STAT3, a hub protein of cellular signaling pathways, is triggered by β-hexaclorocyclohexane

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 µM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect

QCALT: a tile calorimeter for KLOE-2 upgrade

The upgrade of the DA$\Phi$NE machine layout requires a modification of the size and position of the inner focusing quadrupoles of KLOE-2 thus asking for the realization of two new calorimeters covering the quadrupoles area. To improve the reconstruction of $K_L\to 2\pi^0$ events with photons hitting the quadrupoles a calorimeter with high efficiency to low energy photons (20-300 MeV), time resolution of less than 1 ns and space resolution of few cm, is needed. To match these requirements, we are designing a tile calorimeter, QCALT, where each single tile is readout by mean of SiPM for a total granularity of 2400 channels. We show first tests of the different calorimeter components

Direct analysis of sterols from dried plasma/blood spots by an atmospheric pressure thermal desorption chemical ionization mass spectrometry (APTDCI-MS) method for a rapid screening of Smith-Lemli-Opitz syndrome.

Here is proposed a rapid and sensitive method involving atmospheric pressure thermal desorption chemical ionization mass spectrometry (APTDCI-MS) for specific laboratory screening of the Smith– Lemli–Opitz syndrome (SLOS), an inherited defect of cholesterol biosynthesis. Biochemical findings in the blood of SLOS patients are low cholesterol (Chol), high 7- and 8-dehydrocholesterol (DHCs) levels and high DHCs/Chol ratios. The APTDCI proposed method is able to ionize sterols for qualitative and quantitative analysis directly from dried plasma/blood spots. Critical APTDCI parameters – desolvation gas flow and temperature – were optimized analyzing Chol, 7-DHC and cholesteryl stearate standards spotted onto a glass slide acquiring the full scan spectra in positive ion mode. Chol levels in dried plasma spots of unaffected controls (n ¼ 23) obtained by the proposed method were compared with those of the enzymatic method (y ¼ 0.9166x + 0.3811; r ¼ 0.8831) while Chol and DHCs of SLOS patients (n ¼ 9) were compared with the gas chromatography flame ionization detection (GC-FID) method (y ¼ 0.8214x + 0.7388; r ¼ 0.8288). The APTDCI-MS method is also able to differentiate normal from SLOS samples directly analyzing whole blood and washed red cells spotted on paper. In conclusion, the intrinsic analytical high-throughput of APTDCI-MS method for sterol analysis could be useful to screen SLO syndrome

Giant Prolactinoma Embedded by Pseudoaneurysm of the Cavernous Carotid Artery Treated with a Tailored Therapeutic Scheme

The coexistence of intracranial aneurysm (IA) is generally thought to be highest in patients with pituitary adenomas (PAs). Different mechanisms may play a role in aneurysm formation, but whether the PA contributes to aneurysm formation is still unclear. In the literature, there are numerous reported cases of this association; however, the analyses of the characteristics of PAs, aneurysms, and treatment management are rare and limited to a restricted number of case reports. We report a rare case of an embedded aneurysm in a macroprolactinoma treated with therapeutic management tailored to the clinical, neurological, and radiological characteristics of the patient. To select the best treatment, we reviewed the literature and reported the only cases in which the radiological characteristics of aneurysms, PAs, therapeutic management, and patient outcome are described. We aimed to understand what are the variables that determine the best therapeutic management with the best possible outcome. The presence of a large pseudoaneurysm of the internal carotid artery completely embedded in a giant macroprolactinoma is rare and needs a tailored treatment strategy. The importance of the preoperative knowledge of asymptomatic IA coexisting with PA can avoid accidental rupture of the aneurysm during surgical resection and may lead to planning the best treatment. A high degree of suspicion for an associated aneurysm is needed, and if magnetic resonance imaging shows some atypical features, digital subtraction angiography must be performed prior to contemplating any intervention to avoid iatrogenic aneurysmal rupture. Our multimodal approach with the first-line therapy of low-dose cabergoline to obtain prolactin normalization with minimum risks of aneurysms rupture and subsequent endovascular treatment with flow diverter has not been described elsewhere to our knowledge. In the cases, we suggest adopting a tailored low-dose cabergoline therapy scheme to avoid rupture during cytoreduction and initiate a close neuroradiological follow-up program

Improvement of Tuberculosis Laboratory Capacity on Pemba Island, Zanzibar: A Health Cooperation Project.

Low-income countries with high Tuberculosis burden have few reference laboratories able to perform TB culture. In 2006, the Zanzibar National TB Control Programme planned to decentralize TB diagnostics. The Italian Cooperation Agency with the scientific support of the "L. Spallanzani" National Institute for Infectious Diseases sustained the project through the implementation of a TB reference laboratory in a low-income country with a high prevalence of TB. The implementation steps were: 1) TB laboratory design according to the WHO standards; 2) laboratory equipment and reagent supplies for microscopy, cultures, and identification; 3) on-the-job training of the local staff; 4) web- and telemedicine-based supervision. From April 2007 to December 2010, 921 sputum samples were received from 40 peripheral laboratories: 120 TB cases were diagnosed. Of all the smear-positive cases, 74.2% were culture-positive. During the year 2010, the smear positive to culture positive rate increased up to 100%. In March 20, 2010 the Ministry of Health and Social Welfare of Zanzibar officially recognized the Public Health Laboratory- Ivo de Carneri as the National TB Reference Laboratory for the Zanzibar Archipelago. An advanced TB laboratory can represent a low cost solution to strengthen the TB diagnosis, to provide capacity building and mid-term sustainability

Genetic modification of a carcinoma with IL-4 gene increase the influx of dendridic cells relative to other cytokines

Tumor cells genetically modified with certain cytokine genes gain immunogenic properties that allow the development of systemic anti-tumor immunity. Whether different cytokines may influence infiltration of transduced tumors by dendritic cells (DC) has not been investigated. Therefore, we analyzed the C26 murine colon carcinoma genetically modified to release interleukin (IL)-2, IL-4, IL-12, granulocyte colony-stimulating-factor (CSF) or granulocyte-macrophage (GM)-CSF for immunostaining with the monoclonal antibody NDLC145 recognizing the DEC205 determinant which, on tumor sections, is virtually restricted to DC. Infiltrating leukocytes were also characterized for expression of co-stimulatory molecules like CD54, CD86 and major histocompatibility complex class II. The intratumoral DC content was dependent on the type of transduced cytokines with C26/IL-4 being the most abundant in DEC205+ cells. The effect of IL-4 in recruiting DC did not depend on the type of tumor since it was confirmed in the TSA mammary carcinoma. In comparison with C26/GM-CSF, C26/IL-4 had more B7.2+ cells but less Ia+ cells. Furthermore, the hypertrophic skin overlaying tumors producing GM-CSF showed numerous Langerhans cells stained by NDLC145 and the draining lymph nodes showed abundance and paucity of DC in C26/GM-CSF and C26/IL-4, respectively. When injected into the ear pinna, C26/GM-CSF stimulated, whereas C26/IL-4 inhibited DC-mediated priming of delayed-type hypersensitivity reaction by 2,4-dinitro-1-fluorobenzene. These findings prove that transduced cytokines differently influence DC recruitment at the tumor site and DC function in nearby tissues. Along with the other leukocytes and their secondary produced cytokines, DC create an environment in which T cells can be differently modulated. Such a phenomenon may have implications on genetic modification of tumor cells to be used as cancer vaccin