139 research outputs found
Le neuroscienze e la libertà del volere
No full textIn the last 30 years, neurosciences, with their mechanistic approach, have dealt with the study of freedom of the will, a field that is considered typical of philosophy or psychology. The studies in neurosciences have been paradoxically appreciated more by philosophers and psychologists than by the scientists themselves, who have straightened the methodological limits. From the considerations of those limits, coming precisely from the neurosciences themselves, rises an interpretation of the freedom of the will that throws a bridge towards positions that are considered typical of philosophical and psychological theories. </p
Pain emotion and homeostasis
No full textPain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate
Assessing blood flow control through a bootstrap method
No full textIn order to assess blood flow control, the relationship between blood pressure and blood flow can be modeled by linear filters. We present a bootstrap method, which allows the statistical analysis of an index of blood flow control that is obtained from constrained system identification using an established set of pre-defined filters
Salmon calcitonin inhibits human sperm motility in vitro
No full textWe have evaluated by a stroboscopic technique the in vitro effect of salmon calcitonin and human calcitionin on the motility of human migrated spermatozoa. We report here that human calcitonin is uneffective while salmon calcitonin is a potent inhibitor of the sperm motility. This salmon calcitonin action is abolished by the preincubation of the peptide with an anti-salmon calcitonin antiserum, demonstrating the specificity of the effect. In addition, we provide evidence that the release of intracellular calcium represents a necessary step for the action of the peptide. In fact, the salmon calcitonin effect is prevented in a dose-dependent way by dantrolene sodium which inhibits the release of calcium from intracellular stores while the calcium channel blocker verapamil is unefficacious. These results suggest a potential role for calcitonin in regulating human sperm motility. © 1984 Academic Press, Inc. All rights reserved
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
No full textWe 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
SOTTODOMINI DEL RETICOLO ENDOPLASMATICO IN FISIOLOGIA E PATOLOGIA
No full textThe endoplasmic reticulum, the largest organelle of eukariotic cells, presents a very complex architectonical organization that reflects its several functions. It is now well known how this organelle presents many sub-domains to exploit particular functions, such as transport throughout the secretory pathway and degradation of misfolded proteins; sub-domains in the ER can be created also after pathological events.
My Thesis project is dedicated to characterize two sub-domains of the endoplasmic reticulum, one correlated to pathology, and another one commonly present in healthy cells.
Regarding the sub-domain generated in pathological context, I studied VAPB, a membrane protein with a C-terminal anchor (“tail-anchored”), which is resident in the endoplasmic reticulum, whose P56S mutation induces large perinuclear inclusions formation. Considering that such aggregates haven’t still clearly related to any cellular organelle, I decided to study the biogenesis of the wild-type and mutated protein both in vivo and in vitro, and characterize mutant protein generated aggregates. In vitro assays are based on the N-glycosilation of an epitope anchored to the C-terminus of the protein and also on protease protection assays developed in my laboratory, while in vivo experiments are aimed to the morphological evaluation of the inclusions induced by the mutant protein. With such approaches we have demonstrated that both the wild type form and the mutant one insert the membrane of the endoplasmic reticulum, following the post-translational pathway, and the in vitro behaviour of the mutant is indistinguishable from the one of the wild type. However, in vivo, at very early times from the insertion into the endoplasmic reticulum (2 hours), P56S-VAPB organizes into small clusters that then fuse to form large paranuclear inclusions. Such inclusions are positive for some endoplasmic reticulum markers, while they result negative for markers of other organelles. The inclusion continuity with the surrounding endoplasmic reticulum has been demonstrated with FRAP and FLIP analysis. The ultrastructural analysis demonstrated that the inclusions consist of pair of cisternae intermingled by a cytosolic layer of approximately 30 nm. This form of OSER is probably generated by high affinity trans interactions between the cytosolic domains of P56S-VAPB. These results demonstrate that P56S-VAPB causes a dramatic remodelling of the endoplasmic reticulum that can explain the neurotoxic action of the protein.
Regarding the role of endoplasmic reticulum sub-domains in physiology, I focused on a possible role of lipid microdomains in the segregation and plasma membrane transport of membrane proteins. As models for my study I used an endoplasmic reticulum resident protein, cytochrome b5, and an its variant, b5-22, different from the wild-type protein only for its transmembrane domain extended of only 5 aminoacids. Previous studies in my laboratory demonstrated that the b5-22 variant inserts initially in the endoplasmic reticulum, but then it distributes disomogenously within the organelle, concentrating into the tubules and into the exit sites. To investigate the possible role of lipid microdomains in such event, I developed an experimental approach based on the use of radiolabelled, photoactivable lipid probes and I so analyzed the lipid environment of the endoplasmic reticulum in the proximity of b5 wild type and b5-22. With such approach I observed that b5-22 is less accessible to phosphatidylcholine in comparison to the wild-type. This observation suggests that b5-22 distributes into microdomains that are poor of phosphatidylcholine and so enriched of another lipid. Such segregation could lead to the concentration of b5-22 into the exit sites and so the its export from the endoplasmic reticulum. The results obtained illustrate how protein-lipid interactions based on simple physical-chemical parameters can determine the fate of a protein throughout the secretoty pathway
Chronic fentanyl or buprenorphine infusion in the mouse : similar analgesic profile but different effects on immune responses
No full textIt is known that morphine has a negative impact on the immune responses. The potent opioids fentanyl and buprenorphine have recently become available as transdermal preparation for the treatment of chronic pain. We analyze the effect of fentanyl and buprenorphine on splenic cellular immune responses in the mouse. The parameters evaluated were lymphoproliferation, natural killer cell activity and interleukin-2 and interferon-γ production. Drugs were administered acutely at the equianalgesic doses of 0.25 mg/kg for fentanyl and 5 mg/kg for buprenorphine, or delivered continuously with osmotic pumps for 24 h, 3 and 7 days at the rate of 7.5 μg/h per mouse (fentanyl) and 12.5 μg/h per mouse (buprenorphine). After acute administration, a significant decrease of lymphoproliferation is observed in fentanyl-treated animals only. After 24 h of fentanyl administration all the parameters were significantly reduced. After 3 days of fentanyl infusion NK activity had returned to normal values, while all the other parameters were still significantly reduced. In 7 day fentanyl-treated animals immunological tolerance had developed, since no differences with controls were present. In contrast no immune alterations were ever present in buprenorphine-treated animals. No tolerance to the antinociceptive effect of drugs had yet developed. After 1 week of infusion with fentanyl and buprenorphine, new pumps were implanted releasing double amounts of drugs. Neither fentanyl nor buprenorphine-treated animals showed altered immune responses at any time considered. These results indicate that fentanyl and buprenorphine exert different immune effects. Opioid-induced immunosuppression is less relevant in chronic administration than in acute or short-time administration
Age-related changes in mitogen-induced beta-endorphin release from human peripheral blood mononuclear cells
No full textbeta-Endorphin is an opioid peptide synthesized in the pituitary, hypothalamus, and immunocytes, known to affect immune responses both when added in vitro and when its synthesis is increased in vivo (e.g., during stress). We show here that, similar to its concentrations in peripheral blood mononuclear cells, the release of the opioid peptide from these cells after stimulation with polyclonal mitogens such as PHA or Con-A is also age dependent. Moreover, the effect of both mitogens on Ca2+ homeostasis changes with age. Finally, the ionophore ionomycin and the Ca2+ ATPase blocker thapsigargin induce the same age related effect on beta-endorphin release. For these reasons, we suggest that calcium homeostasis might be important for the differences observed in the release of the opioid from cells obtained from younger ( or = 45 years) volunteers
The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and mettastatic colonization in rats
No full textSurgery stress has been shown to be associated in rat with decreased natural killer (NK) cell activity and enhancement of tumor metastasis. We have previously shown that the analgesic drug tramadol stimulates NK activity both in the rodent and in the human. In the present study, we analyze, in the rat, tramadol ability to prevent the effect of experimental surgery on NK activity and on the enhancement of metastatic diffusion to the lung of the NK sensitive tumor model MADB106. The administration of tramadol (20 and 40 mg/kg) before and after laparatomy significantly blocked the enhancement of lung metastasis induced by surgery. In contrast, the administration of 10 mg/kg of morphine was not able to modify this enhancement. The modulation of NK activity seemed to play a central role in the effect of tramadol on MADB106 cells. In fact, both doses of tramadol were able to prevent surgery-induced NK activity suppression, while the drug significantly increased NK activity in normal non-operated animals. Morphine, that in normal rats significantly decreased NK cytotoxicity, did not prevent surgery-induced immunosuppression. The good analgesic efficacy of tramadol combined with its intrinsic immunostimulatory properties suggests that this analgesic drug can be particularly indicated in the control of peri-operative pain in cancer patients
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