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Biomedical subjects

V Covelli

Publications and source records attributed to V Covelli.

At least 55 records · Page 3Linked to original sources

Neutron-induced tumors in BC3F1 mice: effects of dose fractionation.

An experimental study of the biological effectiveness of multifractionated low doses of high-LET radiation was carried out using BC3F1 male mice. They were treated with whole-body irradiation with five equal daily fractions of fission neutrons to yield cumulative doses of 0.025, 0.05, 0.10, 0.17, 0.25, 0.36, 0.535 and 0.71 Gy at the RSV-TAPIRO reactor (mean neutron energy 0.4 MeV, in terms of kerma, y D = 51.5 keV/microns, dose rate 0.004 Gy/min) and were followed for their entire life span. The statistical method described by Peto et al. (IARC Monograph, Suppl. 2, 1980) to establish the existence of a carcinogenic effect in long-term animal experiments was applied to the data sets. This analysis was done for myeloid leukemia and for the presence of selected solid tumors. Myeloid leukemia was absent in the control group and was rarely found in irradiated animals. However, a positive significant trend was found in the dose ranges 0-0.17 Gy and higher. Epithelial tumors were induced at doses from 0.17 Gy on. Tumor occurrence was evaluated further as final incidences with age adjustment for the differences in mortality rates. Survival and incidence data for selected classes of tumors after 0.17, 0.36 and 0.71 Gy were compared with those from a previous experiment at corresponding doses given acutely (dose rate between 0.05 and 0.25 Gy/min). This indicated no marked overall influence of the time regimen of neutron irradiation on survival and tumor induction.

Aging↗

In vivo effects of alprazolam and lorazepam on the immune response in patients with migraine without aura.

Over the past few years, the immunomodulating role of benzodiazepines (BDZ) has been reported in literature. In particular, diazepam is an inhibitory BDZ with regard to its effects on the phagocytic and metabolic activities of polymorphonuclear cells (PMN) and monocytes, while triazolobenzodiazepines (alprazolam and triazolam) upregulate normal human peripheral blood T lymphocyte function. On these grounds, the administration of alprazolam (1 mg/per day for 1 month) in 13 patients with migraine without aura (MWA) and of lorazepam (2 mg/per day for 1 month) in 10 matched MWA subjects has been evaluated in terms of immune response. Results show that before administration of BDZ in both groups of patients phagocytosis and killing of PMN and monocytes were profoundly depressed and the same was true for the lymphocyte-dependent antibacterial activity. After one month treatment lorazepam further decreased lymphocyte function without modifying phagocytic capabilities. On the contrary, alprazolam increased PMN phagocytosis and killing and monocyte phagocytosis without modifying antibacterial activity values. Taken together, these results further support the existence of different classes of BDZ in terms of their immunomodulating capacities. Moreover, alprazolam seems to be a more appropriate BDZ for treating immunocompromised patients, even including MWA patients.

Adolescent↗

Headache and memory impairment. Study on 100 headache patients.

The aim of the present study was to explore the association between memory impairment and primary headache. 100 headache patients (71 females, 29 males, mean age 35.6 +/- 13.8) and 20 healthy subjects (14 females, 6 males, mean age 37.3 +/- 12.1) as control group, were examined: a significant difference between the two groups was found (p < 0.001). The patients were divided into different groups according to the kind of headache, the use of analgesics, the pain side and the illness length: significant differences were found between patients who made a low use of analgesics and the others (p < 0.001); the illness duration also seems to be relevant in the progressive memory impairment, because it strengthens some immunologic and biochemical mechanisms able to favour a progressive mnemonic damage.

Adult↗

Interleukin-1 beta and beta-endorphin circadian rhythms are inversely related in normal and stress-altered sleep.

Normal sleep is associated to physiological nocturnal rises in Interleukin 1 beta (IL 1 beta) secretion. The 24 h pattern of IL 1 beta, beta-Endorphin (beta-EPH), ACTH and cortisol (F) production was evaluated in four male healthy volunteers. Two subjects were unable to sleep, due to the stress of the experiment; in these cases, no detectable plasma IL 1 beta secretion, both diurnal and nocturnal, was present, beta-EPH plasma levels were significantly higher (p < 0.01) than in the subjects who slept regularly and, in one case, increased F plasma levels were also reported. A strong negative correlation between IL 1 beta and beta-EPH plasma levels was present in all the cases. In conclusion, stress-induced sleep alterations might deeply affect both diurnal and nocturnal IL 1 beta plasma secretion, probably due to the hypothalamus-pituitary-adrenal axis (HPAA) activation, and beta-EPH might be the reliable marker of the stress-induced HPAA activation level.

Adrenocorticotropic Hormone↗

On the physiological significance of tumor necrosis factor-alpha in the human amniotic fluid.

Tumor Necrosis Factor (TNF)-alpha and Interleukin (IL)-1 beta levels have been measured in 16 weeks gestation amniotic fluids and mother's sera. Detectable levels of TNF-alpha were found in amniotic fluids, while IL-1 beta was absent. No cytokines were detected in mother's sera. The possible role of TNF-alpha as growth factor for fetal hematopoietic cells is discussed.

Acute-Phase Proteins↗

Neurological damage mediated by cytokines.

Our results suggest that CKs, in particular Interleukin-1 and Tumor Necrosis Factor (TNF)-alpha, are involved in the pathogenesis of some neurological disorders and HIV infection. Infact, we observed an exaggerated spontaneous release of TNF-alpha in patients with migraine without aura. Furthermore, in a broad spectrum of patients with HIV-infection we have also found increased amounts of serum TNF-alfa and IL-1. Interestingly, a strict correlation between plasma lipopolysaccharide (LPS) and IL-1 or TNF-alpha levels seems to exist in both group of patients, thus indicating that LPS could account for the production of CKs in the course of the above diseases.

AIDS Dementia Complex↗

The dose-response relationships for tumor induction after high-LET radiation.

This paper presents a review of several studies conducted in our laboratory to examine the carcinogenic effects in mice of high-LET radiation and, for comparison, of low-LET reference radiation. For some specific end-points the following conclusions can be formulated: i) the dose-response curves for myeloid leukemia and malignant lymphoma can be interpreted in terms of induction and inactivation; in particular, the data confirmed that a linear dependence of the induction on dose is adequate to describe the response to fission neutrons, while a pure quadratic dependence is consistent with the experimental data for low-LET radiation; ii) in the liver, a marked age-dependence was demonstrated for radiation-induced tumors with a much higher susceptibility in young than in old mice; also for these tumors the dose-effect curves can be described by a linear and a quadratic relationships for high- and low-LET radiation, respectively; iii) data on ovarian tumor induction suggested threshold-like dose responses: these peculiar shapes as well as the absence of a clear radiation quality dependence of the curves are difficult findings to explain using a simple model of radiation action, and they might better be related to a non-stochastic effect of hormonal imbalance following irradiation.

Animals↗

Increased spontaneous release of tumor necrosis factor-alpha/cachectin in headache patients. A possible correlation with plasma endotoxin and hypothalamic-pituitary-adrenal axis.

Tumor Necrosis Factor-alpha/cachectin (TNF-alpha/cachectin), Lipopolysaccharide (LPS), ACTH, beta-Endorphin (beta-EPH), and Cortisol (F) levels were determined in 33 Headache patients: 22 patients were affected with Migraine (M) and 11 patients with Chronic Type Tension Headache (CTTH). TNF-alpha/cachectin serum level was detected in 15 out of 22 migraneous patients and in no CTTH patients. Plasma LPS was observed in 11 out of 15 TNF-alpha/cachectin positive migraneous patients (73%) and in 3 out of 11 CTTH patients (27%). A negative correlation was observed between TNF-alpha/cachectin values and either ACTH or beta-EPH. In the group of migraneous patients the presence of serum TNF-alpha/cachectin showed a sensibility of .6 and a specificity of 1. The endocrine and immunological implications concerning these data are discussed.

Adrenocorticotropic Hormone↗

Effects of benzodiazepines on the immune system.

Benzodiazepines (BDZ) are psychotropic drugs largely used in patients with affective disorders. As far as their effects on the immune system are concerned, a few studies have been carried out until now. Diazepam is inhibitory in vitro for the phagocytic functions and the antibody synthesis, being its action mediated via specific receptors on immunocompetent cells. On the contrary, alprazolam results to be enhancing for the antibacterial activity exerted by normal human peripheral blood T lymphocytes in vitro. Taken together, these data point out the different role which BDZ play on the immune response.

Alprazolam↗

Alprazolam enhances the antibacterial activity exerted by normal human peripheral blood lymphocytes.

The effects of two benzodiazepines, diazepam and alprazolam, have been evaluated on the in vitro antibacterial activity exerted by human peripheral blood lymphocytes (PBL). Results demonstrate that diazepam has no influence on this PBL function, while alprazolam is able to enhance this activity in six out of nine normal donors considered. The possible therapeutical implications of these data are discussed.

Adjuvants, Immunologic↗

Role of thymic hormones in neuroimmunomodulation. Their use in patients with phobic disorders.

Many evidences support the existence of a bilateral connection between the thymic gland and the hypothalamic-pituitary-adrenal axis (HPAA). In this respect, neurohormones such as the adrenal corticotropin hormone and glucocorticoids cause thymic involution, while the growth hormone and the prolactin upregulate thymic functions. On the other hand, a thymic hormone, the thymosin fraction 5, activates the HPAA, thus closing-up the regulatory loop between immune system and nervous system. In this review, a clinical trial with two thymic hormones (Timostimolina and Thymopentin) in agoraphobic patients with phagocytic dysfunctions is reported. Results obtained indicate that both substances lead to a partial and temporary immunological recovery, since a further depression of phagocytic activities occurs in coincidence with panic attack. The use of alternative immunomodulators in these patients is discussed.

Adjuvants, Immunologic↗

Somnogenic cytokines with special reference to interleukin-1.

Cytokines (CKs) are involved in the mechanisms of sleep induction, and, in particular, interleukin-1 (IL-1) and tumor necrosis factor-alpha seem to play an important role in the slow-wave sleep. Here are reported two cases of normal sleep and altered sleep in which plasma levels of IL-1 beta have been determined. In the subject with a normal sleep a dramatic increase of this CK has been observed, while beta-endorphin levels were reduced. In the light of these findings, the role of sleep in the host protection is discussed.

Arousal↗

HIV-infection and in vivo lipopolysaccharide-induced release of cytokines. An amplified mechanism of damage to the host.

Bacterial lipopolysaccharides (LPS) or endotoxins are potent triggers of the cytokine (CK) cascade. These CKs are immune mediators which produce many biological effects and could play a detrimental rather than beneficial role in the host. In this review emphasis will be placed on the participation of two CKs, tumor necrosis factor [TNF-alpha and interleukin (IL-1) beta], in the pathogenetic development of HIV infection. We have found that TNF and IL-1 circulate in exaggerated amounts in the blood of HIV-infected subjects from the earliest phases of infection. Furthermore, we have observed a strict correlation between plasma LPS and IL-1 beta levels, thus indicating that endotoxins could account for the production of CKs in the course of HIV infection. Finally, the demyelinating role of TNF-alpha either in experimental models or in the course of AIDS dementia complex is outlined.

Animals↗

Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura?

Migraine without aura (MWA) is a clinical condition characterized by multiple immune deficits, which may play an important role in the pathogenesis of the disease. In this respect, previous studies have demonstrated that patients with MWA exhibit profound dysfunctions of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes. This may correlate with the increased frequency of infectious processes observed in these patients. The overall results suggested to evaluate the presence of circulating cytokines (CKs) in subjects affected by MWA. In particular, the present data point out an exaggerated spontaneous release of tumor necrosis factor (TNF)-alpha in a group of MWA individuals, which correlates with detectable levels of bacterial lipopolysaccharides (LPS) in their plasma. In view of the different biological activities displayed by TNF-alpha in the host, such as effects on the nervous and vascular systems, hemodynamics modifications and demyelinating properties, the intervention of this CK in the pathogenesis of MWA will be discussed.

Humans↗

Neutron carcinogenesis in mice: a study of the dose-response curves.

Several experimental studies have been conducted with the objective to improve our knowledge of the types of dose-response relationships for radiation carcinogenesis in mice exposed to single acute doses. The experimental results on tumor induction have already been published and are here summarized with emphasis on the dependence on radiation quality, age at irradiation, and sex. These data indicate that the bone marrow, liver, and ovaries of the mice tested have an appreciable susceptibility to radiation carcinogenesis. However, the shape of the dose-response relationship depends on the tissue exposed. The data also confirm that a linear relationship is adequate for a conservative description of the dose-effect curves after exposure to low dose of neutrons, while a purely quadratic dependence is not inconsistent with the experimental data obtained using low-LET radiation. Other information which stems from the present analysis is that the susceptibility to radiation induction of liver tumor by fission neutrons decreases in old age. Finally, the experimental data on induction of ovarian tumors suggest a threshold-like dose response.

Aging↗

Absence of a dose-fractionation effect on neoplastic transformation induced by fission-spectrum neutrons in C3H 10T1/2 cells.

We have investigated the effect of fission-spectrum neutron dose fractionation on neoplastic transformation of exponentially growing C3H 10T1/2 cells. Total doses of 10.8, 27, 54, and 108 cGy were given in single doses or in five equal fractions delivered at 24-h intervals in the biological channel of the RSV-TAPIRO reactor at CRE-Casaccia. Both cell inactivation and neoplastic transformation were more effectively induced by fission neutrons than by 250-kVp X rays. No significant effect on cell survival or neoplastic transformation was observed with split doses compared to single doses of fission-spectrum neutrons. Neutron RBE values relative to X rays determined from data for survival and neoplastic transformation were comparable.

Animals↗

Alterations of nonspecific immunity in patients with common migraine.

In 23 patients with common migraine (CM), immune responsiveness and frequency of immunocompetent cells were investigated. In particular, phagocytosis and killing of Candida albicans by polymorphs (PMNs) and monocytes were analyzed. Also, the percentages of CD3+, CD4+, CD8+, natural killer, and CD15+ cells were evaluated by direct immunofluorescence using specific monoclonal antibodies. The results showed deficits of phagocytosis or killing exhibited by PMNs and monocytes. These immunological findings are discussed in terms of perturbation of immune status in CM patients during migraine attacks.

Adult↗