Category: Science Page 1 of 2

A brief guide to antitumor natural product molecule

Since the 1940s, humans have begun to use synthetic, small-molecule inhibitors to treat tumors. A series of drugs, such as alkylating agents, fluorouracil, methotrexate, cyclophosphamide, have been launched on the market. However, most of these molecules have large side effects.

Since the 1940s, humans have begun to use synthetic, small-molecule inhibitors to treat tumors. A series of drugs, such as alkylating agents, fluorouracil, methotrexate, cyclophosphamide, have been launched on the market. However, most of these molecules have large side effects.

 Since the 1950s, drug developers in many countries and regions, including the United States, began to focus on natural small molecules that have anti-cancer effects. For example, the National Cancer Institute (NCI) commissioned botanists in the United States Department of Agriculture (USDA) in 1960 to provide 1,000 plants each year for the National Cancer Chemotherapy Service Center (CCNSC) for the screening of anticancer drugs. Over the years of efforts, more natural products with anti-cancer effects have been found and successfully marketed, becoming star therapeutic drugs in the corresponding field. Let’s see what these natural compounds are.

1. Paclitaxel — the first tubulin inhibitor

Initially, researchers discovered white alkaloid toxic constituents from the branches and leaves of Taxus chinensis (Pilger) Rehd., but they didn’t know what the specific substances are. Then, American researcher Barclay specially extracted taxus samples and screened them for activity and found it has significant antitumor activity. In further extraction studies, researchers found the most active white crystalline monomer in the extract and named it paclitaxel.

Since then, paclitaxel has been found to have a tubulin inhibitory effect. It is also the first tubulin inhibitor to be discovered by humans. In 1984, the FDA approved clinical trials of paclitaxel and officially granted its marketing approval in 1992. At present, paclitaxel has become a recognized broad-spectrum antitumor drug in the world, and further drug development on paclitaxel has not ceased. In 2004, FDA approved the listing of a paclitaxel derivative, docetaxel.

2. Camptothecin

Camptothecin is isolated from Camptotheca Acuminata, a unique plant of the Davidia involucrata family in China, and has significant antitumor effects. Since the research found that camptothecin is different from general chemotherapeutics, the activity of topoisomerase I has attracted great interest from researchers. Starting from the 1960s, many drug developers have begun drug development of camptothecin and its derivatives. FDA approved the listing of camptothecin derivatives topotecan and irinotecan, which marks the expanded contribution of camptothecin to the antitumor combat.

3. Homoharringtonine: still effective in imatinib-resistant populations

Chinese folks have a long history of using Cephalotaxus Fortunei to treat cancer. Subsequent research has proved that the chemical constituents of the plants, including harringtonine, homoharringtonine, hetero harrington Ester base, deoxyharringtonine, and pseudodehydroharringtonine, have significant inhibitory effects on the growth of leukemia cells. In 2012, the FDA accelerated the approval of homoharringtonine for the treatment of leukemia. In particular, homoharringtonine is still effective in imatinib-resistant populations, which has attracted much attention and achieved success.

4. Ginsenoside Rg3: a new class of antitumor drugs

Ginsenoside Rg3 is a dammarane-type tetracyclic triterpenoid saponin, whose chemical structure was determined in 1983, and subsequently proved to have antitumor effects. It is a new class of anti-tumor drugs developed in China and has also obtained a number of international patents. Ginsenoside Rg3 is also one of the representative drugs of natural antitumor products.

5. Vinblastine and colchicine

Vinblastine and vinblastine are isolated from vinca flowers of the oleander family and have been shown to have significant antitumor effects. Eli Lilly and Company has invested a lot of energy in this field, and obtained clinical approval from FDA in 1963 through clinical trials. It is also a classic old medicine in the anti-cancer history. Furthermore, colchicine is also an old medicine targeted for the treatment of cancer, fibrosis and inflammation.

Summary

In addition to the drugs mentioned above, podophyllotoxin, pinnin, indorubin, berberine, agroglycine, anisin, and gossypol are also natural product molecules that have been marketed and play important roles in their respective fields. Moreover, in recent years, with the deepening of the understanding and emphasis on natural products in the drug research and development community, it has brought many new opportunities for the development of natural anti-tumor moleculesPsychology Articles, such as naphthol. It is certain that natural medicine will play a greater role in the antitumor field in the future.

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

The author has been writing articles for 6 years in the area of biochemistry,biology and science.

The author has been writing articles for 6 years in the area of biochemistry,biology and science.

What are the therapeutic implications of gpcr inhibitors

The G protein-coupled receptors (GPCRs) family is the largest family of membrane proteins in humans and an important target for many drugs. There are more than 800 members in this family, including ab…

The G protein-coupled receptors (GPCRs) family is the largest family of membrane proteins in humans and an important target for many drugs. There are more than 800 members in this family, including about 400 olfactory receptors. According to statistics, sales of drugs targeting GPCR account for 27% of the global market. GPCRs have always been one of the important targets for drug discovery because they regulate a wide variety of physiological processes and have targets for drug discovery on the cell surface. Among them, GPCR19 has always been one of the most important targets in the development of new drugs. Moreover, recent research on GPCRs has opened up new strategies for the development of GPCR drugs. For example, allosteric sites that target GPCRs can alter the structure, homeostasis, and function of the receptor, thereby increasing the therapeutic effect. Moreover, an in-depth study of receptor activation mechanisms allows researchers to design agonists that bias activation of specific intracellular signaling pathways, thereby reducing the side effects of activating other signaling pathways. The crystal structures of 44 unique GPCRs and 205 ligand-receptor complexes have been resolved. These findings provide a solid foundation for structure-based drug development and design. Recently, scientists at the University of Copenhagen in Denmark conducted an inventory of all GPCR drugs and GPCR drugs tested in clinical trials.

Major disease indication trends of GPCR inhibitors

Studies have shown that indications for GPCR-targeted drugs are expanding from traditional areas such as hypertension, allergy, anesthesia and schizophrenia to new areas such as AD and obesity. In the past five years, GPCRs have become targets for new indications such as multiple sclerosis (MS), smoking cessation, and short bowel syndrome. Here are some new trends:

1. Central nervous system diseases remain the major disease indications for GPCR modulators

Of the approved GPCR-targeted drugs, 26% of them (at least 79) can be used to treat central nervous system diseases. Since more than 50% of non-olfactory GPCRs are expressed in the cerebral cortex, and neurotransmitter conduction disorders in the GPCR mediator can lead to a variety of neurological and psychological disorders, therefore, neurological diseases will continue to be one of the important indications for GPCR-targeted drugs. Among them, MS, AD, Huntington’s disease and fragile X chromosome syndrome are particularly worthy of attention.

In the field of MS, a drug targeting GPCR has been approved. It is a fingolimod that regulates the function of the S1P1 receptor. In addition, a variety of S1P1 modulators are in clinical phase 2 and phase 3 trials. In addition, drugs targeting cannabinoid receptors and other GPCR targets such as GPR55 are also tested for MS in clinical trials 2 and 3. These advances suggest that more therapies for the treatment of MS through interaction with GPCRs may soon be available.

2. Diabetes is an important indication for the research of GPCR-targeted drugs in the clinical stage

The increase in the market share of drugs for the treatment of metabolic diseases is also reflected in the clinical trials of targeted GPCRs, of which 27 are in the treatment of diabetes and 7 are in the treatment of obesity. As mentioned earlier, peptide drugs targeting the GLP1 receptor have been marketed, but the currently approved drugs are injectable drugs. Oral-type peptide drugs targeting GLP1 receptors and small molecule drugs are in clinical phase 2 and phase 3 test.

In the treatment of diabetes and its complications, there are currently 25 new GPCR targets that are tested in clinical trials. Among the new targets to be noted are GPR119, FFA1 receptor and dopamine D2 receptor.

3. GPCR-targeted drugs in the field of oncology

There are currently 21 anticancer drugs targeting 14 different GPCRs, including GnRH receptor antagonists and SMO receptor inhibitors. In clinical trials, 23 in-situ drugs targeting GPCRs are used to treat cancer, and 7 of them target innovative targets. These innovative targets include chemokine receptors and proteins in the WNT signaling pathway. For example, CCR2 is the target of the monoclonal antibody plozalizumab, which is now in clinical phase 1 trials for the treatment of melanoma. Monoclonal antibodies that target the FZD7 protein in the WNT signaling pathway are used in clinical trials to treat breast and pancreatic cancer.

The future of targeted GPCRs

The proven efficacy of the GPCR family and their important role in diabetes, obesity, AD, and mental illness will continue to be major driving force for GPCR drug discovery. From the current emergence of a large number of new targets and research interests in GPCR structural biology, pharmacology and models, progress in the field of GPCR drug research and development will be further accelerated.

The future of GPCR drug development will be focused on addressing the following key issues:

1. We need appropriate instrumental compounds to determine the biological function of the target and its relevance to the disease. Innovative high-throughput ligand identification methods (such as DNA-encoding libraries) may help discover these compounds.

2. We need improved disease models and genetic engineering systems for target validation. Gene editing techniques such as CRISPR can help with this.

3. Large amounts of compounding and biological data need to be organized into long-term shared databases, such as ChEMBLFeature Articles, Guide to Pharmacology and GPCRdb. These tasks require interdisciplinary collaboration and public-private partnerships in the field of basic and applied GPCR.

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

The author has been writing articles for 6 years in the area of biochemistry,biology and science, especially in the area of inhibitors, APIs, metabolites and impurities.

The author has been writing articles for 6 years in the area of biochemistry,biology and science, especially in the area of inhibitors, APIs, metabolites and impurities.

The importance of construction planning and scheduling

Working with construction, this isn’t just about starting to build. There are so many things that you need to make sure about before you can start building and before construction can actually begin.

This is something that only experienced constructors know. That there are huge planning and scheduling involved before the actual construction can start. This is some of the information and guidance about construction planning and scheduling. For making it easier to understand that there are many things that need to be done before construction can start.

Working with construction, this isn’t just about starting to build. There are so many things that you need to make sure about before you can start building and before construction can actually begin.

This is something that only experienced constructors know. That there are huge planning and scheduling involved before the actual construction can start. This is some of the information and guidance about construction planning and scheduling. For making it easier to understand that there are many things that need to be done before construction can start.

What is construction planning and scheduling?

Now, let us explain what construction planning and scheduling is. This is the process of what construction needs to be done first. The first equipment that needs to be on the scene, and the first workers that need to start working.

This is important to have a plan and schedule in place before construction can start. It is so that there aren’t any delays in waiting for the next equipment and for people wondering what needs to be done next. Without a schedule, due dates for construction will never be met.

An essential aspect of construction and scheduling a series of geotechnical engineering field and lab tests carried out by geotechnical engineering consultants. Such tests include:

Why are construction planning and scheduling important?

Just like any other business, it will be chaos when there isn’t planning and scheduling involved. Workers will not know where and when they are needed. No one will know when they need to be finished so that the next team can start working.

This is basically to ensure a high degree of effectiveness and optimal performance. To make sure that the materials for construction will arrive on time so that the building can proceed. With construction, hold-ups will cost money. And, no one wants to lose money. The only way to prevent this from happening is to have an efficient plan and schedule in place before construction begins. 

What construction planning is all about

With construction planning, there are two basic things that you need to plan. The one is strategic planning, and the other one is operational planning. In order for you to know how to plan these correctly, you need to understand these two better.

Strategic planning is something that is getting done by the project owner’s corporate planners. This is where they decide what project is going to be built, and the due date for the project’s commencement and completion. They are then discussing it with the contractors.

Operational planning is the planning of each construction team. To know when they need to start and when they need to finish, so that the next team can start working. If one team is behind scheduleHealth Fitness Articles, everyone is going to be behind. This is why operational planning should be done correctly. This also includes the planning of materials that need to be delivered on-site.

Steps of construction planning

There are many steps of the construction planning that needs to be processed before the actual construction can take place. They need to make sure that they are considering all the steps so that the construction planning is going according to plan. These are some of the steps for construction planning.

This is everything you’ll need to know about construction planning and scheduling. This explains everything in detail so that you can understand the planning and scheduling a lot better. It is important to make sure that your planning and scheduling are done properly to ensure that the construction is finish in time. To ensure that no late penalties are going to be needed by the construction team.

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

Nancy Whitman is a contributor to leading Brisbane based geotechnical consultancy firm, Soil Surveys.

Nancy Whitman is a contributor to leading Brisbane based geotechnical consultancy firm, Soil Surveys.

5 major steps involved for a project under construction

Construction. It isn’t just about building and making sure that the plans of the project are being followed. There are many things about the construction that you need to know.

There are five primary stages of a project that’s under construction. Phases that need to be followed if you want to have success with your construction. These are the primary steps involved in project in construction. Stages that you might not know about, or that you didn’t realize is the responsibility of the contractor. Without these stages, the whole construction will fall apart.

Construction. It isn’t just about building and making sure that the plans of the project are being followed. There are many things about the construction that you need to know.

There are five primary stages of a project that’s under construction. Phases that need to be followed if you want to have success with your construction. These are the primary steps involved in project in construction. Stages that you might not know about, or that you didn’t realize is the responsibility of the contractor. Without these stages, the whole construction will fall apart.

1) The design phase

The first stage is where the design of the project starts to get shape. This is where the plans are drawn and approved by the client. To make adjustments to ensure that everything is according to the client’s preferences and needs.

You might think that when construction is hired, they immediately start with the building. However, this isn’t like this. They need to make sure that the design of the project is drawn and that everyone is understanding the project completely.

2) Preliminary construction phase

No, this isn’t where the construction starts. This is the pre-construction stage. Where the construction site is getting tested to make sure that the site is fit for this type of project. If the soil is correct and if the plans are adjusted to the results of the pre-construction results.

The people that you will find at a pre-construction stage are agreement administrator, project manager, chief inspector, construction engineer, OHS manager. This stage can’t continue if any one of these people is missing. During this stage, extensive soil testing is performed by a geotechnical engineering firm to determine the viability of the soil and how it will affect structural loads. It is during this time that site investigation and mapping is conducted, as well as comprehensive construction inspections. The outcome of the stringent geotechnical tests that are carried out by the geotechnical engineering company influence the strength of concrete and reinforcement that must be used for project design.

3) Material acquisition phase

This is the stage where the building materials are ordered and where it is getting delivered correctly to the right people. This is normal everyday people that will get and sign for these materials.  This is where they are doing the calculations to ensure that they are using the right amount of stuff directly from the cheaper places.

The materials should not arrive all at the same time. You should make sure that it arrives as the contractors have used it.  Clean and neat.

4) The construction phase

Now you can start with the construction state. The stage where the actual building starts. Where the construction of the building starts. And, where the contractors need to make sure that the deadlines are being met.

This is the part that we all know. The actual building part. Where the material that has arrived is being used to build. Where the inspections in-between the construction is getting done to ensure that the construction is done at the highest level.

5) Post-building phase

This involves the final inspection, the handover to the owners of the building and the final cleanup of the construction from building materials and debris.

With the final inspection, they are inspecting the quality of the building, the building against the plans that the client has asked and against the actual size that it needs to be. If this isn’t the right size, the contractors will be penalized and they won’t get the agreed money after the building project. Sometimes people from the outside are doing the inspections to make sure that everything is according to plan.

These are the stages of a project in construction. Making sure that you are following each stage and to make sure that it is according to the needs of the landowner. If not, the contractor is going to pay money for the delays and for wrongfully installations and buildings. Luckily This isn’t going to be a problem anymoreArticle Submission, and you will know for sure that you are going to construct a building correctly and according to the rules and regulations of the building.

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

Nancy Whitman is a contributor to leading Brisbane based geotechnical consultancy firm, Soil Surveys.

Nancy Whitman is a contributor to leading Brisbane based geotechnical consultancy firm, Soil Surveys.

10 antibody drugs that will receive regulatory approval in the us and europe by 2020 i

The Antibody Society published a report at the end of November 2019, which analyzed the drug development advances in the field of antibodies. According to the report, in 2020, 12 antibody drugs will receive regulatory approval in the US or EU. However, the two drugs in the report, enfortumab vedotin and trastuzumab deruxtecan, have already been approved by the US FDA in advance in mid-to-late December 2019. Both are ADC drugs.

The Antibody Society published a report at the end of November 2019, which analyzed the drug development advances in the field of antibodies. According to the report, in 2020, 12 antibody drugs will receive regulatory approval in the US or EU. However, the two drugs in the report, enfortumab vedotin and trastuzumab deruxtecan, have already been approved by the US FDA in advance in mid-to-late December 2019. Both are ADC drugs.

 

The following is a brief introduction to the remaining 10 antibody drugs in the report. Among them, the first 7 are for non-cancer indications, and the last 3 are for cancer indications.

 

 

Eptinezumab is a humanized IgG1 monoclonal antibody that targets the calcitonin-related gene peptide (CGRP) and was developed for the prevention of migraine. Migraine is a common chronic neurovascular disease, characterized by recurrent severe headaches. CGRP is a neuropeptide that has been shown to be released during migraine attacks, plays an important role in migraine pathophysiology, and is a popular target for migraine drug development.

 

Up to now, there have been 3 monoclonal antibody migraine preventive therapies targeting CGRP and its receptors: Amgen and Novartis Aimovig (targeting CGRP receptors) and Teva Ajovy (targeting CGRP) Lilly Emgality (targeting CGRP). Eptinezumab, developed by Alder BioPharmaceuticals, is administered by intravenous infusion once every 3 months. It has rapid and complete bioavailability, has high specificity and strong binding to CGRP inhibition, and has shown differentiated clinical characteristics in clinical research. In some patients it even showed a 100% response rate. Currently, the drug is under review by the US FDA. If approved, eptinezumab will be the first migraine preventive drug to be administered intravenously every quarter.

 

 

The drug is a fully human IgG1 monoclonal antibody that targets the insulin-like growth factor-1 receptor (IGF-1R) and was developed for the treatment of moderate to severe thyroid eye disease (TED). TED is a progressive, debilitating autoimmune disease caused by autoantigens activating IGF-1R-mediated signaling complexes on cells in the orbit, resulting in a series of negative effects, causing long-term, irreversible damage, including exophthalmos, strabismus, diplopia and even blindness.

 

The drug was developed by Horizon Pharma and the results of a confirmatory phase III OPTIC study published in March 2019 showed that, compared with the placebo group, patients with the teprotumumab treatment group had significantly improved eyeballs (primarily End point, p <0.001). Data from a phase II study showed that teprotumumab treatment resulted in clinically significant and statistically significant reductions in exophthalmos and active TED symptoms (pain, swelling, redness, inflammation).

 

Currently, the drug is undergoing priority review by the US FDA, and the PDUFA target date is March 8, 2020. Previously, the FDA has granted teprotumumab breakthrough medicine qualification, orphan medicine qualification, and fast-track qualification for active TED. Last month, the FDA’s Dermatology and Ophthalmology Drug Advisory Committee (DODAC) unanimously approved and unanimously supported the potential benefits of teprotumumab for active TED outweigh the risks. If approved by the FDA, the drug will be the first to treat active TED.

 

 

Inebilizumab is a humanized monoclonal antibody that targets CD19 and was developed for optic neuromyelitis spectrum disorder (NMOSD), a rare, destructive, complement-mediated central nervous system (CNS) autoimmune disease, which is more common in women. The disease is characterized by relapses, and each relapse leads to the progressive accumulation of disability, including blindness and paralysis, and sometimes even premature death. About 80% of NMOSD patients have aquaporin-4 (AQP4) autoantibodies. These autoantibodies are thought to be produced by plasmablasts and plasma cells, which mainly bind to astrocytes in the CNS, trigger attacks, and damage optic nerve, spinal cord and brain.

 

Developed by Viela Bio, the drug has a high affinity for CD19, a protein widely expressed in B cells, including plasmablasts and some plasma cells that secrete antibodies. Inebilizumab is currently under review by the US FDA. In the United States and the European Union, the drug has been granted orphan drug status for NMOSD, and it has also been awarded breakthrough drug status for NMOSD in the United States.

 

 

Satralizumab is an anti-interleukin 6 receptor (IL-6R) humanized monoclonal antibody, which has been developed for the treatment of NMOSD. NMOSD patients experience severe, unpredictable relapses that directly lead to cumulative, permanent nerve damage. The drug can target IL-6R to inhibit IL-6 signaling. IL-6 is a cytokine and is believed to play a key role in the inflammation of NMOSD, triggering the inflammatory cascade, causing injury and disability.

 

Developed by Roche, Satralizumab is currently under review by the US FDA and accelerated evaluation by the European Union EMA. In the United States and the EU, the drug has been granted orphan drug status for NMOSD. Data from two global phase III clinical studies (SakuraStar, SAkuraSky) confirm the efficacy and safety of satralizumab as a monotherapy and in combination with a baseline immunosuppressant: (1) The SakuraStar study shows that across the entire study population and compared with placebo, satralizumab monotherapy significantly reduced the risk of recurrence by 55%, and reduced the risk of recurrence by 74% in patients with AQP4-IgG4 serology. (2) The SAkuraSky study showed that in the entire study population and compared with placebo + baseline immunosuppressive agents, satralizumab + immunosuppressive treatment reduced the risk of recurrence by 62%, and reduced the risk of recurrence by 79% in patients with AQP4-IgG4 serology.

 

In the United States and the European Union, Soliris is the only drug approved for NMOSD. It is given by intravenous infusion and is administered every 2 weeks during the maintenance period. Satralizumab is administered by subcutaneous injection once every four weeks, and if approved, it will be a more comprehensive treatment option for patients and caregivers.

 

 

Leronlimab is a humanized IgG4 monoclonal antibody that targets blocking chemokine receptor 5 (CCR5), a cellular receptor that plays multiple roles in HIV infection, tumor metastasis, and other immune-mediated diseases, including NASH. In the treatment of HIV infection, the drug belongs to a new class of therapies called viral entry inhibitors that can mask CCR5 and protect these cells from viral infection by blocking the entry of major HIV (R5) subtypes into healthy T cells. At the same time, leronlimab does not seem to interfere with the normal function of CCR5 in mediating the immune response.

 

Data from nine completed clinical studies have shown that leronlimab can significantly reduce or control patients’ HIV viral load in each study. A phase IIb study showed that the drug’s single-agent treatment could prevent HIV escape. Developed by CytoDyn, the drug has been successfully combined with standard antiretroviral therapy for critical phase III studies in HIV-infected patients, and is in the process of rolling forward to the United States FDA for a combined therapy biological product approval application (BLA). In addition to HIVComputer Technology Articles, leronlimab is also being developed for a variety of cancers (including metastatic triple-negative breast cancer and immune diseases.

 

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

The author has been writing articles for 6 years in the area of biochemistry,biology and science, especially in the area of inhibitors, APIs, metabolites and impurities.

The author has been writing articles for 6 years in the area of biochemistry,biology and science, especially in the area of inhibitors, APIs, metabolites and impurities.

Learn bronsted lowry acid is in chemistry

In 1923 Brønsted and Thomas described acids and bases based on whether they donate or accept hydrogen ions (H+). These acids and bases came to be known as Bronsted, Lowry-Bronsted, or Bronsted-Lowry acids and bases. While doing research in chemistry i do attend some conferences like chemisty conference and gained knowledge

In 1923 Brønsted and Thomas described acids and bases based on whether they donate or accept hydrogen ions (H+). These acids and bases came to be known as Bronsted, Lowry-Bronsted, or Bronsted-Lowry acids and bases. While doing research in chemistry i do attend some conferences like chemisty conference and gained knowledge

Learn Bronsted-Lowry Acid Is in Chemistry:

In 1923 Brønsted and Thomas described acids and bases based on whether they donate or accept hydrogen ions (H+). These acids and bases came to be known as Bronsted, Lowry-Bronsted, or Bronsted-Lowry acids and bases.

Bronsted and Thomas defined there substance based on it will donate the hydrogen ion and react with it. In contrast Bronsted bases accepts hydrogen ion and react with other atom. Species which donates are accepts protons are considered as the amphoteric. Attend some chemistry conference with some topic like this will help in reaching experts and sharing knowledge

Where Bronsted theory differs from arrihenius theory as this theory allows both hydrogen cations and anions.

Key points of Bronsted lowery acids and bases:

1.This thoery is proposed in 1923 by the chemists called Bronsted and Thomas.

2.A Bronsted-Lowry acid is such a chemical that donates one or more hydrogen ions in a reaction. In contrast, a Bronsted-Lowry base accepts hydrogen ions. When it donates its proton, the acid becomes its conjugate base.

3.Theory also says that an acid as a proton donor and a base as a proton acceptor.

Arrhenius acid base reaction is based on hydrogen ion liberation in water. Swedish scientist Svante Arrhenius, according to them acids are substances that dissociate in water to yield electrically charged atoms or molecules, called ions, one of which is a hydrogen ion (H+), and that bases ionize in water to yield hydroxide ions (OH−).

An Arrhenius acid produces hydrogen ion by disassociating in water and helping in recognising acids. In other words, an acid increases the concentration of H+ ions in an aqueous solution.

Common examples of Arrhenius acids include: Hydrochloric Acid – HCl. Nitric Acid – HNO3. Sulfuric Acid – H2SO4. Acetic Acid – HCH3CO2.

Main problem is AArrhenius acids produces hydronyum ions when dissipates in water and bases produces hydroxide ions when dissipate in water.
The result of reaction in acids and bases is salt and water are products.
A solution that resisits changes in pH when dissipates in water is called buffer.

When PH greater than 7 then it indicates as acid.

Bronsted theory forwards Arrhenius definition one step further, as a substance no longer needed to be composed of hydrogen (H+) or hydroxide (OH-) ions in order to be classified as an acid or base. For example:
HCl(aq)+NH3(aq)→NH+4(aq)+Cl−(aq)
Hydrochloric acid (HCl) “donates” a proton (H+) to ammonia (NH3) which “accepts” it , forming a positively charged ammonium ion (NH4+) and a negatively charged chloride ion (Cl-). Therefore, HCl is a Brønsted-Lowry acid (donates a proton) while the ammonia is a Brønsted-Lowry base (accepts a proton). Also, Cl- is called the conjugate base of the acid HCl and NH4+ is called the conjugate acid of the base NH3.

This theory, an acid is a substance that can release a proton (like in the Arrhenius theory) and a base is a substance that can accept a proton. A basic salt, such as Na+F-, generates OH- ions in water by taking protons from water itself (to make HF):

F−(aq)+H2O(l)ÌHF(aq)+OH−(2)
When a Brønsted acid dissociates, it increases the concentration of hydrogen ions in the solution, [H+] ; conversely, Brønsted bases dissociate by taking a proton from the solvent (water) to generate [OH−] .

whether a substance is an acid or a basePsychology Articles, count the hydrogens on each substance before and after the reaction. If the number of hydrogens has decreased that substance is the acid (donates hydrogen ions). If the number of hydrogens has increased that substance is the base (accepts hydrogen ions). These definitions are normally applied to the reactants on the left. If the reaction is viewed in reverse a new acid and base can be identified. The substances on the right side of the equation are called conjugate acid and conjugate base compared to those on the left. Also note that the original acid turns in the conjugate base after the reaction is over.

 

 

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

I am srikrishna working as the content writer and digital marketing executive. I have selected the topic for the chemistry conference. As the research purpose i have selected this topic. I have 2 yrs exp in content writing for seo and health related topics

I am srikrishna working as the content writer and digital marketing executive. I have selected the topic for the chemistry conference. As the research purpose i have selected this topic. I have 2 yrs exp in content writing for seo and health related topics

Compliance in the lab gmp vs glp in laboratory studies

When it comes to laboratory processes and validation studies, there is often confusion between Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP). This post aims to clarify it

When it comes to laboratory processes and validation studies, there is often confusion between Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP). This post aims to clarify it

Compliance in the Lab: GMP vs GLP in Laboratory Studies

The life sciences manufacturing industry is full of Good Practice standards. Every step and process is covered under some GxP; from design and testing to the manufacturing and distribution of pharmaceutical products and medical devices. 

 

When it comes to laboratory processes and validation studies, there is often confusion between Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP).

Generally speaking, GLPs are research and study-focused, while GMPs are production and process-focused. However, they have a few other significant differences better understood by defining each.

GLP compliance monitors conditions, processes, documentation, and archiving of studies performed in laboratory settings. Such endeavors require highly accurate and trackable data as well as high-quality results in order to validate and market the final product. The integrity of the data is critical for developing replicable results, as well as the product’s progress to market.

GMP compliance refers to quality assurance in the manufacturing processes, as defined by the local regulatory body to ensure the safety of healthcare products sold in their jurisdiction. “cGMP,” which is essentially just “current” GMP, outlines the specific conditions under which manufacturing can and should occur.

Knowing the differences between GMP and GLP can help differentiate which protocol is called for at which phase of production. The same general principles and requirements apply to the development of drugs, biologics, and medical devices. However, GMP and GLP affect different stages in the processes.

GLP is required during nonclinical laboratory safety studies supporting research and marketing of biocompatibility, toxicology, pharmacology, and other medical products. During “test systems” studies, GLP is also necessary in regards to handling live organisms or microorganisms, as well as plants. In addition, safety and efficacy testing should be performed under GLP.

GMP standards are applied during the batch / lot release (or lot conformance), manufacturing & testing, and medical product marketing phases. Per the facility, the testing phase of components used in clinical trials (active pharmaceutical products, critical excipients) may require GMP compliance. As may testing of stability, process validation, and other supporting activities.

Science and technology are advancing. The steps to take to market a medical product to the public are subject to change, as are the regulations that protect the end users of these products. The impact of automation, AI and augmented reality technologies compliance in the lab is likely to grow. As a resultScience Articles, forward-thinking manufacturers in the life sciences industry are actively looking to adopt innovative technologies to streamline processes and minimize the chances for human error.

 

Read the full post on the DotCompliance Life Science Blog

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

Sharon Yarkoni – Director of Quality Assurance

 

 
 

Sharon Yarkoni is a Quality Assurance Leader at Dot Compliance who works with customers to utilize their QMS software to build safer products on expedited timelines. He has over 14 years of experience in QA/QC and compliance and more than 11 years in several QA management roles within global biological and pharmaceutical companies. He enjoys helping customers successfully navigate regulations across global markets as they bring life changing technologies to market.

Sharon Yarkoni – Director of Quality Assurance

Sharon Yarkoni is a Quality Assurance Leader at Dot Compliance who works with customers to utilize their QMS software to build safer products on expedited timelines. He has over 14 years of experience in QA/QC and compliance and more than 11 years in several QA management roles within global biological and pharmaceutical companies. He enjoys helping customers successfully navigate regulations across global markets as they bring life changing technologies to market.

Birinapant and checkpoint inhibitors in cancer immunotherapy

Cancer immunotherapy is a huge topic. Checkpoint inhibitors, one type of major cancer immunotherapeutic drug, can restore the activity of immune cells to combat cancer cells. Typically, these agents are antibodies: highly specific but bulky proteins that do not readily diffuse through the body.

Cancer immunotherapy is a huge topic. Checkpoint inhibitors, one type of major cancer immunotherapeutic drug, can restore the activity of immune cells to combat cancer cells. Typically, these agents are antibodies: highly specific but bulky proteins that do not readily diffuse through the body.

If scientists want to improve the ability of immune cells to kill cancer cells, then many other tools are needed to discover a larger library of more traditional “small molecules”. What they need, first and foremost, is a way to classify them, a platform for screening thousands of drugs.

This is reported by Emory researchers in a new paper on cell chemistry biology. They also demonstrated that a class of drugs called IAP antagonists, one of which has been applied in clinical trials, can promote immune activity against cancer cells in their systems.

Although checkpoint inhibitors are now approved by the FDA for the treatment of many types of cancer, many patients did not benefit from it. Finding drugs that relax other parts of the immune response can improve outcomes, especially for those cancer types where checkpoint inhibitors are not effective.

The lead author, Dr. Haian Fu, director of the Department of Pharmacology and Chemical Biology at Emory University School of Medicine, said that drug discovery in cancer immunotherapy focuses on extracellular regulatory molecules that are easily accessible.

“This is a powerful co-culture system that enables high-throughput screening of cancer immunotherapy,” Fu said. “There are many targets in the cell. We want to illuminate these intracellular targets.”

In collaboration with Fu, Xiulei Mo, PhD, an Instructor, and his colleagues created a system to test whether compounds can enhance the ability of human immune cells to inhibit cancer cell growth. They call it HTiP for “high-throughput immunomodulatory phenotypic screening platforms.”

The HTiP system uses a mixture of human immune cells in combination with cancer cells carrying known growth-driven mutations. Emory’s researchers began with the well-known oncogene KRAS and compared the effects of cancer cells (colon and lung cancer cell lines) with and without KRAS mutations. The presence of KRAS mutations is immunosuppressive, which means that in the Emory system, KRAS mutations provide resistance against immune cells to kill cancer cells.

Mo screened a library of approximately 2,000 known compounds to isolate the drug birinapant, which was proved to be able to enhance the activity of immune cells on cancer cells and which had little effect on cancer cells. Birinapant is part of a class of drugs called IAP antagonists that have begun to be studied by scientists on their anticancer activity.

“This is a strong evidence of their importance as immune enhancers,” Fu said. “This is a timely verification of our system.” In fact, birinapant is being tested in conjunction with checkpoint inhibitors. The researchers found that the other two IAP antagonists have similar effects in the same system.

The screening platform is independent of the mechanism of KRAS immunosuppression or the precise type of immune cells. Fu noted that most checkpoint inhibitors appear to act on cytotoxic T cells, but the screening platform uses a combination of immune cell types. “The effects in our system may come from any or all of these cell types,” he said.

All that is required is the effect of the compound to reverse the KRAS mutation. He said the system can be easily modified to test the effects of other oncogenic mutations, or to focus on a specific type of tumor antigen-specific immune cells. The team also plans to expand its screening work because 2Free Articles,000 compounds are actually small compared to the number of potential drugs.

 

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

Creative Peptides has been endeavored to the great cause of conquering various diseases, cancers in particular, by offering various research peptides like peptide inhibitors, peptide nucleic acid, tumor antigen derived peptides, isotope labeled peptides, antimicrobial peptides, FRET substrates, ghrelin peptides, fibronectin fragments, etc. 

Creative Peptides has been endeavored to the great cause of conquering various diseases, cancers in particular, by offering various research peptides like peptide inhibitors, peptide nucleic acid, tumor antigen derived peptides, isotope labeled peptides, antimicrobial peptides, FRET substrates, ghrelin peptides, fibronectin fragments, etc. 

The role of ai in medical diagnosis

According to vast media reports, artificial intelligence (AI) technology is developing by leaps and bounds in each passing day with an influence on almost every aspect of our life. There are even views that many people’s work in the future may be replaced by AI. Regardless of the great transformations it might bring about, the active impact of AI on medical diagnosis is what we should applaud for.

According to vast media reports, artificial intelligence (AI) technology is developing by leaps and bounds in each passing day with an influence on almost every aspect of our life. There are even views that many people’s work in the future may be replaced by AI. Regardless of the great transformations it might bring about, the active impact of AI on medical diagnosis is what we should applaud for.

AI diagnoses in skin cancer

A joint study by German, French and American scientists found that artificial intelligence for the diagnosis of skin cancer surpasses dermatologists for the first time, helping to speed up the diagnosis process, helping patients fight cancer early and reducing the risk of normal moles being misdiagnosed as cancer.

According to the report, scientists used the Convolutional Neural Network (CNN) system to create the artificial intelligence system used in this study. CNN mimics the functioning of human brain nerve cells, enabling computers to recognize the immediate image like the human eye. The more images accumulated, the more accurate the judgment of artificial intelligence.

The researchers first entered more than 100,000 images, directed the AI system to distinguish between benign and potentially dangerous lesions, and then showed photos of 100 malignant melanomas or benign sputum to 58 doctors and artificial intelligence systems, comparing the ability to distinguish cancer of the two.

The doctors participating in the test came from 17 countries, more than half of them had over 5 years of medical experience, 19% had 2 to 5 years of experience, and another 29% had less than 2 years of experience. The results of the study showed that doctors correctly judged 86.6% of malignant tumors on average. If clinical data such as the patient’s age, gender, and suspicious wound location are provided, the diagnostic accuracy can be increased to 88.9%, but still less than 95% of artificial intelligence. In addition, doctors can correctly determine 76% of normal benign sputum, which is also lower than 83% of artificial intelligence.

The research team published a paper in Yearbook of Oncology, saying that the convolutional neural network system outperformed most dermatologists. Professor Heisler at the University of Heidelberg in Germany, the leading researcher, pointed out that artificial intelligence systems are less likely to misjudge melanoma, and at the same time are less likely to misjudge malignant tumors, exhibiting higher sensitivity than dermatologists.

The research team said that artificial intelligence will help speed up the diagnosis of skin cancer, allowing doctors to remove early cancer cells before they spread, and avoid unnecessary surgery for patients with benign sputum.

However, the researchers believe that artificial intelligence still can not completely replace the doctor, because the melanoma in the fingers, toes and scalp is difficult to record with photos, and some of the lesions are more special, which makes it more difficult for AI to identify. However, doctors can also help patients find out undetected suspicious wounds. Experts say that there is no way to replace clinical examinations at the current stage.

New algorithm for AI diagnosis can detect Alzheimer’s disease ten years in advance

Alzheimer disease (AD) is a central nervous system degenerative disease with insidious onset and chronic progression. It is the most common type of dementia in old age, mainly manifested as neurocognitive symptoms such as progressive memory impairment, cognitive dysfunction, personality change and language disorder, which seriously affect patients’ life. The etiology and pathogenesis of AD have not been elucidated. The characteristic pathological changes are extracellular senile plaques formed by amyloid beta deposition and neuronal fibrillation in the neuronal cells formed by hyperphosphorylation of tau, and neuronal loss with gliosis.

Recently, researchers at the University of Bari in Italy have developed a new algorithm that can detect tiny structural changes in the brain caused by disease. That is to say, AI can help achieve early detection of Alzheimer’s disease 10 years before the onset of symptoms.

The team trained their artificial intelligence through 67 MRI scans, 38 of which were from Alzheimer’s and 29 from healthy controls. The researchers divided the scan results into small areas and let their artificial intelligence analyze the connections between neurons. After the training was completed, they tested the algorithm by brain scanning 148 subjects. In addition to these tests, there were 48 scans of patients with this condition and 48 scans of people with mild cognitive impairment. Eventually, artificial intelligence was able to comprehensively detect Alzheimer’s disease.

According to reports, the research team’s artificial intelligence algorithm can diagnose 85% of Alzheimer’s disease, and the correct rate of detection of mild cognitive impairment can reach 84%, which makes it an effective tool for early diagnosis of potential Alzheimer’s disease. The significance of this study is that in the future it is possible to seek 10 years of valuable treatment and psychological preparation for Alzheimer’s patients. HoweverFeature Articles, the researchers’ current test data is limited to the neuroimaging project database of the University of Southern California.

Article Tags:
Skin Cancer, Artificial Intelligence, Benign Sputum, Alzheimer’s Disease

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

Creative Peptides is one of the primary suppliers of research peptides, such as Antennapedia Peptides, Chimeric Peptides, HIV-TAT , Nuclear Localization Peptides, Oligoarginine Peptides, MHC-Peptide Tetramer, RGD Peptides, Nucleotides, Nucleosides, and more.

Creative Peptides is one of the primary suppliers of research peptides, such as Antennapedia Peptides, Chimeric Peptides, HIV-TAT , Nuclear Localization Peptides, Oligoarginine Peptides, MHC-Peptide Tetramer, RGD Peptides, Nucleotides, Nucleosides, and more.

Remdesivir is effective in preventing and treating primate coronavirus pneumonia

Earlier this February, the news that Gilead’s drug remdesivir, which is under study, has cured patients with coronavirus spread across the country. In a short time, Remdesivir, an antiviral drug targeting Ebola, became “People’s Hope”. Currently, Phase III clinical trials of Remdesivir in treating Coronavirus Disease 2019 (COVID-19) are still underway, which draw the wide attention of the public.

Earlier this February, the news that Gilead’s drug remdesivir, which is under study, has cured patients with coronavirus spread across the country. In a short time, Remdesivir, an antiviral drug targeting Ebola, became “People’s Hope”. Currently, Phase III clinical trials of Remdesivir in treating Coronavirus Disease 2019 (COVID-19) are still underway, which draw the wide attention of the public.

Recently, Emmie de Wit from the National Institutes of Health (NIH) published results in the journal PNAS, and found that in another non-human primate model of the coronavirus MERS-CoV infection, remdesivir could effectively prevent the virus infection and treat respiratory symptoms and lung damage caused by coronavirus. Despite the use of multiple “equals sign”, we have reason to believe that remdesivir will be the powerful, primary weapon against COVID-19.

Remdesivir is a nucleic acid prodrug with broad-spectrum antiviral activity, and is particularly effective against the deadly Ebola virus. In cell experiments, remdesivir can effectively inhibit the replication of multiple coronaviruses in human respiratory epithelial cells. In animal experiments, remdesivir can effectively treat MERS-CoV and SARS-CoV-induced respiratory syndrome in mice. Therefore, the pharmacodynamics of remdesivir in primates closer to humans has important clinical significance.

Researchers divided healthy macaques into three groups of six. The control group of macaques was injected with placebo, the preventive group was injected with 5 mg/kg of remdesivir 24 hours before MERS-CoV infection, and the treatment group was injected with 5 mg/kg of remdesivir 12 hours after viral infection, and then injected once daily. The researchers performed physical observation on all animals for 6 consecutive days, and then sacrificed to observe the lungs after 6 days. The experiment obtained the following results:

The researchers scored the appetite and fur status of the experimental animals. The higher the score is, the worse the status is. All patients in the control group experienced decreased appetite, fur folds, and respiratory disturbances; the remdesivir prevention group did not show any symptoms of respiratory diseases, and breathing was normal throughout the experiment; the respiratory rate of the treatment group increased, but was significantly lower than that of the control group. From the results of X-ray imaging, the lung infiltration of the animals in the remdesivir prevention and treatment group was significantly less than that in the control group.

The researchers used qRT-PCR to measure the viral nucleic acid content in the lung tissue of animals, and found that the viral lung load of the remdesivir prevention group was 2.5-4 log levels lower than that of the control group, and the viral lung load of the treatment group was also significantly lower than that of the control group, indicating that remdesivir effectively inhibited virus reproduction.

The remdesivir control group had normal lung tissues and no signs of viral infection. The treatment group (5/6) had macroscopic tissue lesions, but the total area was significantly smaller than the control group.

Therefore, pre-administration of remdesivir can completely inhibit the replication of MERS-CoV in the respiratory tract and significantly reduce the possibility of pneumonia infection. Since inpatient transmission accounts for one-third of MERS-CoV cases, prophylactic remdesivir treatment for patients, contacts, and health care workers at high risk for the virus can effectively reduce the number of pneumonia infections.

To date, few other drugs have been able to prevent MERS-CoV so thoroughly that almost no lung tissue lesions are observed. Remdesivir is comparable to hyperimmune plasma therapy and is currently one of the most promising drugs against primate coronavirus infection.

In addition, remdesivir has significant effects after viral infection. In this experiment, remdesivir was injected 12 hours after infection, but at this time it was close to the replication peak of MERS-CoV in Rhesus macaque. In theory, drugs that inhibit viral replication at this point have almost lost control of the virus. But remdesivir is an exception.

In many severe cases of MERS, viral RNA and living organisms can still be detected in respiratory samples a few weeks after the onset of symptoms, most likely due to the extension of the virus’s replication time by the blessing of the underlying disease. Similarly, virus replication was observed to persist longer in immunocompromised Rhesus macaque. Therefore, remdesivir is not only beneficial for patients with early diagnosis of MERS, but also can improve the recovery of patients with severe MERS and underlying diseases.

Other possible treatment options for coronavirus pneumonia

Since the spread of COVID-19 is so fast, the drug development presents a priority. However, the research and development of new drugs is a time-consuming process, which requires huge input of money and effort. Several decades are needed from R & D to mass production. Therefore, to save time, the current clinical trials are based on certain clinical treatment effects or experimental results. In China alone, there are currently 32 clinical trials registered as “COVID-19 pneumonia”, involving drugs such as Fapilavir, Lopinavir/Ritonavir, Darunavir, and glucocorticoids, in addition to Remdesivir.

Anti-HIV drugs can block the enzymes needed for viral replication. During SARS, a small sample clinical trial found that lopinavir/ritonavir has a certain effect on the treatment of SARS. In addition, current in vitro research trials show that lopinavir/ritonavir can inhibit the replication of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) to exert antiviral activity effect.

The application of glucocorticoids in acute respiratory distress syndrome (ARDS) and severe viral pneumonia is still controversial as to whether it can reduce the mortality rate and improve the prognosis of patients. But more clinical trials are still needed.

In addition, China has initiated some trials to test the clinical effects of chloroquine. Chloroquine phosphate can effectively inhibit 2019-nCoV infection at the cellular level, and its role in the human body has yet to be clinically verified.

Traditional Chinese medicine has advantages such as low drug resistance and multi-target mechanism in the treatment of viral infections, so it has broad development prospects. Traditional Chinese medicine (TCM) has played an important role during SARS. In response to the epidemic, TCM experts provided different traditional Chinese medicine prescriptions and proprietary Chinese medicines choices for confirmed patients at different stages of the clinical treatment periods. NowScience Articles, some TCM treatment has begun to show results.

Article Tags:
Traditional Chinese Medicine, Primate Coronavirus, Coronavirus Pneumonia, Respiratory Syndrome, Control Group, Treatment Group, Viral Infection, Prevention Group, Remdesivir Prevention, Viral Lung, Lung Tissue, Tissue Lesions, Clinical Trials, Traditional Chinese, Chinese Medicine

Source: Free Articles from ArticlesFactory.com

ABOUT THE AUTHOR

The author has been writing articles for 6 years in the area of biochemistry,biology and science, especially in the field of inhibitors such as jnj 872, abt 518, PROTAC technology, metabolites, impurities, APIs, etc.

The author has been writing articles for 6 years in the area of biochemistry,biology and science, especially in the field of inhibitors such as jnj 872, abt 518, PROTAC technology, metabolites, impurities, APIs, etc.

Page 1 of 2

Powered by WordPress & Theme by Anders Norén