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1.
J Sch Psychol ; 92: 1-18, 2022 06.
Article in English | MEDLINE | ID: mdl-35618364

ABSTRACT

Students following a preparatory vocational education track seem most in need of an intervention stimulating their competencies and preventing the development of problems in the intrapersonal and interpersonal domain. The aim of the present study was to examine, first, whether Rock & Water, a social emotional learning intervention that uses active forms of learning, is effective in improving students' competencies and preventing problems in the intra- and interpersonal domain, and second, whether intervention effects were influenced by the extent to which multiple systems are involved in the intervention. We conducted a randomized controlled trial with a sample of 7th grade students (N = 1299, Mage = 12.38, 54% boys). Students reported on outcomes of the intra- and interpersonal domains using digital questionnaires. The data were analyzed with Latent Growth Curve models. Results showed that the intervention was most effective when only a core team of teachers was involved in the intervention. The intervention improved several proximal outcomes (i.e., self-control and emotional self-regulation) and distal outcomes in students' intrapersonal and interpersonal domains. The intervention effects were strongest, albeit moderate, in the first year of the intervention. These results show that interventions with an active form of learning and implemented by a core team might be promising interventions for prevocational students, although effort should be put in increasing its effectiveness.


Subject(s)
Self-Control , Water , Child , Emotions , Female , Humans , Learning , Male , Students/psychology
2.
Mucosal Immunol ; 13(6): 969-981, 2020 11.
Article in English | MEDLINE | ID: mdl-32472066

ABSTRACT

This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1+ T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6+, IFN-γ-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, γδ T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.


Subject(s)
Candida albicans/physiology , Candidiasis/immunology , Neutrophils/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocytes/immunology , Uterus/immunology , Vagina/immunology , Animals , Disease Resistance , Female , Humans , Interferon-gamma/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Antigen, T-Cell, gamma-delta/genetics , Vagina/microbiology
3.
Public Health ; 166: 53-56, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30448692

ABSTRACT

OBJECTIVES: This analysis explored the level of psychological distress among primary school teachers in the South West of England as compared with clinical and general population samples. STUDY DESIGN: Secondary analysis of data from the Supporting Teachers and Children in Schools (STARS) trial completed by up to 90 teachers at baseline, 9, 18 and 30 months of follow-up. METHODS: We used the Everyday Feelings Questionnaire (EFQ) as a measure of psychological distress. Baseline data on teachers were compared with a population sample of professionals and a clinical sample of patients attending a depression clinic. RESULTS: Our teacher cohort experienced higher levels of psychological distress than comparable professionals from the general population, which were sustained over 30 months of follow-up. Levels of psychological distress were lower than those found in the clinical sample. Using a cut-point indicative of moderate depression, our data suggest that between 19% and 29% of teachers experienced clinically significant distress at each time-point. CONCLUSIONS: We detected high and sustained levels of psychological distress among primary school teachers, which suggests an urgent need for intervention. Effective support for teachers' mental health is particularly important given the potential impact of poor teacher mental health on pupil well-being, pupil attainment and teacher-pupil relationships.


Subject(s)
School Teachers/psychology , Schools , Stress, Psychological/epidemiology , Adult , Cohort Studies , England/epidemiology , Female , Humans , Male , School Teachers/statistics & numerical data , Surveys and Questionnaires
4.
Oncogene ; 32(6): 747-58, 2013 Feb 07.
Article in English | MEDLINE | ID: mdl-22450746

ABSTRACT

The invasion of squamous cell carcinoma (SCC) is a significant cause of morbidity and mortality. Here, we identify an E3 ligase, Traf6 and a de-ubiquitinating enzyme, Cezanne/ZA20D1, as important regulators of this process in organotypic models. Traf6 can promote the formation of Cdc42-dependent F-actin microspikes. Furthermore, Traf6 has a key role in autocrine interleukin-1ß signalling in SCC cells, which in turn is required to drive the expression of tumour necrosis factor α (TNFα). TNFα acts in a paracrine manner to increase the invasion-promoting potential of carcinoma-associated fibroblasts (CAFs). Exogenous TNFα signalling can restore invasion in cells depleted of Traf6. In conclusion, Traf6 has two important roles in SCC invasion: it promotes cell intrinsic Cdc42-dependent regulation of the actin cytoskeleton and enables production of the paracrine signal, TNFα, that enhances the activity of CAFs.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Endopeptidases/metabolism , Fibroblasts/metabolism , TNF Receptor-Associated Factor 6/metabolism , Autocrine Communication , Humans , Interleukin-1beta/metabolism , Neoplasm Invasiveness , Paracrine Communication , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , cdc42 GTP-Binding Protein/metabolism
5.
Cell Prolif ; 45(3): 225-38, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22507457

ABSTRACT

OBJECTIVES: Hypoxia is an important factor in many aspects of stem-cell biology including their viability, proliferation, differentiation and migration. We evaluated whether low oxygen level (2%) affected human adipose tissue mesenchymal stem-cell (hAT-MSC) phenotype, population growth, viability, apoptosis, necrosis and their adipogenic and osteogenic differentiation potential. MATERIALS AND METHODS: hAT-MSCs from four human donors were cultured in growth medium under either normoxic or hypoxic conditions for 7 days and were then transferred to normoxic conditions to study their differentiation potential. RESULTS: Hypoxia enhanced hAT-MSC expansion and viability, whereas expression of mesenchymal markers such as CD90, CD73 and endothelial progenitor cell marker CD34, remained unchanged. We also found that pre-culturing hAT-MSCs under hypoxia resulted in their enhanced ability to differentiate into adipocytes and osteocytes. CONCLUSIONS: This protocol could be useful for maximizing hAT-MSC potential to differentiate in vitro into the adipogenic and osteogenic lineages, for use in plastic and reconstructive surgery, and in tissue engineering strategies.


Subject(s)
Adipocytes/cytology , Adipogenesis , Cell Differentiation , Mesenchymal Stem Cells/cytology , Osteogenesis , 5'-Nucleotidase/metabolism , Adult , Antigens, CD34/metabolism , Cell Hypoxia , Cell Survival , Cells, Cultured , Female , Humans , Mesenchymal Stem Cells/metabolism , Thy-1 Antigens/metabolism , Tissue Donors , Young Adult
6.
Opt Lett ; 30(24): 3353-5, 2005 Dec 15.
Article in English | MEDLINE | ID: mdl-16389829

ABSTRACT

We demonstrate an optically sectioned fluorescence lifetime imaging microscope with a wide-field detector, using a convenient, continuously tunable (435-1150 nm) ultrafast source for fluorescence imaging applications that is derived from a visible supercontinuum generated in a microstructured fiber.

7.
Clin Exp Pharmacol Physiol ; 28(9): 773-5, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11560127

ABSTRACT

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mg ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.


Subject(s)
Blood Pressure/drug effects , Cosyntropin/administration & dosage , Adrenocorticotropic Hormone/administration & dosage , Adrenocorticotropic Hormone/blood , Adult , Cosyntropin/blood , Female , Heart Rate/drug effects , Humans , Hydrocortisone/blood , Male , Time Factors
8.
J Neuroendocrinol ; 13(6): 524-30, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11412339

ABSTRACT

The insulin hypoglycemia test (IHT) is widely regarded as the "gold standard" for dynamic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to investigate the temporal relationship between a rapid decrease in plasma glucose and the corresponding rise in plasma adenocorticotropic hormone (ACTH), and to assess the reproducibility of hormone responses to hypoglycemia in normal humans. Ten normal subjects underwent IHTs, using an insulin dose of 0.15 U/kg. Of these, eight had a second IHT (IHT2) and three went on to a third test (IHT3). Plasma ACTH and cortisol were measured at 15-min intervals and, additionally, in four IHT2s and the three IHT3s, ACTH was measured at 2.5- or 5-min intervals. Mean glucose nadirs and mean ACTH and cortisol responses were not significantly different between IHT1, IHT2 and IHT3. Combined data from all 21 tests showed the magnitude of the cortisol responses, but not the ACTH responses, correlated significantly with the depth and duration of hypoglycemia. All subjects achieved glucose concentrations of of < or = 1.6 mmol/l before any detectable rise in ACTH occurred. In the seven tests performed with frequent sampling, an ACTH rise never preceded the glucose nadir, but occurred at the nadir, or up to 15 min after. On repeat testing, peak ACTH levels varied markedly within individuals, whereas peak cortisol levels were more reproducible (mean coefficient of variation 7%). In conclusion, hypoglycemia of < or = 1.6 mmol/l was sufficient to cause stimulation of the HPA axis in all 21 IHTs conducted in normal subjects. Nonetheless, our data cannot reveal whether higher glucose nadirs would stimulate increased HPA axis activity in all subjects. Overall, the cortisol response to hypoglycemia is more reproducible than the ACTH response but, in an individual subject, the difference in peak cortisol between two IHTs may exceed 100 nmol/l.


Subject(s)
Hypoglycemia/blood , Insulin , Adrenal Glands/physiopathology , Adrenocorticotropic Hormone/blood , Adult , Blood Glucose/metabolism , Female , Humans , Hydrocortisone/blood , Hypoglycemia/chemically induced , Hypothalamo-Hypophyseal System/physiopathology , Insulin/administration & dosage , Male , Middle Aged , Reproducibility of Results
10.
Clin Endocrinol (Oxf) ; 55(5): 625-33, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11894974

ABSTRACT

OBJECTIVES: Low doses of ACTH [1-24] (0.1, 0.5 and 1.0 microg per 1.73 m2) may provide a more physiological level of adrenal stimulation than the standard 250 microg test, but not all studies have concluded that the 1.0 microg is a more sensitive screening test for central hypoadrenalism. Eight-hour infusions of high dose ACTH [1-24] have also been suggested as a means of assessing the adrenals' capacity for sustained cortisol secretion. In this study, we compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8-h infusion with the standard 250 microg test (HDT) and the insulin hypoglycaemia test (IHT) in patients with hypothalamic-pituitary disease. SUBJECTS AND DESIGN: Three groups of subjects were studied. A healthy control group (group 1, n = 9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n = 12, underwent IHT) and group 3 (n = 21, IHT contraindicated). Six different tests were performed: a standard IHT (0.15 U/kg soluble insulin); a 60-minute 250 microg HDT; three different LDTs using 0.1 microg, 0.5 microg and 1.0 microg (all per 1.73 m2); and an 8-h infusion test (250 microg ACTH [1-24] at a constant rate over 8 h). RESULTS: Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the ACTH [1-24] stimulation tests. Seven of the 9 patients who failed the IHT, failed by a clear margin (peak cortisol < 85% of the lowest normal). Two of the 7 also failed all the ACTH [1-24] tests. Five of the 7 patients had discordant results, four passed the 0.1 LDT, one (out of four) passed the 0.5 LDT, none (out of three) passed the 1.0 LDT, two passed the HDT and three passed the 8-h test. Two patients were regarded as borderline fails in the IHT. Both passed the ACTH [1-24] tests, although one was a borderline pass in the 8-h test. Only five out of the 21 patients in group 3 showed discordance between the HDT and the LDTs. One patient passed the HDT and failed the 0.1 LDT, four patients failed the HDT but passed some of the different LDTS. CONCLUSIONS: We conclude that in the diagnosis of central hypoadrenalism, ACTH [1-24] stimulation tests may give misleading results compared to the IHT. The use of low bolus doses of ACTH [1-24] (1.0, 0.5 or 0.1 microg) or a high dose prolonged infusion does not greatly improve the sensitivity of ACTH [1-24] testing. Dynamic tests that provide a central stimulus remain preferable in the assessment of patients with suspected ACTH deficiency.


Subject(s)
Adrenal Glands/metabolism , Cosyntropin , Hydrocortisone/blood , Hypothalamic Diseases/physiopathology , Pituitary Diseases/physiopathology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cosyntropin/administration & dosage , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Injections, Intravenous , Insulin , Male , Middle Aged , Predictive Value of Tests , Single-Blind Method , Stimulation, Chemical
11.
J Neuroendocrinol ; 12(2): 141-5, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10718909

ABSTRACT

Leptin, produced by adipocytes, has homeostatic effects on body fat mass through inhibition of appetite and stimulation of the sympathetic nervous system. Several studies have reported that high-dose exogenous glucocorticoids increase circulating leptin concentrations in humans. Conversely, leptin has inhibitory effects on the hypothalamic-pituitary-adrenal (HPA) axis, both at the hypothalamic and adrenal levels. We hypothesized that acute hypercortisolism, in the physiological range, may not alter leptin secretion. Four stimuli of the HPA axis were administered to eight healthy male volunteers in a placebo-controlled study. On separate afternoons, in a randomised order, fasting subjects received i.v. injections of saline, naloxone (125 microg/kg); vasopressin (0.0143 IU/kg); naloxone and vasopressin in combination; or insulin (0.15 U/kg; a dose sufficient to induce hypoglycaemia). Plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol and leptin were measured before and for 120 min after the injection. The cortisol secretory response was greatest after insulin-hypoglycaemia, this response was significantly greater than that following naloxone, naloxone/vasopressin, or vasopressin alone. Despite the cortisol release, leptin concentrations were not increased after any stimulus. Insulin-hypoglycaemia was associated with a decrease in leptin concentration at 60 and 90 min, while naloxone did not alter leptin concentrations. However, basal leptin concentrations were positively correlated with integrated ACTH and cortisol responses to naloxone, but did not correlate with ACTH or cortisol responses to the other stimuli. Thus acute elevations of plasma cortisol, in the physiological range, do not appear to influence plasma leptin concentrations. The fall in plasma leptin concentration after insulin-induced hypoglycaemia may reflect catecholamine secretion after this stimulus.


Subject(s)
Hypothalamo-Hypophyseal System/drug effects , Leptin/administration & dosage , Leptin/blood , Pituitary-Adrenal System/drug effects , Adrenocorticotropic Hormone/blood , Adult , Humans , Hydrocortisone/blood , Hypoglycemia/physiopathology , Hypoglycemic Agents/administration & dosage , Hypothalamo-Hypophyseal System/physiology , Insulin/administration & dosage , Male , Middle Aged , Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Pituitary-Adrenal System/physiology , Vasoconstrictor Agents/administration & dosage , Vasopressins/administration & dosage
12.
J Clin Endocrinol Metab ; 84(10): 3648-55, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10523009

ABSTRACT

The efficacy of the standard high dose ACTH stimulation test (HDT), using a pharmacological 250-microg dose of synthetic ACTH-(1-24), in the diagnosis of central hypoadrenalism is controversial. The insulin hypoglycemia test is widely regarded as the gold standard dynamic stimulation test of the hypothalamo-pituitary-adrenal (HPA) axis that provides the most reliable assessment of HPA axis integrity and reserve. Alternatively, a prolonged infusion of ACTH causes a continuing rise in plasma cortisol levels that may predict the adrenals' capacity to respond to severe ongoing stress. In nine normal subjects, we compared plasma ACTH and cortisol levels produced by three i.v. bolus low doses of ACTH-(1-24) (0.1, 0.5, and 1.0 microg/1.73 m2; LDTs) with those stimulated by hypoglycemia (0.15 U/kg insulin) and with the cortisol response to a standard 250-microg dose of ACTH-(1-24). The normal cortisol response to an 8-h ACTH-(1-24) infusion (250 microg at a constant rate over 8 h) was determined using three modern cortisol assays: a high pressure liquid chromatography method (HPLC), a fluorescence polarization immunoassay (FPIA), and a standard RIA. In the LDTs, stepwise increases in mean peak plasma ACTH were observed (12.4 +/- 2.0, 48.2 +/- 7.2, 120.2 +/- 15.5 pmol/L for the 0.1-, 0.5-, and 1.0-microg LDTs, respectively; P values all <0.0022 when comparing peak values between tests). The peak plasma ACTH level after insulin-induced hypoglycemia was significantly lower than that produced in the 1.0-microg LDT (69.6 +/- 9.3 vs. 120.2 +/- 15.5 pmol/L; P < 0.0002), but was higher than that obtained during the 0.5-microg LDT (69.6 +/- 9.3 vs. 48.2 +/- 7.2 pmol/L; P < 0.02). In the LDTs, statistically different, dose-dependent increases in peak cortisol concentration occurred (355 +/- 16, 432 +/- 13, and 482 +/- 23 nmol/L; greatest P value is 0.0283 for comparisons between all tests). The peak cortisol levels achieved during the LDTs were very different from those during the HDT (mean peak cortisol, 580 +/- 27 nmol/L; all P values <0.00009. However, the mean 30 min response in the 1.0-microg LDT did not differ from that in the HDT (471 +/- 22 vs. 492 +/- 22 nmol/L; P = 0.2). In the 8-h ACTH infusion test, plasma cortisol concentrations progressively increased, reaching peak levels much higher than those in the HDT [995 +/- 50 vs. 580 +/- 27 nmol/L (HPLC) and 1326 +/- 100 vs 759 +/- 31 nmol/L (FPIA)]. Significant differences in the basal, 1 h, and peak cortisol levels as determined by the three different assay methods (HPLC, FPIA, and RIA) were observed in the 8-h infusion tests. Similarly, in the HDTs there were significant differences in the mean 30 and 60 min cortisol levels as measured by HPLC compared with those determined by FPIA. We conclude that up to 30 min postinjection, 1.0 microg/1.73 m2 ACTH-(1-24) stimulates maximal adrenocortical secretion. Similar lower normal limits at 30 min may be applied in the 1.0-microg LDT and the HDT, but not when lower doses of ACTH-(1-24) are administered. The peak plasma ACTH level produced in the 1.0-microg LDT is higher than in the insulin hypoglycemia test, but is of the same order of magnitude. The peak cortisol concentration obtained during an 8-h synthetic ACTH-(1-24) infusion is considerably higher than that stimulated by a standard bolus 250-microg dose, potentially providing a means of evaluating the adrenocortical capacity to maintain maximal cortisol secretion. Appropriate interpretation of any of these tests of HPA axis function relies on the accurate determination of normal response ranges, which may vary significantly depending on the cortisol assay used.


Subject(s)
Adrenocorticotropic Hormone/blood , Cosyntropin , Hypoglycemia/blood , Adult , Chromatography, High Pressure Liquid , Cosyntropin/administration & dosage , Dose-Response Relationship, Drug , Female , Fluorescence Polarization Immunoassay , Humans , Hydrocortisone/blood , Hypoglycemia/chemically induced , Insulin , Male , Middle Aged , Radioimmunoassay , Reference Values , Single-Blind Method , Time Factors
13.
J Stud Alcohol ; 60(5): 685-93, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10487739

ABSTRACT

OBJECTIVE: A self-regulation model for predicting alcohol problem recognition among heavy drinking college students (N = 72) was tested. METHOD: The effects of both self-focusing and normative information concerning alcohol use were assessed in a 2 (self-focusing information: present, absent) x 2 (normative information: present, absent) factorial design. RESULTS: A significant two-way interaction on both a Decisional Balance Measure (DBM) and the Contemplation subscale of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) revealed that relative to a control condition, either type of information presented alone increased negative evaluations of drinking and problem recognition, whereas presenting both types of information together had less effect on negative evaluations and even decreased problem recognition. The interaction obtained with DBM scores was further qualified by a three-way interaction that limited this pattern to participants scoring higher on self-deception. The same interactive pattern of self-focusing by normative information on problem recognition approached statistical significance on the Precontemplation subscale. Finally, a thinking-aloud procedure employed to obtain immediate reactions to the presentation of experimental information offered corroborative results, with the joint presentation of self-focusing and normative information triggering the most defensive reactions. CONCLUSIONS: Results and their clinical implications are discussed in terms of a self-regulation model for problem recognition.


Subject(s)
Alcohol Drinking/psychology , Models, Psychological , Problem Solving , Self-Assessment , Surveys and Questionnaires , Adolescent , Adult , Analysis of Variance , Chi-Square Distribution , Female , Humans , Male , Regression Analysis
14.
Arterioscler Thromb Vasc Biol ; 18(4): 577-83, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9555863

ABSTRACT

Some patients with coronary artery disease experience continued progression of one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and markedly lower plasma cholesterol levels. We examined relationships between the progression of coronary artery lesions and plasma lipoproteins, in particular intermediate density lipoprotein (IDL) and its composition, in 38 patients with coronary artery disease who had been treated with simvastatin for 2 years. Patients were given lipid-lowering dietary advice; 3 months later they were started on simvastatin therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target level of plasma cholesterol had not been attained. Progression of lesions was determined by serial quantitative coronary angiography (variability of 5.5%) and was defined as an increase in percent diameter stenosis (%S)> or =10%; regression was defined as a decrease in %S > or =10%. The proportions of cholesteryl esters (CEs) and free cholesterol decreased significantly (P<.001), and proportions of protein and triglycerides increased significantly (P<.001) in IDL during simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in progressors (patients who showed progression of one or more lesions without regression of any lesion). This decrease in IDL CE content in nonprogressors was significantly (P=.01) different compared with the corresponding change in patients classified as progressors. Mean plasma cholesterol concentration tended to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors (-0.39 mmol/L) during the initial 3-month diet period, and these changes were significantly different (P=.02). Furthermore, this change in plasma cholesterol level during the initial diet period was correlated significantly with the change in IDL CE content during the entire study (r=.348, n=38, P=.03). These data suggest that IDL CE content may be a determinant of progression of coronary lesions and may be influenced by compliance with or metabolic response to lipid-lowering dietary advice in patients with coronary artery disease during simvastatin treatment.


Subject(s)
Anticholesteremic Agents/therapeutic use , Arteriosclerosis/blood , Arteriosclerosis/diagnostic imaging , Lipoproteins/blood , Simvastatin/therapeutic use , Adult , Aged , Arteriosclerosis/drug therapy , Cholesterol/blood , Cholesterol Esters/blood , Coronary Angiography , Female , Humans , Lipoproteins, IDL , Male , Middle Aged , Triglycerides/blood
16.
J Clin Endocrinol Metab ; 82(3): 812-7, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9062488

ABSTRACT

PGs influence ACTH secretion. However, their specific role in modulating the activity of the human hypothalamic-pituitary-adrenal (HPA) axis remains unclear. Acetylsalicylic acid (aspirin) inhibits the synthesis of PGs from arachidonic acid by blocking the cyclooxygenase pathway. In this study we administered a single, clinically relevant dose of aspirin before HPA axis stimulation by a bolus dose of iv arginine vasopressin (AVP) to seven normal males using a randomized, placebo-controlled, single blinded design. Aspirin significantly reduced the cortisol response to AVP [mean peak increase from basal, 221.1 +/- 20.1 vs. 165.4 +/- 22.5 nmol/L (P = 0.0456); mean integrated response, 11,199.3 +/- 1,560.0 vs. 6,162.3 +/- 1,398.6 nmol.min/L (P = 0.0116) for placebo aspirin/AVP and aspirin/ AVP, respectively]. The ACTH response was reduced, but did not reach statistical significance [mean peak increase from basal, 7.5 +/- 2.2 vs. 4.3 +/- 0.3 pmol/L (P = 0.0563); mean integrated response, 142.6 +/- 36.0 vs. 96.2 +/- 8.7 pmol.min/L (P = 0.12) for placebo aspirin/ AVP and aspirin/AVP, respectively]. PGs may influence ACTH secretion by being stimulatory or inhibitory to the HPA axis at different levels, such as hypothalamic or pituitary. Which effect predominates in vivo during dynamic activation of the axis may depend on the level at which the secretory stimulus acts. We showed that when normal male volunteers were treated with the PG synthesis inhibitor, aspirin, they had a blunted HPA axis response to the pituitary corticotroph stimulator, AVP.


Subject(s)
Arginine Vasopressin/antagonists & inhibitors , Arginine Vasopressin/pharmacology , Aspirin/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Hypothalamo-Hypophyseal System/drug effects , Pituitary-Adrenal System/drug effects , Adolescent , Adrenocorticotropic Hormone/blood , Adult , Humans , Hydrocortisone/antagonists & inhibitors , Hydrocortisone/blood , Male , Reference Values , Single-Blind Method
18.
Eur J Clin Nutr ; 49(4): 233-41, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7796780

ABSTRACT

OBJECTIVE: The aim of the study was to compare red blood cell (RBC) fatty acid composition, plasma lipids and lipoproteins and dietary intake between urban and rural Melanesian Fijians. DESIGN: A cross-sectional study was performed in a random subsample (n = 154) from a total survey population of 589 subjects. SETTING: Melanesian Fijians living in the relatively urban settlement of Nabua, Suva and On the remote island of Qamea (rural) were studied. RESULTS: The proportions of myristic acid (1.4% versus 0.3%, P < 0.001) and arachidonic acid (10.1% versus 11.4%, P < 0.01) were significantly higher and proportions of oleic acid (14.4% versus 13.2%, P < 0.05) and linoleic acid (11.9% versus 8.1%, P < 0.001) were significantly lower in RBC from rural compared with urban men, and a similar pattern was seen in women. Plasma cholesterol levels were significantly (P < 0.05) higher in the rural subjects. Urban/rural differences in plasma cholesterol levels were not significant when the proportion of RBC myristate was taken into account. CONCLUSIONS: The results suggest that consumption of myristic acid from coconut fat is greater and the intake of linoleic acid is less in Fijians living on a remote island and may contribute to their higher plasma cholesterol levels compared with their urban counterparts.


Subject(s)
Erythrocytes/chemistry , Fatty Acids/blood , Rural Population , Urban Population , Adolescent , Adult , Anthropometry , Black People , Cross-Sectional Studies , Diet , Female , Humans , Lipids/blood , Male , Melanesia , Myristic Acids/blood
19.
Clin Physiol ; 13(2): 143-51, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8453868

ABSTRACT

Plasma cholesteryl ester transfer protein (CETP) activity and distribution of red blood cell (RBC) cholesterol among plasma lipoproteins during incubation of blood were determined in 14 distance runners and 10 sedentary men. Mean plasma CETP activity was similar in the runners (31% 10 microliters-1 18 h-1) and the sedentary men (32% 10 microliters-1 18 h-1). There was significantly (P < 0.05) greater accumulation of cell cholesterol in the HDL fraction (runners: 0.33 mmol l-1; sedentary men: 0.23 mmol l-1) which comprised a significantly (P < 0.05) larger proportion of the total amount of cell cholesterol lost to plasma (runners: 89%; sedentary men: 64%) in incubated blood from the runners. The results of this study suggest that in distance runners, high HDL concentrations are not accompanied by reduced plasma CETP levels but in conjunction with low triglyceride-rich lipoprotein levels in plasma, may promote preferential distribution of cell cholesterol into the 'antiatherogenic' HDL fraction.


Subject(s)
Carrier Proteins/blood , Cholesterol/blood , Glycoproteins , Lipoproteins/blood , Physical Fitness/physiology , Adult , Apolipoproteins B/blood , Body Weight/physiology , Cholesterol Ester Transfer Proteins , Cholesterol, LDL/blood , Erythrocytes/metabolism , Humans , Male , Running , Triglycerides/blood
20.
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