An investigation of the inhibitory potential of Dronedarone on CYP2J2 mediated astemizole metabolism
Dronedarone is an anti-arrhythmic drug approved in 2009 for paroxysmal and persistent atrial fibrillation. It is less toxic than its predecessor Amiodarone as it does not cause systemic toxicity but has the same pharmacological activity. However the administration of dronedarone to permanent AF and heart failure patients leads to increased risk of stroke and cardiac death. The exact mechanism of the toxicity is currently unknown. Extrahepatic Cytochrome P450 enzymes play a dominant role in organ-specific drug metabolism and toxicity. Cytochrome P450 2J2 (CYP2J2) enzyme, a predominant enzyme found in human cardiac myocytes, metabolizes endogenous arachidonic acid (AA) into epoxyeicosatrienoic acids (EETs) which play an important role in maintaining normal cardiac physiology. Inhibition of CYP2J2 and perturbation of AA metabolic pathway could result in exacerbation of cardiac failure. This research aims to find out whether dronedarone inhibits CYP2J2 in a suitable cell model (H9C2) using astemizole as a probe substrate. Our in-house studies using recombinant CYP2J2 enzyme have shown that dronedarone potently inhibits CYP2J2. Rat myoblast cells (H9C2) will be seeded in 12-well plate and differentiated for 4 days. The cells will be then treated with different concentrations of astemizole and incubated for 24 h. The cells will then be harvested, lysed, and the cell lysate will be analyzed using liquid chromatography-mass spectrometry (LCMS). Using multi-reaction monitoring (MRM) on the LCMS, astemizole concentration as well as its CYP2J2-specific metabolite O-desmethylastemizole concentrations will be measured. The presence of O-desmethylastemizole confirms the metabolism of astemizole by CYP2J2 in H9C2 cells. By plotting a Michaelis-Menten kinetics curve, we will be able to determine the Michaelis constant (KM) and maximum rate of reaction (Vmax). H9C2 cells will be then treated with fixed concentration of astemizole while varying the dronedarone concentration. A decrease in metabolite O-desmethylastemizole conce ntration, indicates inhibition of CYP2J2 metabolism by dronedarone. Using this data, Lineweaver-Burke graph will be plotted, to determine the mode and potency of the inhibition. Our preliminary studies showed that the KM value was 2.7μM. This study will be useful in understanding if dronedarone inhibits CYP2J2 which may lead to clinically significant drug-drug interactions, one of the dangers of polypharmacy. Finally this study will shed a new light on the mechanisms for dronedarone mediated cardiac failure exacerbation.
Development of new manufacturing method to generate hydrogen energy by using waste silicon ~ Reuse of waste of the semiconductor industry for hydrogen community ~
Because of the presence of an activated multiple carbon-carbon bond, α,β-unsaturated sulfones are high-reactive compounds which are widely used in organic synthesis. These compounds readily undergo the reactions of nucleophilic addition and pericyclic processes. At the current moment, a wide range of 1,3-dipolar cycloaddition reactions with α,β-unsaturated sulfones as dipolarophilic systems is known. However the interaction of α,β-unsaturated sulfones with azinium ylides is less studied and limited to only a few examples. In the present study, the interaction between a number of stable isoquinolinium and pyridinium ylides with aliphatic and aromatic vinylsulfones has been investigated. We considered the regioselectivity of these reactions. Mostly cycloadditions of isoquinolinium ylides to α,β-unsaturated sulfones led to the mixtures of isomeric sulfonyltetrahydroindolizines in different ratios. Also we found several examples of high-regioselective addition. The stereochemical result of the cycloaddition was examined by methods of 2D correlational 1H-NOESY NMR spectroscopy and X-ray crystallographic analysis. The process of formation of major regioisomer of cycloaddition N-phenacylisoqunolinium ylide to ethylvinylsulfone was highly stereoselective. The series of new sulfonyltetrahydroindolizines with potential bioactivity were obtained. The structure of all products was proved by IR and 1H NMR
Automated Illustration of Text to Improve Semantic Comprehension
Millions of people worldwide suffer from aphasia, a disorder that severely inhibits language comprehension. Medical professionals suggest that individuals with aphasia have a noticeably greater understanding of pictures than of the written or spoken word. Accordingly, we design a text-to-image converter that augments lingual communication, overcoming the highly constrained input strings and predefined output templates of previous work. This project offers four primary contributions. First, we develop an image processing algorithm that finds a simple graphical representation for each noun in the input text by analyzing Hu mo-ments of contours in images from The Noun Project and Bing Images. Next, we construct a da-taset of 700 human-centric action verbs annotated with corresponding body positions. We train support vector machines to match verbs outside the dataset with appropriate body positions. Our system illustrates body positions and emotions with a generic human representation created using iOS’s Core Animation framework. Third, we design an algorithm that maps abstract nouns to concrete ones that can be illustrated easily. To accomplish this, we use spectral clustering to iden-tify 175 abstract noun classes and annotate these classes with representative concrete nouns. Fi-nally, our system parses two datasets of pre-segmented and pre-captioned real-world images (Im-ageClef and Microsoft COCO) to identify graphical patterns that accurately represent semantic relationships between the words in a sentence. Our tests on human subjects establish the system’s effectiveness in communicating text using im-ages. Beyond people with aphasia, our system can assist individuals with Alzheimer’s or Parkin-son’s, travelers located in foreign countries, and children learning how to read.
Biodegrable Roof
It became necessary to implement a project for the use of vegetable waste generated in the process of handling plantain cultivation, harvest and postharvest, since in Mexico at harvest large quantities of vegetable waste is produced, since only the fruit is used wasting the Pseudostem with leaves and spine. Based on this information, you can take advantage of banana fiber as raw materials in the manufacture of biodegradable sheets and support options that are feasible and possible to make alternative. This is an inexpensive process, also friendly with the environment, so that thousands of banana plants that bear fruit after they become sterile and are discarded without realizing their Pseudostem.
An optimal-route algorithm for an intermodal Metro Manila trip planners using multiple parameters
Parameters of traffic, road availability, and fare were integrated into a web-based application for determining the best public transport routes within Metro Manila in order to assist commuters in their travel planning, whether for business or for pleasure. A user-friendly interface was developed to obtain a user’s place of origin and destination, as well as preferences in travel time, mode of transportation, and cost of journey. By accessing the traffic roadway network of the metropolis, a real-time situation of road availability was obtained, and used in a modified Dijkstra’s shortest-path algorithm to produce a model of a real-time adaptive transport network of Metro Manila. From the model, an optimal route that considers the user’s preferences can be determined. This project will be immensely useful in helping both businessmen and tourists in planning their routes that will save on time and money.
IMPACT OF FIRE WOOD COLLECTION ON WEATHER AND CLIMATE OF JIRDIN VILLAGE
Climate is the average weather in a place over a long period. The changes in climate may be due to natural forces or from human activities. There is growing concern among the scientific community regarding climate change. Biodiversity, forest, monsoons, weather are now at risk due to climate change. Today climate change is happening at an increasing rapid rate. One of the causes is deforestation. Firewood collection in one of the major means the felling of trees. Excessive emission of CO2 by burning, which is a green house gas, responsible for increasing the temperature and causing drastic climate change. Hence, to know the impact of firewood collection in drastic climate change we have undertaken a project entitled, “Impact of firewood collection on weather and climate of Jirdin village.”
A New Generation Colorimetric Method for Lead Analysis: APTAMER MODIFIED GOLD NANOPARTICLES
Lead is a toxic element which is used in the production of chemicals, dyes, accumulators and various industrial areas. It may cause complications even extended to death when it is taken consistently in high amounts. Lead poisoning is in the first place among the occupational diseases. It is gaining importance to develop new and sensitive methods for lead analysis. Because lead poisoning can progress without any symptoms and poisoning level (10µg/dL) is low. Disadvantages of the systems used for lead analysis are such as longer detection time, being expensive and difficult to implement. The aim of this project is to develop a new generation method in order to detect lead in blood, based on aptamer modified gold nanoparticles. We detected the lead in terms of color change obtained in gold nanoparticle solutions, with composite biochemosensor that is prepared with 20 & 80 nm sized gold nanoparticles and TBA(Thrombin Binding Aptamer). While immobilizing TBA to the gold nanoparticles, we benefitted from the magnificent surface affinity of the –SH (Thiol) groups that modified to the TBA. Gold nanoparticles that are used in development of our biotechnological method do not stimulate the immune system. The preparation of aptamers in completely sterile medium provides us to use our system in the lead detection of blood. Our method can also be used in the lead detection of mediums such as waste water, food and soil. We have developed a biochemosensor that can be used to detect the presence and absence of Pb2+ by taking into consideration the toxic effect in the human body. Also we detected the presence of lead colorimetrically, in low concentration levels and wide interval values of 4.4 – 11 µg/dL. The developed system is first that; it provides TBA to be used with its complimentary sequence detects the presence of lead colorimetrically and can be used in physiological media such as blood. Also our system can detect lead in amounts that are lower than the poisoning threshold.