Valutazione della sensibilità e specificità del leucogramma, fibrinogenemia ed esame ecografico del torace nella diagnosi precoce di Rodococcosi nel puledro

Introduzione e scopo – La Rodococcosi è una malattia che colpisce il cavallo e l’uomo (soggetti immunodepressi) e dà le maggiori manifestazioni cliniche nei puledri che arrivano a sviluppare una polmonite piogranulomatosa ad ascessi ben evidenziabili radiograficamente e anche ecograficamente. Il batterio in esame è un coccobacillo, Gram +, asporigeno, aerobio obbligato, immobile, tellurico e coprofilo e inoltre è patogeno intracellulare facoltativo, con la capacità di persistere nei macrofagi alveolari per mancata fusione di fagosoma e lisosoma. Si sviluppa molto velocemente nelle feci equine e i puledri possono infettarsi per via orale, ma soprattutto aerogena. Scopo della presente tesi è quello di verificare la sensibilità e la specificità di alcuni esami di laboratorio e dell’esame ecografico nella diagnosi di Rodococcosi del puledro. Materiali e metodi - Lo studio sperimentale si è svolto durante le stagioni riproduttive 2004-2005, durante le quali sono stati esaminati 25 puledri tra i 3,5 e i 5,5 mesi. I soggetti sono stati controllati regolarmente da un punto di vista clinico tramite esame obiettivo generale dell’apparato respiratorio ed esame ecografico delle pleure. I 12 puledri (48%) che non hanno manifestato alcun sintomo di malattia sono stati ritenuti sani e hanno costituito il gruppo di controllo, che è stato sottoposto a prelievi del sangue ogni 15 giorni per un periodo di due mesi (giugno-luglio), con particolare riferimento ai valori di WBC e fibrinogenemia. Il gruppo dei malati (13 soggetti pari al 52% degli esaminati) è stato definito tale sulla base dei rilievi della sintomatologia clinica e sui rilievi ecografici; questi puledri sono stati controllati il giorno della diagnosi, quindi ogni 3 giorni fino alla risoluzione del caso. Risultati e conclusioni – L’aumento della firinogenemia associato a valori nella norma dei WBC è sicuramente indice di patologia respiratoria in atto, ma non di Rodococcosi, in quanto i soggetti non hanno presentato rilievi ecografici e sintomatologia caratteristici (ascessi, murmure respiratorio aumentato e rumori crepitanti) e sono guariti in seguito a terapia antibiotica aspecifica. Di contro, il notevole aumento del valore dei WBC, in concomitanza di valori di fibrinogenemia lievemente aumentati o border line, sembra essere un miglior indice diagnostico di Rodococcosi, poiché sempre associato a rilievi ecografici e sintomatologia specifici e nei soggetti interessati si è dovuti ricorrere ad una terapia specifica (rifampicina, eritromicina e ranitidina) per la guarigione

Altered telomere homeostasis and resistance to skin carcinogenesis in Suv39h1 transgenic mice

The Suv39h1 and Suv39h2 H3K9 histone methyltransferases (HMTs) have a conserved role in the formation of constitutive heterochromatin and gene silencing. Using a transgenic mouse model system we demonstrate that elevated expression of Suv39h1 increases global H3K9me3 levels in vivo. More specifically, Suv39h1 overexpression enhances the imposition of H3K9me3 levels at constitutive heterochromatin at telomeric and major satellite repeats in primary mouse embryonic fibroblasts. Chromatin compaction is paralleled by telomere shortening, indicating that telomere length is controlled by H3K9me3 density at telomeres. We further show that increased Suv39h1 levels result in an impaired clonogenic potential of transgenic epidermal stem cells and Ras/E1A transduced transgenic primary mouse embryonic fibroblasts. Importantly, Suv39h1 overexpression in mice confers resistance to a DMBA/TPA induced skin carcinogenesis protocol that is characterized by the accumulation of activating H-ras mutations. Our results provide genetic evidence that Suv39h1 controls telomere homeostasis and mediates resistance to oncogenic stress in vivo. This identifies Suv39h1 as an interesting target to improve oncogene induced senescence in premalignant lesions

microRNAs control the function of telomeres in cancer

Telomeres are located at the end of chromosomes and consist of DNA tandem repeats that recruit the specialized protein complex “shelterin”. Shelterin has a crucial role in controlling chromosome end protection, telomere recombination and telomere length. Telomeres shorten with every cell division, finally leading to telomere-dysfunction and the induction of senescence or apoptosis. Cancer formation is paralleled by a change in telomere regulation. Re-activation of telomerase ensures the maintenance of telomere function to facilitate unlimited proliferative potential. Importantly, aberrant function of the shelterin complex contributes to tumor formation and genomic instability in human cancer. miRNAs are important regulators of central cancer pathways and are of high clinical relevance. We recently showed that the onco-microRNA miR-155 controls the expression of TRF1 in human breast cancer to promote increased telomere fragility and genomic instability. Importantly, low TRF1 expression correlates with poor prognosis in estrogen receptor positive cancer patients, underlining the clinical relevance of miR-155 dependent regulation of TRF1 in human breast cancer. Our work suggests that multiple miRNAs exist that control telomere function in telomere related pathologies. Identification and functional validation of “telo-miRNAs” is expected to open new avenues in the understanding of telomere related maladies such as cancer and aging

Valutazione dell’utilità del leucogramma, fibrinogenemia ed esame ecografico del torace nella diagnosi precoce della Rodococcosi nel puledro

RIASSUNTO La Rodococcosi è una malattia che colpisce il cavallo ed altri mammiferi compreso l’uomo. Il batterio è un coccobacillo immobile, Gram+, asporigeno, aerobio obbligato, tellurico, coprofilo ed è un patogeno intracellulare facoltativo, con la capacità di vivere nei macrofagi alveolari inibendo la fusione del fagosoma con il lisosoma. Si sviluppa molto velocemente nelle feci equine e i puledri si infettano in particolare per via aerogena quando il batterio è disperso in aerosol. Le manifestazioni cliniche nei puledri che arrivano a sviluppare la polmonite piogranulomatosa sono paucisintomatiche e gli ascessi non sono facilmente rilevabili con la visita fisica, ma ben evidenziabili attraverso l’esame radiografico ed ecografico del torace. Scopo della presente indagine è stato quello di verificare l’attendibilità di alcuni esami di laboratorio e dell’esame ecografico delle pleure nella diagnosi di Rodococcosi del puledro. Lo studio è stato condotto durante le stagioni riproduttive 2004-2005, durante le quali sono stati esaminati 25 puledri tra i 3,5 e i 5,5 mesi. I soggetti sono stati controllati regolarmente con l’esame obiettivo particolare dell’apparato respiratorio e attraverso esame ecografico delle pleure. I 13/25 puledri (52%) che non hanno manifestato alcun sintomo di malattia e sono risultati negativi all’esame ecografico sono stati ritenuti sani e hanno costituito il gruppo di controllo. I puledri sani sono stati sottoposti a prelievi del sangue ogni 15 giorni per un periodo di due mesi (giugno-luglio), per la determinazione di WBC e fibrinogenemia. Il gruppo dei malati (12/25 soggetti pari al 48% degli esaminati) è stato definito tale sulla base dei rilievi clinici, dell’esame immunoistochimico del lavaggio broncoalveolare e sui rilievi ecografici; questi puledri sono stati controllati il giorno della diagnosi, quindi ogni 3 giorni fino alla risoluzione del caso. L’aumento della fibrinogenemia associato a valori nella norma dei WBC è un indice di patologia respiratoria in atto, ma non di Rodococcosi, perchè i soggetti che non hanno presentato rilievi ecografici e sintomatologia caratteristici (ascessi, murmure respiratorio aumentato e rumori crepitanti) sono guariti in seguito a terapia antibiotica aspecifica. Nei puledri con Rodococcosi sono stati osservati aumento dei WBC e della concentrazione della fibrinogenemia, associati a rilievi ecografici caratteristici. In 2/3 soggetti la terapia con eritromicina e rifampicina è risultata efficace, 1/3 è morto. SUMMARY R. Equi infection affects horse, other mammalians and human beings. Rodococcosis in foals causes suppurative broncopneumonia with abscesses, detected by radiography and ultrasonography. R. equi is a soil organism, Gram+, obligate aerobe, fixed, coprophylic, asporigen, facultative intracellular pathogen that persists in macrophages preventing phagosomelysosome fusion. It grows in the manure and the foals became infected by oral and respiratory route transmission. The aim of this work was to verify the usefulness of some laboratory exams and pleural ultrasonography as diagnostic tools of R. equi infection in foals. The study was performed during breeding seasons 2004-2005. Twenty-five foals aged 3,5-5,5 months were examined; 13 foals (52%) were considered healthy and used as control group. Blood samples were obtained every 15 days from each foal to measure WBC and plasma fibrinogen concentration and pleural ultrasound were performed every 15 days. Twelve foals (48%) showed illness (cough, depression, decreased growth, fever, etc.) and were included in the ill group. These foals were examined at the day of diagnosis and every 3 days until the recovery (laboratory exams and pleural ultrasound), 3 of 12 had rodococcosis. In our study, the high value of plasma fibrinogen concentration with normal WBC could be secondary to respiratory disease, but not to R. equi infection. These patients did not showed specific clinical manifestations and ultrasonographic alterations (abscesses, higher respiratory murmur and crackle noises) and they needed only aspecific antibiotic therapy. Marked increase of WBC with moderately increase of plasma fibrinogen concentration might be considered a more diagnostic tool in rodococcosis, because in our study they were associated with specific ultrasonographic and clinical alterations. These foals needed the specific therapy (rifampin associated with erythromycin) for recovery

microRNAs control the function of telomeres in cancer: DOI: 10.14800/rd.282

Telomeres are located at the end of chromosomes and consist of DNA tandem repeats that recruit the specialized protein complex “shelterin”. Shelterin has a crucial role in controlling chromosome end protection, telomere recombination and telomere length. Telomeres shorten with every cell division, finally leading to telomere-dysfunction and the induction of senescence or apoptosis. Cancer formation is paralleled by a change in telomere regulation. Re-activation of telomerase ensures the maintenance of telomere function to facilitate unlimited proliferative potential. Importantly, aberrant function of the shelterin complex contributes to tumor formation and genomic instability in human cancer. miRNAs are important regulators of central cancer pathways and are of high clinical relevance. We recently showed that the onco-microRNA miR-155 controls the expression of TRF1 in human breast cancer to promote increased telomere fragility and genomic instability. Importantly, low TRF1 expression correlates with poor prognosis in estrogen receptor positive cancer patients, underlining the clinical relevance of miR-155 dependent regulation of TRF1 in human breast cancer. Our work suggests that multiple miRNAs exist that control telomere function in telomere related pathologies. Identification and functional validation of “telo-miRNAs” is expected to open new avenues in the understanding of telomere related maladies such as cancer and aging

Biomarkers of oxidative stress to nucleic acids: Background levels and effects of body mass index and life-style factors in an urban paediatric population

The aims of the present study were to establish the background levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), 8-oxo-7,8-dihydroguanine (8-oxoGua) among a group of healthy Italian children, and to evaluate the contribution of some potential interfering/confounding factors to the urinary (u) levels of these biomarkers of oxidised guanine derivatives. The levels of 8-oxodGuo, 8-oxoGuo, 8-oxoGua, and u-cotinine in urine samples from 159 healthy children (5-11years) recruited in a cross-sectional study were measured via liquid chromatography-tandem mass spectrometry. Data regarding the anthropometric and life-style characteristics of the participants were obtained from questionnaires. The 5th-95th percentiles of the levels of 8-oxodGuo, 8-oxoGuo, and 8-oxoGua for all children were 2.4-13.9, 3.8-19.9 and 5.4-79.5μg/L and 2.9-12.6, 4.8-15.2, and 5.1-93.4μg/g creatinine, respectively. Significant correlations were found between the level of 8-oxoGuo and that of 8-oxoGua and 8-oxodGuo but not between the level of 8-oxoGua and that of 8-oxodGuo in all children and in both the male and female subgroups. Multiple linear regression analyses revealed the independent effect of the investigated variables on 8-oxodGuo, 8-oxoGuo, and 8-oxoGua. u-Creatinine was the most significant predictor of the urinary excretion of both 8-oxoGuo and 8-oxodGuo, age displayed a significant positive independent effect on the level of 8-oxoGuo, whereas the weight status according to the BMI was negatively associated with the level of 8-oxodGuo. None of the chosen independent variables influenced the levels of 8-oxoGua

On the first description of tetrapod footprints from Italy: Re-analysis of the original specimen after 150 years

In Italy, vertebrate ichnology developed rather recently, especially starting from the 70’s of the last century. However, fossil footprints from Italian continental successions were known since the 19th century. The first scientific note was published by Curioni (1870), after a short report on the same material by Geinitz (1869). Curioni described and drew a small slab with tetrapod tracks from the lower Permian strata of Lombardy (Collio Formation, upper Trompia Valley, Brescian Alps), found by the private collector Don Bruni, Priest of Collio. Subsequent publications always referred to that description, but the original specimen was never restudied, due also to the absence of information about the repository (Curioni, 1870). The original specimen belongs to the prestigious Curioni collection (donated by Curioni to the Regio Ufficio Geologico in 1877) and is nowadays located in the Italian National Institute for Environmental Protection and Research (ISPRA) in Rome. Grounding on the most advanced ichnological methods, in this paper we provide a redescription of the specimen. The study ultimately confirmed the attribution of the three main tracks (a pes-manus couple and a single manual imprint) to the ichnogenus Amphisauropus, tracks probably produced by seymouriamorph reptiliomorphs. Smaller footprints on the same surface were instead assigned to Dromopus, tracks probably left by diapsid reptiles or bolosaurid parareptiles. The note by Curioni thus represents the first report of vertebrate footprints from Italy, the first description of material assignable to Amphisauropus in the world, and one of the earliest on material referable to Dromopus. The studied slab could also represent the earliest finding of Amphisauropus, although uncertainties on timing of Don Bruni’s discovery exist. We note that only a careful management of the ancient Italian palaeontological heritage allowed our re-analyses of Curioni’s original specimen, almost 150 years after the last study. This study therefore highlights also the role of scientific collections for both preservation and valorisation of geo-palaeontologic heritage.Fil: Marchetti, Lorenzo. Urweltmuseum GEOSKOP; AlemaniaFil: Petti, Fabio Massimo. Museo delle Scienze di Trento; Italia. Università degli studi di Roma "La Sapienza"; ItaliaFil: Bernardi, Massimo. Museo delle Scienze di Trento; Italia. University of Bristol; Reino UnidoFil: Citton, Paolo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Rossi, Roberta. Italian National Institute for Environmental Protection and Research; ItaliaFil: Schirolli, Paolo. Museo Civico di Scienze Naturali; Itali