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Biomedical subjects

J Licinio

Publications and source records attributed to J Licinio.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interleukin 1 receptor antagonist gene expression in rat pituitary in the systemic inflammatory response syndrome: pathophysiological implications.

The systemic inflammatory response syndrome (SIRS) is characterized by endothelial cell activation causing a generalized inflammatory response and cytokine-mediated pathophysiological alterations. The pathophysiology of SIRS involves changes in the functioning of several endocrine glands, including the pituitary. SIRS-induced alterations in pituitary function include activation of the hypothalamic-pituitary adrenal (HPA) axis causing hypercortisolemia, the euthyroid sick syndrome, and cessation of reproductive function. These changes are in part mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1). IL-1 function depends on the local ratio of bioactive IL-1 and IL-1 receptor antagonist. Here we review our studies on IL-1 beta and IL-1ra mRNA levels in the pituitary in a rat model of SIRS. We have found that IL-1 beta mRNA peaked at 2 h after lipopolysaccharide (LPS) administration, increasing twelvefold over control values in the posterior pituitary and fivefold over controls in the anterior pituitary. IL-1ra mRNA levels peaked at 6 h post-LPS administration, later than those of IL-1 beta mRNA. IL-1ra mRNA levels increased tenfold in the anterior pituitary, but were induced only threefold in the posterior pituitary. IL-1ra gene expression is profoundly induced in the pituitary in vivo during systemic inflammation and its induction follows that of IL-1 beta, but it is differentially regulated and tissue-specific, occurring predominantly in the anterior pituitary. Future studies of the effects of IL-1 in the pituitary should take into account the local levels of IL-1ra.

Animals↗
PubMed1997

Cardiovascular and neuroendocrine adjustment to public speaking and mental arithmetic stressors.

In this study, we evaluated cardiovascular, neuroendocrine, and psychological adjustment to repeated presentations of a public speaking and a mental arithmetic task. Brief versions of mental arithmetic tasks have been used widely in previous reactivity studies, and growing attention to more socially salient tasks has led to the increased use of public speaking tasks. However, psychophysiological adjustment during extended and repeated exposure to these tasks has not been delineated. In the present study, 52 healthy men worked on three 8-min presentations of public speaking and of mental arithmetic in a repeated measure design. Both tasks produced substantial cardiovascular, adrenocorticotropic hormone, and cortisol responses; public speaking produced greater changes. Repeated presentations of public speaking produced a stable pattern of cardiac activation, whereas repetitions of the mental arithmetic initially produced large cardiac responses that changed to a more vascular tonus across task periods. Both tasks increased negative moods. However, correlations between the endocrine, cardiovascular, and negative moods were significant only during the public speaking stressor. The public speaking task is a socially relevant experimental protocol for studying reactivity in the laboratory setting and elicits relatively high, stable, and homogeneous responses.

Adrenocorticotropic Hormone↗
PubMed1997

Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder.

OBJECTIVE: Corticotropin-releasing factor (CRF) and somatostatin both play important roles in mediating responses to acute and chronic stress. The purpose of this study was to measure CSF concentrations of CRF and somatostatin in patients with chronic combat-related post-traumatic stress disorder (PTSD) and comparison subjects. METHOD: Lumbar punctures for collection of CSF were performed in Vietnam combat veterans with PTSD (N = 11) and comparison subjects (N = 17). CSF concentrations of CRF and somatostatin were compared between the two groups. RESULTS: CSF concentrations of CRF were higher in the PTSD patients than in the comparison subjects (mean = 29.0 pg/ml, SD = 7.8, versus mean = 21.9 pg/ml, SD = 6.0). This group difference remained significant after covariance for age. CSF somatostatin concentrations in PTSD patients were higher than those of the comparison subjects (mean = 19.9 pg/ml, SD = 5.4, versus mean = 13.7 pg/ml, SD = 8.0). However, covarying for age reduced the level of significance. CONCLUSIONS: Higher CSF CRF concentrations in patients with PTSD may reflect alterations in stress-related neurotransmitter systems. The higher CSF CRF concentrations may play a role in disturbances of arousal in patients with PTSD.

Adult↗
PubMed1997

Plasma leptin levels do not change in patients with Cushing's disease shortly after correction of hypercortisolism.

In the present study, we characterized the changes in plasma leptin levels in patients with pituitary Cushing's disease and in age- and sex-matched controls. Plasma levels of ACTH, cortisol, and leptin were measured before and after iv administration of ovine CRH in controls once and in patients twice (while they had active hypercortisolism and 10 days after successful surgery). Cushing's patients had elevated body mass indexes (34 +/- 1.9 vs. 22.9 +/- 0.8) and plasma leptin levels (35.6 +/- 3.4 vs. 9.2 +/- 1.9 ng/mL) compared to controls, which remained unchanged 10 days after successful transsphenoidal surgery and directly proportional to the body mass index. Plasma leptin levels were not affected by CRH infusion in either the controls or the patients despite clear-cut elevations in plasma ACTH and cortisol. These findings suggest that although acute changes in plasma cortisol do not affect plasma leptin, chronic hypercortisolism results in elevated leptin levels, probably by causing visceral obesity.

Adenoma↗
PubMed1996

Identification of hypothalamic transcripts upregulated by antidepressants.

Identification of quantitative changes in gene expression that occur in the brain after antidepressant treatment can yield novel molecular markers that may be useful in the diagnosis and treatment of major depression. Using a modification of the differential display polymerase chain reaction, we describe the isolation of two transcripts that are differentially expressed in the brain after an 8-week course of antidepressant administration, compared to saline-treated control animals.

Animals↗
PubMed1996

IL-1 beta, IL-1 receptor type I and iNOS gene expression in rat brain vasculature and perivascular areas.

The mechanism by which IL-1 beta exerts its actions in the brain during systemic inflammation is not fully understood, as neither IL-1 receptor gene expression nor IL-1 binding have been identified in significant levels in key areas that respond to IL-1 beta. Having hypothesized that perivascular nitric oxide (NO) might modulate the effects of systemic IL-1 beta in the brain, we studied the expression of the genes encoding for IL-1 beta, the signal-transducing IL-1 receptor type I (IL-1RI) and inducible NO synthase (iNOS) constitutively and during systemic inflammation in vascular and perivascular regions of the rat brain. Our results show that IL-1RI is constitutively expressed at the interface of the vascular wall and perivascular glia. During systemic inflammation there is induction of IL-1 beta gene expression in the vascular wall, accompanied by perivascular induction of iNOS mRNA. We conclude that during systemic inflammation vascular IL-1 beta, binding to vascular and perivascular IL-1RI receptors, may induce perivascular iNOS gene expression, leading to the production of NO and modulation of the effects of IL-1 beta in the brain. We propose that the vascular and peri-vascular induction of iNOS mRNA by IL-1 beta might represent a mechanism for the modulation of the central nervous system effects of peripheral inflammatory mediators.

Animals↗
PubMed1996

The hypothalamic-pituitary-adrenal axis in anorexia nervosa.

Studies examining the function of the hypothalamic-pituitary-adrenal (HPA) axis in anorexia nervosa are reviewed. A principal finding is that of hypercortisolism, associated with increased central corticotropin-releasing hormone levels and normal circulating levels of adrenocorticotropic hormone. Similarities between neuroendocrine findings in anorexia nervosa and in affective disorder are reviewed. The contribution of circadian rhythm disturbances and malnutrition to observed HPA axis abnormalities in anorexia nervosa is also considered. Directions for future research are discussed.

Adrenocorticotropic Hormone↗
PubMed1996

Thyroid function in bulimia nervosa.

Basal thyroid-stimulating hormone (TSH) and thyroid hormone levels were evaluated in 18 women with bulimia nervosa during a period of active binging and vomiting and again after 7 weeks of abstinence from these behaviors and compared to measures in 27 control women. In 10 of the patients and 11 of the controls, the TSH nocturnal surge was calculated from hourly TSH measurements obtained in the afternoon from 1500 to 1900 h and in the night from 2300 to 0400 h. During the binging phase of the illness patients had lower total triiodothyronine (T3) values than controls (p < .001). After 7 weeks without binge eating or purging, patients had lower T3, total thyroxine (T4), free triiodothyronine, free thyroxine (FT4), reverse triiodothyronine and thyroid-binding globulin (TBG) values compared to controls (p < .01) and significant reductions in T3, T4, FT4 and TBG compared to themselves in the active phase of the illness (p < .02). The reduction in thyroid hormone levels was not due to a reduction in the nocturnal thyrotropin surge, since surge values did not differ between normals and patients at either phase of the illness. Bulimics in the binging phase of the illness showed a positive correlation between caloric intake and TSH values (p < .01), suggesting that food binging may stimulate thyroid activity. In sum, these results show a substantial reduction in thyroid hormone levels after 7 weeks of abstinence from binging and vomiting behaviors.

Adult↗
PubMed1996

Inducible nitric oxide synthase gene expression in the brain during systemic inflammation.

Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escherichia coli lipopolysaccharide (LPS). The regulation of peripheral iNOS has been well studied in sepsis, but little is known about iNOS regulation in the brain during systemic inflammation or sepsis. We know that at baseline there is no detectable iNOS gene expression in the brain, but a detailed neuroanatomical study reveals that early in the course of systemic inflammation there is a profound induction of iNOS messenger RNA in vascular, glial and neuronal structures of the rat brain, accompanied by the production of nitric oxide (NO) metabolites in brain parenchyma and cerebrospinal fluid (CSF). We propose that the spillover of nitrite into the CSF has the potential to be a diagnostic marker for systemic inflammation and sepsis. Pharmacological interventions aimed at regulating iNOS function in the brain might represent a new treatment strategy in sepsis. Brain iNOS may be relevant to the pathophysiology, diagnosis and treatment of systemic inflammation and sepsis.

Animals↗