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Biomedical subjects

A E Panerai

Publications and source records attributed to A E Panerai.

At least 19 recordsLinked to original sources

Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity.

To extend the knowledge on the central effects of cytokines, we studied the effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity in rats. After central administration, both tumor necrosis factor alpha and interleukin-1 alpha significantly (P < 0.001) increase the nociceptive thresholds as measured by the hot-plate test. Tumor necrosis factor alpha, but not interleukin-1 alpha decreases spontaneous locomotor activity evaluated by the Animex test. The increase in nociceptive thresholds induced by tumor necrosis factor alpha or interleukin-1 alpha is not affected by the opiate receptor antagonist naloxone, or antisera against the endogenous opioids beta-endorphin, met-enkephalin or dynorphin. The analgesic effect of tumor necrosis factor alpha is completely antagonized by anti-IL-1 antibodies. Moreover, the cyclooxygenase inhibitor indomethacin does not antagonize the increase of nociceptive thresholds induced by either cytokine.

Analgesia

Beta-endorphin concentrations in resting peripheral mononuclear cells and after treatment with PHA or serotoninergic drugs in human aging, Alzheimer's disease, and Down's syndrome.

We measured the concentrations of beta-endorphin in resting peripheral blood mononuclear cells obtained from normal subjects of different ages and from age-matched patients with Down's syndrome or Alzheimer's disease. We also measured beta-endorphin concentrations in peripheral blood mononuclear cells obtained from subjects of different ages after treatment with PHA or serotoninergic drugs. The results show that in normal subjects the concentrations of the peptide increase after 30 years of age and remain constant up to 99 years. After stimulation with PHA, the release of beta-endorphin in cells from subjects older than 30 years increases, leading to a decrease in contents, whereas it is unchanged in younger subjects. In patients with Down's syndrome or Alzheimer's disease, beta-endorphin concentrations in peripheral blood mononuclear cells behave similarly to those in age-matched normal subjects. Treatment in vivo with the serotoninergic agonist chlorimipramine induces an increase in beta-endorphin concentrations in peripheral blood mononuclear cells that is significantly greater in subjects over 30 years old than in younger subjects.

Adult

Effects of two different reversible monoamine oxidase-A inhibitors on nociceptive thresholds in the rat.

The acute effect of two different reversible inhibitors of monoamine oxidase-A on nociceptive thresholds was evaluated in the rat by the tail-flick and hot-plate tests. CGP 11305-A, a monoamine oxidase-A inhibitor that also blocks serotonin reuptake, elicited an increase of latency in the tail-flick and the hot-plate test. Ineffective doses of CGP 11305-A increased nociceptive thresholds when administered in combination with other serotoninergic agents, i.e. chlorimipramine or 5-hydroxytryptophan, at doses that were ineffective alone. CGP 22364-A, a pure inhibitor of monoamine oxidase-A, increased latency only in the hot-plate test. Both compounds decreased spontaneous locomotor activity at the doses effective in the hot-plate test, suggesting that the responses observed in this test are not related to a pure effect on nociceptive thresholds. The data suggest that the increase in serotonin availability induced by monoamine oxidase-A inhibition alone is not sufficient to affect nociceptive thresholds.

Animals

Beta-endorphin concentrations in the peripheral blood mononuclear cells of migraine and tension-type headache patients.

Levels of beta-endorphin in peripheral blood mononuclear cells have been studied as a new approach to investigating opioid tone in migraine and tension-type headache. Sixty-one patients with migraine without aura, 39 with migraine with aura and 23 with episodic tension-type headache were compared with 37 healthy controls. Peripheral blood samples were taken from patients not enduring headache attacks and not undergoing prophylactic treatment. A significant reduction in peripheral blood mononuclear cell beta-endorphin concentrations was observed in migraine patients with and without aura, but not in tension-type headache patients. Altered transmitter modulation to peripheral blood mononuclear cells may be the cause of this alteration, which could be part of a more diffuse opioid system derangement in migraine subjects.

Adult

Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with rheumatic diseases.

The neuroendocrine polypeptide hormone beta-endorphin (beta-END), which is released from various tissues including the anterior pituitary gland and cells of the immune system, has recently been implicated as having an immunoregulatory role. We used a radioimmunoassay to measure beta-END levels in circulating mononuclear leucocytes from normal subjects and patients with various rheumatic diseases. Levels of beta-END in leucocytes from patients were lower than in leucocytes from healthy subjects (P less than 0.001). Whereas levels of beta-END in leucocytes from patients with the various rheumatic disorders were not significantly different, an inverse correlation was found between beta-END levels in leucocytes and expression of rheumatoid factor (P less than 0.025) and erythrocyte sedimentation rate (P less than 0.025). This study demonstrates decreased content of beta-END in cells of the immune system related to parameters of inflammatory activity in rheumatic diseases.

Blood Sedimentation

Cystic ovaries in women affected with hereditary angioedema.

Polycystic ovary (PCO) syndrome is biochemically characterized by abnormal gonadotropin secretion and polycystic ovaries associated with increase in size and functional activity of stromal tissue; multifollicular ovaries (MFO) are defined by the presence of multiple cysts with no increase in stromal tissue. A central (hypothalamic-pituitary) abnormality, including high plasma beta-endorphin (BE) concentrations without simultaneous elevation of ACTH, was reported for subjects with PCO syndrome. Since we have found the presence of high plasma BE concentrations in hereditary angioedema (HANE) during attacks as well as during symptom-free periods, we studied, by means of pelvic ultrasound scanning employed to determine the prevalence of PCO and of MFO, 13 women of reproductive age affected with HANE who were not on oral contraceptives. We have found PCO in 5/13 (38.4%) and MFO in 7/13 (53.8%) HANE patients. Nine patients had oligomenorrhoea (five with PCO, three with MFO, one with normal ovaries), five (three with PCO, two with MFO) were hirsute and only one (with MFO) had weight loss. No patient was obese. Mean plasma LH, testosterone, prolactin, cortisol and ACTH concentrations were normal, while FSH was significantly reduced and LH/FSH ratio increased. BE concentrations were significantly high in all the patients studied. Our results clearly demonstrate that women with HANE frequently have cystic ovaries (polycystic or multifollicular) in the presence of high BE concentrations.

Adolescent

Beta-endorphin, vasoactive intestinal peptide and cholecystokinin in peripheral blood mononuclear cells from healthy subjects and from drug-free and haloperidol-treated schizophrenic patients.

Beta-endorphin, cholecystokinin and vasoactive intestinal peptide were measured in peripheral blood mononuclear cells of healthy controls, and schizophrenic patients at the first diagnosis before any treatment and after 2 or 15 d of treatment with haloperidol. Beta-endorphin concentrations were similar in controls and untreated patients, and increased with treatment. Cholecystokinin concentrations were higher in patients than in controls, and decreased during treatment. Vasoactive intestinal peptide was lower in patients and did not change with treatment. These observations are consistent with measurements of the same peptides in autopsy samples or cerebrospinal fluid. Peripheral blood mononuclear cells might be an useful tool for the study of some neuropeptides in brain.

Adolescent

Mononuclear cell beta-endorphin concentration in women with and without endometriosis.

Seventy-five consecutive patients undergoing laparoscopy for chronic pelvic pain and/or infertility were studied to test whether beta-endorphin concentrations in peripheral mononuclear cells differed according to the presence or absence of endometriosis. Endometriosis was diagnosed in 45 subjects (minimal in 24, mild in 11, moderate in four, and severe in six). Twenty-eight women (62%) with endometriosis and ten (33%) without the disease reported moderate or severe pelvic pain. beta-Endorphin levels were lower in the endometriosis group than in the controls (16.6 +/- 11.2 versus 21.9 +/- 10.5 pg/10(6) cells; P less than .01). This decrease was attributable to reduced beta-endorphin concentrations in the endometriosis patients with moderate or severe pain compared with symptomatic controls (15.5 +/- 10.0 versus 26.3 +/- 7.0 pg/10(6) cells; P less than .01). A significant difference was also found in relation to the cycle phase: The opioid concentration was reduced in the luteal phase in the endometriosis group compared with controls (14.4 +/- 8.4 versus 23.8 +/- 7.5 pg/10(6) cells; P less than .01), but no differences were demonstrated in the follicular and periovulatory phases. beta-Endorphin is capable of modulating the immune response and can be considered as a classical cytokine. Low beta-endorphin production during the luteal phase may have implications in the development and/or maintenance of endometriosis.

Adult

Corticotropin releasing hormone, interleukin-1 alpha, and tumor necrosis factor-alpha share characteristics of stress mediators.

Interleukin-1 alpha and tumor necrosis factor-alpha induce an increase in pain thresholds in the rat. We now show that also the corticotropin releasing hormone induces an analgesic effect that, similarly to what is observed with the two cytokines, is not reversible by naloxone. Moreover, we also show that after the administration of interleukin-1 alpha, tumor necrosis factor-alpha, and corticotropin releasing hormone, naloxone becomes analgesic itself. A similar observation was also made in the human and the experimental animal after exposure to stressful conditions. The results obtained suggest that the two cytokines share with corticotropin releasing hormone some characteristics of stress mediators.

Analgesia

Central beta-endorphin system involvement in the reaction to acute tonic pain.

The involvement of the beta-endorphin (B-EP) system during acute prolonged (tonic) pain was investigated by biochemical and behavioral approaches in freely-moving rats after subcutaneous injection of a small amount of a dilute formaldehyde solution (0.08 ml, 5%) in a forepaw. Beta-endorphin-like immunoreactivity levels were increased over the respective control groups in rats killed 30, 60 and 120 min after injection in discrete regions of the rat brain, namely ventro-medial hypothalamus, ventro-basal thalamus and periaqueductal gray matter, and at 30 and 60 min in postero-medial thalamus. In a separate group of experiments a small amount of anti-B-EP or normal rabbit serum was injected in the lateral ventricle; 6 h later rats received formalin injection as in previous groups and their behavior was scored over the following 2 h. A significant hyperalgesia (as expressed by an increase in the amount of time rats spent licking or chewing the injected paw) was observed 10-50 min and 70-80 min after formalin in the anti-B-EP icv-injected group. Other behavioral parameters such as general motor activity, grooming and limb flexion were not different in the two groups, nor was animal behavior prior to formalin injection. Altogether these data suggest that the central beta-endorphin system is triggered by prolonged noxious stimulation in freely-moving animals, and in turn plays a physiological role in the modulation of the reaction to, or perception of, tonic pain.

Acute Disease

Chronic intrathecal cannulation affects hypothalamic opioids depending on the technique employed.

Previous studies have shown that chronic intrathecal cannulation can interfere with the homeostasis of central opioid peptides. These results show that beta-endorphin and Met-enkephalin concentrations did not change in the hypothalamus of rats bearing a chronic cannula inserted between C8-T1 up to L3 and fixed to the processes transversus T1. These results suggest that chronically cannulated rats can be considered as normal when studying hypothalamic beta-endorphin or Met-enkephalin concentrations, and used in physiological studies, depending on the technique employed.

Animals

Pharmacological modulation of neuropeptides in peripheral mononuclear cells.

The concentrations of beta-endorphin and cholecystokinin were measured in fresh resting peripheral mononuclear cells obtained from rats and human subjects in basal conditions and after different pharmacological treatments. Both in the human and the rat, beta-endorphin concentrations in mononuclear cells, increased after treatment with serotoninergic agonists, decreased after dopaminergic or GABAergic drugs, while the respective antagonists exerted the opposite effect. In vitro, serotoninergic and GABAergic compounds confirmed their roles in the modulation of beta-endorphin in mononuclear cells. Cholecystokinin was never affected by the pharmacological treatments.

Animals

Traditional acupuncture increases the content of beta-endorphin in immune cells and influences mitogen induced proliferation.

We measured beta-endorphin concentrations in peripheral blood mononuclear cells and mitogen-induced T-lymphocyte proliferation in patient who underwent treatment with traditional acupuncture. Traditional acupuncture increased both the concentrations of the opioid in the immune cells and lymphocyte proliferation. Our data are consistent with the hypothesis that traditional acupuncture modulates immune responses in man.

Acupuncture Analgesia

Hypothalamic opiatergic tone during pregnancy, parturition and lactation in the rat.

The concentrations of beta-endorphin have been shown to change in the rat brain during pregnancy and lactation. This study has been performed in order to analyze whether also brain opioid receptors might undergo significant modifications during these two physiological situations. The maximal binding capacity (Bmax) and the constant of affinity (Ka) of the mu-subpopulation of opioid receptors have been evaluated in the hypothalami of female rats at different stages of pregnancy (7, 15 and 22 days), on the day of parturition (12-18 h after delivery) and 6-8 days postpartum (both in lactating and in nonlactating animals). Female rats killed on the day of estrus served as controls. The receptor binding assay has been performed utilizing [3H]-dihydromorphine [( 3H]-DHM) as the ligand for the mu-opioid receptors. Hypothalamic concentrations of beta-endorphin as well as serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin have also been evaluated by radioimmunoassay. The results showed that the concentration of hypothalamic mu-opioid receptors increased during pregnancy, being significantly higher than in the controls at days 15 and 22 of gestation. After delivery, the concentration of these receptors returned towards control values, regardless on whether the animals were lactating or not. The Ka values of [3H]-DHM for the mu-receptors did not change significantly in the different groups of experimental animals. Hypothalamic beta-endorphin content showed a modest though not significant increase at the end of gestation (day 22) and returned to control values 12-18 h after delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals