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Researchers revealed the way for success in gene therapy
Scientists have found a new way to overcome one of the biggest obstacles to the use of viruses for therapeutic genes.
Scientists from the Institute for research at national level have found a way to overcome one of the biggest obstacles to the use of viruses for administration of therapeutic genes, that is, how to prevent the immune system to neutralize the virus before it has delivered its genetic set.
Gene therapy is one of the most promising possibilities for the treatment of genetic disorders such as muscular dystrophy, congenital blindness and hemophilia. Scientists explore gene therapy as a cure for certain types of cancer, neurodegenerative diseases, viral infections and other acquired diseases. In order to obtain a therapeutic gene into cells, scientists use viruses that deliver its genetic material in cells as part of their normal replication process.
Again and again, these efforts were thwarted by the very immune system of the body that damages each viral vector. Thus the therapeutic gene can be delivered to diseased cells and disease raging in full force.
A team led by Louis-Rodino Klapak, PhD, and Jerry Mendel, MD, principal investigator in the Center for Gene Therapy at Nationwide, show for the first time that using a process called plasmapheresis, just before delivery of the virus for gene therapy he is protected long enough to enter the cell and deliver their genetic material.
In a study of gene therapy for the treatment of Duchenne muscular dystrophy (DMD), Dr. Rodino-Klapak using plasmapheresis in a large animal model, and then injected a virus carrying the gene micro-dystrophin. When studying the level of gene expression of the micro-dystrophin in animals, it was found that there is a 500% increase in the gene expression in the animals who received a plasmapheresis.
Dr. Mendel believes that right now, gene therapy seems to work best in patients who have antibodies to the virus. It is this virus is used to supply the necessary gene. It is exactly this gene, which is a therapeutic, curative intent of the organism suffering from a disease. On the other hand, it limits the number of patients who can benefit from gene therapy. This is because in very few patients lacking antibodies against the virus.
Using the method of plasmapheresis repeatedly increases the potential of gene therapy, as this eliminates the obstacle called immune response of the organism.
As gene therapy becomes more widespread, it may be necessary, patients receiving more than one course of treatment.
The main problem is that when you go home after the first treatment, their body develops antibodies to the virus used to deliver the therapeutic gene. The use of plasma in a patient who previously received gene therapy may allow him to be treated again.
EIAgen 25OH-Vitamin D
- Semi liquid Calibrators and Controls
o Stability of reconstituted Calibrators and Controls up to 8 weeks at 2-8° or 4 months at -20°
- 24 months Shelf life
- Breakable wells
- Optical Density <3.0
The 25-Hydroxyvitamin D Total ELISA is powered by unique monoclonal antibodies that express 100% reactivity against 25 OH Vitamin D3 and 83% reactivity against 25 OH Vitamin D2. All in one technology. No extraction step, displacement solution directly into the well. Results in less than 4 hours. Calibrated against ID-LC/MS-MS (reference method). Bar codes an all components.
Price for this unique Assay, CE and FDA approved:
Cat# |
Description |
Kit |
Quantity |
Price |
GDMS 1971 |
25OH Vitamin D Total ELISA |
96T |
1-10 |
€ 125 |
GDMS 1971 |
25OH Vitamin D Total ELISA |
96T |
11-50 |
€ 119 |
GDMS 1971 |
25OH Vitamin D Total ELISA |
96T |
>50 |
€ 110 |
More: Vitamin D Total ELISA
What cells of the immune system exist?
Cells of the immune system are responsible for the maintenance of the immune reactivity of the organism against penetrating viral and bacterial pathogens in the human body, which sometimes can cause dangerous health infections. Initially, the circuit is driven by the production of pluripotent stem cells that differentiate and give rise to clones of B-and T-cell lymphocytes, neutrophils, eosinophils, basophils, monocytes, dendritic cells, mast cells and red blood cells.
Neutrophils are a special type of immune system cells, which are differentiated from myeloid stem cells. They migrate into the bloodstream at himiotaksichen signal from the body. By way of specific Fc-receptor fixed opsonized by the complement system and pathogen invasion within particles. They have the ability to destroy pathogens directly emptied by the strong bactericide them.
Eosinophils are another type of special cells of the immune system. These granules have a strong cytotoxicity to the endothelium, epidermis, neuronal cells and proteins. Their main function is to synthesize mediators and cytokines.
Basophil cells and mast cells contain receptors for immunoglobulin E. Their main function is to synthesize prostaglandins Class 2. They also provide protection against parasites come against immunoglobulin E-mediated allergic reactions. In this way, the body remains secure during falling of animal parasites in the food, which is particularly common in the consumption of food or poorly cleaned poorly processed meat products.
Monocytes have a cytoplasm filled with specific granules. They originate from myeloid stem cells and differentiate into macrophages. Their main function is to phagocytose emptied environmental pathogenic microorganisms. These processes are carried out after activation by interferon or TNF, macrophages subsequently acquire strong cytotoxic activity and have a strong bactericidal effect against pathogens become trapped in the body.
Dendritic cells are antigen presenting cells. They can migrate into the blood and lymph. They are activated by irritation of those who fell in the human pathogenic microorganisms. The next stage of their operation is not present on its surface MHC molecules of the system that is the major histocompatibility complex on. Also involved in the activation of clusters of differentiation in the body - CD-cells.
T lymphocytes very well may be defined as "the heads of special operations to eliminate the invasion and destruction of pathogenic microorganisms." They are produced in the bone marrow pluripotent stem cells and then migrate to the thymus and mature there. Subsequently differentiate and acquire the specific T-cell reactivity - TCR.
Accordingly, this type of cells are involved in the differentiation to a CD- cells , which are clusters of differentiation. CD4 + T - cell specific agents have adjuvant - inducing function . They give rise to a whole new spot in the production of protective cells against emptied into a person's body pathogenic microorganisms. CD8 + T-cell lymphocytes are the next most important clusters that need to be addressed. They have strong cytotoxic and suppressor role. Cast directly to the differentiation of killer cells and suppressor cells when the body is facing the threat of invasive blood-borne viruses and bacteria.
The role of the immune system is to protect the body against foreign antigens, and do not react to cause outbreaks of disease events in the human body. They also prevent the occurrence of cross-reactions between antigens and the invasion of the body's own antigens. That function of the immune system is performed by the T-cells that acquire the ability to execute it in the thymus after three-step reactions.
- The first step is differentiation of a double negative T cell lymphocytes. These are CD4-and CD8-cells.
- The second stage is the occurrence of double positive cells - to develop CD4 + and CD8 + cells.
- The third stage is the mixed cells, where they meet a single positive and single negative T-lymphocytes. There are two possible combinations. The first one is the manifestation of CD4-and CD8 + cells, and the second expression of CD4 + and CD8-cells.
B-cell lymphocytes are another important cellular arm of the immune reactivity of the organism against environmental emptied the invasion of microorganisms. They are involved in humoral immunity by synthesis of antibodies. Each mature B lymphocyte produces only one type specific antibody that is expressed on the surface, such as a B cell receptor. Antibodies react against the onset of the invasion antigens.
NK-cells are a specific cell type. They can be defined as "a SWAT team to fight pathogens." Their name comes from the abbreviation natural killers, which means that they kill directly taken into the body microorganisms without subjecting them to any attempts to phagocytic or neutralization. NK-cells are most pronounced cytotoxicity compared with all other members of the immune response. Thus limiting the spread of virus-infected cells in the human body.
Cancer cells appear to change while moving throughout body
For the majority of cancer patients, it's not the primary tumor that is deadly, but the spread or "metastasis" of cancer cells from the primary tumor to secondary locations throughout the body that is the problem. That's why a major focus of contemporary cancer research is how to stop or fight metastasis.
Previous lab studies suggest that metastasizing cancer cells undergo a major molecular change when they leave the primary tumor -- a process called epithelial-to-mesenchymal transition (EMT). As the cells travel from one site to another, they pick up new characteristics. More importantly, they develop a resistance to chemotherapy that is effective on the primary tumor. But confirmation of the EMT process has only taken place in test tubes or in animals.
In a new study, published in the Journal of Ovarian Research, Georgia Tech scientists have direct evidence that EMT takes place in humans, at least in ovarian cancer patients. The findings suggest that doctors should treat patients with a combination of drugs: those that kill cancer cells in primary tumors and drugs that target the unique characteristics of cancer cells spreading through the body.
The researchers looked at matching ovarian and abdominal cancerous tissues in seven patients. Pathologically, the cells looked exactly the same, implying that they simply fell off the primary tumor and spread to the secondary site with no changes. But on the molecular level, the cells were very different. Those in the metastatic site displayed genetic signatures consistent with EMT. The scientists didn't see the process take place, but they know it happened.
"It's like noticing that a piece of cake has gone missing from your kitchen and you turn to see your daughter with chocolate on her face," said John McDonald, director of Georgia Tech's Integrated Cancer Research Center and lead investigator on the project. "You didn't see her eat the cake, but the evidence is overwhelming. The gene expression patterns of the metastatic cancers displayed gene expression profiles that unambiguously identified them as having gone through EMT."
The EMT process is an essential component of embryonic development and allows for reduced cell adhesiveness and increased cell movement.
According to Benedict Benigno, collaborating physician on the paper, CEO of the Ovarian Cancer Institute and director of gynecological oncology at Atlanta's Northside Hospital, "These results clearly indicate that metastasizing ovarian cancer cells are very different from those comprising the primary tumor and will likely require new types of chemotherapy if we are going to improve the outcome of these patients."
Ovarian cancer is the most malignant of all gynecological cancers and responsible for more than 14,000 deaths annually in the United States alone. It often reveals no early symptoms and isn't typically diagnosed until after it spreads.
"Our team is hopeful that, because of the new findings, the substantial body of knowledge that has already been acquired on how to block EMT and reduce metastasis in experimental models may now begin to be applied to humans," said Georgia Tech graduate student Loukia Lili, co-author of the study.
Body's own antibodies can cause leukemia
Acute lymphoblastic leukemia is the most common form of blood cancer. Patients with leukemia in the body produced abnormal red blood cells. A research group from the UK to establish why some children do not respond to treatment of blood cancer .
The immune system produces millions of different antibodies, but only has a limited amount of DNA that contain "instructions" for this. To generate huge variety of antibodies to protect the body, the DNA is mixed and the excess particles are removed . Particle removal genome likely is the cause resistance to treatment.
Tools used to strengthen the body's resistance to infection, are also one of the reasons for the most common form of childhood leukemia, scientists say. Equipment for the production of millions of antibodies in the immune system can misfire, making the cells more susceptible to becoming cancerous. The findings are published in the journal Nature Genetics. Scientists at the Sanger Institute in Cambridgeshire and the Institute of Cancer Research in London mechanism used DNA shuffling to make antibodies capable of reducing the risk of developing cancer.
In a study conducted on 57 children in E, the scientists compared the DNA of the healthy tissue of each child and the DNA of cancer of white blood cells. These data indicate that there are two phases of the disease. The first change occurred before birth, but the kids did not get ill from leukemia at once, and at the age of four to ten years there were further genetic changes caused by the same principle that immune cells use to produce antibodies. This knowledge leads to the fundamental understanding of the disease, but is unlikely to lead to new therapies.
Experts say that the current therapies debilitating, many patients suffer relapses of cancer. The latest discovery really allow progress in understanding the actual biology, leading to blood cancer and its various forms. The resulting knowledge will develop in the future a more precise treatment, and increase the predictability of the results of the disease. Now nine out of ten sick children have good prospects of long-term survival, said Matt Kaiser, head of research at the children's charity the treatment of leukemia and lymphoma.
Monoclonal Mouse anti-HSV-2 gC antibody
Specificity: In a simple ELISA, 4955-0308 only reacts with HSV-2 gC antigen. It does not react with gD or any other antigen preparations from HSV-1.
Product name: MOUSE ANTI HERPES SIMPLEX VIRUS 2 gC
Catalog Num.: 4955-0308
Quantity: 0.2 mg
Target: HSV-2 gC
Clone: 1073/53
Host: Mouse
Applications: ELISA
Conjugate/Tag/Label: Unconjugated
Purity: Ammonium sulfate precipitation
Reactivity: Herpes Simplex Virus
Datasheet: Monoclonal Mouse anti-HSV-2 gC antibody
Price: 350 €
More: Antibodies
Bovine Cystocercosis ELISA
The GENTAUR Bovine living cysticercosis ELISA is based on 2 mouse monoclonal antibodies that detect only protein of living Cystocerkosis infections. The ELISA can detect Cystocercosis from as low as 10 infections in one adult cattle on 500 ul of crude serum.
The results on Urine are not 100% accurate due to false positives.
Name: Bovine living cysticercosis ELISA
Product reference: 04-bov-cysto-ELISA
Price: 455 Euro / 96 wells
Use: Low detection of living infections, not quantitative but qualitative
Deze ELISA geeft een juiste diagnose in 100% van alle positieve gevallen, wanneer er meer dan 10 cysticercen aanwezig zijn in het karkas( keuringsverslag) Indien er tussen de 1 en 10 cysticercen aanwezig zijn daalt dit naar 65%. In theorie is 1 cysticerc voldoende om een mens te infecteren.
Name: Rabbit polyclonal anti living bovine cystocercosis
Product reference: 04-bov-cysto-rab500
Price: 195 Euro / 500ul
Use: crude rabbit serum used for WB 1/500, ELISA capture antibody
Bovine cystocercosis is a parasitic disease that afflicts the muscles of cattle and is caused by larvae of the human tapewormTaenia Saginata. If people consume beef containing these parasites they can acquire intestinal tapeworm infections.
Bovine cystercosis, also known as bladder worm or beef tape worm, is a parasitc zoonosis due to the cestode Taenia saginata. It causes few symptoms in the animal but it is an important zoonosis. |
Classification |
OIE, List B disease |
Susceptible species |
The beef is a intermediate host and man is the final host. |
Distribution |
Bovine cysticervosis is worldwilde distributed. In the Pacific it is only reported in Australia and New Zealand. |
Clinical signs |
In animals there is usually no clinical sign associated. However heavy infections may cause myocarditis andheart failure associated with developing cysts in the heart. |
Post-mortem findings |
Lesions consist of cysticerci in cysts, they are 5-8 mm by 3-5 mm, translucid and filled with a brownish to pinkish liquid, sometimes the 'head' of the metacestodes can be see as a white spot. Cysts are essentially found in the following muscles:
More rarely cysts are found in the liver, the lungs and the brain. |
Differential diagnosis |
Lesions must be differentiated from sarcosporidiosis and toxoplasmosis. |
Specimens required for diagnosis |
The diagnosis is usually made during meat inspection. However serologic test has been developed. |
Transmission |
Beef usually get infected by grazing on pasture contaminated by human feces (which can come from sewage water or direct pollution). Occasionally in-utero contamination occurs. Human get infected by eating unproperly cooked meat (<60°C) |
Risk of introduction |
Introduction could occur through importation of infected cattle, meat or material contaminated by human feces. Humans can also introduce it into the country. |
Control / vaccines |
Control is done through public hygien and proper meat inspection at slaughterhouse. Cysts can be destroyed by freezing at -18°C for 5 days or at -10°C for 10 days or by cooking at 56°C for 5 minutes. |
References |
|
Detectietest ter confirmatie van de visuele postmortem diagnose van rundercysticercose
IWT project 080132
Chemists have created synthetic antibodies for strengthening immunity
Researchers at the Massachusetts Institute of Technology (MIT) and the University of Hanyang (Hanyang University) created a "synthetic antibodies". As a basis chemists have used carbon nanotubes, which fluoresce under laser irradiation.
Previously, this phenomenon has been used by other investigators, the carbon nanotubes are coated with the natural antibodies. When meeting with certain molecules such structures either light or dimmed, so you can use them as a sort of sensors. However, such sensors are destroyed in the living cell, which significantly limits their period of operation.
To solve this problem MIT chemists replaced by antibodies specifically synthesized amphiphilic polymers. These macromolecules contain regions that interact with water (hydrophilic) or push it (hydrophobic).
Polymers synthesized so that their hydrophobic portions fixed firmly on the surface nanotubok as armature, and constitute a hydrophilic "loops", which form a kind of crown around the particle. Loops arranged strictly along the tube, and the distance between anchors determines which target molecule can hook into the loop and change the nanotube fluorescence.
The uniqueness of this new approach is that before the polymer is attached to the nanotube is impossible to predict the possibility of molecular recognition, looking at the structure of the target and the polymer. That is, the polymer itself can not selectively detect a particular molecule.
In his article, published in the journal Nature Nanotechnology, researchers publish a description of molecular sensors, specific for riboflavin (vitamin B2), estradiol (female sex hormone) and L-thyroxine (thyroid hormone).
Currently, scientists are actively developing on certain neurotransmitters, carbohydrates and proteins. Another important challenge for the research team is to understand exactly what is happening with the polymer and nanoparticle throughout the whole capture specific target molecule.
The researchers believe that their current and future developments in the field of molecular recognition will open huge opportunities for monitoring of diseases such as cancer, multiple inflammations, diabetes and many others in any living organism.
Super antibodies almost won HIV
In AIDS patients as there is only one hope - to antiretroviral therapy, which is based on drugs that prevent HIV from reproducing. Genome recorded in the virus RNA and thus enter the cell it with reverse transcriptase enzyme (reverse transcriptase) makes a copy of its own DNA template RNA. Then, this DNA was self proteins cells begin RNA viral clone. If, for example, to suppress the work of the reverse transcriptase of the virus, it can not reproduce.
But even cocktails of antiretroviral drugs only help to translate the acute phase of the disease chronic. Such therapy can not do anything with the virus, which floats in the blood or in the cell is dormant. Therefore, researchers are looking for a way to get rid of the virus, rather than just suppressing its ability to reproduce. (By the way, the usual anti-HIV therapy is theoretically allows to get rid of the virus, but only under special conditions, and such cases are, unfortunately, rare.)
HIV and human lymphocyte
When it comes to completely banish HIV, all agree that the best anti tool to be found here. On the one hand, it's simple: just find the immunoglobulins, which would learn viral envelope protein have been associated with him and would have signaled an immune killer cells that this complex must be destroyed. The problem, however, is that HIV has enormous variability, and antibodies usually catch only a certain proportion of the virus particles, for the same protein they endowed with a number of differences that make antibodies do not see it.
However, our immune system is still able to cope with such a variety of the virus , creating a broad-spectrum antibodies . The fact that the immune system can produce immunoglobulins that recognize more than 90 % of the species of HIV , scientists discovered in 2010, and this discovery , of course, has given all hope that AIDS is about to fall . But over time it became clear that such antibodies are rare and a huge amount of time , then only in response to a real infection - that is to provoke a synthesis of a vaccine of killed pathogen will not work.
Nevertheless, scholars have continued to work with the likes of antibodies. And not so long ago have found universal antibodies that appear much earlier and look simpler than those observed before - however, proved their versatility and low. But be sure to make yourself immune to produce such antibodies? The experiments showed the two research groups - Deaconess Medical Center Beth Israel and the National Institute of Allergy and Infectious Diseases (both - USA) - immunoglobulins broad-spectrum, just introduced into the blood, effectively reduce the level of HIV.
HIV between epithelial cells (bottom) and lymphocyte (top)
Immediately it should be said that the group of Dan Baruch (Dan Barouch) and Malcolm Martin (Malcolm Martin) experimented with monkeys: macaques infected with simian-human hybrid HIV, which multiply in monkeys, but looked like a human virus. He served as a weapon against a broad-spectrum antibodies obtained from patients with AIDS.
Dan Baruch and his colleagues used a cocktail of three types of antibodies, and, as the researchers write in Nature, in the week of the virus level down so that it can not be detected! A similar result was also when used instead of a mixture of immunoglobulins only one of their kind. Once the content of such antibodies in the blood began to decline, the concentration of the virus rose again, but some monkeys it was still indistinguishably low even without the introduction of additional portions of antibodies.
In another study carried out by Malcolm Martin and his colleagues, we are talking about the same thing , but here researchers have used different types of antibodies against HIV. Again, the concentration of the virus in macaques fell for seven days prior to the indiscernible ( again: undetectable !) Level and remained so for 56 days, until the antibodies do not begin to fade. Then it all depended on how much virus was originally in monkeys , if small, following the disappearance of virus antibodies remained under the control of its own immunity of animals , and if it was originally much, the level began to rise.
Thus, as emphasized by the researchers, the virus disappeared from both the blood and other tissues, and no resistance to the administered antibodies, it appeared. (However, there was one exception: when the second study administered only one antibody and experimental monkey was a 3-year experience of cohabitation with the virus, it has a sustained viral strain.)
In both cases, scientists are not too long treated the virus with human antibodies because they were afraid that the immune system begins to resent monkeys against foreign immune proteins , and perhaps that was the reason that in most cases, the virus recovered . That is, it is not clear whether it is possible to make the effect of the " long-playing ". All this is clear only after a clinical trial , and as for the results described above , the enthusiasm of researchers can understand the first time in a living organism could so much lower level of viremia (alas , previous experiments with antibodies that were placed on humans and mice had a very unimpressive results ) .
What's next? The cost of antibodies is much higher than the anti-retroviral drugs, and to treat them more difficult. But the authors of the work suggest that such antibodies should be connected to conventional anti-HIV drugs: it will reduce the cost of treatment, and is likely to increase its efficiency - if antibodies to add substances harmful to reproduction of the virus in the cell.
The deadliest substance in the world is now found
Scientists have discovered the most poisonous substance known to man to date. However, for the first time, the scientific community decided to keep secret the details of his discovery, as yet not found an antidote to the dangerous substance.
According to the experts, the inhalation of substances produced by the bacterium Clostridium botulinum of only 2 billion per gram can kill an adult.
Toxicant blocking acetylcholine release from nerve cells, responsible for the operation of the muscles. If by chance the substance gets into the body with food, and this can happen, because the bacteria often grow in food - Man Gets botulism and die in a short time from paralysis.
Botulism is typically treated by means of antibodies which are produced artificially. They react to seven known type of disease known to experts from A to G. However, scientists from the California Department of Public Health in Sacramento said they found eight toxin type - H. Toxic substance found in the stool of a child in which they observed the characteristic symptoms of the terrible disease. And, unfortunately, currently not found a way to combat the new disease.