Drug Research - Science topic

Important project Halil İbrahim Bilkay Wishing you success !

The clinical trial process is usually very long (to be counted in several years); gaining the statistical power of medical evidence is delayed in 80% of all phases (0-4), because of the usual lack of volunteers.

Yes validation is must

Meanwhile, the result of my search has been published in Social Theory and Health, you consult the full article here:

It is often the case that a chemical synthesis produces a racemic mixture of products. These can often be separated by chiral chromatography. Perhaps this methodology could be used to decide which fraction has which absolute stereochemistry.

This is the way I understand it.

The same chemical that excites a receptor at a low dosage may be considered to block it at a high dosage, potentially. This only works out if the chemical/drug in question has a dopaminergic effect, but less than that produced by the docking of the 'real' dopamine.

If the individual has LOW dopamine, our chemical that fits into the (previously empty) receptor excites it and produces a dopaminergic effect.

If our individual has HIGH dopamine receptor activity, then our chemical can snug into the receptor and prevent dopamine from docking. This decreases the dopaminergic effect, since this chemical has a weaker dopamine-releasing effect than dopamine would have.

Thus a chemical can have opposite effects depending on its dosage.

A second mechanism that may occur is where high doses may desensitize the receptor, leading to an inhibition effect over time. Here's a paper that discusses this in the context of dopamine:

Hope this was helpful!

Some coagulation factors are not indispensable for normal hemostasis, such as FXII. I'm not sure for PAI-1, but  it's reported that heterozygote deficiency of PAI-1 has observable side effects. And researchers say Amish people lack the gene of PAI-1, thus they are favorable research subjects...

OK.  I think it is a good idea.

In our lab, we follow the protocol in the attached methods article, which includes calculating the fold-resistance. There is a table on page 7 that has cell lines and treatments with a small range of fold-resistance for each which indicates the cells are resistant. Hope this is helpful and good luck with your experiments.

Such studies for in vitro release are carried out using dialysis membrane. You can use beaker method or Franz diffusion cell

You can add pen strep in lower concentration..but it may also affect your results of release study because pen strep is simply antibiotic 

I was looking for better spatial distribution control, the drug is 5-MeO-DMT. This drug cross the blood-brain barrier but at low doses without IMAO will not reach their target sites in time to do the desired experimental effect. As we want to evaluate a single dose effect, the i.c.v injection would be more reliable.

I'm willing to start testing different doses in behavioral tests

DRI needs to be calculated from IC50 values obtained at the same timepoints. Consequently, actual DRI in your example would be higher than 20, because IC50 = 20 uM at 72 hrs in resistant cell line would likely correspond to IC50 > 20 uM at 48 hrs.

Dear C. Jellinek,

The following links contain publications which may be helpful:

Hoping this will be helpful,

Rafik

Sir, with all due respect, in my opinion finasteride does not have any effect on sexual function

Hi Asim,

The gentler way to "clean" the outer buffer of your liposome suspension is dialysis.

make sure to have the same osmomolarity between the dialysis buffer and your drug solution.

there is plenty of dialysis system available i usually use floatalyzer from Sigma Aldrich.

Another way is to use size exclusion chromatography (de-saltling column) but it yield in a small dilution of your sample.

hope it helped

Regards

Etienne

I am a sociologist.  Either of my coauthors who are pharmacologists may be able to answer your question.  Please contact Dr. Glen Hanson at glen.hanson@pharm.utah.edu.  

Why the genes, always the genes...How about DNase low activity?

See HS Taper references long ago also and Daoust R> Tumor  cells that are resistant have lowest DNase activity as well as RNase activity. Papers are accessible through internet at pubmed and J Histochemistry and Cytochemistry>

Dear Angel,

The attached review entitled " Three-Dimensional Cell Culture Systems

and Their Applications in Drug Discovery and Cell-Based Biosensors" might be helpful.

Rafik

Anitbody neutralization assays have been quite extensively used in cell biology or biochemistry experiments. You may check if any works in animals have been attempted with anti-TLR antibodies. Since immunotherapies exist and since TLRs are located on surface (before activation and internalization), this neutralization strategy in principle should work. 

There is a chemical (peptide based) inhibitor against MyD88, by Invivogen. But they may take long time to synthesize and the compound was out of stock when I inquired them like a year ago. 

You can ask a chemical synthesis company to make the peptide for you instead, since the sequence is known. 

Thanks sir for your valuable information

I would not recommend it in gout attacks due to delayed onset if i m not wrong about cyclodextrine function

herewith am attaching the excel file having equation of all model fill the reading of dissolution (drug release) and check the model followed by particular

. 

Dear Shamprasad,

In classification methods, knowing the form of the data helps to choose a right classification methods. Since we usually have few information about that, I propose you to check each classifier method on your problem. A software called Weka is created for this purpose. You can download it from below link:

Based on this software, you can test many classifier methods on your dataset, to find the fittest on your problem.

best regards,

Hamid

By the way, in Germany ADHD is in the TOP 5 diagnoses refer to permissions to buy medical marijuana

For permeability coefficient calculation, please read the following articles:

Stadelmann 1966. Methods Cell Physiol. 2: 143-216.

Stadelmann 1969. Annu. Rev. Plant Physiol. 20: 585-606.

Stadelmann and Lee-stadelmann 1989. Methods Enzymol. 174:246-266.

You must give more details on your experimental design to allow us to give you the more suited answer. Do you follow the cell count in time or not? Do you start from the same cell culture for all concentrations of your drug or not? How many replicates, in which conditions, and so on...

If you have enough different concentrations for each drug, my guess would be to fit a sigmoidal dose-response model (but if cell count is small, it may not be suited due to the inherent discreteness of the results...) --- the exact method to do this fit will depend on the answers to the above questions, and to complete details about your experiment ---. You can then compare parameters of these curves to have your answer.

Before any drugs or even diagnosis it would be wonderful to see a few simple things eliminated... parasites (especially toxoplasmosis), Lymes disease, Pyroluria, Porphyria, heavy metal exposure, medical and other drug reactions, dental and other infections, sleep deprivation, dehydration, nutritional deficiency and changes such as recent vaccines, nicotine patch use, exposure to toxins or sudden life changes. Three days of rest, safety, talk, sleep, hydration and nutrition before any diagnosis. Then 3 more if positive changes are evident.... During this time blood sugar imbalance, over or under thyroid production, faulty methylation, B vitamin deficiency, histamine excess, adrenal imbalance, acetylcholine imbalance and food allergies can be explored.

What if diagnosis and treatment locks in the symptoms along with life long stigma and loss of hope? Perhaps its all a diagnostic error.... There are many areas of resistance to the psychiatric model of treatment and perhaps for good reason. Common sense has to come back into medicine for it to hold its credibility in an age when patients self diagnose via the internet and the lack of real physical evidence of mental illness continues to elude science.

Depending on the chemical structure of the drug (cationic/anionic) and the specific substrates for the transporters (though not too much is known regarding selectivity and specificities) the activation happens.

Since increased expression levels of apoptosis protein expressions in efflux transporter's activation had been positively correlated so apoptotic signaling mechanisms seem to be related in efflux transport activation. Could be both the structure of the chemical substrate/drug and the apoptotic signaling work synergistically.

Thank you Mr. Gulam Husain. I am doing the study following OECD guidelines now.

For transwell assays one usually tries to have non-proliferating cells, so usually it is the best yo use Mitomycic C as written by Ashley Haluck-Kangas or just by serum starvation. I usually serum starve cells overnight before the assay so the proliferation is drastically decreased. Of course, You need to check before with the simple proliferative assay if it works. So, serum starve Your cells or treat them with Mitomycin C, plant them into wells with some space to spare and add Your chemical to some wells, then You will see if it works.

And for the methods - check these books:

the first two are a little older but give a good overwiev of the metodology which does need a very complicated equipment (mostly)

Cell Migration: Developmental Methods and Protocols, ed. Jun-Lin Guan, Methods in Molecular Biology vol. 294

and

Methods in Cell-Matrix Adhesion, ed. Josephine C. Adams, Methods in Cell Biology, vol. 69

and some newer methodology (but needing, e.g., confocal microscope):

Extracellular Matrix Protocols, ed. Aharona Even-Ram, Vira V. Artym, Methods in Molecular Biology vol. 522

Adhesion Protein Protocols, ed. Amanda S. Coutts, Methods in Molecular Biology vol. 1046 (very good chapter about the use of xCELLigence system)

Thanks

Dear Dr Sachan, some paper suggest that there is correlation between cytotoxicity and brine shrimp lethality in plant extracts. But is better using both bioassays

simultaneously as quality control. Other animal models very useful for toxicity in vitro testing are zebrafish and Caenorhabditis elegans, used for measure liver and kidney toxicity in zebrafish embryos. Such as aquatic toxicity testing. With best regards