Morpho-functional analysis of the early changes induced in retinal ganglion cells by the onset of diabetic retinopathy: The effects of a neuroprotective strategy

Retinal ganglion cells (RGCs) are highly susceptible to diabetes-induced metabolic stress. This study describes the early responses of RGCs to hyperglycemia and examines the effects of the neuroprotective somatostatin analog octreotide (OCT)

Parvovirus B19 Infection and Severe Anemia in Renal Transplant Recipients

Kidney transplant (KT) recipients can develop symptomatic Parvovirus (PV) B19 infections, frequently associated with persistent anemia. The aim of this study was to evaluate the prevalence and clinical significance of PV B19 infection in anemic and non-anemic KT patients. Overall, out of 64 patients monitored for the presence of PV B19 by real-time PCR, 2 (3.12%) had an active PV B19 infection, in absence of other viral coinfections. The 2 cases occurred in nonanemic kidney transplant patients group (2/50, 4%), while none of the anemic transplant patients (0/14) was found to suffer from this infection. Moreover, patients affected by active PV B19 infection showed viral loads not exceeding 1 × 105 genome copies/reaction. In conclusion, in this study, PV B19 infection was not common in renal transplant population and wasn't associated with severe anemia

Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy

Neuronal injury plays a major role in diabetic retinopathy (DR). Our hypothesis was that the balance between neuronal death and survival may depend on a similar equilibrium between apoptosis and autophagy and that a neuroprotectant may act by influencing this equilibrium. Ex vivo mouse retinal explants were treated with high glucose (HG) for 10days and the somatostatin analog octreotide (OCT) was used as a neuroprotectant. Chloroquine (CQ) was used as an autophagy inhibitor. Apoptotic and autophagic markers were evaluated using western blot and immunohistochemistry. HG-treated explants displayed a significant increase of apoptosis paralleled by a significant decrease of the autophagic flux, which was likely to be due to increased activity of the autophagy regulator mTOR (mammalian target of rapamycin). Treatment with OCT rescued HG-treated retinal explants from apoptosis and determined an increase of autophagic activity with concomitant mTOR inhibition. Blocking the autophagic flux with CQ completely abolished the anti-apoptotic effect of OCT. Immunohistochemical observations showed that OCT-induced autophagy is localized to populations of bipolar and amacrine cells and to ganglion cells. These observations revealed the antithetic role of apoptosis and autophagy, highlighting their equilibrium from which neuronal survival is likely to depend. These data suggest the crucial role covered by autophagy, which could be considered as a molecular target for DR neuroprotective treatment strategies

Composition of Metallic Elements and Size Distribution of Fine and Ultrafine Particles in a Steelmaking Factory

Background: The characteristics of aerosol, in particular particle size and chemical composition, can have an impact on human health. Particle size distribution and chemical composition is a necessary parameter in occupational exposure assessment conducted in order to understand possible health effects. The aim of this study was to characterize workplace airborne particulate matter in a metallurgical setting by synergistically using two different approaches; Methodology: Analysis of inhalable fraction concentrations through traditional sampling equipment and ultrafine particles (UFP) concentrations and size distribution was conducted by an Electric Low-Pressure Impactor (ELPI+™). The determination of metallic elements (ME) in particles was carried out by inductively coupled plasma mass spectrometry; Results: Inhalable fraction and ME concentrations were below the limits set by Italian legislation and the American Conference of Governmental Industrial Hygienists (ACGIH, 2017). The median of UFP was between 4.00 104 and 2.92 105 particles/cm3. ME concentrations determined in the particles collected by ELPI show differences in size range distribution; Conclusions: The adopted synergistic approach enabled a qualitative and quantitative assessment of the particles in steelmaking factories. The results could lead to a better knowledge of occupational exposure characterization, in turn affording a better understanding of occupational health issues due to metal fumes exposure

Occupational Exposure to Fine Particles and Ultrafine Particles in a Steelmaking Foundry

Several studies have shown an increased mortality rate for different types of tumors, respiratory disease and cardiovascular morbidity associated with foundry work. Airborne particles were investigated in a steelmaking foundry using an electric low-pressure impactor (ELPI+™), a Philips Aerasense Nanotracer and traditional sampling equipment. Determination of metallic elements in the collected particles was carried out by inductively coupled plasma mass spectrometry. The median of ultrafine particle (UFP) concentration was between 4.91 × 103 and 2.33 × 105 part/cm3 (max. 9.48 × 106 part/cm3). Background levels ranged from 1.97 × 104 to 3.83 × 104 part/cm3. Alveolar and deposited tracheobronchial surface area doses ranged from 1.3 × 102 to 8.7 × 103 mm2, and 2.6 × 101 to 1.3 × 103 mm2, respectively. Resulting inhalable and respirable fraction and metallic elements were below limit values set by Italian legislation. A variable concentration of metallic elements was detected in the different fractions of UFPs in relation to the sampling site, the emission source and the size range. This data could be useful in order to increase the knowledge about occupational exposure to fine and ultrafine particles and to design studies aimed to investigate early biological effects associated with the exposure to particulate matter in the foundry industries

Glial fibrillary acidic protein immunoreactive astrocytes in developing rat hippocampus

The developmental pattern of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes was investigated in the hippocampus (subfields CA1, CA3 and CA4) and in the dentate gyrus of male and female rats aged 11, 16, 30, 90 and 150 days by immunohistochemistry associated with image analysis. Analysis was centred on stratum radiatum, a hippocampal area rich in GFAP-immunoreactive astrocytes. The volume of different portions of hippocampus, the number and the size of astrocytes, the intensity of cell body GFAP immunostaining as well as the extension of astrocyte were assessed. A maturation pattern consisting in higher cellular expression of GFAP, an increase in overall cell size and expanding arborisation from the 11th to the 30th postnatal day, followed by stabilisation of these parameters until the 90th day of life, and a subsequent decrease in the oldest age group studied was found. A sex-related different temporal pattern of astrocytes maturation in size and GFAP content was observed in the CA1 subfield only. The increase of GFAP content during pre-weaning ages was less pronounced in females than in males as well as the decrease between the 90th and the 150th day of age. Moreover, the size of astrocytes was larger in females than in males at the 11th and 150th days of life. These findings Suggest that hippocampal astrocytes undergo rapid maturation in the 1st month of postnatal life, followed by a slow consolidation of this process until the 3rd month of life. At 5 months of age, there are still dynamic changes in the mature astrocytes, which become slender and thinner probably as a response to the increased volume of hippocampus noticeable at this age. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Composition of metallic elements and size distribution of fine and ultrafine particles in a steelmaking factory

Background: The characteristics of aerosol, in particular particle size and chemical composition, can have an impact on human health. Particle size distribution and chemical composition is a necessary parameter in occupational exposure assessment conducted in order to understand possible health effects. The aim of this study was to characterize workplace airborne particulate matter in a metallurgical setting by synergistically using two different approaches; Methodology: Analysis of inhalable fraction concentrations through traditional sampling equipment and ultrafine particles (UFP) concentrations and size distribution was conducted by an Electric Low-Pressure Impactor (ELPI+™). The determination of metallic elements (ME) in particles was carried out by inductively coupled plasma mass spectrometry; Results: Inhalable fraction and ME concentrations were below the limits set by Italian legislation and the American Conference of Governmental Industrial Hygienists (ACGIH, 2017). The median of UFP was between 4.00 × 104 and 2.92 × 105 particles/cm3. ME concentrations determined in the particles collected by ELPI show differences in size range distribution; Conclusions: The adopted synergistic approach enabled a qualitative and quantitative assessment of the particles in steelmaking factories. The results could lead to a better knowledge of occupational exposure characterization, in turn affording a better understanding of occupational health issues due to metal fumes exposure

Cost of HAART in Italy: multicentric evaluation and determinants from a large HIV outpatient cohort.

Background: As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression. Methods: With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables. Results: We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782–29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P<0.001) and inversely correlated with current CD4 T-cell count (P=0.024). Site of care held independent prediction of higher costs, with marked control of expenses at sites 2 (P=0.001) and 5 (P<0.001). Conclusion: Higher costs of HAART were strongly associated with previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count at the time of evaluation, with no correlation at all with sex, age, hepatitis C virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically those associated with high prices, at the time of the analysis were still prevalently prescribed to rescue and maintain viral suppression in patients with more complex treatment history. Further analyses of the contribution of the single drug/regimen to the estimated cost are warranted

Obinutuzumab or Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Previously Untreated Diffuse Large B-Cell Lymphoma

Purpose Rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy is the standard of care in previously untreated diffuse large B-cell lymphoma (DLBCL). Obinutuzumab (G) is a glycoengineered, type II, anti-CD20 monoclonal antibody. GOYA was a randomized phase III study that compared G-CHOP with R-CHOP in patients with previously untreated advanced-stage DLBCL. Methods Patients (N = 1,418) were randomly assigned to receive eight 21-day cycles of G (n = 706) or R (n = 712), plus six or eight cycles of CHOP. Primary end point was investigator-assessed progression-free survival (PFS). Results After median observation of 29 months, the number of investigator-assessed PFS events was similar between G (201; 28.5%) and R (215; 30.2%), stratified hazard ratio was 0.92 (95% CI, 0.76 to 1.11; P = .39), and 3-year PFS rates were 70% and 67%, respectively. Secondary end points of independently reviewed PFS, other time-to-event end points, and tumor response rates were similar between arms. In exploratory subgroup analyses, patients with germinal-center B cell-like subtype had a better PFS than did patients with activated B cell-like subtype, irrespective of treatment. Frequencies of grade 3 to 5 adverse events (AEs; 73.7% v 64.7%, respectively) and serious AEs (42.6% v 37.6%, respectively) were higher with G-CHOP compared with R-CHOP. Fatal AE frequencies were 5.8% for G-CHOP and 4.3% for R-CHOP. The most common AEs were neutropenia (G-CHOP, 48.3%; R-CHOP, 40.7%), infusion-related reactions (G-CHOP, 36.1%; R-CHOP, 23.5%), nausea (G-CHOP, 29.4%; R-CHOP, 28.3%), and constipation (G-CHOP, 23.4%; R-CHOP, 24.5%). Conclusion G-CHOP did not improve PFS compared with R-CHOP in patients with previously untreated DLBCL. AEs reported with G were consistent with the known safety profile. Biomarker analyses may help define a future role for G in DLBCL