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Biomedical subjects

I Gunn

Publications and source records attributed to I Gunn.

At least 19 recordsLinked to original sources
PubMed2006

Studies of male reproduction in captive African wild dogs (Lycaon pictus).

Implementation of assisted breeding in the captive African wild dog is restricted by a current lack of knowledge on their reproductive physiology and the apparent difficulty of effectively manipulating the complex social dynamic of the pack in order to conduct reproductive procedures. In this study, we describe protocols for the safe and repeated capture and restraint of the African wild dog (n=7) as well as techniques for assessment of male reproductive function, semen collection and preservation. In a serendipitous finding, captive African wild dogs appeared to display significant seasonal change in male reproduction. Testicular volume and tone, spermatorrhea and the ability to collect semen by electroejaculation all increased significantly during late summer and then subsequently declined by early spring. While there were no detectable seasonal changes in testosterone concentration in the population as whole, the alpha-dominant male in both years of the study, had a highly elevated testosterone concentration compared to subordinate males. Semen collection by electroejaculation during the late summer was most effective in peri-pubertal males (15 months) when all seven electroejaculates were of adequate quality for cryopreservation. In the second breeding season (27 months), there were numerous changes in the pack hierarchy and electroejaculation was not as successful (3/7). The characteristics of electroejaculated semen collected in the breeding season are described for seven animals including the first descriptions and incidence of sperm abnormalities in the species. Semen (n=7) was frozen using a Tris-citrate fructose buffer and final egg yolk and glycerol concentration of 20% and 4%, respectively. Sperm were loaded into 0.25 mL straws, frozen in liquid nitrogen vapor and then thawed at 37 degrees C. Initial post-thaw survival of spermatozoa was encouraging (% motile: 31.8+/-5.8%; rate: 2.8+/-0.3; % intact plasma membranes: 33.4+/-5.3% and the % of damaged acrosomes: 4.4+/-1.5%) but following 2 h incubation at 37 degrees C, post-thaw survival declined markedly.

Animals↗
PubMed2006

Reducing the potential for phlebotomy tourniquets to act as a reservoir for meticillin-resistant Staphylococcus aureus.

The contamination rate of phlebotomy tourniquets with meticillin-resistant Staphylococcus aureus (MRSA) was assessed, and it was determined whether this could be reduced by changes in practice or by the use of a physical barrier. Initially, the tourniquets of both preregistration house officers and phlebotomists were investigated, but as phlebotomists reported significantly more venepunctures daily, the trial continued solely with phlebotomists. Each day, the phlebotomists were supplied with a fresh sterile tourniquet, and after use, the tourniquets were swabbed and cultured. The rate of contamination with MRSA was 32 of 131 (25%) tourniquets. An audit of hand hygiene practice was undertaken and revealed that phlebotomists were performing hand decontamination inadequately between patients and wore wristwatches while working. Education comprising standard infection control methods to encourage good practice was given. After this, a polythene strip was used as a barrier by half of the phlebotomists during all venepunctures. Tourniquets were cultured and replaced daily as before. During this stage of the trial, the rates of contamination were 1 of 46 tourniquets (using a polythene strip) and 1 of 42 tourniquets (without using a polythene strip). In conclusion, phlebotomy tourniquets may be potential vectors for transferring bacteria, including MRSA. Contamination rates, and hence potential risk, can be reduced if hand decontamination is performed. This suggests that contamination of tourniquets is via phlebotomists' hands, not directly from patients' skin. Hand hygiene should be regarded as the most important method by which the spread of organisms can be reduced.

Cross Infection↗
PubMed2001

Oxyntomodulin inhibits food intake in the rat.

Oxyntomodulin is derived from proglucagon processing in the intestine and the central nervous system. To date, no role in the central nervous system has been demonstrated. We report here that oxyntomodulin inhibits refeeding when injected intracerebroventricularly and into the hypothalamic paraventricular nucleus of 24-h fasted rats [intracerebroventricularly and into the paraventricular nucleus, 1 h, oxyntomodulin (1 nmol), 3.1 +/- 0.5 g; saline, 6.2 +/- 0.4 g; P < 0.005]. In addition, oxyntomodulin inhibits food intake in nonfasted rats injected at the onset of the dark phase (intracerebroventricularly, 1 h: oxyntomodulin, 3 nmol, 1.1 +/- 0.19 g vs. saline, 2.3 +/- 0.2 g; P < 0.05). This effect of oxyntomodulin on feeding is of a similar time course and magnitude as that of an equimolar dose of glucagon-like peptide-1. Other proglucagon-derived products investigated [glucagon, glicentin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol), and spacer peptide-1 (intracerebroventricularly and into the paraventricular nucleus, 3 nmol)] had no effect on feeding at any time point examined. The anorectic effect of oxyntomodulin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol) was blocked when it was coadministered with the glucagon-like peptide-1 receptor antagonist, exendin-(9-39) (intracerebroventricularly, 100 nmol; into the paraventricular nucleus, 10 nmol). However, oxyntomodulin has a lower affinity for the glucagon-like peptide-1 receptor compared with glucagon-like peptide-1 (IC(50): oxyntomodulin, 8.2 nM; glucagon-like peptide-1, 0.16 nM). One explanation for this is that there might be an oxyntomodulin receptor to which exendin-(9-39) can also bind and act as an antagonist.

Animals↗
PubMed1999

Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat.

Central nervous system glucagon-like peptide-1-(7-36) amide (GLP-1) administration has been reported to acutely reduce food intake in the rat. We here report that repeated intracerebroventricular (i.c.v.) injection of GLP-1 or the GLP-1 receptor antagonist, exendin-(9-39), affects food intake and body weight. Daily i.c.v. injection of 3 nmol GLP-1 to schedule-fed rats for 6 days caused a reduction in food intake and a decrease in body weight of 16 +/- 5 g (P < 0.02 compared with saline-injected controls). Daily i.c.v. administration of 30 nmol exendin-(9-39) to schedule-fed rats for 3 days caused an increase in food intake and increased body weight by 7 +/- 2 g (P < 0.02 compared with saline-injected controls). Twice daily i.c.v. injections of 30 nmol exendin-(9-39) with 2.4 nmol neuropeptide Y to ad libitum-fed rats for 8 days increased food intake and increased body weight by 28 +/- 4 g compared with 14 +/- 3 g in neuropeptide Y-injected controls (P < 0.02). There was no evidence of tachyphylaxis in response to i.c.v. GLP-1 or exendin-(9-39). GLP-1 may thus be involved in the regulation of body weight in the rat.

Animals↗
PubMed1998

The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism.

We have previously shown that intracerebroventricular BIBP 3226 inhibits NPY induced feeding in rats. However, this was associated with abnormal behaviour, likely to be due to interaction with Y1 receptors involved in mechanisms other than the control of food intake. In order to minimise such interactions we investigated the effects of paraventricular nucleus (PVN) injections of BIBP 3226 and its inactive enantiomer BIBP 3435. Intra-PVN injection of NPY (0.1-2.5 nmol/animal) increased food intake, with an EC50 of approximately 0.15 nmol/animal. Injections of BIBP 3226 and BIBP 3435 (0.25-25 nmol) reduced NPY-induced food intake in a dose responsive manner, with BIBP 3226 reducing food intake by 95%, and BIBP 3435 by 65% at the highest dose tested. The reversibility of the effect of BIBP 3226 was investigated by measuring the feeding response to NPY (0.5 nmol) in animals 1 week after BIBP 3226 injection. The response to NPY was less in animals which had received high doses of BIBP 3226. Animals previously injected with saline vehicle alone showed a normal NPY feeding response. These results suggest that BIBP 3226 may be inhibiting NPY-induced food intake in a non-specific manner, not secondary to inhibition of the Y1 receptor. This does not, however rule out a role for the Y1 receptor in the control of food intake by NPY.

Animals↗
PubMed1997

Peptide analogue studies of the hypothalamic neuropeptide Y receptor mediating pituitary adrenocorticotrophic hormone release.

Hypothalamic neuropeptide Y (NPY) is thought to be important in the regulation of feeding and also in the release of Adrenocorticotrophic hormone (ACTH). Intracerebroventricular administration of NPY to male rats significantly increased plasma ACTH 10 min after injection and stimulated 2-h food intake. A series of analogues of NPY that have a greatly reduced affinity for the Y1 [human pancreatic polypeptide (human PP), NPY(3-36)], the Y2 ([Pro34]NPY, human PP), the Y3 (peptide YY), and the Y6 (human PP) receptor, all markedly stimulated ACTH release. Rat PP, which binds with high affinity to the Y4 receptor, was unable to stimulate ACTH release. A novel analogue fragment [Pro34]NPY(13-36) was synthesized as a ligand with low Y1 and Y2 receptor affinity. Interestingly, neither [Pro34]NPY(13-36) nor the selective Y5 receptor agonist [D-Trp32]NPY stimulated food intake, whereas both significantly increased plasma ACTH. Thus the hypothalamic NPY receptor mediating increases in plasma ACTH has a fragment activation profile unlike the Y1-Y4 or Y6 receptors and appears distinct from the NPY receptor controlling food intake.

Adrenocorticotropic Hormone↗
PubMed1997

Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents.

The adipose tissue hormone, leptin, and the neuropeptide glucagon-like peptide-1 (7-36) amide (GLP-1) both reduce food intake and body weight in rodents. Using dual in situ hybridization, long isoform leptin receptor (OB-Rb) was localized to GLP-1 neurons originating in the nucleus of the solitary tract. ICV injection of the specific GLP-1 receptor antagonist, exendin(9-39), at the onset of dark phase, did not affect feeding in saline pre-treated controls, but blocked the reduction in food intake and body weight of leptin pre-treated rats. These findings suggest that GLP-1 neurons are a potential target for leptin in its control of feeding.

Animals↗
PubMed1997

Neuropeptide Y induced feeding in the rat is mediated by a novel receptor.

There are now six recognized neuropeptide Y (NPY) receptor subtypes (Y1-Y4 and two recently cloned distinct receptors labeled Y5), of which Y1 and one of the Y5's have been suggested could mediate the effect of NPY on feeding. The fragments NPY(2-36) and NPY(3-36), which bind Y1 only poorly, were injected intracerebroventricularly (icv) and found to have similar dose-response relationships to NPY in the stimulation of feeding. However NPY (13-36), which stimulates both Y2 and Y5, caused no increase in food intake, even at high doses. Maximal stimulation with the classical Y1 agonist [Pro34]-NPY produced only 50% of the maximum effect of NPY itself despite fully inhibiting adenylyl cyclase activity in vitro in a Y1 system. The novel fragment [Pro34]-NPY(3-36) is as effective at stimulating food intake as the classical Y1 analogue [Pro34]-NPY but bound to the Y1 receptor with only 1/20th of the affinity of NPY and failed to inhibit adenylyl cyclase through this receptor. [Pro34]-NPY(3-36) is therefore a relatively appetite-selective ligand. Coadministration of high dose NPY(13-36) and [Pro34]NPY did not enhance feeding compared with [Pro34]-NPY alone. In addition, the NPY Y1 receptor antagonist BIBP-3226, which does not bind Y2, Y4, or Y5 receptors, significantly reduced NPY induced feeding. These results indicate that the feeding effect of icv NPY involves a novel receptor and that it is functionally distinct from the recognized receptor subtypes.

Adenylyl Cyclases↗
PubMed1996

A role for central glucagon-like peptide-1 in temperature regulation.

We have already established that central glucagon-like peptide-1 (GLP-1) has a role in the central control of food intake. In this study, experiments were conducted to establish the effect of acute intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of GLP-1 on temperature. Injection of 10 micrograms GLP-1 i.c.v. caused a significant reduction in temperature over the subsequent 2 h and reduced food intake as expected. Both effects were blocked by prior i.c.v. administration of the GLP-1 antagonist exendin 9-39 at a ratio of 30:1. Administration of 300 micrograms GLP-1 i.p. also reduced temperature over the 2 h following injection but had no effect on food intake. Administration of exendin 9-39 alone by the i.c.v. route had no effect on temperature. These results indicate that GLP-1 is a neuropeptide involved in the regulation of temperature. Furthermore, the mechanisms that mediate the effect on temperature may be different from those regulating food intake given the effect on temperature but not food intake of i.p. GLP-1.

Animals↗
PubMed1996

A role for glucagon-like peptide-1 in the central regulation of feeding.

The sequence of glucagon-like peptide-1 (7-36) amide (GLP-1) is completely conserved in all mammalian species studied, implying that it plays a critical physiological role. We have shown that GLP-1 and its specific receptors are present in the hypothalamus. No physiological role for central GLP-1 has been established. We report here that intracerebroventricular (ICV) GLP-1 powerfully inhibits feeding in fasted rats. ICV injection of the specific GLP-1-receptor antagonist, exendin (9-39), blocked the inhibitory effect of GLP-1 on food intake. Exendin (9-39) alone had no influence on fast-induced feeding but more than doubled food intake in satiated rats, and augmented the feeding response to the appetite stimulant, neuropeptide Y. Induction of c-fos is a marker of neuronal activation. Following ICV GLP-1 injection, c-fos appeared exclusively in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and this was inhibited by prior administration of exendin (9-39). Both of these regions of the brain are of primary importance in the regulation of feeding. These findings suggest that central GLP-1 is a new physiological mediator of satiety.

Animals↗
PubMed1995

Use of a stable copper isotope (65Cu) in the differential diagnosis of Wilson's disease.

1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2 h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14-26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32-77 days). 3. The incorporation of 65 Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

Adolescent↗
PubMed1992

The multidisciplinary management of a family with epithelial ovarian cancer.

OBJECTIVE: To describe the management of a family with an inherited predisposition to ovarian and breast cancer. Particular attention is paid to the problems of contraception, screening, prophylactic surgery and hormone replacement therapy. SETTING: The multidisciplinary Grampian Familial Epithelial Ovarian Cancer Study Group. SUBJECTS: 162 members of a family extending over five generations. In the third generation, five of the 10 women died with epithelial ovarian cancer. Three women in generation IV have developed pre-menopausal breast cancer. There are now 78 family members in the fifth generation aged between 2 and 22 years. INTERVENTIONS: Counselling of female family members is started at the age of 18 years. The combined oral contraceptive pill is advocated to suppress ovulation. Gynaecological follow-up after the age of 28 includes yearly pelvic examination, transvaginal ultrasonography and serum CA125 estimation. Laparoscopy with peritoneal cytology is indicated if any part of this yearly assessment is abnormal. Prophylactic oophorectomy is advised between the ages of 35 and 40 years after the family is complete. In generation IV, 20 of the 29 women have undergone prophylactic oophorectomy. Oestrogen hormone replacement therapy with a cyclical progestogen is recommended after prophylactic oophorectomy. Breast cancer screening starts at the age of 25 and involves annual clinical breast examination augmented by mammography and breast ultrasound. CONCLUSIONS: Only by the careful questioning and recording of family history, including at least third degree relatives (cousins), will similar groups with familial ovarian/breast cancer be identified. When predisposing genes are characterized it will be possible to identify carriers within the family and concentrate clinical effort on them while offering appropriate reassurance to those with decreased risk.

Adult↗
PubMed1988

Absence of gradient of thyrotropin receptor antibody and T cell subset distribution between thyroid and peripheral venous blood in patients with Graves' disease prepared for surgery with carbimazole and potassium iodide.

The aim of the study was to examine tri-iodothyronine, thyroxine, thyroid antibody and thyrotropin receptor antibody levels in thyroid and peripheral venous blood at the time of surgery in patients with Graves' disease. T cell subset patterns in peripheral and thyroidal venous blood were compared to the distribution of T cell subset patterns within the thyroid gland itself. The results showed that at the time of surgery there were no significant differences in any of the parameters measured between thyroidal and peripheral venous samples. T cell subset patterns within the thyroid gland were subjectively similar to those in the venous samples.

Autoantibodies↗