Factors That Determine The Optimal Concentrations Of Par2 Essay

Factors That Determine The Optimal Concentrations Of Par2 Essay

Length: 1294 words (3.7 double-spaced pages)

Rating: Better Essays

Open Document

Essay Preview

c.2b Dose response studies for PAR2 activity modulators in vivo. Initially we will determine the optimal concentrations of PAR2 modulating compounds to use for the studies and assess for toxic effects in our humanized PAR2 mouse. After administering PAR2 modulating compounds to the lungs we will estimate their half-life in both lung and serum using HPLC/MS. While detailed pharmacokinetics of the PAR2 modulating compounds is not a central goal of this application, this will assist optimizing dosing of the PAR2 modulating compounds. After pharmacokinetic assessment we will determine optimal concentrations of the compounds for in vivo studies. A limited number of PAR2 humanized mice (three mice/concentration of PAR2 modulator x eight concentrations) will be used to determine optimal doses. Initial concentration ranges will be determined by the in vitro testing already completed or done as part of Specific Aim 1. We will assess a one week exposure to of PAR2 modulating compounds, the same as shown in our preliminary data. It is possible, if not likely, that there could be more than one dose of these compounds that has a biological effect. Table 1 shows the effect of these compounds in vitro, and demonstrates that some of them have partial agonism or antagonism depending on their concentration. We will select the optimal concentrations that impact inflammation, sensitization, or lung function and analyze them in greater detail and with better resolution in c.2c.
Planned observations to assess responses to PAR2 modulating compounds include lung inflammation (BALF for total cells, neutrophils, eosinophils, and macrophages as well as semi-quantitative histologic assessment). We will use ELISA (on BALF) and RTPCR (on lung tissue) to as...

... middle of paper ...

...out we have in hand, and we have received institutional funding for this and have ordered the mice. If there were insurmountable problems the experiments could be completed with non-humanized wild-type C57B6 mice. Both the PAR2-/- and the humanized PAR2 mouse are on C57B6 backgrounds.
The research environment provides all the institutional support needed to successfully complete and analyze the proposed experiments. The proposed analysis of the mice involves techniques that our laboratory has developed expertise in, including allergen exposure in mice, assessment of lung function by Flexivent, and the immunologic assessment of allergic lung inflammation. Alternatives, such as using multiplexed bead arrays for cytokine analysis and using morphometric analysis of lung tissue if semi-quantitative histology scoring lacks resolution for the studies will be considered.

Need Writing Help?

Get feedback on grammar, clarity, concision and logic instantly.

Check your paper »

Determine the Concentration of Calcium Hydroxide Essay

- Determine the Concentration of Calcium Hydroxide 2HCl (aq) + Ca (OH)2(aq) [IMAGE] 2H20(l) + CaCl2(s) In this experiment I need to find out the concentration of calcium hydroxide. I am provided with 250cm3 of limewater, which has been made such that it contains 1g dm-3 of calcium hydroxide. To increase the accuracy of the results it would be helpful if the volume of the alkali equalled the volume of the acid used, and I know that the concentration of the alkali is approximately 1gmdm-3 which is roughly equal to 0.013mol by using the equation Mole = Mass / Mass of one mole =[IMAGE] =0.013 moldm-3 Also I am provided with hydrochloric acid, which has a c...   [tags: Papers]

Free Essays
459 words (1.3 pages)

To Determine the Concentration of Limewater Essay

- To Determine the Concentration of Limewater Apparatus: â–¡ 10cm3 volumetric pipette â–¡ marker pen â–¡ teat pipette â–¡ rinse bottle and distilled water â–¡ bench cloth â–¡ 250cm3 beaker â–¡ small funnel â–¡ 100cm3 beakers â–¡ 1dm3 volumetric flask and stopper â–¡ 100cm3 burette with stand Chemicals: â–¡ Standardised 2.00mol dm-3 HCl acid solution. â–¡ Approx. 1g dm-3 Ca(OH)2 in 250cm3 of limewater. â–¡ Methyl orange indicator Balanced equation: Ca(OH)2 + 2HCl à CaCl2 + 2H2O Safety: â–¡ Wear safety goggles and lab coats through out the experiment....   [tags: Free Essays]

Free Essays
385 words (1.1 pages)

Investigation to Determine the Effect of a Range of Different Concentrations of Sugar Solutions on the Potato Cells

- Investigation to Determine the Effect of a Range of Different Concentrations of Sugar Solutions on the Potato Cells Aim My aim is to set up an investigation to determine the effect of a range of different concentrations of sugar solutions on potato cells. I predict that the higher the concentration the more the length and mass of the potato chip will decrease. The lower the concentration the more the length and mass of the potato chip will increase. This should happen due to the law of osmosis....   [tags: Papers]

Free Essays
1000 words (2.9 pages)

Essay about Different Concentrations Of Sucrose And Water Solutions

- The four different dialysis tubes containing four different concentrations of sucrose/ water solutions, in two different concentrations of solutions was a great representation of osmosis (Fig. 2). The water in the dialysis tubing of A, (1%) left the areas of low concentration in attempts to equal out the areas of high concentration of sucrose (10%), in the container to reach equilibrium. The bag had started with a total mass of 10.4g and was weighed in 15 minute intervals for an hour. In the first 15 minutes, bag A had weighed 10.2g, losing .2g of water....   [tags: Concentration, Solution, Tonicity, Chemistry]

Better Essays
771 words (2.2 pages)

The Effect Of Modulation Of Par2 Signaling Using Vivo Vitro Models Of Allergic Asthma

- (120-126). However, we have recently shown that our potent/specific PAR2 activators can act apically to alter salt and water movement in primary cultured mouse tracheal epithelial cells (109), and thus have developed a model that better fits natural exposure in healthy and/or susceptible individuals -- apical application. Because PAR2 expression has been reported to increase in asthmatic airways (74), and, because increased PAR2 expression in animal models increases the inflammatory response (106), if time allows, we will consider using asthmatic cell cultures (available from Lonza) in our experiments to better evaluate the ability for optimized PAR2 modulators to affect asthmatic allergic r...   [tags: Asthma, Lung, Inflammation, Immune system]

Better Essays
1022 words (2.9 pages)

If The Optimal Ph For Trypsin Essay

- When our group began our experiment we started with the hypothesis: “If the optimal pH for trypsin is 8, then reactions occurring in environments above or below will result in lower proteolytic activity and thereby slow reaction rates.” After testing several pH’s 5, 7, 8, 9, and 11 it is impossible to fully accept or reject our hypothesis that we set especially using the rationale about trypsin in the small intestines. By trypsin being located in the small intestines where the pH is 8 one would believe that any other pH whether above 8 or below 8 would cause for trypsin to have a slower proteolytic activity....   [tags: Temperature, Fahrenheit, Celsius, Absolute zero]

Better Essays
943 words (2.7 pages)

The Effect Of Auxin Concentrations On The Growth Rate Bean Plant Essay example

- In this investigation different concentrations of Auxin mixtures (no Auxin, 2mg, 10mg and 50mg) were applied to the stem cutting of a Dwarf French Bean plant and in findings which Auxin concentrations had the greatest effect of the growth rate bean plant. In relation to the research question, this investigation was carried out to prove homeostasis in plants. The hypothesis states that when the plant stem is cut, and replaced with an Auxin mixture, which is made up of Ethanol, Lanolin and Auxin powder, is in replacement of the stem....   [tags: Plant morphology, Fern, Plant stem]

Better Essays
1021 words (2.9 pages)

Acid Concentrations And The Germination Rate Of The Seeds Essays

- From concentrations of 0 ppm to 2500ppm, there is a clear trend created between the gibberellic acid (GA3) concentrations and the germination rate of the seeds. With the exception of the 1000ppm data point, as the seeds were exposed to water with higher gibberellic acid concentrations (up to 2500ppm), they showed a reduction in the time taken for a visible seedling to break the surface coating of the seeds. This overall trend confirmed the first aspect of the hypothesis, which stated that increasing gibberellic acid concentrations would lead to faster germination rates....   [tags: Germination, Seed, Gibberellin, Abscisic acid]

Better Essays
1242 words (3.5 pages)

Optimal Size Of A Firm Essay examples

- Optimal Size Of A Firm The optimum size of a firm is a very subjective idea. The ways in which size can help or hinder a firm vary from which angle you a looking at the situation from. Size can have its benefits and its drawbacks, and each firm will have its own benefits and drawbacks that come from either increasing in size, or remaining small, and these will depend on the market in which the firm is in, the current economy, and in some cases the preferences of the manager(s). For example a small firm may be small for many reasons....   [tags: essays research papers]

Free Essays
861 words (2.5 pages)

The Optimal Foraging Theory Essay

- The Optimal Foraging Theory Abstract.Ý The theory of optimal foraging and its relation to central foraging was examined by using the beaver as a modelÝ (summarizes the Introduction). Beaver food choice was examined by noting the species of woody vegetation, status (chewed vs. not-chewed), distance from the water, and circumference of trees near a beaver pond in North Carolina (summarizes the Methods).Ý Beavers avoided certain species of trees and preferred trees that were close to the water.Ý No preference for tree circumference was noted (summarizes the Results).Ý These data suggest that beaver food choice concurs with the optimal foraging theory (summarizes...   [tags: Papers]

Better Essays
1458 words (4.2 pages)