Serotonin-mediated cyclic AMP inhibitory pathway in platelets of patients affected by panic disorder

Cyclic adenosine monophosphate (cAMP) pathway abnormalities have been suggested to be involved in anxiety disorders including panic (PD). The present study sought at investigating the downstream inhibitory adenylyl cyclase (AC) pathway activated by 5-HT in platelets obtained from 22 patients with a diagnosis of PD versus 22 healthy volunteers. In PD patients, a significant impairment of 5-HT potency to inhibit AC was observed. One month of treatment with paroxetine induced a significant increase of 5-HT potency in T1 patients close to the control values. [(35)S]GTPgammaS binding studies showed that in PD patients, a reduction of 5-HT receptor-G protein coupling occurred without any significant changes in G protein levels. These findings demonstrated that (1) a reduction of the inhibitory AC pathway activated by 5-HT occurred in platelets from PD patients; (2) the reduced 5-HT responsiveness in PD was related to an impairment of 5-HT receptor-G protein coupling, and (3) after 1 month of treatment with paroxetine, such a dysfunction significantly reversed together with a significant improvement of clinical symptoms.     

Depressive symptoms and academic self-image in adolescence

The aim of this paper was to specifically analyse the relationship between the different components of academic self-image, defined as the way adolescents represent themselves as students, and self-reported depressive symptoms, assessed with the Children's Depression Inventory (CDI), in a non-clinical sample of 298 adolescents. We considered both adolescents' beliefs about their own cognitive functioning in academic performance and beliefs about their emotional attitude in achievement situations. Our data indicate that the pattern of correlation between emotional beliefs about schooling and learning are significantly related to CDI scores, but this correlation is not evident for the cognitive beliefs. This pattern of correlation is affected by actual school functioning, because correlation between CDI and beliefs is much more significant in subjects without school failure. Differences between gender in CDI scores, beliefs about schooling and learning, and pattern of correlation are considered. These results can enable to focus supporting psychological interventions on more specific targets.     

Efficacy of post-exposure treatment of yellow fever with ribavirin in a hamster model of the disease

Ribavirin was evaluated as a potential treatment of yellow fever (YF) in a hamster model of the disease. Ribavirin treatment during the first five days after YF virus infection improved survival, reduced tissue damage in target organs (liver and spleen), prevented hepatocellular steatosis, and normalized alanine aminotransferase levels. The results of this study suggest that ribavirin may be effective in the early treatment of YF, and that its mechanism of action in reducing liver pathology in YF virus infection may be similar to that observed with ribavirin in the treatment of chronic hepatitis C virus infection.     

Robotics in general surgery: personal experience in a large community hospital

HYPOTHESIS: Robotic technology is the most advanced development of minimally invasive surgery, but there are still some unresolved issues concerning its use in a clinical setting. DESIGN: The study describes the clinical experience of the Department of General Surgery, Misericordia Hospital, Grosseto, Italy, in robot-assisted surgery using the da Vinci Surgical System. RESULTS: Between October 2000 and November 2002, 193 patients underwent a minimally invasive robotic procedure (74 men and 119 women; mean age, 55.9 years [range, 16-91 years]). A total of 207 robotic surgical operations, including abdominal, thoracic and vascular procedures, were performed; 179 were single procedures, and 14 were double (2 operations on the same patient). There were 4 conversions to open surgery and 3 to conventional laparoscopy (conversion rate, 3.6%; 7 of 193 patients). The perioperative morbidity rate was 9.3% (18 of 193 patients), and 6 patients (3.1%) required a reoperation. The postoperative mortality rate was 1.5% (3 of 193 patients). CONCLUSIONS: Our preliminary experience at a large community hospital suggests that robotic surgery is feasible in a clinical setting. Its daily use is safe and easily managed, and it expands the applications of minimally invasive surgery. However, the best indications still have to be defined, and the cost-benefit ratio must be evaluated. This report could serve as a basis for a future prospective, randomized trial.     

Acceptability,validity and reliability of the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS): a pilot study

This paper reports on the acceptability, reliability and validity of the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS), a new instrument exploring the interactive pathway between substance abuse and psychiatric disorders. Psychiatric outpatients with (n = 21) and without (n = 32) substance abuse comorbidity according to the DSM-IV, non-psychiatric subjects with opioid dependence (OD, n = 14) and normal controls (n = 33) were assessed with the SCI-SUBS. The presence or absence of psychiatric disorders was determined with the Structured Clinical Interview for DSM IV (SCID). The SCI-SUBS was well accepted by participants. The internal consistency of the domains was satisfactory (between 0.64 and 0.93). Domain scores of OD subjects were significantly higher than those of controls and of psychiatric patients without substance abuse. The cut-off point on the SCI-SUBS total score at which there was optimal discrimination between the presence and the absence of a DSM-IV diagnosis of substance abuse was 45. The pilot version of the SCI-SUBS has satisfactory internal consistency and construct validity.     

Post-reperfusion changes of monocyte function in coronary blood after extracorporeal circulation

BACKGROUND: Neutrophil and mononuclear cell functional changes represent a hallmark of inflammation during cardiopulmonary bypass and cardiovascular surgery. Knowledge of mechanisms underlying monocyte functional modulation in coronary blood may be useful to develop protective interventions that can limit ischemia/reperfusion injury. METHODS: Samples of 13 patients were drawn from venous coronary sinus before cardioplegic arrest and after reperfusion. The following parameters were studied: surface molecules expression (CD18, CD11b, CD44, CD162, CD15s, CD80, CD86, CD16, CD49d, CD29, CD25, HLA-DR, Toll-like receptor-4 [TLR-4], CXCR1, CCR2, CCR5, CX3CR1), oxidative burst response, monocyte-platelet conjugates (using antibodies against CD45, CD14, CD41a), and platelet activation (CD62P, PAC-1). Enzyme-linked immunosorbent assays were performed to measure levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Coronary reperfusion down-modulated monocyte molecules expression, especially for CD18 (P = 0.048), CD44 (P = 0.0035), CD49d (P = 0.0029), CD29 (P = 0.032), HLA-DR (P < 0.0001), TLR-4 (P = 0.0109), CCR2 (P = 0.0184), CCR5 (P = 0.0396), and CX3CR1 (P < 0.0001). A marginal increase (P = 0.062) of a normalized adhesion index between monocytes and platelets was observed at reperfusion. No variations were detected for the monocyte oxidative burst and platelet activation. Increased levels of IL-6 (P = 0.013), TNF-alpha (P = 0.0272), and IL-10 (P = 0.0008) were measured after cardioplegia. CONCLUSIONS: The lack of CD11b and CD25 variations and of the oxidative burst exclude monocyte activation at reperfusion. The high after-cardioplegia level of IL-10, the decreased expression of HLA-DR and TLR-4, and the absence of IL-1beta and IL-8 suggest an IL-10-mediated functional depression of monocyte, including their adhesive and migratory capacities. The lack of an after-cardioplegia orientation toward IL-10 producing a "macrophage-like" CD14+/CD16+ phenotype might mean that myocardial infiltrating lymphocytes are the main source of IL-10. Moreover, the increased after-cardioplegia levels of IL-6 and TNF-alpha might be due to myocardial and endothelial activations. The increased adhesion index between monocyte and platelets, without receptor variations, suggests a monocyte membrane modification induced by extracorporeal circulation.     

Spheroid‐based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma

Chondrosarcoma (CS) is a cartilage malignancy of adulthood that is treated by surgery alone, since chemotherapy is considered ineffective. Unfortunately, a large proportion of patients with CS develop lung metastases, and several die of the disease. In this study, we compared 3D‐spheroid cultures and conventional cell monolayer models in order to identify the best way to select anticancer agents that could be effective for the systemic control of CS. Using SW1353 cells, we developed a three‐dimensional (3D) in vitro culture model to mimic in vivo features of CS microenvironment and evaluated the efficacy of different drugs to modulate CS cell proliferation and survival in 2D versus 3D‐cultures. Doxorubicin (DXR) and cisplatin, that are widely employed in sarcomas, were less effective on 3D‐CS spheroids when compared to standard monolayer models, whereas treatment with the ionophore salinomycin (SAL) had a strong cytotoxic effect both on 2D and 3D‐cultures. Furthermore, as demonstrated by the reduced viability and the enhanced DXR nuclear localization, SAL enhanced DXR cytotoxicity in 3D‐CS spheroids also at sub‐lethal doses. SAL activity on 3D‐CS spheroids was mediated by a significant induction of apoptosis via caspase activation. This study demonstrates that preclinical tests significantly differ in monolayer and 3D cultures of CS cells. Using this approach, SAL, alone or, at sub‐lethal concentrations, in combination with DXR, represents a promising agent for the systemic treatment of CS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2305–2312, 2018.

     

Aphidicolin-sensitive specific common fragile sites: A biomarker of exposure to pesticides

In this work, we analyzed the aphidicolin-sensitive common fragile sites in seven females and four males occupationally exposed to pesticides and in ten controls. The same males had been monitored one year earlier in a previous study by the same authors. Results showed enhanced expression in exposed subjects at eight bands, namely, 6q25, 7p22, 7q22, 7q32, 13q14, 14q24, 16q22, and 16q23. Most of these bands were fragile sites andbreakpoints involved in chromosome rearrangements found in hematopoietic tumors. Moreover, six of these bands were already detected, with enhanced expression, in the first monitoring carried out on male subjects. These results indicated that fragile sites analysis is a reproducible cell response to human exposure to pesticides. Environ. Mol. Mutagen. 29:250-255, 1997 © 1997 Wiley-Liss, Inc.     

Reduction of blood coagulation and monocyte-platelet interaction following the use of a minimal extracorporeal circulation system (Synergy) in coronary artery bypass grafting (CABG)

Cardiovascular surgery with cardiopulmonary bypass (CPB) induces activation of blood coagulation and systemic inflammation involved in post-operative complications. Our study evaluated the impact of the minimal extracorporeal circulation (mini-CPB) system (Synergy, Sorin Group) on these functional aspects. Twenty patients were randomly assigned to standard CPB (n = 10) or to Synergy (n = 10). Platelet expression of PAC-1, and monocyte/granulocyte-platelet conjugates were evaluated by flow cytometry. A leukocyte-platelet adhesion index was calculated after cell number normalization. ELISAs were performed to measure IL-6 and TNF-alpha, thrombin-antithrombin III complexes (TAT), prothrombin fragments (F1+2), beta-thromboglobulin (beta-TG) and sP-selectin (sCD62P). Blood samples were drawn at the time of anesthesia (T1), at the end of CPB (T2), and at 4 (T3) and 24 hours (T4) after weaning from CPB. All patients were similar for clinical characteristics. When compared to standard CPB, the Synergy showed lower levels of the monocyte-platelet adhesion index at T2 (0.023 +/- 0.005 vs 0.063 +/- 0.013, P = 0.0092) and T4 (0.031 +/- 0.003 vs 0.055 +/- 0.005, P = 0.0017), TAT complexes at T2 (27.175 +/- 5.967 vs 86.592 +/- 5.415, P = 0.0005) and T3 (26.977 +/- 2.468 vs 45.146 +/- 4.365, P = 0.0041), F1+2 fragments at T2 (2.222 +/- 0.226 vs 4.249 +/- 0.292, P = 0.0009), and sP-selectin at T3 (115.17 +/- 19.623 vs 169.554 +/- 19.709, P = 0.0703) and T4 (108.542 +/- 6.429 vs 140.799 +/- 14.771, P = 0.0833). In summary, the Synergy exhibited a lower post-operative activation of blood coagulation, together with a reduced interaction between circulating monocytes and platelets.