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Biomedical subjects

S L Freeman

Publications and source records attributed to S L Freeman.

At least 19 recordsLinked to original sources
PubMed2006

Luminal glucose sensing in the rat intestine has characteristics of a sodium-glucose cotransporter.

The presence of glucose in the intestinal lumen elicits a number of changes in gastrointestinal function, including inhibition of gastric emptying and food intake and stimulation of pancreatic and intestinal secretion. The present study tested the hypothesis that Na(+)-glucose cotransporter (SGLT)-3, a member of the SGLT family of transport proteins, is involved in detection of luminal glucose in the intestine. Gastric emptying, measured in awake rats, was significantly inhibited by perfusion of the intestine with glucose (60 and 90 mg); this effect was mimicked by alpha-methyl glucose (nonmetabolizable substrate of SGLT-1 and -3) but not 2-deoxy-d-glucose (substrate for GLUT-2) or isoosmotic mannitol. Gastric motility and intestinal fluid secretion, measured in anesthetised rats, were significantly inhibited and stimulated, respectively, by duodenal glucose but not galactose, which has a much lower affinity for SGLT-3 than glucose. Duodenal glucose but not galactose stimulated the release of 5-HT into mesenteric lymph and stimulated the discharge of duodenal vagal afferent fibers. mRNA for SGLT-3 was identified in the duodenal mucosa. Together these data suggest that detection of glucose in the intestine may involve SGLT-3, possibly expressed by enterochromaffin cells in the intestinal mucosa, and release of 5-HT.

Animals↗
PubMed2006

Relationship between the fertile period and sperm transport in the bitch.

Following ejaculation into the vagina, dog sperm remain functionally competent for many days, acquire the ability to fertilize, and are delivered to an appropriate site within the uterine tube synchronously with the appearance of fertile oocytes. The mechanisms involved in regulating this system are complex, and allow for sperm storage within the female reproductive tract. The aim of this paper is to review current knowledge of the transportation of sperm and their biology within the reproductive tract of the bitch.

Animals↗
PubMed2005

Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies.

REASONS FOR PERFORMING STUDY: Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. OBJECTIVES: To study pharmacokinetics and cardiopulmonary effects of i.v. DEX. METHODS: Pharmacokinetics of 3.5 microg/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 45 and 60 mins after administration of DEX 3.5 microg/kg bwt i.v. Data were analysed using ANOVA for repeated measures, and where appropriate Dunnett's t test was used to detect differences from resting values (P < 0.05). RESULTS: Within 2 h after DEX administration, plasma levels were beyond limits of quantification (0.05 ng/ml). Mean values for kinetic parameters for mature and old ponies were: Cmax (ng/ml) 4.6 and 3.8, t 1/2 (min) 19.8 and 28.9 and AUC (ng.min/ml) 34.5 and 44.3, respectively. Heart rate, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure did not change significantly compared to presedation values throughout the 60 min observation period. Compared to presedation values, stroke volume and mixed venous PO2 were reduced for the first 5 mins, paralleled by an increase in systemic and pulmonary vascular resistance. Cardiac index was reduced for the first 10 mins, arterial blood pressures at 20, 30 and 45 mins and respiratory rate throughout the 60 min observation period, but no change in arterial PO2 or PCO2 occurred. CONCLUSIONS: DEX administration i.v. causes similar cardiopulmonary changes to those caused by other alpha-2 adrenoceptor agonists, but of very short duration. DEX is redistributed particularly rapidly. POTENTIAL RELEVANCE: DEX might be safer for sedation of horses because of its very short-lasting cardiopulmonary side effects. For long duration sedation, its kinetics favour its use as a continuous infusion.

Aging↗
PubMed2004

Nitric oxide inhibitable isoforms of adenylate cyclase mediate epithelial secretory dysfunction following exposure to ionising radiation.

BACKGROUND: Hyporesponsiveness of the intestinal epithelium to secretagogues occurs in different models of intestinal injury, including radiation enteropathy, and in human disease. While this impairment of barrier function has been linked to increased inducible nitric oxide synthase (iNOS) activity, the cellular target of NO in this phenomenon is not known, although recent studies suggest that some isoforms of adenylate cyclase are inhibited by NO. AIMS: To determine adenylate cyclase isoform distribution in colonic epithelial cells and, in particular, the physiological significance of NO inhibitable adenylate cyclase isoforms 5 and 6 in radiation induced epithelial secretory dysfunction. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, and immunohistochemistry were used to examine adenylate cyclase expression. The responsiveness of mouse colon to secretagogues 72 hours post-15 Gy gamma radiation or following in vitro exposure to NO donors was measured in Ussing chambers. Also, cAMP, cGMP, and ATP levels were measured. RESULTS: RT-PCR, immunocytochemistry, and immunohistochemistry showed that adenylate cyclase 5 was expressed in mouse colon, and isoforms 5 and 6 were expressed in human biopsies and intestinal epithelium. Pharmacological studies showed that these isoforms are functionally important in chloride secretion. NO mediated hyporesponsiveness to secretagogues is primarily a result of decreased adenylate cyclase activity, and not G(i) activation or decreased cellular ATP levels. CONCLUSIONS: NO inhibitable isoforms of adenylate cyclase are expressed in mouse and human secretory colonic epithelia, and appear to be the target of radiation induced NO to reduce the responsiveness to cAMP dependent secretagogues.

Adenosine Triphosphate↗
PubMed2003

Medetomidine-ketamine anaesthesia induction followed by medetomidine-propofol in ponies: infusion rates and cardiopulmonary side effects.

REASONS FOR PERFORMING STUDY: To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. OBJECTIVES: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. METHODS: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ventilation was spontaneous (F(I)O2 > 0.9). Cardiopulmonary measurements were always taken before electrical stimulation, 15 mins after anaesthesia induction and at 25 min intervals. RESULTS: Anaesthesia induction was excellent and movements after pain stimuli were subsequently gentle. Mean propofol infusion rates were 0.89-0.1 mg/kg bwt/min. No changes in cardiopulmonary variables occured over time. Range of mean values recorded was: respiratory rate 13.0-15.8 breaths/min; PaO2 29.1-37.9 kPa; PaCO2 6.2-6.9 kPa; heart rate 31.2-40.8 beats/min; mean arterial pressure 90.0-120.8 mmHg; cardiac index 44.1-59.8 ml/kg bwt/min; mean pulmonary arterial pressure 11.8-16.4 mmHg. Recovery to standing was an average of 31.1 mins and ponies stood within one or 2 attempts. CONCLUSIONS: In this paper, ketamine anaesthesia induction avoided the problems encountered previously with propofol. Cardiovascular function was remarkably stable. Hypoxaemia did not occur but, despite F(I)O2 of > 0.9, minimal PaO2 in one pony after 4 h anaesthesia was 8.5 kPa. POTENTIAL RELEVANCE: The described regime might offer a good, practicable alternative to inhalation anaesthesia and has potential for reducing the fatality rate in horses.

Anesthetics, Dissociative↗
PubMed2002

Cardiovascular effects of romifidine in the standing horse.

The cardiovascular effects of romifidine, an alpha-2 adrenoreceptor agonist, were investigated in six horses using two doses (80 and 120 microg kg(-1)) in a cross-over study design. Cardiac index and mixed venous oxygenation were significantly decreased at 15 and 30 minutes after both doses of romifidine. Systemic vascular resistance was significantly increased with romifidine (120 microg kg(-1)). Arterial blood pressure increased initially and then gradually decreased; the doses of decrease was significant at 90 and 120 minutes with romifidine 80 and 120 microg kg(-1). There were minimal differences between the two doses of romifidine, and both should be used with care especially in horses with cardiovascular compromise, or when used in combination with other cardiovascular depressant drugs.

Animals↗
PubMed2001

Radiation-induced acute intestinal inflammation differs following total-body versus abdominopelvic irradiation in the ferret.

PURPOSE: The studies were designed to investigate the differences in the intestinal inflammatory response following abdominopelvic or total-body irradiation in a ferret model. MATERIALS AND METHODS: Ferrets were exposed either to total-body or to abdominopelvic gamma-radiation (5 Gy) and various parameters of inflammation studied in the jejunum, ileum and colon 2 and 7 days later. RESULTS: Abdominopelvic and, to a greater extent, total-body irradiation caused weight loss by 7 days. White blood cell counts were reduced in both groups, but more so following total-body irradiation. Myeloperoxidase activity was significantly increased in the ileum 2 days after abdominopelvic irradiation, but it was reduced after total-body irradiation. Total-body irradiation increased tissue prostaglandin E2 levels in all regions at 2 days and decreased jejunal leukotriene B4 levels in the jejunum at both time points. Ileal prostaglandin E2 levels were increased 2 days after abdominopelvic irradiation. Expression of inducible nitric oxide synthase was not altered by either irradiation protocol. CONCLUSIONS: The data show that there are regional differences in the intestinal response to irradiation, depending on whether it was delivered to the whole body or locally to the abdominopelvic region. In particular, the ileum exhibited an acute increase in myeloperoxidase activity following abdominopelvic but not total-body irradiation.

Animals↗
PubMed2001

Cardiopulmonary effects of prolonged anesthesia via propofol-medetomidine infusion in ponies.

OBJECTIVE: To determine cardiopulmonary effects of total IV anesthesia with propofol and medetomidine in ponies and effect of atipamezole on recovery. ANIMALS: 10 ponies. PROCEDURE: After sedation was induced by IV administration of medetomidine (7 microg/kg of body weight), anesthesia was induced by IV administration of propofol 12 mg/kg) and maintained for 4 hours with infusions of medetomidine (3.5 microg/kg per hour) and propofol 10.07 to 0.11 mg/kg per minute). Spontaneous respiration was supplemented with oxygen. Cardiopulmonary measurements and blood concentrations of propofol were determined during anesthesia. Five ponies received atipamezole (60 microg/kg) during recovery. RESULTS: During anesthesia, mean cardiac index and heart rate increased significantly until 150 minutes, then decreased until cessation of anesthesia. Mean arterial pressure and systemic vascular resistance index increased significantly between 150 minutes and 4 hours. In 4 ponies, PaO2 decreased to < 60 mm Hg. Mean blood propofol concentrations from 20 minutes after induction onwards ranged from 2.3 to 3.5 microg/ml. Recoveries were without complications and were complete within 28 minutes with atipamezole administration and 39 minutes without atipamezole administration. CONCLUSIONS AND CLINICAL RELEVANCE: During total IV anesthesia of long duration with medetomidine-propofol, cardiovascular function is comparable to or better than under inhalation anesthesia. This technique may prove suitable in equids in which prompt recovery is essential; however, in some animals severe hypoxia may develop and oxygen supplementation may be necessary.

Adrenergic alpha-Antagonists↗
PubMed2001

Infusion of a combination of propofol and medetomidine for long-term anesthesia in ponies.

OBJECTIVE: To determine the minimal infusion rate of propofol in combination with medetomidine for long-term anesthesia in ponies and the effects of atipamezole on recovery. ANIMALS: 12 ponies. PROCEDURE: Ponies were sedated with medetomidine (7 microg/kg of body weight, IV). Ten minutes later, anesthesia was induced with propofol (2 mg/kg, IV). Anesthesia was maintained for 4 hours, using an infusion of medetomidine (3.5 microg/kg per hour, IV) and propofol at a rate sufficient to prevent ponies from moving after electrical stimulation. Arterial blood pressures and blood gas analysis, heart rates, and respiratory rates were monitored. For recovery, 6 ponies were given atipamezole (60 microg/kg, IV). Induction and recovery were scored. RESULTS: Minimal propofol infusion rates ranged from 0.06 to 0.1 mg/kg per min. Mean arterial blood pressure was stable (range, 74 to 86 mm Hg), and heart rate (34 to 51 beats/min) had minimal variations. Variable breathing patterns were observed. Mean PaO2 (range, 116 to 146 mm Hg) and mean PaCO2 (range, 48 to 51 mm Hg) did not change significantly with time, but hypoxemia was evident in some ponies (minimal PaO2, 47 mm Hg). Recovery was fast and uneventful with and without atipamezole (completed in 20.2 and 20.9 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of a combination of medetomidine and propofol was suitable for prolonged anesthesia in ponies. Recovery was rapid and uneventful. A combination of propofol and medetomidine may prove suitable for long-term anesthesia in horses. Monitoring of blood gases is essential because of potential hypoxemia.

Adrenergic alpha-Antagonists↗
PubMed2001

Effect of romifidine on gastrointestinal motility, assessed by transrectal ultrasonography.

A technique of transrectal ultrasonography was developed to investigate the effects of romifidine 80 and 120 microg/kg bwt on intestinal motility in the horse. Motility of the small intestine, caecum and left ventral colon were assessed following injection of romifidine and a saline control, using a blinded, cross-over study design in 6 horses. Measurements were taken at 15, 30, 60, 120, 180 and 240 min after drug administration. There was a slight nonsignificant decrease in motility in the control group over the 4 h study period. Both doses of romifidine produced a marked decrease in gastrointestinal motility and were associated with the presence of reduced (nonpropulsive) contractions. Transrectal ultrasonography proved suitable for monitoring changes in the type and frequency of intestinal motility in the horse.

Adrenergic alpha-Agonists↗
PubMed2000

Cardiopulmonary effects of romifidine and detomidine used as premedicants for ketamine/halothane anaesthesia in ponies.

The cardiopulmonary effects of romifidine at 80 microg/kg (R80) or 120 pg/kg (R120), and detomidine at 20 pg/kg (D20) when used as premedicants for ketamine/halothane anaesthesia were investigated in six ponies. Using a blinded crossover design, acepromazine (0-04 mg/kg) was administered followed by the alpha-2 agonist. Anaesthesia was induced with ketamine at 2.2 mg/kg and maintained with halothane (expired concentration 1.0 per cent) in oxygen for three hours. During anaesthesia, arterial blood pressure, cardiac index, PaO2 and PmvO2 decreased, and systemic vascular resistance and PaCO2 increased. The cardiac indices for R80, R120 and D20 were, respectively, 39, 39 and 32 ml/kg/minute at 30 minutes and 29, 29 and 26 ml/kg/minute at 180 minutes. The alpha-2 agonists had similar cardiovascular effects, but PaO2 was significantly lower with R120. The quality of anaesthesia was similar in all three groups.

Analgesics↗
PubMed2000

Investigation of romifidine and detomidine for the clinical sedation of horses.

The effects of two intravenous doses of romifidine (80 and 120 microg/kg) and one dose of detomidine (20 microg/kg) were compared in a blinded study in 30 horses requiring to be sedated for routine dental treatment. Several physiological parameters were assessed before and for two hours after the administration of the drugs, and the horses' teeth were rasped 30 minutes after they were administered. Romifidine produced a dose-dependent effect on most parameters. Detomidine at 20 microg/kg was similar to romifidine at 120 microg/kg in the magnitude of its sedative effects, but was similar to romifidine at 80 pg/kg in its duration. There were no significant differences between the three treatments in terms of the clinical procedure score.

Analgesics↗
PubMed2000

Contact of dog spermatozoa with homologous uterine tube epithelium prolongs flagellar activity in relation to the stage of the estrous cycle.

There is scant information about the storage of spermatozoa within the reproductive tract of the bitch. In several species the uterine tube plays a significant role in sperm storage. The present study was performed to investigate the interaction between spermatozoa and the epithelium of the uterine tube, in particular how this interaction might influence the flagellar activity of spermatozoa in relation to the stage of the estrous cycle. Epithelium was harvested from uterine tubes of 24 bitches at various stages of the estrous cycle (estrus, luteal phase or anestrus), and cultured with pooled spermatozoa collected from 6 dogs. Spermatozoa rapidly bound to the epithelial surface by their heads and the majority of attached spermatozoa were motile. The intimate association between spermatozoa and the uterine tube epithelium maintained motility in a manner that was related to the stage of the estrous cycle. Flagellar activity was significantly greater for spermatozoa bound to estrous epithelium than epithelium from the luteal phase or anestrus. On average, approximately 10% of spermatozoa that were attached to the uterine tube epithelium of estrous bitches retained their flagellar activity for 48 h after innoculation. There was no apparent influence of the region of the uterine tube on this effect. These findings suggest that the uterine tube may form a functional spermatozoal reservoir in the bitch.

Animals↗
PubMed2000

Modulation of hyperoxia-induced TNF-alpha expression in the newborn rat lung by thalidomide and dexamethasone.

The effect of high oxygen concentrations on lungs of neonatal rats was studied. In addition, some oxygen-exposed animals were treated with either dexamethasone or thalidomide. No gross histologic changes were noted in the lungs following exposure to 95% oxygen nor were there changes in the total number or the phenotypic distribution of BAL cells obtained from these lungs compared to lungs from air exposed (control) neonatal rats. The majority of the BAL cells were CD45+ leukocytes (macrophages). However, when BAL cells were exposed to LPS in vitro, TNF-alpha production was higher in cells from rats exposed to 95% oxygen compared to cells from rats exposed to ambient air. In addition, lung TNF-alpha and IL-6 mRNA levels were increased after exposure to 95% oxygen. In the lungs of animals treated with either dexamethasone or thalidomide, TNF-alpha mRNA levels were reduced, while only dexamethasone treatment also reduced IL-6 mRNA levels.

Animals↗
PubMed2000

Interleukin-12 differentially regulates expression of IFN-gamma and interleukin-2 in human T lymphoblasts.

Interleukin-12 (IL-12) is known to upregulate expression of interferon-gamma (IFN-gamma) by activated T cells. However, the effects of IL-12 on production of other Th1-type cytokines are less well defined. In this study, we examined the effects of IL-12 on expression of several cytokines, including IFN-gamma, IL-2, tumor necrosis factor-alpha (TNF-alpha), and IL-10, by primary human CD3(+) T cells. Although purified resting T cells were largely nonresponsive to IL-12 stimulation, anti-CD3-activated T cell blasts were strongly responsive, as demonstrated by the ability of IL-12 to induce Stat4 DNA-binding activity. Restimulation of T lymphoblasts on immobilized anti-CD3 monoclonal antibodies (mAb) induced rapid expression of TNF-alpha mRNA and more gradual increases in mRNA levels for IL-2, IFN-gamma, and IL-10. IL-12 markedly upregulated expression of IFN-gamma and IL-10 but downregulated expression of IL-2 in a dose-dependent and time-dependent manner. The levels of IL-2 produced by IL-12-treated T cells correlated inversely with the levels of IL-10. Moreover, neutralization of IL-10 activity with anti-IL-10 antibodies normalized IL-2 production by IL-12-treated T cells, confirming that the inhibition of IL-2 production by IL-12 was IL-10 mediated. Thus, IL-12 amplified expression of IFN-gamma and IL-10 and, via its ability to upregulate production of IL-10, inhibited expression of IL-2. These findings demonstrate that IL-12 differentially regulates expression of the Th1-type lymphokines, IFN-gamma and IL-2, in T lymphoblasts.

Cells, Cultured↗
PubMed2000

Introducing residents to a career in management: the Physician Management Pathway.

To prepare their students and residents for the practice of medicine in a rapidly changing environment, medical educators must teach the business of medicine as well as the science and art of medicine. Recognizing the value of and demand for physician leaders, the authors sought to introduce residents to diverse aspects of medical administration within the context of an academically rigorous internal medicine residency program. The Physician Management Pathway (PMP) was developed in 1997 to expose interested residents to the management concepts employed by physician managers; to help physician trainees begin to develop the leadership and technical skills they will use as physician managers; to provide career mentoring; to provide experiences that enrich the resident's training in clinical medicine; to enhance resident-directed educational activities; and to produce physicians who can successfully work in any health care environment. The PMP curriculum consists of a monthly seminar series, a preceptorship experience in the second year of residency, and a supervised project in the third year. The program was not designed to provide competency in management, but rather is intended to provide an opportunity for new physicians to explore options in this exciting and changing profession.

Curriculum↗
PubMed2000

Ionizing radiation induces iNOS-mediated epithelial dysfunction in the absence of an inflammatory response.

Ionizing radiation induces intestinal epithelial hyporesponsiveness to secretagogues through an unknown mechanism. We investigated the role of the inducible isoform of nitric oxide (NO) synthase (iNOS)-derived NO in radiation-induced hyporesponsiveness. C57BL/6 mice were sham treated or exposed to 10-Gy gamma-radiation and were studied 3 days later. Tissues were mounted in Ussing-type diffusion chambers to assess chloride secretion in response to electrical field stimulation (EFS) and forskolin (10 microM). Transport studies were also repeated in iNOS-deficient mice. White blood cell counts were significantly lower in irradiated mice, and there was no inflammatory response as shown by myeloperoxidase activity and histological assessment. iNOS mRNA levels and nitrate/nitrite concentrations were significantly elevated in irradiated colons. iNOS immunoreactivity localized to the epithelium. Colons from irradiated wild-type, but not iNOS-deficient, mice exhibited a significant reduction in the responsiveness of the tissue to EFS and forskolin. The hyporesponsiveness was reversed by L-N(6)-(1-iminoethyl)lysine, 1400W, and dexamethasone treatments. iNOS-derived NO mediates colonic hyporesponsiveness 3 days after irradiation in the mouse in the absence of an inflammatory response.

Animals↗