Teratogenic effects of gabapentin on the skeletal system of Balb/C mice fetuses

Objectives: To evaluate the effects of gabapentin )GBP( administration on mice fetuses. Methods: This study was carried out in Birjand University of Medical Sciences during 2008. Thirty Balb/c pregnant mice were divided randomly into 3 groups: 2 experimental groups that received 25 mg/kg )I( and 50 mg/kg )II( of GBP intraperitoneally for the first 15 days of pregnancy, and a control group that received normal saline. External observations of day 18 fetuses and skeleton double staining were performed. Results: Both experimental groups showed similar disorders that can be categorized as the following: 1( decrease of fetal body weight and increase of fetal resorption, 2( macroscopic malformations, and 3( skeletal malformations. Fetal body weights were significantly lower, and fetus resorptions were significantly higher in both treated groups compared to the control group. Macroscopic malformations included exencephaly, limbs defects, brachygnathia, vertebral column deformity, and fetuses with severe retarded growth. Skeletal malformations included delayed ossification, scoliosis, calvaria deformity, and mandibular hypoplasia. Conclusion: This study revealed that GBP can induce previously unreported severe malformations if it is used continuously during the implantation, neurulation, and organogenesis stages of pregnancy. Therefore, it is suggested that great caution should be exercised in using GBP during the early stages of pregnancy until further studies are performed to better understand these effects

Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice

Background: Carbamazepine is an antiepileptic drug used widely for the treatment of epileptic seizures and neuropathic pain. Several malformations in humans, mainly neural tube defects, have been reported as a consequence of its use during pregnancy. The association between maternal use of carbamazepine and congenital eye malformations is not very well understood. Objective: The purpose of this study was to examine this association after intraperitoneal injection of carbamazepine during the period of organogenesis in mice. Methods: Balb/c timed-pregnant mice were divided into 4 experimental and control groups. Two experimental groups received daily intraperitoneal injections of 15mg/kg (group I) or 30mg/kg (group II) of carbamazepine on gestational days 6 to 15. Two control groups received normal saline or Tween 20 (polysorbate 20). Dams underwent Cesarean section on gestational day 18 and embryos were harvested. External examination for eye malformations, routine histological processing of malformed fetuses to study eye morphology, and skeletal staining were performed. Results: The mean weight and crown-rump of the fetuses in both experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, calvarial deformity, vertebral deformity, short tail, and brachydactyly. Premature opening of one or both eyes with mild to severe exophthalmos occurred in the 2 experimental groups. Deformed lens, retinal folds with undeveloped layers, and corneal folds with absence of surface epithelium were detected in both experimental groups. Conclusions: This study, to the best of our knowledge, showed for the first time that intraperitoneal administration of carbamazepine at clinically comparable doses during organogenesis can induce several eye malformations in mice. The implication of these results needs to be considered when carbamazepine is administered during human pregnancy. © 2010 Informa UK Ltd

Putting the Customer Back in the Center of SOA with Service Design and User-Centered Design

This article introduces a methodology used for designing the online presence of a Swiss SME providing Cloud Services. The Web application used for the purchasing and administration, backed by a Service-Oriented Architec-ture (SOA), has been designed to be customer-centric using a combination of different techniques borrowed from the fields of ethnomethodology, service de-sign and user-centered design. The tools employed include service blueprint de-sign and affinity diagram analysis followed by prototyping and subsequent usa-bility evaluation. This collaborative methodology explained with the help of the applied research project use case is seen to yield excellent results in terms of customer-orientation

Evaluation of NPP1 as a novel biomarker of coronary artery disease: A pilot study in human beings

Purpose: Coronary artery calcification (CAC) is utilized as an important tool for global risk assessment of cardiovascular events in individuals with intermediate risk. Ecto phosphodiesterase/nucleotide phosphohydrolase-1(ENPP1) converts extracellular nucleotides into inorganic pyrophosphate and it is a key regulator of tissue calcification that adjusts calcification in tissues like vascular smooth muscle cells. The main purpose of this clinical study was to find out the correlation between ENPP1 serum concentration and CAC in human for the first time. Methods: In this study 83 patients (16 diabetic patients and 67 non-diabetic patients) with coronary artery disease who fulfilled inclusion and exclusion criteria, entered the study. For all patients a questionnaire consisting demographic data and traditional cardiovascular risk factors were completed. Computed tomography (CT)-Angiography was carried out to determine coronary artery calcium score and enzyme-linked immunosorbent assay (ELISA) method was used for measuring ENPP1 serum concentrations. Results: There was a reverse significant correlation between ENPP1 serum concentration and total CAC score and also CAC of right coronary artery (RCA) (P < 0.05) in non-diabetic patients. Conclusion: On the basis of our results, ENPP1 serum concentration may be a suitable biomarker for coronary artery disease at least in non-diabetic patients. However, more studies with higher sample size are necessary for its confirmation. © 2018 The Authors

a festival at the interstices of value systems

This chapter puts observations made in previous parts of this book into perspective, as it highlights the diversity of positionalities in internal relations in the context of the organization of an Iranian cultural festival. As agents that appeared in previous chapters come to interact with the young and unexperienced organizer, Behruz, during fundraising activities and at the festival itself, it becomes clear that their exchanges are driven by multiple, partly compatible, partly competing strategies of capital creation deriving from individual or collective politics of value within a large variety of local and transnational social fields

Seven HCI Grand Challenges

This article aims to investigate the Grand Challenges which arise in the current and emerging landscape of rapid technological evolution towards more intelligent interactive technologies, coupled with increased and widened societal needs, as well as individual and collective expectations that HCI, as a discipline, is called upon to address. A perspective oriented to humane and social values is adopted, formulating the challenges in terms of the impact of emerging intelligent interactive technologies on human life both at the individual and societal levels. Seven Grand Challenges are identified and presented in this article: Human-Technology Symbiosis; Human-Environment Interactions; Ethics, Privacy and Security; Well-being, Health and Eudaimonia; Accessibility and Universal Access; Learning and Creativity; and Social Organization and Democracy. Although not exhaustive, they summarize the views and research priorities of an international interdisciplinary group of experts, reflecting different scientific perspectives, methodological approaches and application domains. Each identified Grand Challenge is analyzed in terms of: concept and problem definition; main research issues involved and state of the art; and associated emerging requirements

A prebiotic, Celmanax™, decreases Escherichia coli O157:H7 colonization of bovine cells and feed-associated cytotoxicity in vitro

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>O157:H7 is the most common serovar of enterohemorrhagic <it>E. coli </it>associated with serious human disease outbreaks. Cattle are the main reservoir with <it>E. coli </it>O157:H7 inducing hemorrhagic enteritis in persistent shedding beef cattle, however little is known about how this pathogen affects cattle health. Jejunal Hemorrhage Syndrome (JHS) has unclear etiology but the pathology is similar to that described for <it>E. coli </it>O157:H7 challenged beef cattle suggestive that <it>E. coli </it>O157:H7 could be involved. There are no effective treatments for JHS however new approaches to managing pathogen issues in livestock using prebiotics and probiotics are gaining support. The first objective of the current study was to characterize pathogen colonization in hemorrhaged jejunum of dairy cattle during natural JHS outbreaks. The second objective was to confirm the association of mycotoxigenic fungi in feeds with the development of JHS and also to identify the presence of potential mycotoxins. The third objective was to determine the impact of a prebiotic, Celmanax™, or probiotic, Dairyman's Choice™ paste, on the cytotoxicity associated with feed extracts <it>in vitro</it>. The fourth objective was to determine the impact of a prebiotic or a probiotic on <it>E. coli </it>O157:H7 colonization of mucosal explants and a bovine colonic cell line <it>in vitro</it>. The final objective was to determine if prebiotic and probiotic feed additives could modify the symptoms that preceded JHS losses and the development of new JHS cases.</p> <p>Findings</p> <p>Dairy cattle developed JHS after consuming feed containing several types of mycotoxigenic fungi including <it>Fusarium culmorum</it>, <it>F. poae</it>, <it>F. verticillioides</it>, <it>F. sporotrichioides</it>, <it>Aspergillus</it><it>flavus</it>, <it>Penicillium roqueforti, P. crustosum, P. paneum </it>and <it>P. citrinum</it>. Mixtures of Shiga toxin - producing <it>Escherichia coli </it>(STEC) colonized the mucosa in the hemorrhaged tissues of the cattle and no other pathogen was identified. The STECs expressed Stx1 and Stx2, but more significantly, Stxs were also present in the blood clot blocking the jejunum. Mycotoxin analysis of the corn crop confirmed the presence of fumonisin, NIV, ZEAR, DON, 15-ADON, 3-ADON, NEO, DAS, HT-2 and T-2. Feed extracts were toxic to enterocytes and 0.1% Celmanax™ removed the cytotoxicity <it>in vitro</it>. There was no effect of Dairyman's Choice™ paste on feed-extract activity <it>in vitro</it>. Fumonisin, T-2, ZEAR and DON were toxic to bovine cells and 0.1% Celmanax™ removed the cytotoxicity <it>in vitro</it>. Celmanax™ also directly decreased <it>E. coli </it>O157:H7 colonization of mucosal explants and a colonic cell line in a dose-dependent manner. There was no effect of Dairyman's Choice™ paste on <it>E. coli </it>O157:H7 colonization <it>in vitro</it>. The inclusion of the prebiotic and probiotic in the feed was associated with a decline in disease.</p> <p>Conclusion</p> <p>The current study confirmed an association between mycotoxigenic fungi in the feed and the development of JHS in cattle. This association was further expanded to include mycotoxins in the feed and mixtures of STECs colonizing the severely hemorrhaged tissues. Future studies should examine the extent of involvement of the different STEC in the infection process. The prebiotic, Celmanax™, acted as an anti-adhesive for STEC colonization and a mycotoxin binder <it>in vitro</it>. Future studies should determine the extent of involvement of the prebiotic in altering disease.</p

Genetic Determinants of Phosphate Response in Drosophila

Phosphate is required for many important cellular processes and having too little phosphate or too much can cause disease and reduce life span in humans. However, the mechanisms underlying homeostatic control of extracellular phosphate levels and cellular effects of phosphate are poorly understood. Here, we establish Drosophila melanogaster as a model system for the study of phosphate effects. We found that Drosophila larval development depends on the availability of phosphate in the medium. Conversely, life span is reduced when adult flies are cultured on high phosphate medium or when hemolymph phosphate is increased in flies with impaired Malpighian tubules. In addition, RNAi-mediated inhibition of MAPK-signaling by knockdown of Ras85D, phl/D-Raf or Dsor1/MEK affects larval development, adult life span and hemolymph phosphate, suggesting that some in vivo effects involve activation of this signaling pathway by phosphate. To identify novel genetic determinants of phosphate responses, we used Drosophila hemocyte-like cultured cells (S2R+) to perform a genome-wide RNAi screen using MAPK activation as the readout. We identified a number of candidate genes potentially important for the cellular response to phosphate. Evaluation of 51 genes in live flies revealed some that affect larval development, adult life span and hemolymph phosphate levels