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Biomedical subjects

M Criscuolo

Publications and source records attributed to M Criscuolo.

At least 37 records · Page 2Linked to original sources

Adrenergic and serotoninergic receptors mediate the immunological activation of corticosterone secretion in male rats.

In order to elucidate the mechanism of action of immune agents on corticosterone secretion, the present study evaluated the possible involvement of some neuronal pathways (serotoninergic, noradrenergic/adrenergic) in the lipopolysaccharide (LPS)-induced corticosterone release in male rats. Serotoninergic antagonists, mianserin (5-HT2C receptor blocker) or pindolol (5HT1A receptor blocker) or noradrenergic/adrenergic antagonists, prazosin (alpha 1-adrenoceptor blocker) or propranolol (beta-adrenoceptor blocker), were intraperitoneally (i.p.) injected before (5 min) the administration of LPS. In each experiment a group of rats i.p. injected with vehicle served as controls. Animals were sacrificed by decapitation 90 min after administration of LPS and trunk blood was collected for corticosterone radioimmunoassay. Results showed that pretreatment with mianserin, but not with pindolol, significantly reduced plasma corticosterone levels following administration of LPS (p < 0.05); prazosin attenuated the plasma corticosterone response to LPS (p < 0.05), while propranolol did not induce significant change. The present study indicated that serotoninergic and noradrenergic/adrenergic pathways are involved in the immunoneuroendocrine modulation of hypothalamus-pituitary-adrenal function in rats. In particular, it is probably mediated by the activation of 5-HT2C receptors and of alpha 1-adrenoceptors, while type 1A serotonin receptors or beta-adrenoceptors do not seem to be involved in such a phenomenon.

Adrenergic alpha-Antagonists↗

Estrous cycle- and acute stress-related changes of rat ovarian immunoreactive corticotropin-releasing factor.

Corticotropin-releasing factor (CRF), the major regulator of the stress response within the central nervous system, is also present at peripheral sites, including the gonads, and the gene encoding its own receptor can be finely induced in selective ovarian compartments in both control and stressful conditions during the gonadal life cycle. The present study, therefore, investigated the influence of both gonadal function and estrous cycle on the immunoreactive CRF (irCRF) contents in the immature and adult rat ovary. In addition, the effect of an acute (5 min) or chronic intermittent (twice a day for 4 days) cold swimming stress on ovarian irCRF contents was evaluated. High-performance liquid chromatography (HPLC), gel-chromatography (Sephadex G-75, 45 x 1 cm) and a direct radioimmunoassay were performed to measure irCRF ovarian contents. The HPLC elution profile of irCRF in ovarian tissues of adult rats was superimposable on that of synthetic rat/human CRF and gel-chromatograms performed according to the phase of the estrous cycle revealed higher irCRF contents at proestrus. Total irCRF ovarian content was undetectable both in control and acute stressed immature rats, while adult rats showed the highest values at proestrus (p < 0.0001). The acute stress exposure induced a significant increase (p < 0.0001) of irCRF ovarian contents only at proestrus, without affecting irCRF at the other phases of the estrous cycle. Finally, no significant changes were found in ovarian irCRF after chronic intermittent stress. The proestrus-related changes of ovarian irCRF, confirming the adult ovary as an extrahypothalamic source of CRF, may constitute a neuropeptidergic signal involved in the gonadal reproductive cycle. Furthermore, the stress-related changes of ovarian irCRF indicated that the gonad may be locally sensitive to acute stressful stimuli.

Acute Disease↗

The changing histopathology of primitive lung cancer.

This study was performed on 1710 lung epithelial malignant tumours, diagnosed in the biennia 1963/1964 (42 cases), 1973/ 1974 (293), 1983/1984 (637) and 1993/1994 (738). It was aimed at evaluating whether, over a time span that long, the distribution of the histopathological patterns could have changed. The neoplasms were classified according to the WHO criteria (1981). From our data, a striking increase becomes apparent for all histotypes. Squamous cell carcinoma holds the leading position both among males and females, even though its rate of increase tends to slow down among males. Analogous trend is observed for all the other histotypes but adenocarcinoma. Among females, the rate of increase continues to accelerate for all histotypes but large cell carcinoma. The male to female ratio is ranging from 2:6 for adenocarcinomas to 12:1 for squamous cell carcinomas. In conclusion, impressive changes seem to have occurred in the frequency of the different lung oncotypes over this time span, especially for adenocarcinoma (increasing trend) and large cell carcinoma (decreasing trend). It also seems worth underlying that the marked increase among females could make lung carcinoma the number one cause of cancer-related deaths in this sex.

Adenocarcinoma↗

[Bulletin of breast disease: results of the 1990-1994 quinquennium].

All mammary lesions diagnosed at the Institute of Pathological Anatomy of the University of Modena have been systematically filed since 1990 and reported in a bulletin, which is issued twice a year and delivered to health operators. So far, 5.188 cases of breast lesions, comprising 1.999 non-neoplastic pathologies, 1.040 benign tumors, 1.943 primary malignant neoplasms and 206 recurrences, have been filed. During the quinquennium 1990-1994, a progressive numerical reduction in diagnoses of non-neoplastic lesions coupled to an increase of benign tumors has been observed, whereas the number of primary malignant tumors has not changed. In particular, a statistically significant increase in diagnoses of carcinoma-in-situ and of fibrocystic disease associated with moderate-risk lesions (atypical hyperplasias) has been detected, whereas the number of cases of single fibrocystic disease has decreased. This reduction, however, is not significant. A slight increase of breast carcinomas smaller than 1 cm and 2 cm, coupled to a decrease of those exhibiting dimensions between 2 and 5 cm, has been found. The collection and systematic analysis of cases of mammary lesions appears to represent a useful tool to study the incidence of different breast pathologies in the general populations. It can also be viewed as a simple way to test the reliability of diagnostic methods used for selection of surgical cases.

Adult↗

Involvement of mu-opioid receptors in the modulation of pituitary-adrenal axis in normal and stressed rats.

The availability of the most selective, high-affinity, natural opioid agonists for mu-receptors (dermorphin-DM) and delta-receptors (deltorphin-DT) has provided the possibility for in vivo studying of the role of acute and chronic activation of mu- and delta-opioid receptors on the functional activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, both in basal conditions and in response to an acute stress in adult male rats. Plasma corticosterone (CS) and beta-endorphin-like-immunoreactivity (beta-EP-LI) levels were measured by specific radioimmunoassays before and after 5 and 30 minutes from the exposure to cold (3 +/- 0.5 C) water and forcing them to swim for 10 minutes (acute cold swimming stress). Acute administration of DM, the specific mu-receptor agonist, enhanced basal and stress induced plasma levels of CS and beta-EP-LI. These effects were antagonized by pretreatment with naloxone, specific mu-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist. Long-term administration of DM did not alter resting plasma levels of CS and beta-EP-LI, but significantly reduced stress-induced increase of these hormones. Both the acute and chronic administration of the DT, highly selective delta-opioid receptors agonist, failed to modify resting and stress induced hormone levels. Our present data show that DM throughout mu-opioid receptors, but not DT, modulates the response of HPA axis to acute stress in rats, increasing or decreasing the release of CS and beta-EP-LI when acutely or chronically administered, respectively.

Adrenal Glands↗

Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats.

The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.

Animals↗

Evidence for a role of neurosteroids in modulation of diurnal changes and acute stress-induced corticosterone secretion in rats.

The neurosteroid allopregnanolone has been shown to be a potent ligand of gamma-aminobutyric acid (GABA)-A receptors and enhances its receptor-mediated inhibitory events. Since central GABA plays a major inhibitory role, via GABA-A receptors, in hypothalamic-pituitary-adrenal (HPA) function in rats, the present study has evaluated the effect of passive immunoneutralization of allopregnanolone on diurnal changes in corticosterone secretion and acute stress-induced corticosterone secretion in rats. In the first protocol, four groups of male rats (prepubertal, fertile, castrated adult and aged) and three groups of female rats (prepubertal, fertile at different phases of the estrous cycle and aged) were studied. Rats were injected intracerebroventricularly (i.c.v.) with 10 microliters anti-allopregnanolone serum or 10 microliters normal rabbit serum (control) 24 h before exposure to an acute cold swimming stress, and sacrificed either before stress or after 5 min stress. In the second protocol, fertile male or female rats at diestrus II were injected i.c.v. with anti-allopregnanolone serum or normal rabbit serum and sacrificed on the following day at 10.00 or 18.00. Truncal blood samples were collected for measuring plasma corticosterone. Our results showed that there was no significant difference in basal plasma corticosterone levels between antiserum-treated and control rats of both sexes. However, in male rats, central injection of antiserum to allopregnanolone significantly potentiated plasma corticosterone response to stress in prepubertal and adult fertile rats as well as in castrated rats. Likewise, in female rats, the stress response of plasma corticosterone was enhanced by passive immunoneutralization of allopregnanolone in prepubertal and fertile rats throughout the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression.

A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.

Acquired Immunodeficiency Syndrome↗

Metastatic breast carcinoma presenting as urinoma.

A rare case of breast carcinoma metastatising to ureter and presenting as urinoma is described. Reviewing the literature, only few cases of urinoma due to metastasis from breast carcinoma have to date been reported. The diagnostic role of immunohistochemical study in defining the disease is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Ontogeny of the circadian rhythm in medial basal hypothalamic beta-endorphin content in female rat.

The present study evaluated the possible role of estrogens in generating the circadian rhythm of medial basal hypothalamus content at the time of puberty in female rats. Accordingly, changes in medial basal hypothalamus beta-endorphin (beta-EP) content were investigated in female rats, before and at puberty. Groups of intact or ovariectomized rats were studied after estradiol-benzoate or placebo treatment. The results showed that circadian rhythm of beta-EP content of medial basal hypothalamus is absent in prepubertal rats, while it appears at puberty, associated to a significant increase of beta-EP concentration. The primary involvement of steroids in generating this circadian rhythm was supported by the finding that estradiol-benzoate treatment caused a precocious appearance of beta-EP hypothalamic diurnal changes in prepubertal rats. Moreover, estradiol-benzoate replacement restored the loss of beta-EP nocturnal increase induced by ovariectomy in pubertal animals. Therefore, these data support the significant role of estrogen in inducing the circadian rhythm of beta-EP content in medial basal hypothalamus at the time of puberty in female rats.

Aging↗

Acute stress- or lipopolysaccharide-induced corticosterone secretion in female rats is independent of the oestrous cycle.

The aim of the present study was to test whether oestrous cycle is associated with the hypothalamus-pituitary-adrenal (HPA) axis function. Thus, corticosterone secretion in rats was investigated following lipopolysaccharide (LPS), acute cold-swimming or ether stress or synthetic corticotrophin-releasing factor (CRF) administration throughout the oestrous cycle. Moreover, plasma corticosterone response to cold-swimming stress or LPS administration also was studied at different times of day on pro-oestrus of di-oestrus-I. The following observations were obtained: the morning plasma corticosterone levels in control rats did not differ with the stage of the oestrous cycle; plasma corticosterone levels increased significantly following LPS administration (2 mg/kg, ip) or following acute exposure to cold (4 degrees C)-swimming or ether stress. However, this increase in plasma corticosterone levels was not related to the stage of the oestrous cycle; synthetic CRF injection induced an increase in plasma corticosterone levels constant on di-oestrus-I and pro-oestrus; plasma corticosterone response to LPS administration or acute cold-swimming stress showed diurnal changes, with the lowest values at 18.00 h, which was independent of the oestrous cycle. By showing the unchanged corticosterone response to LPS, to acute stress and to exogenous CRF throughout the oestrous cycle, and the independence of the diurnal pattern of stress response on the oestrous cycle, the present study suggests that the oestrous cycle has no influence on the HPA activity under the present experimental conditions in rats.

Animals↗

Pituitary and ovarian interleukin-1 alpha content changes according to estrous cycle and acute stress exposure.

A complex interaction between the immune and neuroendocrine systems has been established. In particular, cytokines are known to be one of the mediators of the stress response, and modulate hormone secretion by acting in the brain, pituitary and gonads. The aim of the present study is to investigate whether pituitary and ovarian interleukin-1 alpha (IL-1 alpha) content changes according to the estrous cycle. In addition, the possible pituitary and ovarian IL-1 alpha changes in rats exposed to acute (5 min) or chronic intermittent (twice a day for 4 days) cold swimming stress were studied. The IL-1 alpha content of ovarian and pituitary homogenates was measured by a sensitive and specific radioimmunoassay. Immunoreactive IL-1 alpha (irIL-1 alpha) was detectable only in ovaries collected in rats at proestrus and estrus while not in those collected at diestrus I and II. The highest values were found at proestrus. No significant changes were found in ovarian irIL-1 alpha content in rats exposed to acute or chronic intermittent stress in comparison to control rats. In the pituitary, no difference in IL-1 alpha content was found throughout the estrous cycle. Acute stress induced a significant increase in pituitary irIL-1 alpha content only at proestrus (p < 0.01), however, no significant differences were found in comparison to control rats after chronic intermittent stress. The proestrus-related changes of ovarian IL-1 alpha may constitute a hormone-dependent signal within the ovary that is involved in the ovulatory process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Salivary gland tumors: revision of 391 cases according to the new WHO classification.

We reviewed 391 cases of salivary gland tumors collected in a 13 year period at the Institute of Pathological Anatomy of the University of Modena, according to the new WHO classification (1991). A diagnosis of pleomorphic adenoma was changed in adenoid cystic carcinoma. Within malignant tumors, 16 cases were reclassified, and new entities, such as polymorphous low-grade adenocarcinoma, papillary cystoadenocarcinoma and salivary duct carcinoma were introduced. Mucoepidermoid carcinomas were subdivised in low-grade and high-grade tumors, but at the follow-up histological grade did not correlate with clinical behaviour of the lesions.

Adolescent↗

Prognostic significance of nucleolar organizer regions in recurrent pleomorphic adenomas of salivary glands.

Pleomorphic adenoma (PA) is the commonest tumor of salivary glands. It is considered a benign tumor which may recur and rarely metastatize. There are no reliable histological criteria for predicting recurrences of PA. In this paper, Ag-NOR expression, evaluated by means a computer assisted image analysis system, has been tested on 11 cases of PA, their recurrences, 10 non recurrent PA and 5 cases of carcinoma ex PA. Mean AgNOR count, mean AgNOR area and mean AgNOR area/particle were determined in each group. AgNOR count and area did not show any significant differences between recurrent and non recurrent PA. On the contrary, AgNOR area/particle seems to be a useful tool in predicting the clinical behaviour of this lesion.

Adenoma, Pleomorphic↗

A randomized, placebo-controlled, blind anti-AIDS clinical trial: safety and immunogenicity of a specific anti-IFN alpha immunization.

HIV-induced cytokine dysregulation, including overproduction of the antiproliferative and cytolytic IFN alpha cytokine, represents a major component of the immune disorders characterizing AIDS. To block the overproduction of IFN alpha we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFN alpha immunization. The safety and immunogenicity of this multicomponent vaccine were tested in mice, Cercopithecus, two HIV noninfected individuals, and six HIV-1 seropositive immunocompromised patients enrolled in a 1-year open clinical trial. We now report the result of a 9-month short-term randomized, blind, placebo-controlled clinical trial (Phase I/II) performed in HIV-1 patients (22 individuals) to confirm safety/tolerance of the anti-IFN alpha vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV component(s). Three groups of patients received inactivated IFN alpha (i-IFN alpha) associated with the immunomodulator P40 with HIV-1 antigens (groups B and C) or without (group A), and one group (D) was placebo. The clinical follow-up documented among those receiving i-IFN-alpha showed that none developed AIDS and/or required antiretroviral chemotherapy. Viral load did not increase and CD4 cell count as well as cell-mediated immunity (CMI) stabilized or even significantly increased in group A. Immunogenicity of the preparations was determined by a positive delayed-type hypersensitivity (DTH) reaction to i-IFN alpha and the presence of serum antibodies to i-IFN alpha and to HIV-1 peptides, occurring only in treated patients. As previously planned, based on these safety data, the trial has been extended for an additional year and all patients were switched to protocol A (i-IFN alpha+P40). This second period of the trial, now open and ongoing, should allow us to evaluate further the innocuity of the i-IFN alpha preparation and whether anti-IFN alpha vaccine could provide a long-lasting CD4 cell count as well as CMI stabilization.

AIDS Vaccines↗

Proliferating cell nuclear antigen/cyclin in incidental carcinoma of the prostate.

Monoclonal antibody to proliferating cell nuclear antigen (PCNA) has been used to identify the growth fraction in ten cases of benign prostatic hyperplasia (BPH), in 20 prostatic microcarcinomas (PMC) and in 30 cases of infiltrating prostatic carcinoma (PC). Ten year follow-up was available on all cases by means of clinical, serological, radiological and echographic examinations. The percentage of PCNA-staining nuclei was independently counted by two observers. Statistical analysis showed significant differences between PCNA/cyclin score of BPH and PMC without recurrences with respect to those of PMC with progression and of PC. PCNA immunostaining may represent a reliable method for assessing cellular proliferative activity. It may be used as a more powerful diagnostic hallmark of PMC than patterns of non-malignant microglandular proliferation and is also a useful additional test for assigning histological grades to PMC and PC. Statistical analysis indicated that PCNA/cyclin index was an independent significant prognostic indicator of predicting malignant progression (P < or = 0.01) and survival rates (P < or = 0.05) of PC and PMC (> 5 mm diameter).

Aged↗

Effect of chronic intermittent stress on rat pregnancy and postnatal development.

The present study evaluates the effect of chronic intermittent cold-swimming stress on body weight gain of pregnant rats and subsequent development of the offsprings after birth, till peripubertal stage. When stress was administered during the first half (1-11 days) of gestation, weight gain of pregnant rats was significantly lower at the 9th and 11th days (P < 0.05 vs. control, respectively). No differences of weight gain in comparison with control rats were found at term gestation in pregnant rats exposed to stress continuously. Similarly, stress administered, starting from 12th day till term gestation, had no effect on weight gain. Even though weight gain of pregnant rats during the second half of pregnancy in group stress 1-11 was restored to normal values, a high mortality rate of neonates 1, 2 and 3 weeks after birth was found in this group (P < 0.02, 0.01 and 0.001 vs. controls). There was no significant difference between stressed and control groups with respect to the number or body weight of litters, as well as weight gain of neonates during the first 21 days of life. In addition, in offsprings from all stressed groups, a high number of small for date animals was found after 14 days of life, and 74.4% of these small for date animals died during the peripubertal period. The present data demonstrate that the exposure to stress in utero may induce damaging effects on postnatal development.

Animals↗

Superinduction of mitogen-stimulated interferon-gamma production and other lymphokines by Sendai virus.

We observed that Sendai virus preinduction of peripheral blood mononuclear cells and subsequent mitogenic stimulation resulted in: (i) Superproduction of interferon-gamma, (IFN-gamma) (ii) an increase in interleukin-2 (IL-2) synthesis that correlates with DNA synthesis when stimulated with phytohemagglutinin (PHA) or pokeweed mitogen (PWM) after treatment with the Sendai virus, while stimulation with Protein A from Staphylococcus aureus was not affected, and (iii) enhanced tumor necrosis factor-alpha (TNF-alpha) production in response to bacterial lipopolysaccharide (LPS). Treatment of monocyte cultures with LPS and cycloheximide or actinomycin-D inhibited the superinduction phenomenon. When cycloheximide was added at the viral induction time, the inhibition of TNF-alpha superproduction and DNA synthesis was still observed. These results suggest that Sendai virus lymphocyte superinduction is specific for a particular stimulatory pathway, not dependent on mRNA accumulation, and probably mediated by induction of an activating protein.

CD4-CD8 Ratio↗