An integrated approach to evaluate PAH exposure

Introduction - An integrated evaluation of PAH exposure should consider different routes of absorption, reliability and specificity of biomarkers of dose, and individual susceptibility. Material and Methods - The present study investigated the exposure to PAHs in coke oven workers (n=100), asphalt pavers (n=98) and ground construction workers (n=47), by means of environmental exposure and biological monitoring. Results \u2013 Personal exposure to total airborne PAHs [from naphtalene to indeno(1,2,3-cd)pyrene] in coke oven workers (median 140 \ub5g/m3), was much higher than in pavers exposed to bitumen fumes (0.6 \ub5g/m3), or in construction workers (0.4 \ub5g/m3),. Urinary 1-hydroxypyrene (1-HOP) in end-shift samples was significantly higher in cokeoven workers (2.2 \ub5g/l) than in asphalt pavers (0.7 \ub5g/l) and in construction workers (0.4 \ub5g/l). An increasing trend in 1-HOP levels, over the workweek and the workshift was registered. A similar trend was observed for urinary 2-hydroxyfluorene (2-FLE) and 3-hydroxyphenanthrene (3-PHE) as well as for some unmetabolised PAH in urine. In smokers with low exposures an important contribution to biomarkers was given by tobacco smoking. PAH-DNA adducts in peripheral blood lymphocytes were not associated with external exposure. Genetic polymorphisms of metabolic and DNA repairing enzymes (CYP1A1, GSTM1, GSTT1, XPD) did not appear to influence the levels of biomarkers. Total dermal contamination of PAHs in pavers, assessed in a subgroup of workers (n=22), ranged from 23 to 623 \ub5g. Significant correlations between dermal phenanthrene or pyrene and 1-HOP (r = 0.41 and 0.55), suggest that dermal exposure significantly contributes to the internal dose of these compounds. Conclusion \u2013 Our results suggest that urinary biomarkers of PAHs, integrating exposure from all sources and routes, are reliable tools for risk assessment in occupational health

Carbon disulfide. Just toxic or also bioregulatory and/or therapeutic?

The overview presented here has the goal of examining whether carbon disulfide (CS2) may play a role as an endogenously generated bioregulator and/or has therapeutic value. The neuro- and reproductive system toxicity of CS2 has been documented from its long-term use in the viscose rayon industry. CS2 is also used in the production of dithiocarbamates (DTCs), which are potent fungicides and pesticides, thus raising concern that CS2 may be an environmental toxin. However, DTCs also have recognized medicinal use in the treatment of heavy metal poisonings as well as having potency for reducing inflammation. Three known small molecule bioregulators (SMBs) nitric oxide, carbon monoxide, and hydrogen sulfide were initially viewed as environmental toxins. Yet each is now recognized as having intricate, though not fully elucidated, biological functions at concentration regimes far lower than the toxic doses. The literature also implies that the mammalian chemical biology of CS2 has broader implications from inflammatory states to the gut microbiome. On these bases, we suggest that the very nature of CS2 poisoning may be related to interrupting or overwhelming relevant regulatory or signaling process(es), much like other SMBs

Role of plants in anticancer drug discovery

Cancer is one of the major causes of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Worldwide the alarming rise in mortality rate due to cancer has fuelled the pursuit for effective anticancer agents to combat this disease. Finding novel and efficient compounds of natural origin has been a major point of concern for research in the pharmaceutical sciences. Plants have been seen to possess the potential to be excellent lead structures and to serve as a basis of promising therapeutic agents for cancer treatment. Many successful anti-cancer drugs currently in use or their analogues are plant derived and many more are under clinical trials. This review aims to highlight the invaluable role that plants have played, and continue to play, in the discovery of anticancer agents.We acknowledge the University of Pretoria for Postdoctoral fellowship to J.K. and B.A.M.http://www.elsevier.com/locate/phytolhb2017ChemistryGenetic

Alterazioni del fondo oculare nell'ipertensione sistemica felina:aspetti clinici, diagnostici e terapeutici

L’ipertensione sistemica può danneggiare alcuni organi che presentano un ricco apporto vascolare tra cui il globo oculare. L'esame delle strutture oculari, in particolare la valutazione del fundus, è infatti condizione essenziale nella diagnosi di molte patologie sia oculari sia sistemiche. A questo proposito, la variazione del calibro dei vasi retinici, la loro tortuosità così come la presenza di emorragie, edemi o distacchi della retina possono fornire importanti informazioni riguardo a molti tipi di patologie sistemiche tra cui l’ipertensione. La diagnosi di retinopatia ipertensiva è di carattere qualitativo e avviene attraverso la valutazione diretta del fundus tramite l’impiego di oftalmoscopi (indiretto e diretto). Questo giudizio soffre però di soggettività, potendo risultare a volte poco attendibile. Per ovviare a questo svantaggio dell'analisi classica, ovvero clinica e manuale, un valido aiuto può venir offerto dall'analisi di immagine retinica automatica o semiautomatica. Questa è potenzialmente in grado di offrire informazioni di tipo diagnostico oggettive. Allo stato attuale non esistono sistemi di analisi retiniche specifici per pazienti veterinari. Nello specifico, il primo obiettivo della ricerca è stato quello di un approfondimento clinico e diagnostico delle alterazioni del fundus in pazienti felini ipertesi. Per questo è stato eseguito uno studio epidemiologico delle alterazioni del fundus nella popolazione esaminata, composta per l’appunto da pazienti felini ipertesi. Abbiamo identificato la presenza di lesioni retiniche, classificandole clinicamente e valutandone infine l’evoluzione in funzione della diagnosi e quindi della terapia. Il secondo obiettivo, in particolare, è stato quello di verificare se il software di analisi di immagine retiniche Vampire (Vascular Assesment and Measuremet Platform for Images of the Retina), potesse essere validato in medicina veterinaria. Tale piattaforma è stata sviluppata per la medicina umana dalla scuola di informatica dell’università di Dundee (Scozia) e appositamente modificata per il fundus felino dagli stessi creatori. La presente ricerca è stata approvata dall’Organismo Preposto al Benessere Animale dell’Università di Pisa e sviluppata con il coordinamento del Dipartimento di Scienze Veterinaria (Università di Pisa), in collaborazione con la School of Computing (Università di Dundee, Scozia) e il Dipartimento di Medicina Animale, Produzioni e Salute (Università di Padova). Tutti i soggetti arruolati sono stati esaminati presso un unico centro (Clinica Veterinaria San Marco, Padova) nel periodo compreso tra Gennaio 2015 e Aprile 2016

Routes to the arylglycoside core of neocarzinostatin and to combretastatin D-2

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Correlation between the Severity Prediction Index score (SPI-2) and tear production in 100 critically ill dogs admitted to the intensive care unit

urpose: To determine the relationship between the severity of a systemic disease and tear production (TP) in critically ill dogs admitted to the intensive care unit. Methods: One hundred dogs of various breeds and both sexes were enrolled in the study. Inclusion criteria were as follows: presence of a severe systemic disease, no anesthesiological procedures within the previous 24 h, and no therapy with drugs that could interfere with TP. Another inclu- sion criterium was the absence of any ocular abnormalities assessed by slit-lamp biomi- croscopy, indirect ophthalmoscopy, and applanation tonometry preceded by the Schirmer Tear Test type I in both eyes. For each dog the illness severity was calculated by a diagnosis independent score (Severity Prediction Index - SPI-2) which predicts probability of survival based on variation of 7 clinical parameters within 24 h of admission. Data were statistically analyzed and the Spearmann test was used to detect a possible correlation between SPI-2 score and TP. Results: In the 53 male and 47 female dogs no statistical difference in TP was found between left and right eyes. No significant effect of both, age and body weight on TP was detected. A difference related to gender was found, with intact male dogs showing a lower TP. The variables SPI-2 and TP in the critically ill dogs were correlated (P < 0.0001) and a positive correlation was detected (rs 0.957). Conclusion: This study demonstrated that tear production tends to decrease in dogs with lower SPI-2 scores, in other words in the more critically ill dogs