Generation of iPSC lines derived from skin fibroblasts of two healthy controls using non-transmissible form of Sendai Virus.

We established two iPSC lines starting from skin fibroblasts of two healthy individuals using Sendai-virus-based technique. The obtained iPSCs were characterized showing same STR profile as starting fibroblasts, normal karyotype, loss of stemness vectors, expression of stemness markers, both through real-time PCR and immunofluorescence, (OCT4, SOX2, TRA-1-60, NANOG and SSEA4) and in vitro differentiation into three germ layers.

Determining the Aethalometer multiple scattering enhancement factor C from the filter loading parameter.

Light-absorbing aerosols heat the atmosphere; an accurate quantification of their absorption coefficient is mandatory. However, standard reference instruments (CAPS, MAAP, PAX, PTAAM) are not always available at each measuring site around the world. By integrating all previous published studies concerning the Aethalometers, the AE33 filter loading parameter, provided by the dual-spot algorithm, were used to determine the multiple scattering enhancement factor from the Aethalometer itself (hereinafter CAE) on an yearly and a monthly basis. The method was developed in Milan, where Aethalometer measurements were compared with MAAP data; the comparison showed a good agreement in terms of equivalent black carbon (R2 = 0.93; slope = 1.02 and a negligible intercept = 0.12 µg m-3) leading to a yearly experimental multiple scattering enhancement factor of 2.51 ± 0.04 (hereinafter CMAAP). On a yearly time base the CAE values obtained using the new approach was 2.52 ± 0.01, corresponding to the experimental one (CMAAP). Considering the seasonal behavior, higher experimental CMAAP and computed CAE values were found in summer (2.83 ± 0.12) whereas, the lower ones in winter/early-spring (2.37 ± 0.03), in agreement with the single scattering albedo behavior in the Po Valley. Overall, the agreement between the experimental CMAAP and CAE showed a root mean squared error (RMSE) of just 0.038 on the CMAAP prediction, characterized by a slope close to 1 (1.001 ± 0.178), a negligible intercept (-0.002 ± 0.455) and a high degree of correlation (R2 = 0.955). From an environmental point of view, the application of a dynamic (space/time) determination of CAE increases the accuracy of the aerosol heating rate (compared to applying a fixed C value) up to 16 % solely in Milan, and to 114 % when applied in the Arctic at 80°N.

Inspiratory Effort and Respiratory Mechanics in Patients with Acute Exacerbation of Idiopathic Pulmonary fibrosis: A Preliminary Matched Control Study.

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.

Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device).

BACKGROUND: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. METHODS: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. RESULTS: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. CONCLUSIONS: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration.

INTRODUCTION: The mainstay therapy for Parkinson's disease (PD) relies on L-3,4-dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. METHODS: Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). 6-OHDA animals were treated orally with L-DOPA/BE for 28 days, starting 28 days after 6-OHDA injection. At the end of treatment, in vivo colonic transit was evaluated by a radiologic assay. Electrically stimulated (ES) cholinergic contractions were recorded in vitro from colonic preparations, while acetylcholine release was measured in the incubation medium. Choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) expression as well as eosinophil and mast cell density were examined in the colonic wall by immunohistochemistry. Colonic TNF and IL-1ß levels were also assayed. RESULTS: 6-OHDA animals displayed: 1) decrease in in vivo colonic transit; 2) impairment of ES-stimulated cholinergic contractions; 3) decreased acetylcholine release from myenteric nerves; 4) decrease in ChAT and increase in GFAP myenteric immunopositivity; 5) increase in eosinophil and mast cell density; 6) increase in TNF and IL-1ß levels. Treatment with L-DOPA/BE elicited an improvement of in vivo and in vitro colonic motor activity, a normalization of acetylcholine release, ChAT immunopositivity, as well as pro-inflammatory cytokine patterns, ganglionic GFAP levels, eosinophil and mast cell density. CONCLUSION: Under dopaminergic nigrostriatal denervation, treatment with L-DOPA/BE ameliorated colonic motility through a normalization of myenteric cholinergic neurotransmission, along with an improvement of colonic inflammation.

Multidrug-resistant tuberculosis outbreak in an Italian prison: tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays.

The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice.

Response of colonic motility to dopaminergic stimulation is subverted in rats with nigrostriatal lesion: relevance to gastrointestinal dysfunctions in Parkinson's disease.

BACKGROUND: Constipation is extremely common in patients with Parkinson's disease (PD) and has been described in PD animal models. In this study, we investigated whether a PD-like degeneration of dopaminergic neurons of the substantia nigra can influence peristalsis in colonic segments of rats by impacting on enteric dopaminergic transmission. METHODS: Male, Sprague-Dawley rats received a unilateral injection of neurotoxin 6-hydroxydopamine (6-OHDA), or saline, into the medial-forebrain-bundle. Peristaltic activity was recorded in isolated colonic segments, in baseline conditions and following exposure to combinations of D2 receptor (DRD2) agonist sumanirole and antagonist L-741626. Dopamine levels and DRD2 expression were assessed in the ileum and colon of animals. We also investigated the involvement of the dorsal motor nucleus of the vagus (DMV) - a potential relay station between central dopaminergic denervation and gastrointestinal (GI) dysfunction - by analyzing cytochrome c oxidase activity and FosB/DeltaFosB expression in DMV neurons. KEY RESULTS: We observed profound alterations in the response of colonic segments of 6-OHDA lesioned animals to DRD2 stimulation. In fact, the inhibition of colonic peristalsis elicited by sumanirole in control rats was absent in 6-OHDA-lesioned animals. These animals also showed reduced DRD2 expression in the colon, along with elevation of dopamine levels. No significant changes were detected within the DMV. CONCLUSIONS & INFERENCES: Our results demonstrate that selective lesion of the nigrostriatal dopaminergic pathway subverts the physiological response of the colon to dopaminergic stimulation, opening new perspectives in the comprehension and treatment of GI dysfunctions associated with PD.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

Predictive value of isolated DLCO reduction in systemic sclerosis patients without cardio-pulmonary involvement at baseline.

Impaired diffusing capacity of the lung for carbon monoxide (DLCO) was frequently observed in systemic sclerosis (SSc) patients, generally related to the presence of interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications. The objective was to investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients. Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5), without any clinical, radiological (high resolution computed tomography), and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre. Patients with DLCO <55% (15 patients; group A) were compared with those with normal DLCO (82 patients; group B), at baseline and at the end of follow-up. At baseline, patients of group A showed significantly higher percentage of anticentromere autoantibodies compared to group B (13/15, 86.6% vs 48/82, 58.5%; p=0.044). More interestingly, at the end of long-lasting clinical follow-up (11.6±6.7 years), pre-capillary PAH (right heart catheterization) solely developed in some patients of group A (3/15, 20% vs 0/82; p=0.003). In SSc patients, the presence at baseline of isolated, marked DLCO reduction (<55% of predicted) and serum anticentromere autoantibodies might characterize a peculiar SSc subset that may precede the development of PAH. Therefore, careful clinical follow-up of patients with isolated moderate-severe DLCO reduction should be mandatory.

Lung involvement in systemic sclerosis: role of high resolution computed tomography and its relationship with other pulmonary and clinico-serological features.

The study investigated the characteristic of interstitial lung disease in a large series of systemic sclerosis (SSc) patients by means of HRCT and the correlations between functional lung parameters, serological features and the extent of lung involvement evaluated by high-resolution computed tomography (HRCT). One hundred and seven SSc patients, consecutively investigated by means of HRCT, standard chest X-ray, and pulmonary function tests, were retrospectively evaluated. Chest radiogram and HRCT scores were strongly associated (Pearson’'s r=0.82, p < .0001); moreover, the first significantly correlated with spirometric parameters, even if weakly. Anti-Scl70 and anti-centromere antibodies were associated with higher (p=0.01) and lower HRCT score (p=0.0002), respectively. The extension of interstitial lung involvement in SSc evaluated with HRCT is directly proportional to functional lung parameters. HRCT, spirometry and DLco should be considered essential in the core-set of non-invasive diagnostic tools for the first-line assessment of scleroderma lung involvement.

Long-term management of IPF with pirfenidone - a clinical case study with 5 years follow-up.

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung disease that is associated with a median survival of 2-5 years from initial diagnosis. To date, the search for an effective treatment has involved numerous clinical trials of investigational agents but without significant success. Nevertheless, research over the past 10 years has provided us with a wealth of information on its histopathology, diagnostic work-up, and a greater understanding of its pathophysiology. Specifically, IPF is no longer thought to be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is increasingly understood to be the result of a fibroproliferative and aberrant wound healing cascade. The development of therapeutic targets has therefore shifted in accordance with this paradigm change. Emerging clinical data from recently published and ongoing trials investigating new potential pharmacological agents should be considered in the routine clinical management of these patients. Based upon encouraging results from randomised-controlled trials showing a positive effect in slowing decline in pulmonary function and reducing disease progression, pirfenidone was approved in 2011 as the first treatment in patients with IPF. This case study describes the clinical course of a patient enrolled into the Phase III and open-label extension studies of pirfenidone.

Effect of breed, sex, age and body weight on echocardiographic measurements in the equine species.

Little is known about the effect of various animal's signalment variables on echocardiographic reference values in the equine species. This study was performed to evaluate the effect of sex, breed, age and body weight (BW) on echocardiographic measurements in the equine species. Echocardiography was performed on 212 ponies or horses of various breeds, aged from 1 day to 37 years old (mean±SD: 7.8 ± 5.8 years), BW 38-890 kg (mean ± SD: 421 ± 133 kg), and free of cardiac disease. Fifty of those animals aged from 2 months to 35 years old (mean ± SD: 11.6 ± 6.4 years old); BW 77-662 kg (mean ± SD: 436 ± 135 kg) were also examined using the pulsed-wave Doppler mode. Standard two-dimensional and M-mode echocardiography were performed on all animals. Standard pulsed-wave Doppler examination of each cardiac valve was performed on the 50 first examined animals. Data were analysed using a general linear model including the effect of sex, age, breed and BW after logarithmic transformation of the data. Therefore, the same analysis was performed separately on animals aged ≤ 2 years-old and on older animals. All dimensional echocardiographic measurements were significantly affected by BW and most of them were significantly affected by breed, but not by sex. Only the aortic and the pulmonary artery internal diameter were significantly affected by age. None of the Doppler measurements were significantly affected by the tested variables. In conclusion, in the equine species, dimensional echocardiographic reference values should be established using regression equations as a function of BW, which could increase the diagnostic value of this leading technique in equine cardiology. Breed could also have an effect on those measurements.

Traditional and quantitative assessment of acid-base and shock variables in horses with atypical myopathy.

BACKGROUND: Descriptions of acid-base disturbances in atypical myopathy (AM) are limited. OBJECTIVES: Describe and compare traditional and quantitative acid-base abnormalities and cardiovascular shock status in horses with AM at admission. ANIMALS: 34 horses with AM, 15 healthy controls. METHODS: Retrospective case-control study. Records were searched for shock variables (packed cell volume [PCV], blood urea nitrogen [BUN], heart and respiratory rate) and acid-base variables (venous blood gas analysis, electrolytes, total protein, lactate) on admission. Base excess (BE) of free water (BEfw), chloride (BEcl), total protein (BEtp), and unidentified anions (BEua), anion gap (AG), measured strong ion difference (SIDm), and concentration of total nonvolatile weak acids ([Atot]) were calculated. Acid-base classifications, using simplified strong ion model and traditional approach, and shock grades were assigned. A 2-sample Wilcoxon rank-sum test and Bonferroni correction compared variables in AM cases versus control horses. Significance was P < .05/16 for acid-base and P < .05/5 for shock variables. RESULTS: Tachycardia, tachypnea, and normal to increased PCV and BUN were common in AM cases. Respiratory, metabolic acid-base alterations, or both were mainly caused by respiratory alkalosis, lactic acidosis, and SIDm alkalosis, alone or in combination. Evaluated variables (except pH, potassium concentration, total protein, and related calculations) were significantly different (P < .001) between AM cases and control horses. The strong ion model provided a more accurate assessment than the traditional approach and identified mixed derangements. CONCLUSIONS AND CLINICAL IMPORTANCE: Acid-base derangements should be evaluated in horses with AM and this preferably with the strong ion model.

Description of a specific bronchial provocation test for the diagnosis of occupational asthma due to platinum salts.

BACKGROUND: Occupational exposure to platinum salts may cause the onset of skin and respiratory disorders with an IgE-mediated allergic mechanism. The diagnosis of occupational asthma due to platinum salts was, in a small number of cases, achieved also via occupational specific bronchial provocation tests (sBPT), which until now were conducted by pouring platinum salt dusts from one tray to another or by direct aerosoling of hexachloroplatinate solutions into the patient's airways. METHODS: Here we describe an original occupational sBPT based on atomization of solutions of ammonium hexachloroplatinate, at increasing concentrations, in a 5 m3 challenge room: the starting solution is a 1:100 dilution of the preset threshold of the patient's skin reactivity to the substance. In the absence of a bronchoconstrictive response, the following concentration is atomized (each time 10 times higher than the previous one), until the maximum concentration, 10(-2) M, is reached. The patient is not in the challenge room during atomization of the solutions, but enters when this operation has been completed and remains there for 15 minutes, unless he/she shows signs of respiratory trouble before that time. After each exposure, the patient is clinically monitored, with respiratory function tests at preset times, until at least 8 hours after the end of the exposure. RESULTS AND CONCLUSIONS: The test allowed identifying a respiratory hypersensitivity specifically to platinum as cause of asthma in two precious metal workers, with the onset of immediate bronchospasm in one patient and biphasic bronchospasm in the other. Compared to the sBPT by pouring a mixture of platinum salt dusts from one tray to another, the method we designed offers a better standardization of bronchial stimulation and, compared to direct aerosoling of hexachloroplatinate into the patient's airways, it has the advantage of reproducing the respiratory risk conditions occurring in the workplace and offers better safety guarantees for the patient, since it reduces the risk of onset of serious asthmatic or even systemic responses in subjects highly hypersensitive to this metal.

Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson's disease.

BACKGROUND: We have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson's disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats. METHODS: hMSCs were labeled both with a membrane intercalating dye, emitting in the near- infrared 815 nm spectrum, and the nuclear counterstain, Hoechst 33258. Effects of near-infrared dye on cell metabolism and proliferation were extensively evaluated in vitro. Tagged hMSCs were then administered to parkinsonian rats bearing a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, via two alternative routes, ie, intrastriatal or intranasal, and the cells were tracked in vivo and ex vivo using near-infrared technology. RESULTS: In vitro, NIR815 staining was stable in long-term hMSC cultures and did not interfere with cell metabolism or proliferation. A significant near-infrared signal was detectable in vivo, confined around the injection site for up to 14 days after intrastriatal transplantation. Conversely, following intranasal delivery, a strong near-infrared signal was immediately visible, but rapidly faded and was completely lost within 1 hour. After sacrifice, imaging data were confirmed by presence/absence of the Hoechst signal ex vivo in coronal brain sections. Semiquantitative analysis and precise localization of transplanted hMSCs were further performed ex vivo using near-infrared imaging. CONCLUSION: Near-infrared technology allowed longitudinal detection of fluorescent-tagged cells in living animals giving immediate information on how different delivery routes affect cell distribution in the brain. Near-infrared imaging represents a valuable tool to evaluate multiple outcomes of transplanted cells, including their survival, localization, and migration over time within the host brain. This procedure considerably reduces the number of animal experiments needed, as well as interindividual variability, and may favor the development of efficient therapeutic strategies promptly applicable to patients.

Interactions of neurotransmitter systems during postnatal development of the rat hippocampal formation: effects of cisplatin.

The distribution of neuroimmunohistochemical markers for the serotoninergic, noradrenergic, glutamatergic and GABAergic systems (respectively, 5HT(2A)R, ß1AR, GluR 2/3 and GAD65/67) was determined in the hippocampal formation at stages PD11, PD17 and PD30 of postnatal development of untreated rats and cisplatin-treated rats after a single injection of the drug at 10days of life. In the different time points the neurons of the dentate gyrus and Cornu Ammonis progressively acquire mature morphological characteristics, and cell genesis, migration of interneurons and differentiation of mossy cells occur. Cisplatin induced decrease in immunoreactivity for most of the selected neurotransmitter markers, thereby altering the postnatal development of circuits in the hippocampal formation. Cisplatin also brought out clear evidence for an interaction between excitatory and inhibitory neurotransmitter markers during the postnatal maturation of cells and fiber projections containing GluR2/3 and GAD65, despite the fact that glutamatergic neurons and GABAergic interneurons are divergent in their source of genesis and in their mode of migration. In fact, GluR2/3 immunofluorescence was increased in the principal cells early, at PD11, possibly to reduce the calcium influx into the cell. Moreover, cisplatin might cause a loss of GABAergic interneurons early and reduction of fiber projections to hippocampal layers due to altered cell migration or to cell injury; late changes, particularly in GAD67 cell number in the dentate gyrus did not result in redistribution or recovery in treated rats. With the use of cisplatin it has been demonstrated here for the first time that the critical differentiation of dentate gyrus hilar ß1AR and GluR2/3 mossy cells takes place between PD11 and PD17. Changes in neurotransmitter marker immunopositivity occurred subsequently to cytoarchitectural changes in the dentate gyrus and Cornu Ammonis which were already evident one day after cisplatin injection, suggesting that degeneration and cell loss may have occurred. Cisplatin was found to be a useful tool for following CNS development and for understanding how hippocampal neuronal networks react to injury. Furthermore, cisplatin-induced neurotoxicity may be used to reveal useful information on the genesis, migration and distribution, and differentiation of distinct types of hippocampal neurons.

[Cancer screening programme in health care workers]. / Applicazione di screening antitumorali in una popolazione di operatori sanitari.

From the 2002 through 2009 years 419 health care workers of the Hospital of Lecco, occupationally exposed to X-ray, were invited to undergo a cancer screening programme for the early diagnosis of cervical, breast, colorectal and prostate cancers. A total of 341 subjects performed the screening tests with an overall compliance of 83,8%; the participation rate to each test was significantly higher than that of general population. Breast cancer was diagnosed and treated in 5 women, cervical premalignant lesions in 8 women and colorectal adenomas in 13 subjects; no prostate cancer was detected. The participation rate, the premalignant and malignant findings and the cost-effectiveness analysis are consistent with the possibility that cancer screening programme can be set out as health promotion activity in health care workers.