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Biomedical subjects

C A Pedersen

Publications and source records attributed to C A Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Infusion of an oxytocin antagonist into the medial preoptic area prior to progesterone inhibits sexual receptivity and increases rejection in female rats.

Central administration of an antagonist to the neuropeptide oxytocin (OT) has been shown to block the progesterone-induced facilitation of female sexual receptivity. In this study we examined the effects of infusing an OT antagonist (OTA) into various brain sites before rats were injected with 250 micrograms progesterone (P). Ovariectomized animals were injected daily for three consecutive days with 1 microgram estradiol benzoate and then on the fourth day were infused into the medial preoptic area (MPOA), medial basal hypothalamus (MBH) or ventral tegmental area with either 250 ng/microliter/side OTA or artificial cerebrospinal fluid vehicle. Animals were tested in an arena made of two white polyethylene cages connected by a tunnel that allowed passage of the female but not of the larger male. Several receptive and non-receptive behaviors were recorded for a 15-min period beginning 4 hr after P injection. Animals infused with OTA into the MPOA before P showed an increase in the frequency and total duration of fighting with males and the frequency of audible vocalizations made by females. OTA infusions also increased the frequency of mounts that did not result in a lordosis posture. OTA infusions into the MPOA also reduced the frequency and total duration of lordosis postures in response to mounts. OTA infusions into the MBH and VTA had no effect on measures of sexual behaviors. Blocking OT transmission in the MPOA resulted in increased rejection behaviors and decreased receptivity in females when infused before systemic P injection.

Animals↗
PubMed1994

Estrogen increases affinity of oxytocin receptors in the medial preoptic area-anterior hypothalamus.

Analysis of binding data from saturation experiments using a radiolabeled oxytocin antagonist ([125I]OTA) demonstrated an increase in binding affinity after treatment with 5 micrograms estradiol benzoate (EB) for 3 days in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVX) rats. Analysis of data from competition experiments revealed high- and low-affinity [125I]OTA binding sites in the MPOA-AH, the medial basal hypothalamus (MBH), and hippocampus of OVX controls. Three days of EB treatment reduced low-affinity binding sites in the MPOA-AH and MBH, but not in the hippocampus. Treatment of membrane fractions from the MPOA-AH of oil-treated OVX rats in vitro with 100 nM OT or with estrogen or progesterone conjugated to bovine serum albumin (E-BSA and P-BSA) also reduced low-affinity [125I]OTA binding sites but BSA alone did not.

Animals↗
PubMed1994

Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats.

Pregnant rats were treated either throughout gestation (GD 1-20) with 30 mg/kg per day (chronic cocaine) or with one 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls. On Day 6 postpartum, 83% of chronic cocaine-treated dams pinned and attacked an intruder male 8 or more times during a 10-min observation period, whereas only 4% of acute cocaine-treated and none of the saline-treated dams exhibited this much aggression.

Aggression↗
PubMed1994

Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas.

Oxytocin binding (Bmax) was found to be higher in the ventral tegmental area (VTA) and the medial preoptic area (MPOA) at midparturition compared with Pregnancy Days 15-17 or Postpartum Days 5-7 in rat dams. Pup retrieval and assuming a nursing posture over pups were blocked in parturient dams by infusions of an oxytocin antagonist into the VTA or MPOA and by infusions of a vasopressin (V1) antagonist into the MPOA. These results implicate oxytocin in the VTA and MPOA and vasopressin in the MPOA, as well as a parturition-associated rise in oxytocin binding in these sites in the postpartum activation of maternal behavior.

Animals↗
PubMed1994

Decreased platelet deposition and smooth muscle cell proliferation after intramural heparin delivery with hydrogel-coated balloons.

BACKGROUND: In vitro and in vivo studies have demonstrated both anticoagulant and antiproliferative effects of heparin. The purpose of this study was to assess the effect of local intramural delivery of heparin, using heparin-coated hydrogel balloons, on platelet deposition and early smooth muscle cell proliferation after in vivo balloon angioplasty. METHODS AND RESULTS: The effects of local heparin delivery were assessed during balloon angioplasty of porcine peripheral arteries. All balloon dilatations were performed with oversized hydrogel balloons coated with a known quantity of heparin. Balloon dilatations in contralateral vessels with uncoated hydrogel balloons served as study controls. The pharmacokinetics of heparin delivery were assessed using 3H-heparin to quantitate heparin wash-off from the balloon surface, heparin delivery to the arterial wall, and intramural persistence of drug. Platelet deposition at 1 hour after balloon injury was quantified using 111In-labeled platelets. Smooth muscle cell proliferation was assessed 6 to 7 days after angioplasty with immunohistochemical staining for proliferating cell nuclear antigen. 3H-heparin wash-off from the hydrogel balloon surface occurred rapidly, with approximately 95% of the heparin coating disappearing within 10 seconds in the intact circulation. Approximately 2% of heparin on the balloon surface was delivered intramurally at the time of angioplasty. Intramural heparin dissipated rapidly, although small amounts of intramural heparin could still be detected for at least 48 hours. In comparison to control vessels, there was less 111In-platelet deposition (P = .002) and less medial smooth muscle cell proliferation (P = .03) in heparin-treated vessels. CONCLUSIONS: Local intraluminal delivery of heparin at the time of balloon angioplasty with heparin-coated hydrogel balloons results in intramural deposition of drug that persists for at least 48 hours. This in vivo technique significantly decreases platelet deposition and early smooth muscle cell proliferation after angioplasty injury.

Angioplasty, Balloon↗
PubMed1993

Sexual activity decreases oxytocin receptor densities in the thymus.

Sexual interactions have multiple effects on oxytocin systems in the brain. In the present study we observed that allowing estrogen-progesterone treated ovariectomized rats to be mounted ten times by a male significantly decreased the density (beta max) of thymic oxytocin receptors. Animals were ovariectomized and after recovery injected once daily for three consecutive days with 0.5 microgram estradiol benzoate (EB) followed by an injection of 500 micrograms progesterone on the fourth day 4-5 hr before testing. They were either placed in a cage with a sexually-active male until mounted ten times (mounted) or were briefly placed in the cage and removed before being mounted (unmounted). Both groups were then killed and their thymuses aseptically removed. Computerized analysis of saturation binding data showed that the densities of oxytocin receptors from mounted animals were significantly (p < 0.02) lower than those of unmounted controls (beta max for unmounted animals = 8.45 +/- 0.84 fmol/mg protein; and for mounted rats = 5.5 +/- 0.33 fmol/mg protein; t6 = 3.23). The possibility is discussed that sexual activity reduces thymic oxytocin receptors which may alter immune responsiveness to sexually-transmitted diseases.

Animals↗
PubMed1993

Acute cocaine treatment decreases oxytocin levels in the rat hippocampus.

We examined the effects of an acute cocaine treatment on oxytocin levels in the whole hippocampus, ventral tegmental area (VTA) and amygdala in ovariectomized rats pretreated with 10 micrograms estradiol benzoate. Cocaine treatment significantly reduced oxytocin levels both in picograms/area and picograms/mg wet weight in the hippocampus but had no significant effect on levels in the VTA and amygdala. These data represent the first evidence for the reduction of oxytocin levels as a result of an acute cocaine treatment.

Amygdala↗
PubMed1993

Menstrual cycle and premenstrual syndrome: modifiers of cardiovascular reactivity in women.

Fifteen women prospectively diagnosed with PMS and 15 non-PMS women were each tested twice for cardiovascular stress reactivity and behavioral performance, once during the follicular phase and once during the luteal phase of their cycle. Although blood pressure and heart rate responses to stress did not differ across the menstrual cycle in either group of women, for the non-PMS women, differences in hemodynamic responses were observed across the 2 phases. The luteal phase was associated with greater stroke volume responses and lesser vascular tone. For the PMS women, none of their cardiovascular measures differed across their cycle. Instead, these women showed significantly attenuated blood pressure and heart rate responses compared with non-PMS women, irrespective of cycle phase.

Adult↗
PubMed1993

Economic impact of cost-containment strategies in third party programmes in the US (part I).

The rising cost of healthcare has strained the resources of governments, private third parties and individuals with responsibility to pay for it. Various strategies have been used in an attempt to control costs. This article examines the economic impact of 4 such strategies: (a) cost sharing; (b) prescription limits; (c) rebates; and (d) cost limits. Cost sharing has been successful at reducing utilisation of prescription drugs, although the effects have not been uniform across therapeutic categories. However, the long term effect on cost and utilisation of other medical services, and the impact on overall health status, remain largely unknown. Some evidence suggests that utilisation of other services may increase. The available data regarding drug rebate programmes have been descriptive in nature. However, the designs employed in this research do not establish a direct causal relationship between rebate programmes and changes in Medicaid drug expenditure. Furthermore, still unknown is the degree of cost shifting and the effect of the rebate programme on other large public and private drug purchasers. The Maximum Allowable Cost programme led to direct savings in drug costs, but the size of these savings was variable and uncertain because of administrative costs of the programme. The Estimated Acquisition Cost programme has not resulted in significant savings.

Cost Control↗
PubMed1993

An immunocytochemical search for infectious agents in Crohn's disease.

Microorganisms have long been suspected of causing Crohn's disease (CD); however, an etiologic agent has yet to be identified. Few studies have employed immunocytochemistry (ICC) to examine tissue from patients with CD for microbial antigens. We investigated 36 formalin-fixed tissues from 16 patients with CD with ICC. No evidence of adenovirus, Borrelia, Brucella, BVDV, Campylobacter, Campylobacter-like organisms, Chlamydia, coronavirus, CMV, EBV, Legionella, mycobacteria, Pseudomonas, rotavirus, Salmonella, Shigella, staphylococci, Toxoplasma gondii, Treponema, or Yersinia was found. ICC identified E. coli and streptococcal antigens in 11 (69%) and 10 (63%) of the 16 cases studied, respectively. Escherichia coli immunoreactivity was located in ulcers, within the lamina propria, and along fissures. Streptococcal immunolabeling occurred within mucosal epithelial cells, in the lamina propria, in ulcers, along fissures, in granulomatous inflammation including multinucleate giant cells, and in lymph nodes. These results suggest that some of the granulomas in CD may result from immunologic processing of bacterial antigens following their penetration through a compromised mucosa. E. coli and streptococcal antigens may contribute to the pathogenesis of CD.

Antigens, Bacterial↗
PubMed1992

Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression.

The effects of major depression on peripheral blood natural killer cell phenotypes and natural killer cell activity were studied by comparing depressed and normal control subjects. Depressed subjects exhibited (1) significant reductions in Leu-11 (CD16) natural killer effector cells and natural killer cell activity and (2) a dissociation of the normal positive correlation between the percentage of Leu-11 cells and natural killer cell activity. These findings suggest that alterations in the availability and the killing capacity of circulating Leu-11 natural killer cells appear to be responsible for depression-related reductions in natural killer cell activity. Moreover, men with major depression showed marked reductions in Leu-11 cells, natural killer cell activity, and Leu-7 (HNK-1) lymphocytes compared with normal control men. By contrast, depressed women did not differ significantly from normal control women on any of these three immune function measures. Severity of depression as assessed by Hamilton Rating Scale for Depression scores was not associated with natural killer cell activity or Leu-7 lymphocyte levels in either men or women with major depression. Hamilton Rating Scale for Depression severity ratings were, however, strongly inversely correlated with Leu-11 lymphocyte counts among men, but not women, with major depression. These data begin to elucidate the immunological mechanisms by which natural killer cell activity is altered in depression and suggest that some measures of immunity may be differentially affected in male and female subjects with the syndrome of major depression.

Adolescent↗
PubMed1992

Cytokeratin immunohistochemical examination of liver biopsies in infants with Alagille syndrome and biliary atresia.

Identifying bile duct epithelium is sometimes difficult with standard histologic techniques. The availability of antibodies to specific cytokeratin (CK) intermediate filaments has allowed identification of CK expressed by bile duct epithelium. Formalin-fixed, paraffin-embedded liver tissue from five infants (aged 1-12 months) with Alagille syndrome and five infants with biliary atresia (aged 1.5-11 months) were pepsin digested then reacted with a combination of anti-cytokeratin monoclonal antibodies using an avidin-biotin immunoperoxidase technique. Liver tissue obtained at autopsy from infants without primary liver disease (aged 22 weeks gestation to 24 months) was treated similarly for comparison. Control specimens showed progression from prominent immunoreactivity of the ductal plate cells at the rim of the portal tract (22-24 weeks gestation) to incorporation of tubular ductal structures into portal tract mesenchymal tissue (26-34 weeks gestation) and formation of intensely immunoreactive mature discrete interlobular ducts with progressive loss of cytokeratin immunoreactivity of the ductal plate cells (1-24 months). In contrast, biopsies from infants with Alagille syndrome showed few immunoreactive interlobular ducts. Biopsies from infants with Alagille syndrome less than 2 months old showed only immunoreactivity of single ductal plate cells or small ductules at the periphery of the portal tracts. Biopsies from some infants greater than 3 months old showed increased numbers of immunoreactive cells in groups and anastomosing bands lacking true lumens and extending into the fibrous bridges between adjacent portal areas (neoductular proliferation).(ABSTRACT TRUNCATED AT 250 WORDS)

Alagille Syndrome↗
PubMed1992

Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.

OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.

Adolescent↗