Forecasting of the first hour aftershocks by means of the perceived magnitude.

The majority of strong earthquakes takes place a few hours after a mainshock, promoting the interest for a real time post-seismic forecasting, which is, however, very inefficient because of the incompleteness of available catalogs. Here we present a novel method that uses, as only information, the ground velocity recorded during the first 30 min after the mainshock and does not require that signals are transferred and elaborated by operational units. The method considers the logarithm of the mainshock ground velocity, its peak value defined as the perceived magnitude and the subsequent temporal decay. We conduct a forecast test on the nine M  ≥ 6 mainshocks that have occurred since 2013 in the Aegean area. We are able to forecast the number of aftershocks recorded during the first 3 days after each mainshock with an accuracy smaller than 18% in all cases but one with an accuracy of 36%.

Cystic pancreatic tumors: should we resect all of them?

OBJECTIVE: Pancreatic cystic tumors are relatively rare tumors and only 1% of them are malignant. They are often asymptomatic and detected as incidental findings through diagnostic imaging. Currently there are no universal guide lines for the correct clinical approach to pancreatic cystic lesions. Cross-sectional imaging demonstrates some typical morphological features that determine the pre-operative diagnosis of the pancreatic cystic lesions (serous or mucinous cystadenoma, intraductal papillary mucinous neoplasms). In addition, endoscopic ultrasonography permits the collection and analysis of the fluid content. The aim of this paper is to describe our case load in the management of pancreatic cystic neoplasms and propose some criteria for choosing between surgical or conservative approaches. PATIENTS AND METHODS: 12 patients with pancreatic cystic neoplasms were retrospectively evaluated. They were studied using cross-sectional imaging modalities (computed tomography and magnetic resonance); endoscopic ultrasonography was performed in 7 patients. RESULTS: In each patient a careful evaluation of several factors (age, comorbidity, imaging features, symptoms, life expectancy) conditioned our clinical decision. Among our 12 patients, surgical resection was performed in 7 cases. DISCUSSION: The treatment of pancreatic cystic lesions is still a dilemma because even in the presence of malignant potential, pancreatic surgery remains very complicated and demolitive. Many factors need to be considered in the management of cystic pancreatic tumors. The most important include histological type, location, size, age and clinical condition of the patient. CONCLUSIONS: A correct multidisciplinary pre-operative diagnosis is mandatory. Surgery should only be performed in selected cases.

A histochemical approach to the evaluation of the in vivo cytotoxicity of the nitrobutadienes (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate in mice liver and kidney.

Two new molecules (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) and (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) in previous studies showed interesting antiproliferative activity in vitro. Furthermore, toxicological tests and histological analysis provided promising results, in particular for 1-Naph-NMCB that displayed lower toxic activity both in terms of lethal effect and tissue damage of the main organs. Finally, studies of the antitumour activity in vivo confirmed the efficacy of both molecules, though with some differences in tumour selectivity and levels of activity. In this investigation the activities of some specific enzymes, acid phosphatase (AcPase), alkaline phosphatase (AlkPase), catalase (Cat), succinic dehydrogenase (SDH), glucose-6-phosphatase (G6Pase) and K+ p-nitrophenyl phosphatase (K+ pNPPase) were studied in the liver and kidney as histopathological biomarkers, to assess the effects of the two compounds in organs generally involved in the metabolism and excretion of different drugs. As oxidative stress may also develop as a consequence of the toxic effect of chemicals, reactive oxygen species (ROS) production was evaluated by a histochemical method. The results indicated that some enzyme activities and ROS expression changed in a dose-related manner. Nevertheless, neither in the liver nor in the kidney were dramatic toxic effects evident. By contrast, the variations of some enzyme activities (AlkPase, AcPase, Cat, K+ pNPPase) were interpreted as possible defensive mechanisms for tolerating high dosage of the compounds.

Human urotensin II induces tissue factor and cellular adhesion molecules expression in human coronary endothelial cells: an emerging role for urotensin II in cardiovascular disease.

BACKGROUND: Human urotensin II is an 11-aminoacid peptide with a controversial role in the human cardiovascular system. Indeed, urotensin effects on vascular reactivity and in heart failure are well documented, while its potential role in the pathophysiology of athero-thrombosis is still unknown. This study investigates the effects of urotensin on tissue factor (TF) and VCAM-1/ICAM-1 expression in human coronary endothelial cells (HCAECs). METHODS AND RESULTS: Urotensin induced TF-mRNA transcription as demonstrated by real time PCR and expression of TF that was functionally active as demonstrated by procoagulant activity assay. In addition, urotensin induced expression of VCAM-1 and ICAM-1 as demonstrated by FACS analysis. VCAM-1 and ICAM-1 were functionally active because they increased leukocyte adhesivity to HCAECs. Urotensin-induced expression of TF and of VCAM-1/ICAM-1 was mediated through the Rho A-activation of the transcription factor, NF-kappaB, as demonstrated by EMSA. Indeed, lovastatin, an HMG-CoA reductase inhibitor, by modulating the Rho activation, and NF-kappaB inhibitors, suppressed the urotensin effects on TF and CAMs. CONCLUSIONS: Data of the present study, although in vitro, describe the close relationship existing between urotensin II and athero-thrombosis, providing for the first time support for the view that this peptide might have not only vasoactive functions but it might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Although future studies are required to clarify whether these mechanisms are also important in the clinical setting, this report supports an emerging new role for urotensin II in the pathogenesis and progression of cardiovascular disease.

Modulation of costimulatory molecules CD80/CD86 on B cells and macrophages by stress proteins GroEL, GroES and DnaK.

The aim of this study was to evaluate the effect of the Heat Shock Proteins GroES, GroEL and DnaK on the expression of the costimulatory molecules CD80/CD86 in B cells and macrophages. The interactions among these molecules are able to highly influence the immune response through the regulation of cytokine liberation which, on their own, are able to regulate the immunological response by a feedback mechanism. Our results showed that, on B cells, GroES and GroEL stimulated the expression of CD86 but did not induce the increase of the CD80 expression. CD86 peak expression showed a peak after 24-48 h of culture and decreased 60h after the stimulation. GroES and GroEL also stimulated the expression of CD80 and CD86 on macrophages. The same HSPs did not modify the expression of CD80 and CD86 on cells having characteristics of activated macrophages, the A-THP-1 cell line. DnaK did not induce any increase in the expression of CD80 and CD86 on lymphocytes or macrophages.

Lipoteichoic acid and muramic acid modulate the expression of CD80/CD86 on THP-1 cells and CD28/CD152 on Jurkat cells.

The aim of this study is to evaluate the effect of lipoteichoic acid (LTA) and muramic acid (MA) on costimulatory molecules CD80/CD86 on THP-1 cells and CD28/CD152 on Jurkat cells. The interactions between these molecules strongly influence the immune response through the regulation of cytokine release which, on its own, is able to regulate the immunological response by a feedback mechanism. Our results show that LTA and MA regulate expression of CD86 on macrophages while the expression of CD80 remains unmodified. LTA and MA increase the expression of CD86 on THP-1 cells, a macrophage cell line. MA increased Jurkat T cells CD152 expression.

Coinfection with BHV-1 modulates cell adhesion and invasion by P. multocida and Mannheimia (Pasteurella) haemolytica.

Viruses are thought to facilitate bacterial infections of the respiratory tract. The present study shows the effect of BHV-1 on Pasteurella multocida and Mannheimia haemolytica adherence and invasion of MDBK cells. The virus-infected MDBK cells become more susceptible to the adherence of both species of Pasteurella. The observed adherence increase depends on the length of virus pre-incubation time and on virus concentration. When MDBK cells are not infected with virus, they are only invaded by P. multocida, while M. haemolytica is not able to penetrate. The viral infection favours also the invasion by M. haemolytica.

Thymic carcinoma, systemic lupus erythematosus, and hypertrophic pulmonary osteoarthropathy in an 11-year-old boy: a novel association.

Thymic carcinoma is exceptionally rare in children and it has never previously been associated with autoimmune disorders. The authors report the case of an 11-year-old boy with thymic carcinoma, hypertrophic pulmonary osteoarthropathy, and an autoimmune disease that resembled systemic lupus erythematosus. To their knowledge, this is the first case of such complex clinical findings. The tumor was of high grade histologically and the boy died after 1 year, in spite of chemotherapy and radiotherapy. A review is presented of the available medical literature on thymic malignancy in childhood.

Spontaneous rupture of a giant hemangioma of the liver.

Hemangiomas are frequent benign tumors of the liver. Symptoms (abdominal pain and fullness) are mostly seen in giant lesions. Rupture is the most severe complication, can occur spontaneously, with intraperitoneal bleeding, in 1-4% of hemangiomas and has been described in about 30 cases in the international literature with a high mortality (about 60%). This complication is the principal indication for surgery. Although spiral CAT scan and MR are actually the most efficacious imaging methods for study of liver hemangiomas, after Echography, emergency techniques that allows a simultaneous therapeutic approach--as is angiography--are preferable. Trans-arterial embolization (TAE) is in fact useful to stop bleeding and then to perform a safer surgery. A successful embolization can delay the surgical resection of the hemangioma for the time necessary to recover from the hemodynamic distress. Aside from the success of angiographic approach, surgery remains mandatory, effective in stopping the bleeding and in preventing re-bleeding or other complications of TAE such as abscess, fever, etc.. Intraoperative echography currently is the best method to identify vasculo- biliary anatomy and to perform a correct resection. The absence of risk factors for spontaneous rupture of liver hemangiomas, makes this event unpredictable. The best treatment for non-ruptured hemangiomas is still controversial but surgery is usually limited to symptomatic tumors larger than 10 cm.

Thrombectomy of the inferior vena cava from recurrent low-grade endometrial stromal sarcoma: case report and review of the literature.

We report a rare case in which a patient successfully underwent surgical removal from the inferior vena cava of a neoplastic thrombus induced by a recurrent low-grade endometrial stromal sarcoma. The patient was admitted with severe acute renal failure and a large edema on the right lower extremity. One year previously she had undergone hysterectomy and adnexectomy due to an endometrial stromal sarcoma with involvement of the tuba. Because of complete thrombosis of the right internal and common iliac veins and the inferior vena cava, she underwent thrombectomy of the inferior vena cava. The postoperative course was complicated by hydruric renal failure induced by a acute tubular necrosis. At 6-month follow-up, the patient was asymptomatic with normal renal function. The ileocaval axis was patent on magnetic resonance imaging. Only 5 cases of intracaval extension of endometrial stromal sarcoma have been reported. Surgical treatment is viable due to excellent prognosis of the low-grade endometrial stromal sarcoma (80-100% 5-year survival) and likely fatal heart failure in untreated cases.

[Renal artery stenosis in pediatric age. Clinical and instrumental observations of two patients]. / Stenosi dell'arteria renale in età pediatrica. Dati clinici e strumentali su due pazienti.

Two male patients, four and six years old, affected with monolateral renal artery stenosis are reported. One of them presented recurrent facial nerve palsy, while the other was affected by renal calculosis. The diagnostic suspicion was confirmed by arteriography. They were submitted respectively to aortorenal bypass and nephrectomy, with blood pressure normalization.

TNF-alpha expression and herpes simplex infection in human monocytes treated with growth hormone, prolactin and insulin.

We evaluated the in vitro effect of growth hormone (GH), prolactin (PRL) and insulin treatment of human monocytes on Herpes simplex virus type 1 (HSV-1) infection. GH and PRL increased cell susceptibility to infection which was related to a slight TNF-alpha expression and release. Insulin had no significant effect. Cells activated with lipopolysaccharide (LPS) and then treated with PRL showed a lower susceptibility to HSV infection related to a significant increase in TNF-alpha expression and release. On the contrary, GH and insulin increased the susceptibility to infection of activated cells but did not modify TNF-alpha expression with respect to cells treated only with hormones.

Aggressive angiomyxoma of the vulva: expression of estroprogestinic receptors and follow-up.

PURPOSE OF INVESTIGATION: To analyze aggressive angiomyxoma hormone-dependency. METHOD: Estroprogestinic receptor expression was studied by immunohistochemistry in 5 patients with aggressive angiomyxoma of the vulva. RESULTS: The immunohistochemical results confirm the positivity of angiomyxoma for estrogen and progesterone receptors. CONCLUSIONS: We hypothesized that the concomitant factor favoring neoplastic growth is a different genetic substrate specific in the female sex. Analysis of the data regarding the distribution of angiomyxomas in different age groups has strengthened this hypothesis suggesting that this tumor is correlated with complete maturity, in all probability hormonal. However it cannot be excluded that the tumor begins to develop at an early age, but since it has a slow growth rate, the phenomenon is delayed and is related to hormonal stimulation.

[Acute pre-hepatic portal thrombosis: diagnosis and therapy]. / La trombosi portale acuta pre-epatica. Diagnosi e terapia.

Portal vein thrombosis is a rare pathology. The etiopathogenetic causes that most frequently lead to this pathology are myeloproliferative syndromes. The authors present a case of acute pre-hepatic portal vein thrombosis and discuss its etiopathogenesis, diagnosis and therapy.

Serum levels of eosinophil cationic protein in allergic diseases and natural allergen exposure.

BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic performed mediator stored in eosinophil granules and released under various in vitro and in vivo conditions. OBJECTIVE: This study was carried out to evaluate the clinical value of ECP as a marker of allergic inflammation. METHODS: ECP was measured by a competitive radioimmunoassay in serum samples from 265 patients and 45 matched control subjects and related to the type of allergic disease (asthma, rhinitis, conjunctivitis) and to the type of allergic sensitization. RESULTS: All the patient groups studied showed significantly higher levels of serum ECP than control groups (p < 0.001). The type of sensitization was shown to be the only variable influencing ECP serum levels. In fact, subjects sensitized to perennial allergens had significantly higher ECP values than subjects with seasonal allergy (p < 0.001), whereas in patients with seasonal allergy ECP levels were significantly increased only during the pollen season. Differences in ECP values between various allergic diseases or age groups were only due to a nonhomogeneous distribution of the type of sensitization or to time of sera collection. CONCLUSIONS: Results obtained indicate that persistent natural exposure to a sensitizing allergen is responsible for a measurable increase in serum ECP levels in patients with allergy.

Presentation of peptides by cultured monocytes or activated T cells allows specific priming of human cytotoxic T lymphocytes in vitro.

The conditions favouring effective specific cytotoxic T lymphocyte (CTL) priming have been exploited to set up a simple and reproducible method to induce a primary CTL response in vitro. We report that cultured monocytes, as well as activated T cells, pulsed with exogenous HLA-A2 binding immunogenic peptides, can induce primary peptide-specific CTL responses in vitro in a Th-independent manner. Primary viral peptide-induced CTL were HLA-A2 restricted, and recognized both peptide-pulsed target cells and targets infected with recombinant vaccinia virus expressing viral endogenous antigens. In addition, both cultured monocytes and activated T cells primed peptide-specific CD8+ T cells depleted from the CD45RO+ memory cell fraction. The efficiency of CTL priming by monocytes was dependent upon the strong up-regulation of class I, adhesion and co-stimulatory molecules occurring spontaneously upon in vitro culture. The inability of unseparated peripheral blood mononuclear cells to mount a peptide-specific CTL response could be reverted by direct co-stimulation of responding CD8+ T cells by soluble B7.1 or a stimulatory anti-CD28 antibody, that allowed a specific response to take place. Although co-stimulation via the B7-CD28 interaction appeared sufficient to trigger CTL responses, it was not essential for CTL priming, since neither anti-B7.1 mAb nor soluble CTLA-4 inhibited induction of primary CTL response. This new method for induction of specific CD8+ T cell response in vitro may be exploited in adoptive immunotherapy in cancer or in HIV-infected patients.

Resistance to Fas-mediated apoptosis in human hepatoma cells.

CTLs- and lymphokine-induced apoptosis of infected hepatocytes during the course of chronic viral hepatitis is thought to be important for both disease termination and prevention of hepatocellular transformation. We therefore studied apoptosis induced by Fas (APO-1 or CD95)-a widely expressed cell surface receptor whose ligand is involved in lymphocyte cytotoxicity-in a set of human hepatoma cell lines. As normal hepatocytes, all of the human hepatoma cell lines tested do express detectable amounts of Fas on their surface. Nevertheless, only PLC/PRF/5 cells undergo apoptosis following treatment with anti-Fas. Systematic cloning and sequence analysis of the Fas cDNA did not show mutations in the Fas gene in any of the cells lines tested. However, due to alternative splicing, 5 to 10% of the Fas cDNAs are deleted of 63 internal nucleotides corresponding to the transmembrane domain, thus encoding for a soluble and secreted form of Fas (Fas delta TM), potentially able to neutralize anti-Fas or Fas-Ligand. Although we could not demonstrate a direct correlation between resistance of different hepatoma cell lines to Fas mediated death and endogenous expression of this transcript, we show that PLC/PRF 5 stable transfectants overexpressing Fas delta TM are less sensitive to anti-Fas than control cells. In three different cell lines, resistance to anti-Fas was overcome by treatment with the protein synthesis inhibitor cycloheximide. Although this could suggest the existence of short-lived repressors of the Fas-activated apoptotic signalling pathway(s), we show that translational inhibition is not required for the synergistic effect of cycloheximide to take place, and that resistant hepatoma cells can be sensitized to anti-Fas by subinhibitory concentrations of this protein synthesis inhibitor. Since cycloheximide is able to activate intracellular signalling independently on its effects on protein synthesis, we suggest that it might provide a costimulatory signal that cooperates with Fas in the induction of cell death and that, at least in the cells we tested, resistance to Fas is not an active process involving gene transcription and translation but only the consequence of an inadequate apoptotic stimulation.