increased the number of small follicles (58.9 vs 29.9; SEM = 9.7; P less than .05) and reduced the number of atretic follicles (3.8 vs 11.3; SEM = 1.1; P less than .05). The predominant effect of insulin on reducing number of atretic follicles was in the small size class (.6 vs 6.9; SEM = .6, P less than .01). Follicular fluid estradiol and progesterone were not affected by treatments; however, testosterone concentrations in large follicles were lower in gilts with higher backfat (32.5 vs 59.9 ng/ml; SEM = 4.0; P less than .05). Systemic LH, FSH, glucagon, cortisol, PUN, NEFA, estradiol, and testosterone were not affected by insulin or level of feeding. However, GH was lower in gilts that had higher backfat (overall average of 3.2 vs 2.8 ng/ml; SEM = .1; P less than .05). Insulin reduced atresia and altered intrafollicular IGF-I independently of body condition and without sustained effects on other hormones.

Animals↗
PubMed1990

Exogenous insulin and additional energy affect follicular distribution, follicular steroid concentrations, and granulosa cell human chorionic gonadotropin binding in swine.

The objective was to determine whether exogenous insulin and dietary energy interact to affect follicular development in gilts. In a 2 x 2 x 2 completely randomized design, main effects were level of dietary energy (5771 or 9960 kcal metabolizable energy/day beginning on Day 12 of the estrous cycle), insulin dosage (0 or 0.4 IU/kg twice daily beginning on Day 15 of the cycle), and day of cycle at ovary removal (Day 17 or Day 19). Percentage of follicles designated small (less than or equal to 3 mm diameter) decreased from Day 17 to Day 19 of the cycle, and the percentage of large follicles (greater than or equal to 7 mm) increased (p less than 0.05). Insulin interacted with day of the cycle (p less than 0.05) to affect distribution of medium (4-6 mm) and macroscopically atretic follicles. Percentage of atretic follicles increased from Day 17 to Day 19 in saline-treated (from 15.5% to 38.2%) but not in insulin-treated animals (6.3% to 10.7%). Percentage of medium (4-6 mm) follicles decreased from Day 17 to Day 19 in saline-treated gilts (from 41.7 to 16.6%) but not in insulin-treated gilts (39.8% to 35.1%). Intrafollicular testosterone and progesterone concentrations were not affected by treatments. In medium follicles, the ratio of estradiol to progesterone was greater (p less than 0.05) for insulin-treated gilts on Day 17 than for the other treatment combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Poly(DL-lactide-co-glycolide)/norethisterone microcapsules: an injectable biodegradable contraceptive.

Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.

Animals↗