Cadmium influences the 5-fluorouracil cytotoxic effects on breast cancer cells

The aim of the research was to evaluate a heavy metal, cadmium (Cd), which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-fluorouracil (5-FU), after exposure to different concentrations of cd. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 µM) to the cells treated with Cd (5 µM–20 µM) did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer

Long-acting bronchodilators improve exercise capacity in COPD patients : a systematic review and meta-analysis

Background: We carried out a systematic review and meta-analysis with the aim to evaluate the efficacy of long-acting bronchodilators on exercise capacity in COPD patients. Methods: The endpoints were the efficacy of long-acting bronchodilators (altogether, and by single classes) vs. placebo in modifying endurance time (ET), inspiratory capacity (IC) and dyspnea during exercise, taking into consideration the outcomes according to different patients' inclusion criteria and exercise methodology. Results: Twenty-two studies were deemed eligible for analysis. Weighted mean increase in ET resulted of 67 s (95% CI ranges from 55 to 79). For isotime IC and dyspnea during exercise, weighted improvements were 195 ml (162-229), and - 0.41 units (- 0.56 to - 0.27), respectively. The increase in trough IC was 157 ml (138-175). We found a trend in favour of LAMA compared to LABA in terms of ET. In the 11 studies which reported a value of functional residual capacity > 120% as inclusion criterion, weighted mean increase in endurance time was 94 s (65 to 123); however we did not find any significant correlation between ET and mean trough IC (P: 0.593). The improvement of ET in the 5 studies using walking as exercise methodology resulted of 58 s (- 4 to 121). Conclusions: Long-acting bronchodilators improve exercise capacity in COPD. The main effect of long-acting bronchodilators seems to be a decrease of basal IC rather than a modification of dynamic hyperinflation during exercise. The efficacy in terms of endurance time seems higher in studies which enrolled patients with hyperinflation, with a similar efficacy on walking or cycling

Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72

A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for similar to 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for similar to 60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis

Conoscenze, attitudini e pratiche sulla tubercolosi tra gli studenti italiani: risultati preliminari

Introduzione La tubercolosi (tbc) rappresenta un problema di Sanit\ue0 Pubblica riemergente a livello globale, come indicato dall'Organizzazione Mondiale della Sanit\ue0 (OMS) a partire dal 1993. In Italia, il tasso di notifica di TB negli ultimi anni \ue8 risultato inferiore a 10 casi per 100.000 abitanti, soglia entro la quale un Paese \ue8 definito dall'OMS "a bassa incidenza". Tra i soggetti pi\uf9 a rischio di contrarre l'infezione figurano gli operatori sanitari e gli studenti dei Corsi di Laurea dell'area medica. La corretta conoscenza della malattia rappresenta il presupposto per le attivit\ue0 di prevenzione e controllo. La presente indagine ha lo scopo di valutare le conoscenze sulla tbc degli studenti dei Corsi di Laurea dell'area sanitaria in Italia. Metodi L'indagine \ue8 stata svolta in 14 Universit\ue0 Italiane attraverso un questionario predisposto dal GISIO (Gruppo Italiano Studio Igiene Ospedaliera) e somministrato al termine delle lezioni dei corsi di Igiene e Medicina Preventiva. Il questionario raccoglieva diversi item: corso di laurea, eziologia della tbc, prognosi, trattamento e prevenzione dell'infezione. Risultati Sono stati reclutati 1.855 studenti (66,5% di sesso femminile), di cui 520 iscritti al corso di laurea in Medicina e Chirurgia e 1.335 ai corsi di laurea delle professioni sanitarie. Il 95% degli intervistati conosce l'eziologia della tbc, ed il 77% afferma l'esistenza di potenziali forme di malattia extra-polmonari; il 67% riporta che la tbc non trattata ha una letalit\ue0 superiore al 50%, mentre il 76% evidenzia la necessit\ue0 di una assunzione prolungata di antibiotici, con probabilit\ue0 di sviluppare una farmaco-resistenza (79%). Il 28% sottolinea come la maggior parte delle infezioni decorrono in maniera asintomatica. L'87% degli intervistati conosce l'esistenza di un vaccino anti-tbc, mentre il 69% ritiene che non sia completamente efficace ed il 42% che sia costituito dal bacillo di Calmette-Guerin. L'88% degli studenti identifica la prova tubercolinica quale test di screening dell'infezione latente, il restante 12% la indica come test di laboratorio, vaccino o terapia. Conclusioni Anche se la maggior parte degli studenti conosce la tbc, una parte (rilevante per alcuni quesiti) evidenzia importanti carenze conoscitive, ad esempio quelle concernenti la frequenza di forme latenti o la composizione del vaccino. I dati ottenuti indicano un basso livello di attenzione nei confronti della malattia, probabilmente legato ad una scarsa percezione del rischio. Risulta necessario, pertanto, potenziare le strategie formative nei Corsi di Laurea, con particolare attenzione alla prevenzione del rischio biologico in ambito assistenziale