Synthesis and cytotoxicity of potential tumor-inhibitory analogues of trimelamol (2,4,6-tris[(hydroxymethyl)methylamino]-1,3,5-triazine) having electron-withdrawing groups in place of methyl

In exploring the structural features which determine the antitumor activity of 2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14. Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of experimental rodent and human ovarian tumor cell lines similar to those shown by 1, the cyanomethyl analogue (15) having the most favorable profile. Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1. Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min, and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This cyanomethyl analogue was also the most water-soluble, being comparable to 1 whereas 5 and 13 were poorly soluble.     

Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions

BACKGROUND: Previous work from our laboratory demonstrated that interleukin (IL)-6 plays a potentially critical role in postreperfusion myocardial injury and is the major cytokine responsible for induction of intracellular adhesion molecule (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICAM-1 induction is necessary for neutrophil-associated myocyte injury. We have previously demonstrated the induction of IL-6 in the ischemic myocardium, and the current study addresses the cells of origin of IL-6. METHODS AND RESULTS: In the present study, we combined Northern blot analysis and in situ hybridization to demonstrate IL-6 gene expression in cardiac myocytes. Isolated ventricular myocytes were stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, preischemic lymph, and postischemic lymph. Unstimulated myocytes showed no significant IL-6 mRNA expression. Myocytes stimulated with preischemic lymph showed minimal or no IL-6 mRNA expression, whereas myocytes stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, or postischemic lymph showed a strong IL-6 mRNA induction. Northern blot with ICAM-1 probe revealed ICAM-1 expression under every condition that demonstrated IL-6 induction. We then investigated the expression of IL-6 mRNA in our canine model of ischemia and reperfusion. Cardiac myocytes in the viable border zone of a myocardial infarction exhibited reperfusion-dependent expression of IL-6 mRNA within 1 hour after reperfusion. Mononuclear cells infiltrate the border zone and express IL-6 mRNA. CONCLUSIONS: Isolated cardiac myocytes produce IL-6 mRNA in response to several cytokines as well as postischemic cardiac lymph. In addition to its production by inflammatory cells, we demonstrate that IL-6 mRNA is induced in myocytes in the viable border zone of a myocardial infarct. The potential roles of IL-6 in cardiac myocytes in an infarct border are discussed.     

Spermatid injection into human oocytes. I. Laboratory techniques and special features of zygote development

Spermatid injection into the oocyte cytoplasm has been shown recently to yield viable human embryos developing to term after transfer to the mother. This study provides details of the laboratory techniques related to round spermatid injection (ROSI) and elongated spermatid injection (ELSI) and focuses on some special features of zygote development associated with the use of these types of sperm precursor cells for fertilization. A spermatid-enriched fraction was obtained by centrifugation of cells from azoospermic ejaculates through a discontinuous Percoll gradient column. Individual round or elongated spermatids were identified in this fraction and injected deep into oocytes. Oocyte activation was boosted by a vigorous aspiration of the ooplasm at the time of injection. The fertilization rates after ROSI and ELSI were 45 and 44% respectively. A single large syngamy nucleus was detected in 36% of the zygotes that previously showed two normal-sized pronuclei. This condition did not appear to delay the first cleavage division. These observations underscore the importance of distinguishing the syngamy nucleus of diploid zygotes from the female pronucleus of haploid, parthenogenetically activated eggs.     

The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta).

The role of the amygdala in dyadic social interactions of adult rhesus monkeys (Macaca mulatta) was assessed after bilateral ibotenic acid lesions. Social, nonsocial, and spatial behaviors of amygdalectomized and control monkeys were assessed in 3 dyadic experiments: constrained, unconstrained, and round robin. Lesions produced extensive bilateral damage to the amygdala. Across all experiments, the amygdalectomized monkeys demonstrated increased social affiliation, decreased anxiety, and increased confidence compared with control monkeys, particularly during early encounters. Normal subjects also demonstrated increased social affiliation toward the amygdalectomized subjects. These results indicate that amygdala lesions in adult monkeys lead to a decrease in the species-normal reluctance to immediately engage a novel conspecific in social behavior. The altered behavior of the amygdalectomized monkeys may have induced the increased social interactions from their normal companions. This is contrary to the idea that amygdalectomy produces a decrease in social interaction and increased aggression from conspecifics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adequacy of medical referrals to hospital emergency service

OBJECTIVE: To assess the correctness and diagnostic concordance in referrals of patients to hospital Casualty Departments (CD); and the possible differences between rural and urban health centres (HC) as well as between general practitioners (GP) and family and community medicine (FCM) specialists. DESIGN: Observational study of a crossover nature. SETTING: Health area 1 in the province of Badajoz. PATIENTS AND OTHER PARTICIPANTS: 800 patients, referred to their local hospital Casualty Department. MEASUREMENTS AND MAIN RESULTS: 50.5% of all referrals were considered justified. 15.1% of the patients referred were admitted to hospital. 50.7% of referrals from GPs were found to be correct, against 47% from FCM specialists; and 49% of those referred from rural HCs were correct, as against 45.9% of those referred from urban HCs (no significant differences). Only 54% of referrals had a diagnostic hypothesis, with diagnostic concordance at 50%. There was diagnostic concordance in 28.1% of GP referrals, against 33.3% of FCM specialists; and in 27.5% of those from rural HCs against 26.1% from urban HCs (no significant differences). CONCLUSIONS: We found no differences in the correctness of referrals or diagnostic concordance of patients seen in the CD of our city's health area, neither between patients referred from rural and urban HCs, nor between patients referred by GPs and FCM specialists.     

An automated Thixo‐Forging Plant for Steel Parts

The scope of the article is to describe the automated production of a thixoformed steel part. The production plant was set up within a prototype initiative at the Institute of Metal Forming in cooperation with the Institute of Automatic Control of RWTH Aachen University and industrial partners. Preliminary experiments showed that the quality of the formed parts varied to a great extent due to changing production conditions since the handling of the billet was carried out manually. To eliminate the possible disturbances introduced by the manual handling of the billet, an automation concept has been elaborated in order to guarantee a defined production environment. An industrial robot (KUKA) fulfils the handling tasks like the feeding of the induction coil with the feedstock material and the placing of the heated billet into the hydraulic press. The removal of the formed part from the press is realised by a simple mechanical device in order to be able to use only one gripper. The design of the gripper ensures a minimal heat loss during handling. The induction coil, the gripper system and the cavity are flooded with inert gas in order to prevent scaling. The sequence control for the production of a part is realised on the controller of the robot which provides sufficient PLC functionality and can be easily equipped with the required I/O components to trigger the different automation components.