Cytotoxic Effect of Progesterone, Tamoxifen and Their Combination in Experimental Cell Models of Human Adrenocortical Cancer.

Progesterone (Pg) and estrogen (E) receptors (PgRs and ERs) are expressed in normal and neoplastic adrenal cortex, but their role is not fully understood. In literature, Pg demonstrated cytotoxic activity on AdrenoCortical Carcinoma (ACC) cells, while tamoxifen is cytotoxic in NCI-H295R cells. Here, we demonstrated that in ACC cell models, ERs were expressed in NCI-H295R cells with a prevalence of ER-ß over the ER-α.Metastasis-derived MUC-1 and ACC115m cells displayed a very weak ER-α/ß signal, while PgR cells were expressed, although at low level. Accordingly, these latter were resistant to the SERM tamoxifen and scarcely sensitive to Pg, as we observed a lower potency compared to NCI-H295R cells in cytotoxicity (IC50: MUC-1 cells: 67.58 µM (95%CI: 63.22-73.04), ACC115m cells: 51.76 µM (95%CI: 46.45-57.67) and cell proliferation rate. Exposure of NCI-H295R cells to tamoxifen induced cytotoxicity (IC50: 5.43 µM (95%CI: 5.18-5.69 µM) mainly involving ER-ß, as their nuclear localization increased after tamoxifen: Δ A.U. treated vs untreated: 12 h: +27.04% (p < 0.01); 24 h: +36.46% (p < 0.0001). This effect involved the SF-1 protein reduction: Pg: -36.34 ± 9.26%; tamoxifen: -46.25 ± 15.68% (p < 0.01). Finally, in a cohort of 36 ACC samples, immunohistochemistry showed undetectable/low level of ERs, while PgR demonstrated a higher expression. In conclusion, ACC experimental cell models expressed PgR and low levels of ER in line with data obtained in patient tissues, thus limiting the possibility of a clinical approach targeting ER. Interestingly, Pg exerted cytotoxicity also in metastatic ACC cells, although with low potency.

AC Corrosion of Carbon Steel under Cathodic Protection Condition: Assessment, Criteria and Mechanism. A Review.

Cathodic protection (CP), in combination with an insulating coating, is a preventative system to control corrosion of buried carbon steel pipes. The corrosion protection of coating defects is achieved by means of a cathodic polarization below the protection potential, namely -0.85 V vs. CSE (CSE, copper-copper sulfate reference electrode) for carbon steel in aerated soil. The presence of alternating current (AC) interference, induced by high-voltage power lines (HVPL) or AC-electrified railways, may represent a corrosion threat for coated carbon steel structures, although the potential protection criterion is matched. Nowadays, the protection criteria in the presence of AC, as well as AC corrosion mechanisms in CP condition, are still controversial and discussed. This paper deals with a narrative literature review, which includes selected journal articles, conference proceedings and grey literature, on the assessment, acceptable criteria and corrosion mechanism of carbon steel structures in CP condition with AC interference. The study shows that the assessment of AC corrosion likelihood should be based on the measurement of AC and DC (direct current) related parameters, namely AC voltage, AC and DC densities and potential measurements. Threshold values of the mentioned parameters are discussed. Overprotection (EIR-free < -1.2 V vs. CSE) is the most dangerous condition in the presence of AC: the combination of strong alkalization close to the coating defect due to the high CP current density and the action of AC interference provokes localized corrosion of carbon steel.

The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

OBJECTIVE: To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). RESEARCH DESIGN AND METHODS: Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. RESULTS: We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. CONCLUSIONS: The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

Impaired diffusing capacity for carbon monoxide in children with type 1 diabetes: is this the first sign of long-term complications?

We assessed the presence of lung dysfunction in children with type 1 diabetes, evaluated as reduced diffusing capacity of the lung for carbon monoxide (DLCO), and its components: membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc). A total of 42 children, aged 15.6 ± 3.8 years, with type 1 diabetes for 8.3 ± 5.5 years, and 30 healthy age and sex-matched peers were recruited for the study. Lung volumes and spirometric dynamic parameters were assessed by plethysmography. Single-breath DLCO was measured according to international recommendation. DM and Vc volume were calculated. Lung volumes were significantly reduced in young patients with type 1 diabetes when compared to controls. Moreover, DLCO was reduced in patients compared to controls (78% ± 16% vs. 120% ± 1%, P = 0.0001). However, when differentiating DM and Vc compartments, we observed a significant impairment only about Vc (34 ± 20 ml vs. 88 ± 18 ml; P = 0.0001), while no difference was observed about DM compartment (23 ± 4 vs. 26 ± 3 ml/min/mmHg, P = 0.798). Whether this might be seen as the "first" sign of microangiopathic involvement in patients with type 1 diabetes has to be confirmed on larger groups but is still fascinating. Meanwhile, we suggest to screen DLCO in all patients with type 1 diabetes.

In vivo confocal microscopy of meibomian glands in contact lens wearers.

PURPOSE: To evaluate by in vivo laser scanning confocal microscopy (LSCM) the morphologic changes in the meibomian glands (MGs) and the status of periglandular inflammation in contact lens wearers (CLWs) and to investigate the correlations between clinical and confocal findings. METHODS: Twenty CLWs and 20 age- and sex-matched control subjects were consecutively enrolled. Each participant completed an Ocular Surface Disease Index questionnaire and underwent a full eye examination, including tear film break-up time, fluorescein and lissamine green staining, and Schirmer test. LSCM of the MGs were performed to determine the cell density of the mucocutaneous junction epithelium, acinar unit density and diameter, glandular orifice diameters, meibum secretion reflectivity, and inhomogeneous appearance of the glandular interstice and acinar wall. RESULTS: All clinical parameters showed statistically significant differences between groups (P < 0.01, Mann-Whitney U test) except the Schirmer test. Confocal data (Mann-Whitney U test) showed significantly decreased basal epithelial cell density (P < 0.01), lower acinar unit diameters (P < 0.05), higher glandular orifice diameters (P < 0.05), greater secretion reflectivity (P < 0.01), and greater inhomogeneity of the periglandular interstices (P < 0.05) in CLWs compared with controls. The duration of contact lens wear was correlated with the acinar unit diameters (P < 0.05, Spearman). CONCLUSIONS: Morphologic changes in the MGs shown by LSCM were interpreted as signs of MG dropout, duct obstruction, and glandular inflammation. A comprehensive LSCM evaluation of the ocular surface in CLWs could better clarify the role of MG dropout and eyelid margin inflammation on the pathogenesis of CL-induced dry eye.

In vivo confocal microscopy of conjunctival roundish bright objects: young, older, and Sjögren subjects.

PURPOSE: To investigate by laser scanning confocal microscopy (LSCM) the density of presumed epithelial, presumed goblet, and presumed inflammatory cells in the tarsal conjunctiva of healthy young and older subjects and in patients with Sjögren's syndrome (SS). To evaluate the interobserver variability and to compare the measured densities with known age-related and SS-related changes. METHODS: The authors studied 24 eyes of 12 healthy young subjects (8 women, 4 men; average age, 26 years; age range, 21-30 years), 24 eyes of 12 healthy older subjects (10 women, 2 men; average age, 68 years; age range, 67-74 years), and 24 eyes of 12 patients with SS (10 women, 2 men; average age, 62 years; age range, 49-72 years). The inferior tarsal conjunctiva of each patient was examined in vivo by LSCM. The density of the three cell types was independently analyzed by two masked investigators. RESULTS: The density of presumed epithelial, presumed goblet, and presumed inflammatory cells was significantly higher in SS patients than in both control groups (P < 0.001; Mann-Whitney U test). The densities for presumed goblet cells calculated by the two investigators were significantly different from one another (P < 0.01, Mann-Whitney U test) and were not correlated. CONCLUSIONS: LSCM is a promising tool that should profoundly change the study of the ocular surface, but it requires accurate standardization before it is used in clinical practice.

End of life in children with cancer: experience at the pediatric oncology department of the istituto nazionale tumori in Milan.

BACKGROUND: Coping with end-stage pediatric cancer patients and the related bereavement is a challenge for all the caregivers involved. PROCEDURE: Forty-seven cancer patients who died in 2006 were assessed as concerns the main place of care in the end stage of their disease, their symptoms, the palliative treatments received, and the site of death. RESULTS: The end stage was managed at the Istituto Nazionale Tumori Pediatric Oncology Department in 61% of cases, at home in 26%, and in hospices or other hospital facilities in 11%. Pain was the most common symptom, followed by asthenia, anorexia, dyspnea, and nausea/vomiting. About half the patients died at home, 8.5% at our institute, 43% at other hospitals, and 8.5% in hospices. CONCLUSIONS: The care of pediatric cancer patients during the end stage of their disease is the responsibility of the caregivers who have followed them up since their diagnosis. However, it would be useful to establish an exchange of information and expertise between pediatric oncologists and the other facilities involved (hospices, other hospitals) or people assisting patients at home (family, family pediatrician/general practitioner GP).

Congenital facial infiltrative lipoma in a calf.

The clinical and pathologic findings related to an infiltrative facial lipoma in a 5-month-old female Holstein Friesian calf are reported. The tumor was congenital, increased in size with time, and deformed the left side of the face and cranial bones. The clinical condition of the calf was good; the only detectable abnormalities were poor weight gain and decreased motility of the left upper lip. Clinical and radiologic data indicated the mass was not removable. Muscle and lymph node invasion by tumor tissue were detected histologically. Infiltrative lipoma is a rare variety of lipoma that has been reported in dogs, cats, horses, and humans. Although its cytologic characteristics are those of a benign tumor, in this patient the invasiveness of the neoplasm was associated with poor prognosis.