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Recently, a promising HIV experimental vaccine failed to prevent experiment participants from infection. And it’s reported that gut microbiome interfere with the effect of the vaccine. Another important finding for the reasons of failure is that protein-binding antibodies were found in the blood that had not been injected with the experimental vaccine.

The vaccine is HVTN 505, the most promising one in recent years, but the development process stopped in 2013 for that, it was found failed to protect experiment participant from infecting with HIV in the trial period.

Good news is that scientists have found the main reason, which will give direction to the new successful HIV vaccine R&D.

It’s the first time that scientists found microbiome played an interfering role in the process when a vaccine took effect. At present scientists propose a hypothesis that microbiome is the origin of the failure, and the hypothesis will lead new studies on the influence of microbiome on immune system.

By tracking the reason of why the vaccine failed to work, scientists found after the injection of the vaccine, a type of antibody will be produced. The antibody is also produce at very young age after the child is given to birth, but there won’t be such antibody made when the human body goes into maturity in adulthood.

Scientists also found the antibody on people that were naturally infected with HIV virus. And when they test the people who received the experimental vaccine, they found similar situation. The vaccine would boost the production of antibodies that bound with HIV protein and other bacteria. Antibodies protein binding with virus and microbiome in the blood of participant before the vaccine injection were also found, which showed that the vaccine driven antibodies were produced by B cells in bodies.

And now scientists think that the HIV protein mimic helpful gut bacteria by binding with other bacteria, and then escape from the attack of immune system. But all is in the stage of brave guess, more researches are needed to find out the real reason of the failure, and lay a better foundation for the R&D of new HIV vaccine.

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Protein binding assay is used to test the protein binding extent. In other words, it’s to measure the binding level of a protein. Before finding out what protein binding assay is, the definition of protein binding should be clearly understood.

Generally, protein binding determines a drug’s efficacy in human bodies. It can both strengthen and weaken the effect of drugs, but in different ways. Protein binding, as it means literally, refers to protein making bond with other substances, which in the pharmacological context is the bond that drugs make to the molecules in blood, like red blood cells and membrane.

Protein binding level can be used to describe the drug efficiency. The drugs bound with other molecules won’t perform its medical properties, whilst the unbound drug will take the responsibility and carry out the tasks it shoulder. If 90% percent of a drug bond to other substance and become bound drugs, the rest 10% unbound drug will keep in the blood stream and take medical effect. That’s how protein binding determines drug efficacy. The bound drugs still can take effect but the ability will be detracted. The more bonds they make, the lower medical property level will be performed. Fewer bonds directly lead to smaller size, meaning better ability of passing through tissues.

How does the binding be made? That’s a kind of complicated question to answer. Proteins combine with other molecules including proteins at binding sites, a protein may contain several such sites, which are always in the form of indentations. The binding will be made when a molecule fit into the indentation. Thus more indentations a protein has, the bigger the protein will be after being bound. Protein binding will change with its surrounding alteration, like stress and pregnancy.

However, the indentation is not available for a fixed type of molecule; it can be filled by any molecules that fit to it chemically, which pose danger to bodies. If two drugs are taken by a patient at the same time, and both of them bond to a same type of molecule, but one is with stronger ability to combine with the targeted molecule, thus the other drug will remain more unbound and effective protein in the blood and take effect. In this way overdose situation may appear.

Protein binding assay

Protein binding assay is designed to identify the tendency of a protein to combine with other molecules. In the assay, plasma or tissue will be employed. With these substances, protein will be incubated for a certain period, and then they will pass through a very accurate filter. The unbound proteins can successfully pass the filter, however the bound ones can’t for that they are enlarged by the binding with other molecules.

Drug that are newly developed will be tested with protein binding assay to roughly determine the amount of free drug will be existed in blood stream and take effects, which is a must-have process before a newly invented drug can be put into market.

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The new class of malarial compounds can cure malaria from a very complete way by killing the parasites caused by malaria. And another good news for this new finding is that the newly found compound can help stop malaria at the very beginning stage with a low cost at about $1, and it’s very promising to be a single dose drug for malaria treatment. Bad news is that the compound has very poor physicochemical property, which is under improvement by the research team that has found them.

The number of people that get malaria is huge and about 584,000 died of the disease in 2013 only. Most cases of malaria happened in Africa, where sanitary condition is very poor, providing environment for malaria’s spread. Thus a cure way for this epidemic is in urgent need.

The new compound kills Plasmodium which is the origin of malaria drug resistance and the major cause for most severe types of malaria. The compound works by targeting a protein synthesis, a necessary part of the parasite.

The research team did a lot of work to find this compound. By screening about 5000 kinds of compound which are potential to kill the malaria parasite, the compound class was picked out for it can kill types of parasites not a single one. Poor physicochemical property is the most distinct character of the compound, and now scientists are trying to improve its quality in this area by design, synthesis and physiochemical testing.

The compound is aimed to reach the level of DDD107498 in physicochemical properties. Since the compounds that reach this level in properties has longer plasma half-life and better pharmaceutical quality in metabolic stability , fatherly, they will carry with less drug toxicity.

antimalaria

With the physicochemical properties leveling up to DDD107498, it will be of great potential to make the compound be a single dose drug to prevent and cure malaria, but with another drug to work in compliance, the compound will better function in the battle with the parasites for decreasing drug resistance. That’s to say the effect of the compound will more obvious.

However, it’s still unknown for the scientists that how long it will take for the compound to develop resistance for malaria in human bodies and it’s kind of difficult to recognize that. At present, the compound is in the stage of being tested for its safety. If result is proved to be positive, the compound will go into clinical trial in about one year.

Physicochemical properties of a newly found compound should be carefully examined and with the present technology, such properties can be improved to reach an ideal state.

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market

A research aiming to investigate the worldwide ADME-toxicology market situation was carried out in three regions , which are America, Asia Pacific, and EMEA( Europe, Middle East, and Africa ). The research mainly take the revenue made by the sales of products involved in the in vivo and in vitro testing technologies into consideration. After a relatively throughout investigation, it’s estimated that there would be a 10.65% compound annual growth rate during the five years from the present year ( the year of 2015 ) to 2019.

ADME-toxicology products principally including instruments, assays systems, reagents, and software solutions. Besides with revenues generated by these products, the research also considered the companies who are leading in the sales. Agilent Technologies, Bio-rad laboratories, Promega, Sigma Aldrich are key companies in the industry was taken references during the research. Along with those companies are some prominent companies, like Creative-Animodel providing ADME Services, Cytopulse, Entelos and Li-CORE Biosciences etc.

Market drivers are from biotechnology companies, pharmaceutical enterprises and some drug discovery institutes, the business of which will frequently involve in ADME-toxicology tests and related materials, as well as equipment. Absolutely, choosing these companies for references is because that they are the main consumers in the field.

Growing at a 10.65% annual rate is a quite high increasing level for the industry. However, the rate is influenced by many other aspects, among which the most challengable one is the high cost for the advances and innovation in technologies and equipment, remaining a lot of work to be done.

In all, it can be concluded from the research that there will be increasing market shares for enterprises in the future five years but requires the companies themselves to be up-leveled in the advances of both products and services, besides may need them to re-schedule the investment strategies on technology and equipment improvement.

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Recent studies show that plasma can be a contributing factor to wound healing, and it helps the open wound on skin heal quickly. The finding is being transformed into a new technology for the treatment of skin disorders, and it will probably results in a portable device.

Wounds are inevitable in our daily lives and the situation is especially serious for the little children and the elderly people. With little attention the wound will deteriorate or even need the wound bearers to go to hospital. And in the often case, it won’t be very short to be healed for the wounds, some of them takes as long as 6 weeks or longer. However the new plasma treatment can prevent the skin disorders like Atopic dermatitis, psoriasis and temporary wound from deterioration and occasionally save the time and energy for going to hospital often.

In the process, cold plasma will directly work on the skin in the atmospheric condition, during which electrode will directly put in a place very close to skin and responsibly skin will act like the other electrode, in this way a complete plasma connection is created and there will be a electric field formed converting the involved area into non-thermal plasma.

But how does the plasma work to accelerate the process of healing? With the formation of electric field, pulse will come into being, which will stimulate the angiogenesis process by increasing the blood flow to the wound area, thus achieving the effect of accelerating the process of healing.

This plasma treatment for open wound combines several therapies being available in the market, including UV, electrotherapy and ozone. But plasma is the one with highest level of effectiveness.

What about the safety? Before the therapy being put into market, the priory issue should be considered is safety, since it’s never been applied on human beings. The researching institute has carried out a risk-benefit analysis to check the property and the answer is positive. It won’t bring side effect or harmfulness to the human bodies when using it.

With the help of the new treatment for skin disorders and occasional wounds healing at a faster speed. People will suffer from the pain for less days and it helps to reduce the risk of infection by a large scale. The research results will be quickly turned into products making people benefiting from it. And some ambitious researchers are conceiving the idea of making a portable device which can be owned by household.

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ADME is the process that drugs take effects at a molecule level once they are absorbed, and it’s the abbreviation of absorption, distribution, metabolism, and excretion, covering the whole course of drug taking effects in the bodies of human and rodent animals. Thus ADME Services will meet a wide range of related biochemical needs. Generally there are in vitro ADME services and in vitro services.

In vivo ADME services require higher on technologies and expertise, as live rodent animals like rats and dog will be involved, while the in vitro services put more stress on the equipment needed in the experiments.

Furtherly, ADME services are classified into two categories, ADME studies support and custom services. ADME studies like physicochemical studies work on the determination of drug molecule properties, including solubility, chemical stability, PMAPA Permeability, aiming to find out the performance of the test agent in any micro-circumstance, then contribute to the drug design process.

Rodent studies are a part of the ADME studies, designed to test the effect that drug will present on the carriers. Furthermore, bioequivalence studies are also under ADME studies, and they are settled to assess the biologically equivalent drug of the test agent.

ADME custom services consist of pharmacokinetic analysis of blood, metabolite isolation and  characterization, bioavailability evaluations, formulation screening and optimization and etc. Pharmacokinetic analysis of blood is to observe the drug effect changes in blood with time variation, and all other services in this category is to better understand the drug properties and performance to present a better final drug with good treatment effect but less side effect and addiction.

ADME studies and services can help the pharmaceutical companies and related research labs from all sides by providing professional support and detailed information in vivo or in vitro from the absorption of drugs to the excretion, and finally assist them in probing more about the property and performance of a drug.

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As a part of ADME studies, rodent study plays an important role in learning the behavior of animals during the pharmaceutical researches or just with the aim to learn more about the animals themselves. A recent research oriented to explore if there is prosocial behaviors between the individual rat was done. And it showed that there is such kind of behaviors existing.Rats are notorious as breakers. They can eat anything that is edible for them, like cushion, couch, electronics, even human flesh. Thus they leave a bad impression on people. To find out weather rats have empathy to their kind is the aim of the research.

Two rats were put into different side of a box, there is a wall with a locked door between the two sides. And one side is drowned with water, which is very wet, and the other side is dry and with good ventilation. When the rat in water is at the edge of drowning, the rat in the other side probed to open the door and after several trials the door opened, then the drowning rat was saved

In addition, researchers exchanged the role of the two rats, and the result was surprising. It shows that the rat in the dry counterpart which had the experience of drowning opened the door at a much faster speed. But later experiments showed that the presentation of the rat in danger mattered, which would motivate the helper rat to learn to open the door more quickly.

Furthermore, researchers also studied the behaviors of rats when they were faced with the choices of helping the distressed rat or opening the other door for food. Surprisingly, they chose to save the rat in danger firstly and then open the door heading for food.

All the experiments carried out in the study show that rats do have compassion toward their distressed fellows,  though they are always considered cruel breakers by people.

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ADME
What’s ADME

When we talk about ADME, that means four processes taken place when the drug molecule was administered to humans or animals bodies. They are Absorption, Distribution, Metabolism, Excretion, and ADME is the acronym that has been used for decades to describe such studies.

In fact, the ADME affects the drug levels in plasma and tissues, as well as the kinetics of its exposure to the tissues, which influence the performance of the drug.