Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma.

BACKGROUND: Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. METHODS: A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. RESULTS: A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was -8.19/min (±15.54/min) and baseline to 2 hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. CONCLUSION: Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

Am I choosing the right career? The implications of COVID-19 on the occupational attitudes of hospitality management students.

The hospitality industry is under threat from COVID-19 and the possibility of future crises remains very real. To improve understanding of how such a crisis impacts the attractiveness of pursuing a career in the hospitality industry, this study examines the effects of negative emotions invoked by COVID-19 on hospitality management students' occupational attitudes. Using a sample of 425 students, we find that in addition to diminishing their occupational identification and in turn, job choice intentions, that the effects of these negative emotions are channeled through three salient motivational pathways, namely self-efficacy, intrinsic and extrinsic motivation, and passion. Thus, the study not only advances theory by providing a more nuanced conceptualization of the effects of negative emotions on occupational attitudes but it identifies important leverage points that can be harnessed to help mitigate the harmful emotional effects of a crisis, such as COVID-19, important and timely contributions that the authors hope will benefit aspiring hospitality industry talent and help restore the attractiveness of careers in the hospitality industry. Future research directions and implications to theory and practice are discussed.

Leaders matter morally: The role of ethical leadership in shaping employee moral cognition and misconduct.

There has long been interest in how leaders influence the unethical behavior of those who they lead. However, research in this area has tended to focus on leaders' direct influence over subordinate behavior, such as through role modeling or eliciting positive social exchange. We extend this research by examining how ethical leaders affect how employees construe morally problematic decisions, ultimately influencing their behavior. Across four studies, diverse in methods (lab and field) and national context (the United States and China), we find that ethical leadership decreases employees' propensity to morally disengage, with ultimate effects on employees' unethical decisions and deviant behavior. Further, employee moral identity moderates this mediated effect. However, the form of this moderation is not consistent. In Studies 2 and 4, we find that ethical leaders have the largest positive influence over individuals with a weak moral identity (providing a "saving grace"), whereas in Study 3, we find that ethical leaders have the largest positive influence over individuals with a strong moral identity (catalyzing a "virtuous synergy"). We use these findings to speculate about when ethical leaders might function as a "saving grace" versus a "virtuous synergy." Together, our results suggest that employee misconduct stems from a complex interaction between employees, their leaders, and the context in which this relationship takes place, specifically via leaders' influence over employees' moral cognition. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium.

E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.

Identification of new potent phthalazine derivatives with VEGFR-2 and EGFR kinase inhibitory activity.

Efforts to develop new antitumor agents are now directed towards multitarget therapies that are believed to have high potency and low tendency to resistance compared to conventional drugs. Herein, we highlighted the synthesis and antitumor activity of five series of phthalazine-based compounds featuring a variety of bioactive chemical fragments at position 1 of the phthalazine nucleus. The antitumor activity of the target compounds was performed against fourteen cancer cell lines where all compounds were active in the nanomolar level. In addition, the mechanism of action of the target compounds was investigated through an enzymatic inhibitory assay against VEGFR-2 and EGFR kinases, revealing potent and preferential activity toward VEGFR-2. Binding mode of the most active compounds was studied using docking experiment.

Performance of an electro-optical solar compass in partially obscured Sun conditions.

Solar compasses are designed to accurately find true North on sunny days. However, no data on their performance are available when sunlight is partially blocked, e.g., by a cloud. We have measured, for the first time to the best of our knowledge, the performance of one of the most accurate electro-optical solar compasses (accuracy better than 0.01 deg) as a function of the solar disk obscuration during the Sun's eclipse on 20 March 2015. The measurements show that the accuracy level is mainly dependent on the asymmetry of the obscuration with respect to the main axis of the optical detection system and, to a lesser extent, on the percentage of the solar disk covered. In particular, azimuth measurement suffered a maximum deviation of 0.08 deg when 35% of the solar disk was asymmetrically obscured. The deviation was smaller when 46% of the solar disk was more symmetrically obscured. This experiment demonstrates that, even in the case of a partially obscured Sun, the electro-optical solar compass maintains an accuracy better than magnetic and electronic compasses.

Contact X-ray microscopy of living cells by using LiF crystal as imaging detector.

In this paper, the use of lithium fluoride (LiF) as imaging radiation detector to analyse living cells by single-shot soft X-ray contact microscopy is presented. High resolved X-ray images on LiF of cyanobacterium Leptolyngbya VRUC135, two unicellular microalgae of the genus Chlamydomonas and mouse macrophage cells (line RAW 264.7) have been obtained utilizing X-ray radiation in the water window energy range from a laser plasma source. The used method is based on loading of the samples, the cell suspension, in a special holder where they are in close contact with a LiF crystal solid-state X-ray imaging detector. After exposure and sample removal, the images stored in LiF by the soft X-ray contact microscopy technique are read by an optical microscope in fluorescence mode. The clear image of the mucilaginous sheath the structure of the filamentous Leptolyngbya and the visible nucleolus in the macrophage cells image, are noteworthiness results. The peculiarities of the used X-ray radiation and of the LiF imaging detector allow obtaining images in absorption contrast revealing the internal structures of the investigated samples at high spatial resolution. Moreover, the wide dynamic range of the LiF imaging detector contributes to obtain high-quality images. In particular, we demonstrate that this peculiar characteristic of LiF detector allows enhancing the contrast and reveal details even when they were obscured by a nonuniform stray light.

Model-based determination of the influence of textile fabric on bioassay analysis and the effectiveness of a textile slow-release system of DEET in mosquito control.

BACKGROUND: Determining the effectiveness of a product in repelling mosquitoes or other flying insects is a difficult task. One approach is to use a bioassay with textile fabric. We investigated the role of the textile substrate in a bioassay with a numerical model, and compared the outcome with known results for DEET. The model was then used to determine the effectiveness of textile slow-release formulations based on coatings, and results were compared with those of a field study in the Cameroon. Slow-release formulations are difficult to evaluate with standard tests, as the compound needs a build-up time not present in these tests. RESULTS: We found excellent correspondence between the model and the known DEET results without matching parameters. Slow-release approaches are deemed possible but have several drawbacks. Modelling can help in identifying optimal use conditions. The field test with a slow-release system performed better than anticipated by the model, with initially more than 90% repellency. DEET-coated textile was considered not to be marketable, however. CONCLUSION: We advise that bioassays characterise in more detail the type of textile fabric used so as to allow conclusions to be drawn by textile modelling. As regards coated-textile slow-release systems, more research is needed. We nevertheless advise usage mainly at entry points, e.g. as scrims.

Determinants of quality of life in ovarian cancer survivors: a pilot study.

OBJECTIVE: Ovarian cancer treatments and outcomes vary substantially, yielding a diverse group of survivors. Few data exist on quality of life (QoL) concerns and the foremost needs of these patients. Our goal was to conduct a pilot study to determine the QoL needs of ovarian cancer survivors to establish priorities for future interventions. METHODS: In this cross-sectional study, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and OV28) QoL questionnaires and one investigator-derived questionnaire were administered in an outpatient setting. Clinical parameters were abstracted and tested for associations with QoL measures. RESULTS: A total of 102 women consented to participate and completed all components. Their mean age was 58 years (range 29 to 85), with 80% having epithelial ovarian carcinoma and 66% high-grade serous carcinoma. Women with stage I (28%), II (15%), III (47%), and IV (10%) lesions were represented in the primary treatment (25%), surveillance (46%), recurrent (23%), and palliative (7%) phases of the survivorship continuum. Fifty-one percent characterized their disease burden as "quite a bit" or "very much," and this did not vary by histology or diagnoses. Global QoL did not vary by clinico-pathologic parameters. Cardiovascular and respiratory comorbidities were associated with EORTC scores in physical functioning (P=0.027 for cardiovascular and P=0.041 for respiratory), global QoL (P=0.03 for cardiovascular and P=0.039 for respiratory), and sexual health (P=0.025 for cardiovascular). Task completion/memory/concentration, anxiety, and fatigue were the distress categories given highest priority by respondents. CONCLUSION: In women with ovarian cancer, clinical factors such as age, stage, and histology did not have a significant impact on QoL. Psychosocial factors have a larger impact on global QoL than physical symptoms.

Objectif : Les traitements contre le cancer de l'ovaire et leurs résultats varient considérablement, il en résulte donc un groupe diversifié de survivantes. Nous ne disposons que de peu de données sur les questions liées à la qualité de vie (QdV) de ces patientes et sur leurs besoins les plus criants. Nous avions pour objectif de mener une étude pilote visant à déterminer les besoins des survivantes du cancer de l'ovaire en matière de QdV afin d'établir les priorités pour ce qui est des futures interventions. Méthodes : Dans le cadre de cette étude transversale, les questionnaires sur la QdV de la European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 et OV28) et un questionnaire formulé par les chercheurs ont été administrés au sein d'une clinique externe. Les paramètres cliniques ont été résumés et analysés en vue d'y déceler des associations avec les mesures de la QdV. Résultats : Au total, 102 femmes ont consenti à participer à l'étude et ont rempli toutes les composantes requises. Leur âge moyen était de 58 ans (plage : de 29 à 85); 80 % d'entre elles présentaient un carcinome épithélial de l'ovaire et 66 % présentaient un carcinome séreux de haut grade histologique. Les femmes présentant des lésions de stade I (28 %), de stade II (15 %), de stade III (47 %) et de stade IV (10 %) étaient représentées dans les phases « traitement primaire ¼ (25 %), « surveillance ¼ (46 %), « récurrent ¼ (23 %) et « palliatif ¼ (7 %) du continuum de la survie. Cinquante et un pour cent des répondantes ont caractérisé le fardeau de la maladie comme étant « plutôt lourd ¼ ou « très lourd ¼ et cette façon de répondre ne variait pas en fonction de l'histologie ou du diagnostic. La QdV globale ne variait pas en fonction des paramètres clinico-pathologiques. Des comorbidités cardiovasculaires et respiratoires ont été associées aux scores EORTC en ce qui concerne le fonctionnement physique (P = 0,027 pour ce qui est des comorbidités cardiovasculaires et P = 0,041 pour ce qui est des comorbidités respiratoires), la QdV globale (P = 0,03 pour ce qui est des comorbidités cardiovasculaires et P = 0,039 pour ce qui est des comorbidités respiratoires) et la santé sexuelle (P = 0,025 pour ce qui est des comorbidités cardiovasculaires). L'incapacité d'achever une tâche / les troubles de la mémoire et de la concentration, l'anxiété et la fatigue figuraient parmi les catégories de détresse auxquelles les participantes ont accordé la priorité absolue. Conclusion : Chez les femmes qui présentent un cancer de l'ovaire, des facteurs cliniques tels que l'âge, le stade et l'histologie n'exerçaient pas un effet significatif sur la QdV. Les facteurs psychosociaux exercent un effet plus important sur la QdV globale que les symptômes physiques.

Understanding the role of embarrassment in gynaecological screening: a qualitative study from the ASPIRE cervical cancer screening project in Uganda.

OBJECTIVE: To define embarrassment and develop an understanding of the role of embarrassment in relation to cervical cancer screening and self-collected human papillomavirus (HPV) DNA testing in Uganda. DESIGN: Cross-sectional, qualitative study using semistructured one-to-one interviews and focus groups. PARTICIPANTS: 6 key-informant health workers and 16 local women, purposively sampled. Key informant inclusion criteria: Ugandan members of the project team. Focus group inclusion criteria: woman age 30-69 years, Luganda or Swahili speaking, living or working in the target Ugandan community. EXCLUSION CRITERIA: unwillingness to sign informed consent. SETTING: Primary and tertiary low-resource setting in Kampala, Uganda. RESULTS: In Luganda, embarrassment relating to cervical cancer is described in two forms. 'Community embarrassment' describes discomfort based on how a person may be perceived by others. 'Personal embarrassment' relates to shyness or discomfort with her own genitalia. Community embarrassment was described in themes relating to place of study recruitment, amount of privacy in dwellings, personal relationship with health workers, handling of the vaginal swab and misunderstanding of HPV self-collection as HIV testing. Themes of personal embarrassment related to lack of knowledge, age and novelty of the self-collection swab. Overall, embarrassment was a barrier to screening at the outset and diminished over time through education and knowledge. Fatalism regarding cervical cancer diagnosis, worry about results and stigma associated with a cervical cancer diagnosis were other psychosocial barriers described. Overcoming psychosocial barriers to screening can include peer-to-peer education, drama and media campaigns. CONCLUSIONS: Embarrassment and other psychosocial barriers may play a large role at the onset of a screening programme, but over time as education and knowledge increase, and the social norms around screening evolve, its role diminishes. The role of peer-to-peer education and community authorities on healthcare cannot be overlooked and can have a major impact in overcoming psychosocial and social barriers to screening.

Healthy eating guidelines for a school jurisdiction: collaborative design and implementation.

PURPOSE: Healthy eating is a determinant of optimal growth, and schools provide an ideal setting in which to influence students' diets. The Healthy Eating Guidelines Initiative (HEGI) was a partnership among education, health, and community stakeholders to develop and implement healthy eating guidelines across a school jurisdiction. An evaluation was conducted to examine the potential impact of the HEGI on the school food environment and students' self-reported diets. METHODS: All schools in the jurisdiction were invited to participate in the evaluation. Participating schools included elementary, middle, high, and mixed grades schools. A school environment assessment and a student questionnaire were used to collect data before and after the HEGI. RESULTS: Twenty-two (71%) of 31 schools participated in the evaluation. The guidelines were successfully implemented in 17 of these 22 schools. Overall, a greater proportion of students reported healthier eating behaviours at the conclusion of the HEGI. In particular, a greater proportion of students in schools with cafeteria-style food service showed significantly improved self-reported dietary behaviours. These changes were not seen among students at schools with limited or no on-site food service. CONCLUSIONS: The findings are consistent with those of previous studies, and indicate that guidelines for a school jurisdiction can have a positive impact on the school food environment and students' food intake. The HEGI shows promise as a strategy to promote healthy eating among students.

Teacher-pupil model: improving poultry health and management through children.

The perception of risks of exposure to avian influenza and other poultry diseases among adults in Tanzania is influenced by their previous experiences, beliefs, and values, which can stand in the way of learning new approaches. We tested a novel disease risk communication approach centered on elementary school pupils, involving their teachers and parents. Age-appropriate training modules were developed and taught to teachers who then taught their pupils through extracurricular activities. The pupils practiced what they learned through club projects and subsequently transmitted what they learned to their parents. In 2009 we developed a poultry health and production curriculum as part of efforts to prevent and control poultry diseases, including avian influenza, in Tanzania. The curriculum developed for veterinarians and veterinary paraprofessionals was adapted for use with elementary school children and translated into Kiswahili. Twenty teachers from 10 primary schools in Mzumbe ward, Morogoro, were trained by poultry veterinary extension experts on teaching the curriculum to standard 5 pupils (ages 11-12 yr). Pupils and teachers practiced the curriculum in four demonstration chicken coops established on the grounds of the Changarawe, Lubungo, Masanze, and Mzumbe primary schools. By October 2011, at the conclusion of the funded project, a total of 202 girls and 193 boys had been trained. Additionally, 34 adults from surrounding villages made official learning tours to the schools and received training from their children and teachers involved in the projects. With at least 75% of the 395 pupils coming from different households, it can be safely assumed that over 250 households have heard about poultry disease risks and how to manage poultry to prevent those risks.

Synthesis and molecular modeling studies of anti-inflammatory active 1H-pyrrolizine-5-carboxamides.

A variety of N-aryl-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamides 5, 6, 8, and 9 were synthesized via reaction of the 2-amino derivatives 4 with acid chlorides and aromatic aldehydes. Meanwhile, 4a,b were obtained through the reaction of 2-pyrrolidinylidenepropanedinitrile 1 with chloroacetanilides 2a,b. In addition, the tricyclic pyrimido[5,4-a]pyrrolizines were formed through conducting the reaction of 4a,b with 90% formic acid. Anti-inflammatory activity screening of some synthesized compounds utilizing in vivo acute carrageenan-induced paw edema standard method in rats exhibited that the prepared heterocycles possess considerable pharmacological properties especially, 4a, 4b, 10a, and 10b which reveal remarkable activities relative to diclofenac sodium (reference standard). Ulcerogenic liability of the highly promising synthesized anti-inflammatory active agents were evaluated and 4a and 4b showed ulcerogenic liability lower than that of the standard used drug. Molecular modeling studies were initiated herein in order to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.

Regulation of protein kinase C Apl II by serotonin receptors in Aplysia.

Serotonin (5-hydroxytryptamine, 5HT) is the neurotransmitter that mediates dishabituation in Aplysia. Serotonin mediates this behavioral change through the reversal of synaptic depression in sensory neurons (SNs). However, the 5HT receptors present in SNs and in particular, the receptor important for activation of protein kinase C (PKC) have not been fully identified. Using a recent genome assembly of Aplysia, we identified new receptors from the 5HT(2) , 5HT(4) , and 5HT(7) families. Using RT-PCR from isolated SNs, we found that three 5HT receptors, 5HT(1Apl(a)) , 5HT(2Apl) , and 5HT(7Apl) were expressed in SNs. These receptors were cloned and expressed in a heterologous system. In this system, 5HT(2Apl) could significantly translocate PKC Apl II in response to 5HT and this was blocked by pirenperone, a 5HT(2) receptor antagonist. Surprisingly, pirenperone did not block 5HT-mediated translocation of PKC Apl II in SNs, nor 5HT-mediated reversal of depression. Expression of 5HT(1Apl(a)) in SNs or genistein, an inhibitor of tyrosine kinases inhibited both PKC translocation and reversal of depression. These results suggest a non-canonical mechanism for the translocation of PKC Apl II in SNs.

Synthesis and vasodilation activity of some novel bis(3-pyridinecarbonitrile) derivatives.

A variety of bis(2-alkoxy-6-aryl-3-pyridinecarbonitriles) 4a-m were prepared via reaction of bis(2-propen-1-ones) 3a-g with malononitrile in the appropriate alcohol in the presence of KOH. The reaction was assumed to take place via Michael addition followed by cyclization due to the alkoxide nucleophilic attack at one of the nitrile groups. This assumption was substantiated by the reaction of ylidenemalononitrile 5 with the corresponding acetophenone 2 in the appropriate alcohol in the presence of KOH. The starting bis(2-propen-1-ones) 3e and f were prepared stereoselectively as E,E'-geometric isomer via condensation of bisbenzaldehyde 1 with substituted acetophenones 2e and f in ethanolic KOH solution. Vasodilating activity screening of the synthesized compounds 4a-g and 4i-m utilizing isolated rat's thoracic aorta pre-contracted by norepinephrine hydrochloride exhibited that many of the tested compounds reveal considerable vasodilating properties, especially 4e and f which reveal remarkable activities.

Structural basis of substrate recognition and specificity in the N-end rule pathway.

The N-end rule links the half-life of a protein to the identity of its N-terminal residue. Destabilizing N-terminal residues are recognized by E3 ubiquitin ligases, termed N-recognins. A conserved structural domain called the UBR box is responsible for their specificity. Here we report the crystal structures of the UBR boxes of the human N-recognins UBR1 and UBR2, alone and in complex with an N-end rule peptide, Arg-Ile-Phe-Ser. These structures show that the UBR box adopts a previously undescribed fold stabilized through the binding of three zinc ions to form a binding pocket for type 1 N-degrons. NMR experiments reveal a preference for N-terminal arginine. Peptide binding is abrogated by N-terminal acetylation of the peptide or loss of the positive charge of the N-terminal residue. These results rationalize and refine the empirical rules for the classification of type 1 N-degrons. We also confirm that a missense mutation in UBR1 that is responsible for Johanson-Blizzard syndrome leads to UBR box unfolding and loss of function.

Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets.

OBJECTIVES: Testosterone formulations that have more steady-state pharmacokinetics, such as subcutaneously implanted testosterone pellets, may cause less erythrocytosis than i.m. injections of shorter acting androgen esters. We, therefore, sought to define the prevalence, predictors, and proximate basis (role of erythropoietin) for polycythemia (hematocrit >0.50) in hypogonadal men receiving testosterone implants long term. DESIGN: A cross-sectional study was conducted in an academic andrology center with a longitudinal subgroup analysis. PATIENTS: A total of 158 hypogonadal men aged 14-84 years (mean age 46.7 years) treated on average for 8 years (range 0-21 years). MEASUREMENTS: Trough blood testosterone and hematocrit. Serial serum erythropoietin concentrations were measured in 16 volunteers. RESULTS: Positive univariate associations between polycythemia (hematocrit >0.50) and log(testosterone) (odds ratio (OR) 24.7, 95% confidence interval (CI): 4.3, 141.2, P<0.01) and age (OR 1.1, 95% CI: 1.0, 1.1, P=0.03) and a borderline relationship with current smoking (OR 4.2, 95% CI: 0.9, 20.0, P=0.08) were unveiled. A sensitivity analysis using alternate definitions of polycythemia was performed to capture all potential covariants. Multivariate regression analysis incorporating all potential covariants disclosed the independent OR of developing polycythemia (after adjusting for smoking and age) for log(testosterone) to be 15.0 (95% CI: 2.5, 90.8). Duration of testosterone therapy did not alter the risk of polycythemia. A direct relationship between testosterone and erythropoietin was observed (P=0.05). CONCLUSIONS: Higher trough serum testosterone concentrations but not duration of treatment predict the development of polycythemia in men receiving long-acting depot testosterone treatment.

Regioselective synthetic approaches towards 1,2,8,9-tetraazadispiro[4.1.4.2]trideca-2,9-dien-6-ones of potential antimicrobial properties.

Reaction of 2,5-bis(arylmethylidene)cyclopentanones 1a-d with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a,b) in 1:2 molar ratio proceeds in a high regioselective manner affording monocycloadducts 3 and dicycloadducts in the form of two isomers 4, 5. Single crystal X-ray diffraction studies of the isolated crystalline form of 3c support the established structure and indicate that the formed product is 7E, 4S, 5R. Antimicrobial activity screening of the synthesized compounds 3-5, utilizing a variety of gram-positive (Staphylococcus aureus, Enterococcus fecalis and Streptococcus agalactiae), gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris) and yeast (Candida albicans), exhibited that all the prepared analogues acquire promising activities against both gram-positive and gram-negative bacteria especially compounds 3b, 4a (antimicrobial active agents against gram-positive bacteria) and 3c (antimicrobial active agent against gram-negative bacteria).

Synthesis of [1,2,4]triazolo[1,5-a]pyridines of potential PGE2 inhibitory properties.

A variety of 5-amino-6,8-dicyano-1H-[1,2,4]triazolo[1,5-a]pyridin-4-ium-2-thiolate containing compounds 3a-i, 5a-c were prepared via reaction of arylidenemalononitriles 1a-c, 4a and 4b with 2-[(substituted amino)thiocarbonyl]cyanoacetohydrazides 2a-d in refluxing ethanol in the presence of triethylamine. Anti-inflammatory activity screening of the synthesized compounds (at a dose of 50mg/kg body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method in rats exhibited that the prepared heterocycles possess considerable pharmacological properties especially, 3f, 3h, 5b and 5c which reveal remarkable activities relative to indomethacin (which was used as a reference standard at a dose of 10mg/kg body weight). PGE(2) inhibitory properties of the highly promising synthesized anti-inflammatory active agents (3f, 3h, 5b and 5c) were determined by PGE(2) assay kit technique, which reveal remarkable activity coinciding greatly with the observed anti-inflammatory properties. Anti-tumor activity screening of 3b and 3e, as representative examples of the synthesized compounds, at a dose of 10 microM utilizing 59 different human tumor cell lines, representing leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate and kidney exhibited that the tested compounds reflect mild or no activity at all against most of the used human tumor cell lines. However, compound 3e reveals considerable anti-tumor properties against leukemia CCRF-CEM and HL-60(TB) cell line.

Facile synthesis of bis(4,5-dihydro-1H-pyrazole-1-carboxamides) and their thio-analogues of potential PGE(2) inhibitory properties.

A variety of bis(3-aryl-4,5-dihydro-1H-pyrazole-1-thiocarboxamides) 2a-h were prepared via reaction of bis(2-propen-1-ones) 1a-h with thiosemicarbazide in ethanolic KOH solution. Meanwhile, bis(3-aryl-4,5-dihydro-1H-pyrazole-1-carboxamides) 3a-d were obtained through reaction of 1a-d with semicarbazide hydrochloride in refluxing with acetic acid. Anti-inflammatory activity screening of the synthesized compounds 2a-f,h; 3a-d (at a dose of 50mg/kg of body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method in rats exhibited that many of the tested compounds reveal considerable anti-inflammatory properties, especially 2e and f which reveal remarkable activities relative to indomethacin (which was used as a reference standard at a dose of 10mg/kg of body weight). Ulcerogenic liability for the most promising prepared anti-inflammatory active agents (2b,c,e and f) (at a dose of 50mg/kg of body weight) using indomethacin as a reference standard (at a dose of 10mg/kg of body weight) indicated that compounds 2b and c exhibit lower ulcer index values than the used reference standard itself. PGE(2) inhibitory properties of the highly promising synthesized anti-inflammatory active agents (2b,c,e and f) were determined by PGE(2) assay kit technique, which reveal remarkable activities coincide greatly with the observed anti-inflammatory properties.