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C J Scott

Publications and source records attributed to C J Scott.

At least 37 records · Page 2Linked to original sources
PubMed1998

The distribution of estrogen receptors in the brainstem of female sheep.

Estrogen receptors (ER) have been mapped in the brainstem of the female sheep with immunocytochemistry. A small group of ER-positive cells was found in the lateral and ventrolateral medulla and a larger number in the nucleus of the solitary tract. ER-positive cells were abundant in the area postrema. In the rostral brainstem a small number of ER-positive cells were found in the lateral and dorsal regions of the periaqueductal gray area, and some immediately lateral to the fourth ventricle. Many ER-positive cells were also present in the region around the superior cerebellar peduncle, particularly in the lateral parabrachial nucleus. These results describe for the first time the distribution of ER in the brainstem of the sheep and indicate that the majority of estrogen-containing cells are located in structures involved in the regulation of cardiovascular parameters and fluid balance.

Animals↗
PubMed1998

Neonatal immunization against gonadotropin-releasing hormone (GnRH) results in diminished GnRH secretion in adulthood.

The effects of neonatal immunization against GnRH were studied in sheep after they had reached adulthood (3-4 yr) and the antibody titers had fallen to undetectable levels. The immunized animals had small gonads, and the females did not have large follicles (>3 mm) or corpora lutea in their ovaries. Compared with controls, the immunized animals had low or nondetectable levels of LH and FSH in peripheral plasma, and the immunized animals generally failed to respond to a single i.v. GnRH challenge. After ovariectomy, the control ewes, but not the immunized ewes, showed an elevation in plasma LH and FSH levels. The sampling of hypophysial portal blood, with a newly described method, showed that the secretion of GnRH was reduced in the immunized animals, but the amount of GnRH in the median eminence was similar in the control and immunized ewes. The pituitary content of LH and FSH was reduced in the immunized ewes as was messenger RNA for the gonadotropin subunits and the GnRH receptor. These data indicate that neonatal immunization does not affect the synthesis of GnRH in adulthood but reduces the secretion of GnRH, causing long-term sterility in these animals.

Animals↗
PubMed1998

Effect of infusing gamma-aminobutyric acid receptor agonists and antagonists into the medial preoptic area and ventromedial hypothalamus on prolactin secretion in male sheep.

We investigated the effects of gamma-aminobutyric acid (GABA) agonists muscimol and baclofen (GABA(A) and GABA(B) agonists, respectively) and antagonists bicuculline methiodide (BMI, GABA(A) antagonist) or 2-hydroxysaclofen (SAC) and CGP 55845A (GABA(B) antagonists) on prolactin (PRL) secretion in castrated rams. The drugs were applied by microdialysis into either the medial preoptic area (mPOA) or ventromedial hypothalamus (VMH). Dialysis of baclofen into the mPOA significantly increased mean PRL (p < 0.05), whereas SAC caused a small, but significant decrease (p < 0.01). Dialysis of either muscimol or BMI into the mPOA had no effect on prolactin. In the VMH, baclofen significantly increased (p < 0.01) mean PRL but SAC and CGP 55845A were ineffective, whereas dialysis of either muscimol or BMI increased mean prolactin (p < 0.01). These results show that infusion into the mPOA of drugs that affect GABA(B) receptor alter PRL release, whereas infusion of a GABA(A) agonists and antagonist was without effect on PRL release. In contrast, infusion of both GABA(A) and GABA(B) agonists and a GABA(A) antagonist into the VMH altered PRL secretion. This suggest that GABAergic neurons in both regions participate in regulating PRL secretion, but by different receptor systems.

Animals↗
PubMed1997

Hypothalamic sites of action for testosterone, dihydrotestosterone, and estrogen in the regulation of luteinizing hormone secretion in male sheep.

Testosterone (T) inhibits LH secretion partly by acting at unknown sites within the brain to inhibit GnRH secretion. We tested the hypothesis that the preoptic area (POA) and arcuate-ventromedial region (ARC/VMR), areas rich in androgen and estrogen (E) receptors, are neural sites at which T and the T metabolites, dihydrotestosterone (DHT) and estrogen (E), act to suppress LH secretion. Bilateral guide cannulae were surgically implanted into either the POA or ARC/VMR of castrated male sheep. Experiments were conducted under a long day photoperiod to maximize the inhibitory effect of the steroids. In Exp 1, all sheep (n = 6/site) sequentially received bilateral implants of cholesterol (CHOL), T, or E at each site. Jugular blood samples were taken at 10-min intervals for 4 h both immediately before implant insertion and 5 days later. In Exp 2, all sheep (n = 6/site) sequentially received bilateral implants of CHOL, DHT, or E at each site according to a latin square design. Blood samples were taken before and 7 days after implant insertion. In Exp 3, which followed the same design as Exp 2, implants of E, T, or DHT were placed only in the ARC/VMR. In the final experiment, the effects of T and CHOL implants in the ARC/VMR were compared. Neither T, DHT, nor CHOL implants at either site affected LH secretion. In contrast, E treatment in the ARC/VMR suppressed mean plasma LH levels (P < 0.01), primarily due to an increase in interpulse interval (P < 0.01). Estrogen implants in the POA caused a small, but nonsignificant (P > 0.05), decrease in mean LH levels in the first experiment and an increase in LH interpulse interval (P < 0.05) in the second experiment. These results suggest that the ARC/VMR and possibly the POA are sites at which E acts to reduce GnRH secretion in male sheep.

Animals↗
PubMed1997

Enhancing patient outcomes through an understanding of intercultural medicine: guidelines for the practitioner.

As cultural and ethnic diversity increase within American society, physicians face new challenges in recognizing patients' culturally defined expectations about medical care and the cultural/ethnic dictates that influence physician-patient interactions. Patients present to practitioners with many mores related to concepts of disease and illness, intergenerational communication, decision-making authority, and gender roles. In addition, many cultural groups follow folk medicine traditions, and an increasing number of Americans seek treatment by practitioners of alternative therapies before seeking traditional western medical attention. To facilitate patient assessments, enhance compliance with health care instructions, and thus achieve the best possible medical outcomes and levels of satisfaction, practitioners must acknowledge and respect the cultural differences patients bring to medical care environments.

Complementary Therapies↗
PubMed1996

Influence of testosterone on LHRH release, LHRH mRNA and proopiomelanocortin mRNA in male sheep.

The mechanism whereby testosterone (T) reduces pulsatile LHRH and LH release is unknown. We tested the hypothesis that hypothalamic levels of LHRH mRNA decrease and proopiomelanocortin (POMC) mRNA increase coincident with reduced LHRH release induced by either long-term or short-term T treatment in male sheep. Experiment 1 examined the effect of long-term T exposure on LHRH and LH release and LHRH and POMC mRNA levels. Yearling Suffolk rams were castrated and assigned to one of four treatments: 1) castrated (n = 4); 2) castrated, portal cannula (n = 5); 3) castrated+T (n = 4) and 4) castrated+T, portal cannula (n = 4). T-treated males received ten 10-cm silastic T-implants immediately after castration. Surgical placement of devices for collecting hypophyseal-portal blood occurred 2 to 3 months after castration. Seven to 10 days after surgery, blood samples were collected at 10-min intervals for 8 h from portal cannulated males or for 5 h from non-cannulated males to assess pulsatile LHRH and/or LH release. Immediately after blood sample collection, hypothalamic tissue was collected for in situ measurement of LHRH or POMC mRNA. T-treatment decreased (P < 0.01) mean LHRH and LH and decreased (P < 0.01) LHRH and LH pulse frequency. T did not significantly affect (P > 0.10) silver grain area per LHRH neuron, but decreased (P < 0.01) silver grain area per POMC neuron. Portal cannulation tended to decrease (P = 0.057) silver grain area per LHRH neuron without significantly affecting (P > 0.10) LHRH cell numbers while reducing (P < 0.01) silver grain area per POMC neuron and POMC cell numbers. A second experiment examined the effect of 72 h of T-infusion on LHRH and POMC mRNA levels. Castrated yearling males were assigned to receive either vehicle (n = 4) or T (768 ug/kg/day; n = 4). Blood samples were collected at 10 min intervals for 4 h prior to and during the final 4 h of infusion. Infusion of T decreased (P < 0.01) mean LH and LH pulse frequency. T did not significantly affect (P > 0.10) silver grain area per LHRH neuron or LHRH cell numbers. T reduced (P < 0.01) silver grain area per POMC neuron without affecting (P > 0.10) POMC cell number. We reject our hypothesis and conclude that reduced LHRH or heightened POMC gene expression are not mechanisms whereby T reduces pulsatile LHRH release in male sheep.

Animals↗
PubMed1996

Differential regulation of luteinizing hormone release by gamma-aminobutyric acid receptor subtypes in the arcuate-ventromedial region of the castrated ram.

We investigated the effects on LH secretion of infusing gamma-aminobutyric acid (GABA) agonists muscimol and baclofen (GABAA and GABAB receptor agonists, respectively) into either the medial preoptic area (mPOA) or the arcuate-ventromedial region (ARC-VMR) of the hypothalamus of castrated rams during the nonbreeding season. Bilateral microdialysis of artificial cerebrospinal fluid for 4 h followed by treatment with artificial cerebrospinal fluid, baclofen (1 mM), or muscimol (1 mM in the ARC-VMR, 250 microM in the mPOA) for 4 h was carried out on three separate occasions in random order. Simultaneously, jugular venous blood was collected at 10-min intervals, and plasma later was assayed for LH. The estimated dose of baclofen delivered to each unilateral microdialysis site was 7.9 micrograms; for muscimol, it was 1.1 micrograms for the mPOA and 4.5 micrograms for the ARC-VMR. In the mPOA, baclofen had no detectable effect, whereas muscimol had a delayed suppressive effect on mean LH (P < 0.01). In the ARC-VMR muscimol rapidly reduced mean LH (P < 0.01). In contrast, baclofen increased mean LH (P = 0.01) and LH pulse amplitude (P = 0.05) without altering the LH interpulse interval (P > 0.10). These results support the involvement of GABAA receptors in the mPOA in regulating LH secretory patterns. More importantly, both GABAA and GABA(B) receptors in the ARC-VMR appear to differentially modulate LH and, presumably, GnRH release. Whether GABA acts directly on the GnRH neuron or indirectly through other neural systems remains to be determined.

Animals↗
PubMed1995

Disruption of reproductive rhythms and patterns of melatonin and prolactin secretion following bilateral lesions of the suprachiasmatic nuclei in the ewe.

To determine whether the photoperiodic responses of reproductive and prolactin (PRL) rhythms in the ewe requires an intact suprachiasmatic nucleus (SCN) driving the pineal rhythm of melatonin secretion, four groups of ovary-intact ewes over a 6-year period were subjected to bilateral (n = 40) or sham lesions (n = 15) of the SCN. Animals were exposed to an alternating 90-120 day photoregimen of 9L:15D and 16L:8D photoperiods. Blood samples taken twice weekly were assayed for prolactin and for progesterone to monitor oestrous cycles. On several occasions blood samples also were taken at hourly intervals for 24 h and analyzed for melatonin. Melatonin concentrations in sham lesioned ewes were basal during the lights-on period and rose robustly during darkness. Those sheep bearing unilateral lesions of the SCN (n = 13) or where the lesion spared the SCN entirely (n = 8) had patterns of melatonin secretion similar to sham ewes. The remaining ewes, having complete (n = 9) or incomplete bilateral (n = 8) destruction of the SCN, with one exception, had disrupted patterns of melatonin secretion. The nature of this disruption varied from complete suppression to continuously elevated levels. In lesioned ewes where melatonin secretion was not affected the onset and cessation of ovarian cycles were similar to sham ewes; stimulation of oestrous cycles under 9L:15D and cessation of oestrous cycles under 16L:8D. In contrast, 13 of 17 ewes with disrupted melatonin secretion also exhibited disrupted patterns of ovarian activity. In these animals oestrous cycles were no longer entrained by photoperiod but still occurred in distinct clusters, that is, groups of cycles began and ended spontaneously. Sheep with normal melatonin patterns showed low levels of PRL secretion during short days and elevated PRL levels during long days. However, 8 of 13 ewes with disrupted melatonin showed patterns of PRL secretion that were no longer entrained by photoperiod. A minority of ewes with disrupted melatonin patterns still showed reproductive (n = 4) and PRL (n = 5) responses similar to those of sham-lesioned ewes. These results show that bilateral destruction of the SCN in the ewe disrupts the circadian pattern of melatonin secretion and that this disruption usually, but not always, is associated with altered photoperiodic responses. These results strongly suggest that the SCN are important neural elements within the photoperiod time-keeping system in this species. A role for the SCN in the generation of endogenous transitions in reproductive activity (refractoriness) and prolactin secretion is not supported.

Animals↗
PubMed1995

The role of neuropeptide Y (NPY) in the control of LH secretion in the ewe with respect to season, NPY receptor subtype and the site of action in the hypothalamus.

Neuropeptide Y1-36 (NPY1-36) acts through Y1 and Y2 receptors while the C-terminal NPY fragments NPY18-36 and N-acetyl[Leu28,31]pNPY24-36 act only through the Y2 receptor. We have investigated the effects of intracerebroventricular (i.c.v.) administration of NPY1-36, NPY18-36 and N-acetyl[Leu28,31]pNPY24-36 on LH secretion in the ovariectomised (OVX) ewe. These peptides were administered into a lateral ventricle (LV) or the third ventricle (3V) of OVX ewes during the non-breeding and breeding seasons. Microinjections of NPY were also made into the preoptic area (POA) during both seasons to investigate the effects of NPY at the level of the GnRH cell bodies. Tamed sheep were fitted with 19 gauge guide tubes into the LV, 3V or the septo-preoptic area (POA). Jugular venous blood samples were taken every 10 min for 3 h. Sheep were then given NPY1-36 (10 micrograms), NPY18-36 (100 micrograms) or saline vehicle into the LV; N-acetyl[Leu28,31]pNPY24-36 (100 micrograms), NPY1-36 (10 micrograms or 100 micrograms), NPY18-36 (10 micrograms or 100 micrograms) or saline vehicle into the 3V, or NPY1-36 (1 microgram, 5 micrograms, 10 micrograms) into the POA. Blood sampling continued for a further 3 h. LH was measured in plasma by radioimmunoassay. LV or 3V injection of 10 micrograms NPY1-36 caused a small but significant (P < 0.025) increase in the interval from the last pre-injection pulse of LH to the first post-injection LH pulse during the breeding season. Other LH pulse parameters were not significantly affected. NPY18-36 did not produce any significant change in LH pulsatility when injected into the LV, and neither peptide had any effect on plasma prolactin or GH levels. There was a significant (P < 0.01) reduction in LH pulse frequency after 3V injection of 10 micrograms and 100 micrograms NPY and 100 micrograms NPY18-36. Pulse amplitude was reduced by 3V administration of the Y2 agonist, N-acetyl[Leu28-31]pNPY24-36 and 100 micrograms NPY18-36. When the amplitude of the first post-injection LH pulse was analysed, 10 micrograms NPY also had a significant (P < 0.05) suppressive effect. During the non-breeding season, 100 micrograms NPY1-36 (but not 10 micrograms) decreased (P < 0.01) LH pulse frequency. LH pulse amplitude was significantly (P < 0.01) decreased by 100 micrograms NPY18-36. Doses of 10 micrograms NPY1-36 and 100 micrograms NPY18-36 had greater inhibitory effects on pulse frequency during the breeding season but the suppressive effect of 100 micrograms NPY was similar between seasons. Microinjections of NPY into the POA decreased (P < 0.01) average plasma LH levels during the non-breeding season at a dose of 10 micrograms but did not significantly affect pulse frequency or amplitude. We conclude that a substantial component of the inhibitory action of NPY on LH secretion in the absence of steroids is mediated by the Y2 receptor. This inhibition is probably exerted by way of a presynaptic action on GnRH terminals in the median eminence as NPY does not modulate the frequency or amplitude of LH pulses at the level of the GnRH cell bodies in the POA.

Animals↗
PubMed1995

An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients.

The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.

Aged↗
PubMed1994

Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse.

Atherosclerosis is a complex disease with both genetic and environmental determinants. Apolipoprotein (Apo) E-deficient mice have been created that are highly susceptible to atherosclerosis. In order to assess the role of human apolipoprotein (hApo) A-I and high density lipoprotein (HDL) in atherosclerosis susceptibility, transgenic mice overexpressing the hApo A-I gene were crossed with Apo E-deficient mice. Apo E-/-, hApo A-I mice with two-fold elevation in HDL cholesterol have markedly diminished atherosclerosis with less fibroproliferative lesions by 8 months of age. A strong reciprocal relationship between HDL cholesterol levels and atherosclerosis was found with HDL levels accounting for 78% of the observed variance in mean lesion area. The effect of HDL on atherosclerosis resistance was independent of non-HDL cholesterol.

Aging↗
PubMed1994

Adrenergic regulation of growth hormone secretion in the ewe.

This study examined the role of the adrenergic system in the regulation of growth hormone (GH) secretion in sheep. Intravenous infusion of noradrenaline (0.5 microgram/kg per min for 2 hr) totally suppressed plasma GH concentrations. Concomitant treatment of animals with the beta-adrenergic antagonist propranolol completely blocked the noradrenaline-induced suppression of GH. In contrast, intravenous injection of the centrally acting alpha 2-agonist clonidine (2 micrograms/kg) elicited a release of GH. To further investigate the central adrenergic regulation of GH secretion 10 micrograms of noradrenaline or adrenaline was microinjected (1 microliter) directly into the preoptic area of the hypothalamus of ovariectomized ewes. When the time of injection coincided with a GH trough period, both noradrenaline and adrenaline caused an increase in plasma GH concentrations, whereas if the injection coincided with an endogenous pulse of GH no additional GH response was obtained. In conclusion, these results provide evidence for the involvement of the adrenergic system in the regulation of GH secretion in sheep. Centrally, adrenergic pathways exert a stimulatory effect on GH release via an alpha 2-adrenergic system, whereas peripherally adrenergic pathways exert an inhibitory effect via beta-adrenergic mediated mechanisms. Furthermore, adrenergic stimulation of the preoptic area may inhibit somatostatin activity and directly facilitate a GH pulse. Alternatively, adrenergic innervation of the preoptic area may influence neurons (somatostatin or other) that project to the arcuate nucleus and stimulate the release of GH-releasing factor.

Animals↗
PubMed1993

A preliminary study of cardiopulmonary resuscitation by circumferential compression of the chest with use of a pneumatic vest.

BACKGROUND: More than 300,000 people die each year of cardiac arrest. Studies have shown that raising vascular pressures during cardiopulmonary resuscitation (CPR) can improve survival and that vascular pressures can be raised by increasing intrathoracic pressure. METHODS: To produce periodic increases in intrathoracic pressure, we developed a pneumatically cycled circumferential thoracic vest system and compared the results of the use of this system in CPR (vest CPR) with those of manual CPR. In phase 1 of the study, aortic and right-atrial pressures were measured during both vest CPR (60 inflations per minute) and manual CPR in 15 patients in whom a mean (+/- SD) of 42 +/- 16 minutes of initial manual CPR had been unsuccessful. Vest CPR was also carried out on 14 other patients in whom pressure measurements were not made. In phase 2 of the study, short-term survival was assessed in 34 additional patients randomly assigned to undergo vest CPR (17 patients) or continued manual CPR (17 patients) after initial manual CPR (duration, 11 +/- 4 minutes) had been unsuccessful. RESULTS: In phase 1 of the study, vest CPR increased the peak aortic pressure from 78 +/- 26 mm Hg to 138 +/- 28 mm Hg (P < 0.001) and the coronary perfusion pressure from 15 +/- 8 mm Hg to 23 +/- 11 mm Hg (P < 0.003). Despite prolonged unsuccessful manual CPR, spontaneous circulation returned with vest CPR in 4 of the 29 patients. In phase 2 of the study, spontaneous circulation returned in 8 of the 17 patients who underwent vest CPR as compared with only 3 of the 17 patients who received continued manual CPR (P = 0.14). More patients in the vest-CPR group than in the manual-CPR group were alive 6 hours after attempted resuscitation (6 of 17 vs. 1 of 17) and 24 hours after attempted resuscitation (3 of 17 vs. 1 of 17), but none survived to leave the hospital. CONCLUSIONS: In this preliminary study, vest CPR, despite its late application, successfully increased aortic pressure and coronary perfusion pressure, and there was an insignificant trend toward a greater likelihood of the return of spontaneous circulation with vest CPR than with continued manual CPR. The effect of vest CPR on survival, however, is currently unknown and will require further study.

Aorta↗
PubMed1993

Studies on the neuronal systems involved in the oestrogen-negative feedback effect on gonadotrophin releasing hormone neurons in the ewe.

Oestrogen can act on the brain to exert negative and positive feedback effects on the secretion of gonadotrophin releasing hormone (GnRH), but this cannot be effected through the GnRH cells themselves because they have no oestrogen receptors. We have used intraventricular injection of agonists and antagonists of various transmitters to determine which systems are involved in the control of GnRH by steroid hormones. We have also developed a model for the injection of drugs directly into the medial pre-optic area of the sheep brain to study the action on the GnRH cell bodies. Opioid systems seem to be involved in the mediation of the feedback effects of progesterone, but not oestrogen. Noradrenaline appears to be involved in the negative feedback regulation of GnRH secretion during the anoestrous period. Thus, under the strong negative influence of oestrogen at this time GnRH/luteinizing hormone (LH) secretion is reduced but can be restored by the preoptic micro-injection of noradrenaline. Gamma-amino-butyric acid (GABA) agonists and antagonists inhibit LH secretion when injected into the medial pre-optic region of the hypothalamus of ovariectomized ewes with or without oestrogen treatment. We have no evidence that GABA is involved in the negative feedback regulation of GnRH, since neither agonists nor antagonists will reverse the effects of steroid feedback. There appears to be a shift in the GABA receptor subtype function with season; in the breeding season only GABAA ligands are effective, whereas during the non-breeding season both GABAA and GABAB type ligands will affect LH secretion. This suggests that the seasonal shift in responsiveness to the negative feedback effects of oestrogen involves a shift in the function of GABA receptor subtypes.

Animals↗