Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Diterpenoids from the Roots of Agastache rugosa

从土藿香根中得到两个二萜化合物，藿香酚（２）及异藿香酚（３）。经光谱解析（ＩＲ，ＵＶ，ＨＲＭＳ及ＮＭＲ谱），确定它们的结构分别为１１，１４ｄｉｈｙｄｒｏｘｙ１２ｍｅｔｈｏｘｙ１９（４→３）ａｂｅｏａｂｉｅｔａ４，（１８），８，１１，１３ｔｅｔｒａｅｎ７ｏｎｅ（２）和１１，１４ｄｉｈｙｄｒｏｘｙ１２ｍｅｔｈｏｘｙ１９（４→３）ａｂｅｏａｂｉｅｔａ３，８，１１，１３ｔｅｔｒａｅｎ７ｏｎｅ（３）藿香酚（２）为一新的化合物，而异藿香酚（３）系首次从天然界分离得到，二者为一对异构体。     

Evidence for the presence of a type III secretion system in diffusely adhering Escherichia coli (DAEC).

Diffusely adhering Escherichia coli (E. coli) strains (DAEC) represent a potential cause of diarrhoea in infants, and the detection of type three secretion system (TTSS) genes in DAEC would substantiate their pathogenic nature. In this work, four isolates of DAEC, recovered from stools of diarrhoeic children, were analysed by PCR, in order to detect the presence of TTSS genes. Primers targeted to the escC, escJ, escN and escV, some of the most conserved TTSS genes in enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC), were used in order to verify the occurrence of homologous genes in our DAEC isolates. By this approach, we were able to characterise DNA fragments corresponding to putative escJ and escN genes in all DAEC isolates. Furthermore, DNA fragments homologous to the escC and escV genes were also amplified from all isolates. Besides the similarity found among the DAEC esc homologues with EPEC and EHEC esc genes, the nucleotide sequence analysis of the flanking regions of the amplified DNA fragments suggests that the putative DAEC esc genes are organised in the same manner as observed in EPEC and in EHEC strains. The results described here provide strong evidence for the presence of a TTSS in the DAEC strains analysed, implicating a pathogenic nature of these isolates.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Asthma caused by cyanoacrylic glues

Cyanoacrylate-based glues have been reported as producing dermatitis and bronchial asthma. The paper describes the case of a patient occupationally exposed to Loctite 406, who developed irritation of the skin and mucosae of the face and late bronchial asthma. Preventive measures for subjects exposed to cyanoacrylic instant glues are discussed.     

Shape changes produced in detergent extracted bovine retinal pigment epithelium when exposed to ATP. A comparison with fibroblasts and smooth muscle cells

The response of single detergent treated bovine retinal pigment epithelial cells in culture to ATP was measured with an image analyser. The most pronounced contraction was produced by 1.0 mM ATP with most change taking place in the first 10 min. At 1 h the area had decreased by about 33%, perimeter 22% and maximum length 25%. By way of comparison rabbit skin fibroblasts had a decreased area of approximately 40%, perimeter 25% and maximum length 22%. Bovine aortic smooth muscle cells on the other hand decreased in area by 55%, perimeter 40% and maximum length 36%. It is hoped that this assay may be used to evaluate drugs which could counteract contractile events in proliferative vitreoretinopathy.