Sinteza i farmakološka evaluacija 3-cikloheksil-2-supstituiranih hidrazino-3H-kinazolin-4-ona kao analgetika i antiinflamatorika

A series of novel 3-cyclohexyl-2-substituted hydrazino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from cyclohexyl amine. Title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic behavior. The compound 3-cyclohexyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (4c) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities compared to the reference standard diclofenac sodium. Interestingly, test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid.Reakcijom amino skupine 3-cikloheksil-2-hidrazino kinazolin-4(3H)-ona s različitim aldehidima i ketonima sintetizirani su novi 3-cikloheksil-2-supstituirani hidrazino-kinazolin-4(3H)-oni. Početni spoj 3-cikoheksil-2-hidrazino kinazolin-4(3H)-on pripravljen je iz cikloheksilamina. Sintetizirani spojevi testirani su na analgetsko i protuupalno djelovanje te ulcerogena svojstva. Spoj 3-cikloheksil-2-(1-metilbutiliden-hidrazino)-3H-kinazolin-4-on (4c) imao je najjače analgetsko i protuupalno djelovanje, nešto jače nego referentni spoj diklofenak natrij. Osim toga, testirani spojevi imaju samo blago ulcerogeno djelovanje u usporedbi s acetilsalicilnom kiselinom

How Flies Are Flirting on the Fly

Background  Flies have some of the most elaborate visual systems in the Insecta, often featuring large, sexually dimorphic eyes with specialized “bright zones” that may have a functional role during mate-seeking behavior. The fast visual system of flies is considered to be an adaptation in support of their advanced flight abilities. Here, we show that the immense processing speed of the flies’ photoreceptors plays a crucial role in mate recognition. Results  Video-recording wing movements of abdomen-mounted common green bottle flies, Lucilia sericata, under direct light at 15,000 frames per second revealed that wing movements produce a single, reflected light flash per wing beat. Such light flashes were not evident when we video-recorded wing movements under diffuse light. Males of L. sericata are strongly attracted to wing flash frequencies of 178 Hz, which are characteristic of free-flying young females (prospective mates), significantly more than to 212, 235, or 266 Hz, characteristic of young males, old females, and old males, respectively. In the absence of phenotypic traits of female flies, and when given a choice between light emitting diodes that emitted either constant light or light pulsed at a frequency of 110, 178, 250, or 290 Hz, males show a strong preference for the 178-Hz pulsed light, which most closely approximates the wing beat frequency of prospective mates. Conclusions  We describe a previously unrecognized visual mate recognition system in L. sericata. The system depends upon the sex- and age-specific frequencies of light flashes reflecting off moving wings, and the ability of male flies to distinguish between the frequency of light flashes produced by rival males and prospective mates. Our findings imply that insect photoreceptors with fast processing speed may not only support agile flight with advanced maneuverability but may also play a supreme role in mate recognition. The low mating propensity of L. sericata males on cloudy days, when light flashes from the wings of flying females are absent, seems to indicate that these flies synchronize sexual communication with environmental conditions that optimize the conspicuousness of their communication signals, as predicted by sensory drive theory

‘They’re more like ordinary stroppy British women’: Attitudes and expectations of maternity care professionals to UK-born ethnic minority women

Objective To explore the attitudes and expectations of maternity care professionals to UK-born ethnic minority mothers. Methods Qualitative in-depth interviews with 30 professionals from eight NHS maternity units in England that provide services for large proportions of women of black Caribbean, black African, Indian, Pakistani and Irish descent. Results All the professionals reported providing care to both UK-born and migrant mothers from ethnic minorities. Most of them felt that they could differentiate between UK-born and migrant mothers based mainly on language fluency and accent. ‘Westernized dress’ and ‘freedom’ were also cited as indicators. Overall, professionals found it easier to provide services to UK-born mothers and felt that their needs were more like those of white English mothers than those of migrant mothers. UK-born mothers were generally thought to be assertive and expressive, and in control of care-related decision-making whereas some South Asian Muslim women were thought to be constrained by family influences. Preconceived ideas about ethnic minority mothers' tolerance of pain in labour, use of pharmacological pain relief measures and mode of delivery were recurring themes. Women's education and social class were felt to be major influences on the uptake of maternity care, regardless of ethnicity. Conclusions Professionals appeared to equate the needs of UK-born ethnic minority women with those of white English women. Overall, this has positive implications for care provision. Despite this, specific behavioural expectations and unconscious stereotypical views were evident and have the potential to affect clinical practice

Effects of Dabigatran in Mouse Models of Aging and Cerebral Amyloid Angiopathy

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) (Tg N = 7; WT N = 10) or vehicle (Tg N = 9; WT N = 7) by gavage for 4 weeks. Anticoagulation effects of DE were confirmed using thrombin time assay. No mice experienced intracerebral hemorrhage. Cerebral microhemorrhage analysis, performed using Prussian-blue and H&E staining, showed no significant change in either number or size of cerebral microhemorrhage in DE-treated animals. Analysis of biochemical parameters for endothelial activation (ICAM-1), blood-brain barrier disruption (IgG, claudin-5, fibrinogen), microglial activation (Iba-1), or astrocyte activation (GFAP) showed neither exacerbation nor protective effects of DE in either Tg2576 or WT mice. Our study provides histological and biochemical evidence that aged mice, with or without predisposing factors for brain hemorrhage, tolerate anticoagulation with dabigatran. The absence of dabigatran-induced intracerebral hemorrhage or increased frequency of acute microhemorrhage may provide some reassurance for its use in high-risk patient populations

Lactadherin blocks thrombosis and hemostasis in vivo : correlation with platelet phosphatidylserine exposure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73556/1/j.1538-7836.2008.03010.x.pd

A simple test of quantumness for a single system

We propose a simple test of quantumness which can decide whether for the given set of accessible experimental data the classical model is insufficient. Take two observables $A,B$ such that for any state $\psi$ their mean values satisfy $0\leq \leq \leq 1$. If there exists a state $\phi$ such that the second moments fulfill the inequality $>$ then the system cannot be described by the classical probabilistic scheme. An example of an optimal triple $(A,B,\phi)$ in the case of a qubit is given.Comment: 3 pages, no figures, corrected typos, text essentially amende

Intelligent Software for Ecological Building Design

Building design is a complex process because of the number of elements and issues involved and the number of relationships that exist among them. Adding sustainability issues to the list increases the complexity of design by an order of magnitude. There is a need for computer assistance to manage the increased complexity of design and to provide intelligent collaboration in formulating acceptable design solutions. Software development technology today offers opportunities to design and build an intelligent software system environment that can serve as a reliable intelligent partner to the human designer. In this paper the authors discuss the requirements for an intelligent software design environment, explain the major challenges in designing this environment, propose an architecture for an intelligent design support system for sustainable design and present the existing technologies that can be used to implement that architecture

Genetic and Pharmacological Modifications of Thrombin Formation in Apolipoprotein E-deficient Mice Determine Atherosclerosis Severity and Atherothrombosis Onset in a Neutrophil-Dependent Manner

Background: Variations in the blood coagulation activity, determined genetically or by medication, may alter atherosclerotic plaque progression, by influencing pleiotropic effects of coagulation proteases. Published experimental studies have yielded contradictory findings on the role of hypercoagulability in atherogenesis. We therefore sought to address this matter by extensively investigating the in vivo significance of genetic alterations and pharmacologic inhibition of thrombin formation for the onset and progression of atherosclerosis, and plaque phenotype determination. Methodology/principal findings: We generated transgenic atherosclerosis-prone mice with diminished coagulant or hypercoagulable phenotype and employed two distinct models of atherosclerosis. Gene-targeted 50% reduction in prothrombin $(FII^{−/WT}:ApoE^{−/−})$ was remarkably effective in limiting disease compared to control $ApoE^{−/−}$ mice, associated with significant qualitative benefits, including diminished leukocyte infiltration, altered collagen and vascular smooth muscle cell content. Genetically-imposed hypercoagulability in $TM^{Pro/Pro}:ApoE^{−/−}$ mice resulted in severe atherosclerosis, plaque vulnerability and spontaneous atherothrombosis. Hypercoagulability was associated with a pronounced neutrophilia, neutrophil hyper-reactivity, markedly increased oxidative stress, neutrophil intraplaque infiltration and apoptosis. Administration of either the synthetic specific thrombin inhibitor Dabigatran etexilate, or recombinant activated protein C (APC), counteracted the pro-inflammatory and pro-atherogenic phenotype of pro-thrombotic $TM^{Pro/Pro}:ApoE^{−/−}$ mice. Conclusions/significance: We provide new evidence highlighting the importance of neutrophils in the coagulation-inflammation interplay during atherogenesis. Our findings reveal that thrombin-mediated proteolysis is an unexpectedly powerful determinant of atherosclerosis in multiple distinct settings. These studies suggest that selective anticoagulants employed to prevent thrombotic events may also be remarkably effective in clinically impeding the onset and progression of cardiovascular disease

Suboptimal asthma care for immigrant children: results of an audit study

<p>Abstract</p> <p>Background</p> <p>Little is known on the scope and nature of ethnic inequalities in suboptimal asthma care for children. This study aimed to assess (1) ethnic differences in suboptimal asthma care for children with an asthma exacerbation who consulted a physician, and (2) ethnic differences in the nature of suboptimal care.</p> <p>Methods</p> <p>All children aged 6–16 years who during a period of six months consulted the paediatric department of the Academic Medical Centre-University of Amsterdam or one of the six regional primary care centres with an asthma exacerbation were included. Clinical guidelines were systematically converted to review criteria following the strategy as proposed by the Agency for Health Care Policy and Research. Based upon these review criteria and their experience experts of two multidisciplinary panels retrospectively assessed the quality of care and its (possible) failure to prevent the occurrence of asthma exacerbation.</p> <p>Results</p> <p>Only a small number of children (n = 35) were included in the analysis as a result of which the ethnic differences in suboptimal care were not significant. However, the results do indicate immigrant children, in particular 'other non-Western' children (n = 11), more frequently to receive suboptimal care related to the asthma exacerbation when compared to ethnic Dutch children. Furthermore, we found the nature of suboptimal care to differ with under-prescribing in the 'other non-Western' group (n = 11), lack of information exchange between physicians in the Surinamese/Antillean group (n = 12) and lack of education, and counselling of patients and parents in the ethnic Dutch (n = 12) as the most relevant factor.</p> <p>Conclusion</p> <p>Ethnic inequalities in the scope and nature of suboptimal asthma care for children in the Netherlands seem to exist. For the non-western immigrant groups the results indicate the importance of the prescription behaviour of the medical doctor, as well as the supervision by one health care provider.</p