Stability, in-Vitro and in-Vivo Release Studies from Metronidazole Ointments

The influence of ointment formulation on the stability, the in-vitro release and the in-vivo absorption through the skin of rabbits was investigated. The choice of the selected ointments has no influence on the drug stability with the exception of an acidified emulsion base. A good correlation between in-vitro release and in-vivo absorption was found revealing that metronidazole was quickly released and effectively absorbed from a polyethylene glycol base.     

Post-traumatic stress disorder and smoking: a systematic review.

We conducted a systematic review of what is known about the relationship between post-traumatic stress disorder (PTSD) and smoking to guide research on underlying mechanisms and to facilitate the development of evidence-based tobacco treatments for this population of smokers. We searched Medline, PsychINFO, and the Cochrane Central Register of Controlled Trials and identified 45 studies for review that presented primary data on PTSD and smoking. Smoking rates were high among clinical samples with PTSD (40%-86%) as well as nonclinical populations with PTSD (34%-61%). Most studies showed a positive relationship between PTSD and smoking and nicotine dependence, with odds ratios ranging between 2.04 and 4.52. Findings also suggest that PTSD, rather than trauma exposure itself, is more influential for increasing risk of smoking. A small but growing literature has examined psychological factors related to smoking initiation and maintenance and the overlapping neurobiology of PTSD and nicotine dependence. Observational studies indicate that smokers with PTSD have lower quit rates than do smokers without PTSD. Yet a few tobacco cessation treatment trials in smokers with PTSD have achieved quit rates comparable with controlled trials of smokers without mental disorders. In conclusion, the evidence points to a causal relationship between PTSD and smoking that may be bidirectional. Specific PTSD symptoms may contribute to smoking and disrupt cessation attempts. Intervention studies that test behavioral and pharmacological interventions designed specifically for use in patients with PTSD are needed to reduce morbidity and mortality in this population.     

Prediction of psychoticlike symptoms in hypothetically psychosis-prone college students.

Correlates of psychotic and psychoticlike symptoms were examined in 60 college students who scored deviantly high on the Perceptual Aberration Scale. High scorers on this scale who also scored high on both the Impulsive Nonconformity Scale and the Depression subscale of the General Behavior Inventory (GBI) showed the most deviant psychotic and psychoticlike symptoms. Moreover, performance on a task of referential communication, the Password Task, was significantly related to such symptoms. The Perceptual Aberration Scale, the Impulsive Nonconformity Scale, and the GBI Depression subscale are recommended for concurrent use in mass screening to select individuals likely to exhibit psychotic or psychoticlike symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Outplacement: Client characteristics and outcomes.

Outplacement firms developed in response to corporate downsizings to assist former upper-level employees in seeking reemployment. An important question for practitioners who assist clients in outplacement is how the personal characteristics that clients bring to the situation influence their success in finding a new job. The present archival study examined demographic variables, previous job history, and personality characteristics as predictors of outplacement outcomes. Outplacement duration was predicted by previous income, and new earnings were predicted by previous earnings, sex, and years with previous employer. The need for prospective, longitudinal research that examines the coping process in outplacement is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating a graphical notation for modelling software development methodologies

This work aims at evaluating a graphical notation for modelling software (and other kinds of) development methodologies, thus demonstrating how useful the graphical aspects can be for sharing knowledge between the people responsible for documenting information and those responsible for understanding and putting it into practice. We acknowledge the importance of having a common set of symbols that can be used to create, use and disseminate information for a larger audience than is possible today with a variety of alternatives and lack of a common ground. Using a cognitive dimensions framework, we make a standard evaluation of the elements and diagrams of the notation proposed to support the ISO/IEC 24744 methodology metamodel standard, considering the trade-offs between different dimensions. We suggest improvements to this existing notation based on this analysis, in the context of improving communication between creators and users of methodologies.     

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H₂S) is a cardioprotector. Previous research proposed a positive role of H₂S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H₂S, which decreases the expression of adenosine A_2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.     

The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.     

Quantification of secondary structure prediction improvement using multiple alignments

The use of multiple sequence alignments for secondary structurepredictions is analysed. Seven different protein families, containingonly sequences of known structure, were considered to providea range of alignment and prediction conditions. Using alignmentsobtained by spatial superposition of main chain atoms in knowntertiary protein structures allowed a mean of 8% in secondarystructure prediction accuracy, when compared to those obtainedfrom the individual sequences. Substitution of these alignmentsby those determined directly from an automated sequence alignmentalgorithm showed variations in the prediction accuracy whichcorrelated with the quality of the multiple alignments and distanceof the primary sequence. Secondary structure predictions canbe reliably improved using alignments from an automatic alignmentprocedure with a mean increase of 6.87percnt;, giving an overallprediction accuracy of 68.5%, if there is a minimum of 25% sequenceidentity between all sequences in a family.     

THE “UCKRON-1” TEST PROBLEM FOR REACTION ENGINEERING MODELING

Testing kinetic models against a “true” and detailed kinetic expression was the aim of the Workshop on Kinetic Model Development at the Denver AIChE Meeting in August, 1983. For this purpose an artificial reaction mechanism was created, based on the known thermodynamics of the methanol synthesis as a framework. The kinetic rate laws, that were derived from this mechanism, were made thermodynamically consistent by achieving agreement between equilibrium constants calculated at various temperatures from the given, real original thermodynamic relationship and those calculated from the detailed reversible kinetic expressions.

Using the artificial kinetics as the "true" one, CSTR experiments were simulated. The results of a statistically designed set of experiments were published after 5% random error was added to the data. Participation was invited for all interested to correlate the data, develop kinetic models and to calculate the performance of the specified reactor.

The results of 19 submitted entries are summarized with the conclusion that the models had more differences than were expected, but their predictive values were not as different as was anticipated, if the extreme high production rates due to thermal runaways are not considered. This in turn points out the necessity to check models experimentally, in pilot plant, not only for predicted optimum, but also for calculated runaway conditions. Models which did not capture the true character of this reaction failed to predict the onset of runaway reactions.     

Microstructure and morphology of amine-cured epoxy coatings before and after outdoor exposures—An AFM study

Atomic force microscopy (AFM) has been used to study the morphology and microstructure of an amine-cured epoxy before and after outdoor exposure. Measurements were made from samples prepared in an essentially CO₂-free, H₂O-free glove box and from samples prepared in ambient conditions. For those prepared in a CO₂-free glove box, AFM imaging was conducted on (1) an unexposed air/coating surface, (2) an unexposed coating bulk, (3) an unexposed coating/substrate interface, and (4) a field exposed air/coating surface. For samples prepared in ambient conditions, only the unexposed air/coating surface was investigated. The same regions of the exposed samples were scanned periodically by the AFM to monitor changes in the surface morphology of the coating as UV exposure progressed. Small angle neutron scattering and Fourier transform infrared spectroscopy (FTIR) studies were performed to verify the microstructure and to follow chemical changes during outdoor exposure, respectively. The results have shown that amine blushing, which occurs only under ambient conditions, had a significant effect on the surface morphology and microstructure of the epoxy. The surface morphology of the samples prepared under CO₂-free, dry conditions was generally smooth and homogeneous. However, the interface and the bulk samples clearly revealed a two-phase structure consisting of bright nodular domains and dark interstitial regions, indicating an inhomogeneous microstructure. Such heterogeneous structure of the bulk was in good agreement with results obtained by small angle neutron scattering of unexposed samples and by AFM phase imaging of the degraded sample surface. The relationship between submicrometer physical changes and molecular chemical degradation is discussed. Presented at the 82nd Annual Meeting of the Federation of Societies for Coatings Technology, October 27–29, 2004, in Chicago, IL.