University of Cagliari

About: University of Cagliari is a education organization based out in Cagliari, Italy. It is known for research contribution in the topics: Population & Dopamine. The organization has 11029 authors who have published 29046 publications receiving 771023 citations. The organization is also known as: Università degli Studi di Cagliari & Universita degli Studi di Cagliari.

Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites

Abstract: Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin (IL) 1α, IL-6, tumor necrosis factor (TNF) α and interferon (IFN) γ, have been proposed as mediators of cancer cachexia. These data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. To elucidate this we studied the relationship between total serum leptin and serum cytokines IL-1α, IL-6, TNFα as well as the production of leptin and cytokines by peripheral blood mononuclear cells (PBMC) isolated from cancer patients. Sixteen advanced cancer patients (mainly stage IV) with tumors at different sites were included in the study. The serum levels of leptin in cancer patients were significantly lower than those of healthy individuals at all times (7 a.m., noon, 3 p.m.). No significant differences were found in circadian rhythm between patients and controls. Serum levels of IL-1α, IL-6, and TNFα were significantly higher in cancer patients than in healthy individuals. An inverse correlation between serum levels of leptin and IL-6 was found in cancer patients. The production in culture of leptin by unstimulated PBMCs and those stimulated by phytohemagglutinin M or by phorbol myristate acetate isolated from cancer patients was very low; no differences were observed in comparison with leptin production by PBMCs from healthy individuals.

Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling

Abstract: A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell type- and subcellular compartment-specific manner. We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ(9)-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ(9)-tetrahydrocannabinol treatment. These findings indicate that cell type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.

SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade?

Abstract: The influence of the D1 antagonist SCH 23390 on the motivational properties of rewarding (morphine, nicotine and diazepam) and aversive (naloxone, phencyclidine and picrotoxin) drugs was studied in the rat in a two-compartment place-conditioning paradigm, which included a pre-conditioning test for spontaneous place-preference. The specific D1 dopamine-receptor antagonist SCH 23390 (0.05 mg/kg SC), paired with both compartments or, separately, with the preferred or with the non-preferred compartment, failed to affect the spontaneous unconditioned preference of the animal. Pairing of morphine (1.0 mg/kg SC), nicotine (0.6 mg/kg SC) or diazepam (1.0 mg/kg IP) with the less preferred compartment induced significant preference for that compartment. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments completely blocked the place-preference induced by morphine, nicotine and diazepam. Naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) or picrotoxin (2.0 mg/kg IP) paired with the preferred compartment elicited place-aversion. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments abolished also the place-aversion induced by naloxone, phencyclidine and picrotoxin. The results indicate that blockade of dopamine transmission blocks the motivational properties of rewarding as well as aversive stimuli. It is suggested that neuroleptics rather than simply blocking the rewarding impact of positive reinforcers (anhedonia, lack of pleasure) exert a more general influence on conditioned behaviour by blocking the affective impact of negative as well as positive reinforcers (apathy, lack of motivation).

Relevance of residue 116 of HLA‐B27 in determining susceptibility to ankylosing spondylitis

Abstract: Ankylosing spondylitis (AS) is an autoimmune disorder strongly associated with HLA-B27. A direct role of B27 molecules in the disease pathogenesis has been postulated, possibly by presenting to T cells an as-yet unidentified arthritogenic peptide that triggers the autoimmune response. There are nine HLA-B27 alleles differing from each other at one or more amino acid positions. It is important, for the identification of the arthritogenic peptide, to define which alleles, and therefore which polymorphic positions, predispose to the disease. Here, we report that HLA-B*2709 is not associated with AS, as it was not found in patients. HLA-B*2709 differs from the most frequent and disease-associated HLA-B*2705 allele for a single substitution (His vs. Asp) at position 116. Amino acid 116 is located at the bottom of the groove where the antigenic peptide sits, and it has been proven to influence the peptide-binding specificity of HLA class I molecules. The most likely interpretation of these data is that the differences in charge and size that accompany the His-to-Asp substitution exclude the acceptance of the arthritogenic peptide.