Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats

<p>Abstract</p> <p>Background</p> <p>Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARγ agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats.</p> <p>Methods</p> <p>Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-γ expression were examined by western blotting.</p> <p>Results</p> <p>Our data shows involvement of TNF-α in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-γ in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-γ directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications.</p> <p>Conclusion</p> <p>To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer.</p

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Histology and histochemistry of the venom apparatus of the black scorpion Androctonus crassicauda (Olivier, 1807) (Scorpiones: Buthidae)

The venom apparatus of the black scorpion Androctonus crassicauda has been characterized histologically and histochemically in the present study. The results showed that this apparatus consists of paired venom glands, each of which initially presents its own canal and posteriorily both fuse into a single common one. Each gland is covered by a sheath of striated muscle and is lined with extensively folded secretory epithelium (formed of non-secretory and secretory venom-producing cells). The outcomes also revealed that the venom-producing cells of both glands produce neutral mucosubstances, sialomucins, sulfomucins and proteins, but are devoid of glycogen. Cysteine, tyrosine, tryptophan and arginine were also detected along with activities of acid and alkaline phosphatases, mitochondrial adenosine triphosphatase, aminopeptidase, cholinesterase and non-specific esterases. Structure and secretion of scorpion venom glands are discussed within the context of the present results