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Mosaic vaccine for HIV
Posted on March 31st, 2010 No commentsMosaic vaccines are synthetic peptides, generated by an algorithm that cover all combinations of known sequences of HIV antigen. The most challenging problem to solve in order to produce an effective vaccine against HIV is the high rate of variability in viral genome. Indeed, viruses tend to mutate rapidly to prevent the host’s immune defences; variations between individuals and different regions have been also reported.
Thus, HIV vaccines must initiate an immune response that recognizes a wide range of epitopes from several strains and from mutated variants of particular epitopes. Two studies have been published about mosaic vaccines. The first one has evaluated the effect of three mosaic vaccines, namely against gag, pol and env antigens on cellular culture. Some evidences of improved cellular response have been described. These results have been confirmed by the second study where only mosaic gag antigen has been kept in account. Up to date mosaic vaccines have been tested only in animal models and some concerns about the goodness of the model have been risen. It has been suggested a further confirmation by using SIV as infecting agent that can better contaminate animal than HIV. Nevertheless, these studies seem promising and give a realistic hope to obtain HIV vaccine. -
Acute gastroenteritis in children
Posted on March 29th, 2010 No commentsAcute gastroenteritis affects numerous children at least one time in their infancy and childhood. This disease is usually due to viral infection and none treatment is suggested to treat the infection self. In contrast, more concerns are due to dehydration associated with vomiting and diarrhoea.
Dehydration is treated with oral or intravenous intake of fluid, but generally intravenous treatment is preferred because the high likelihood of emesis may reduce benefits. Anti- emetic drugs are not suggested for children for their important adverse effects. Anyway, several studies have been reported in literature that show the effectiveness of ondansetron, an antagonist of serotonin receptor. This drug has been initially developed to treat nausea following chemotherapy in cancer patients; up to date ondansetron seems also promising to care emesis in children during acute gastroenteritis. The major benefit is the reduction of vomiting episodes that make possible to use also oral rehydration treatment. Furthermore, duration of hospital staying or admission rate are also reduced after ondansetron treatment, showing a financial advantage in comparison to traditional approaches. In conclusion, these studies are very important to demonstrate and ascertain the effectiveness of drugs in children in well structured trials. It’s auspicial that other drugs will be analysed at the same manner. -
Novel technique to diffract molecules
Posted on March 25th, 2010 No commentsAnkylography is a novel technique that is setting up to determine the three-dimensional structure of proteins or in general macromolecules. This technique is based on the opportunity to measure the diffraction pattern through a spherical detector.
A coherent x-ray beam is launched over a single particle and the diffraction records of scattered waves is registered on a curved surface. In this way, the three- structure of an object is encoded by the 2D spherical pattern and is solved in a single shot.
Ankylography is currently at the beginning, but several applications have been already imagined: for instance, it will be possible to study the enzymatic conformational changes in the real time of the reaction, thus making realistic the opportunity to develop drugs and inhibitors for each enzymatic state. Indeed, the biggest difference between ankylography and traditional x- ray diffraction is the capability in the first case to determine the structure of a single molecule and not an average of different conformations.
To do this, additional studies and developments are needed, from a new generation of powerful x- ray generators to algorithms to elaborate the huge amount of data derived from similar experiments. Fortunately, US and Europe governments are interested in ankylography and seem to invest money in it. -
The IntOGen interface
Posted on March 23rd, 2010 No commentsSometimes, there is a gap between experimental biology and clinical medicine while a continuous interchange would be auspicial to well direct experiments and keep updated the therapies. An interesting tool has been developed at the Barcelona Medical Research Park (Spain).
IntOGen is a frame work that collects, integrates and manages data derived from genome- wide experiments on large scale projects such as the Cancer Genome Atlas and the International Cancer Genome Consortium. Scientists manually annotate all samples by using the International Classification of Disease for Oncology vocabulary, in terms of tumour topography and morphology. Furthermore, they apply statistical methods to identify the most relevant alterations, by analyzing multiple studies on the same kind of tumour. Finally, they consider the role of whole biological modules, such as a pathway, to demonstrate the involvement of a single gene altered. The website www.intogen.org is available for free and allows to know modules and genes important in cancer, share experiments and analyze data in the context of cancer. This interface has been built to fill the gap between medicine and molecular biology. Similar tools should be really useful not only for cancer but also for other kind of diseases, such as neurodegenerative disorders. -
Application of molecular biology to medicine
Posted on March 19th, 2010 No commentsModern medicine is based on evidence. Despite few years ago, physicians based their diagnosis and therapies on their previous experiences, now clinical trials, approved protocols and worldwide accepted treatment help physicians to make the better choice for their patients. To reach this important goal, molecular medicine gave a big contribution. Molecular medicine is a novel branch of medicine in which molecular biology or biochemistry techniques are usually used to accomplish exams and screening or diagnose the diseases. Molecular biology labs have worked as research and development department to improve protocols or set up novel methodologies at the beginning just to be used for research purposes, then applied to diagnosis. For instance, we could focus our attention on the polymerase chain reaction, namely the PCR.
This techniques has been developed to produce DNA portion in vitro and has quickly revolutionized molecular biology, allowing cloning, sequencing and in general gene manipulation. The improved type of PCR, the real time PCR is now currently used in modern hospital to detect certain diseases, such as recidivate leukemia in patients’ blood or gene signature in familial diseases. Other important tools which have found a good application in diagnosis are the monoclonal/ polyclonal antibodies. Several techniques employed antibodies to detect proteins in cellular lysates through western blotting, or directly in whole cells, through the immuno-chemistry and molecular imaging. As well as, it’s also possible to purify small amount of native protein through immuno-precipitation and so on. Antibodies are really largely used in biochemistry labs and some techniques are applied also in diagnostic labs.
For instance, we can talk about the ELISA assay, normally used to quantify serum proteins or cell sorting analysis, in which some antibodies that specifically recognize surface proteins are used to separate different kind of cells. Finally, also cellular biology gave important results in modern medicine. The capability to culture in vitro cellular populations changes the therapeutic opportunity for a lot of diseases. For instance, now it’s possible to select healthy cellular population in leukemic patient, propagate it in vitro and then draft it, reducing in this way several problems of rejection and immuno-suppressive events. We can continue to talk about other examples of molecular, biochemical or cellular protocols that have found a great application in clinics. This overview strongly confirms how scientific advances are important because they have an immediate benefit on modern medicine and as a consequence on the human life. It’s important to remember that not only good protocols, but also good quality of science and good data management and reporting are two further parameters to improve modern medicine, but this is the topic for another post!!! -
Nuocytes, a novel cell type
Posted on March 15th, 2010 No commentsA recent work published in Nature demonstrates the existence of a new class of cells, namely noucytes. This cells seem really important for the type II immuninity. The type II immunity protects our body from parasitic helminth infections, by promoting the release of type II cytokines, activating eosinophiles and goblet cells and secreting mucus and IgE.
The same system is also responsible for asthma and other allergic disfunctions. Nuocytes are a novel component of innate immune system and seem involved in IL13 release during the first steps of helminth infection. Nuocytes primarily respond to IL25 and IL33 stimuli either in vitro or in vivo, then start the immune response. Lack of IL25 ad IL33 cytokines determines nuocytes expansion failure and lastly severe defect in worm expulsion. Thus, nuocytes play a crucial role in body defense and this and subsequent studies will help us to understand better the mechanism of action of innate immune system. Nuocytes will represent a new possible target for immune stimulating molecules in order to increase the protection versus infection, as well as it could be possible that new anti asthma drugs will be directly act on this class of cells. -
Reproducibility Is A Must
Posted on March 13th, 2010 No commentsReproducibility and reliability are two important values for scientists that influence either credibility and the opportunity to obtain good results. A definition of reproducibility can be the ability to repeat a protocol (whatever kind of protocol) and gain the same conclusion. Reproducibility could evaluated into a laboratory when several operators perform at the same time or in different time an experiment. If the protocol is reproducible, all experiments will give the same result, otherwise the protocol is not reproducible.
No tricks or wizardries can be accepted in science. So, it must be possible to repeat what has been already done. What about reproducibility is true for one lab. is also true for the whole scientific community. When an experiment or a protocol is published, all details must be explained to repeat the same results. Indeed, a protocol could give good results if applied to other models as well as the same results could be verified in other system. Reproducibility allows science advances and without it science looses its mean and its value. Reliability is strictly connected to reproducibility but usually involves the single lab. To obtain reproducible results it’s very important to note everything concerns the experiment (material, protocol, dilution and so on) and keep in order reagents and original files. Only in this way science still be credible. -
The Transgenic Potato
Posted on March 11th, 2010 No commentsThe Transgenic Potato
A novel transgenic potato has been approved in Europe to be cultured and marketed. This potato is patented by BASF, an important German company that is a leader in antibiotic drug for agriculture and veterinary. Transgenic potato has a resistance versus carboxicillin and kanamycin, two antibiotics largely used to fight culture contamination and disruption.
This genetic modification should improve culture yield without interfering with nutritional and biophysical properties of the vegetable. A further improvement has been reported also in the amount of amid that is increased in percentage in this potato. For this reason, OGM potato should be conveniently used in paper manufacturer and animal feeding. This last application has generated a lot of discussion and anxiety. Indeed, since it would be possible to use bigger amount of antibiotics to protect potato culture, animals should be eat more antibiotics and lastly also human that eat meat from animals could ingest more drugs. For this reason, attentive and serious control must be done, in order to preserve human health from future problems related to antibiotic intolerance, resistance or toxicity. In summary, biotechnology could proficiently help to improve culture conditions, but security measures must be kept in mind. -
The relationship between thalassemia and atherosclerosis
Posted on March 9th, 2010 No commentsSardinia is an Italian island where thalassemia incidence is really high. Giving the complications of atherosclerotic disease and the necessity of frequent blood transfusions for thalassemic patients, scientists from the University of Cagliari (Italy) were interested in the relationship between these two diseases.
They provided a genetic analysis of patients affected by thalassemia major or intermedia in comparison with age matched healthy controls, by checking genes involved in iron detoxification and in cholesterol metabolism. Indeed, cholesterol levels are a crucial factor to determine the atherosclerotic lesions as well as iron overload, especially in heart, is important to cause cardiovascular complications. They identified an increase of TNFa and ACAT mRNA levels, involved in iron metabolism and cholesterol metabolism, respectively and a reduction of Hepcidin and ILa. Serum iron levels were higher in patients than in control, while HDLs were lower. Since gene expression was altered in factor that had a key role in cholesterol metabolism rather than in iron homeostasis, scientists suggested that possible cardiovascular complications in patients affected by thalassemia intermedia were due, at least in part, to the occurrence of premature atherosclerotic lesions. By contrast, the role of iron overload was further confirmed in thalassemia major patients. This preliminary study allows clarifying how relationship between important diseases, such as thalassemia and atherosclerosis, may contribute to complicate the clinical profile. -
Hela cells, a story lasting 60 years.
Posted on March 4th, 2010 1 commentHenrietta Lacks died in 1951 at the Johns Hopkins hospital in Baltimore because of an aggressive form of cervical cancer. She would be probably unknown now, if your cells hadn’t been extracted and cultured as HeLa cells. Scientists of every molecular biology and cellular lab know about these cells because they have used them at least one time or because they have studied their application on biology books. However, it’s very interesting the history about HeLa cells.
Henrietta was 31 years old when she died and she had five children. She was the unwitting protagonist of the story, because on 1950s none informed consent was asked her. Doctor Gey and his wife had all scientific merits to make possible HeLa cell culture. They put these cells on Petri dishes; at that time they were performing a lot of experiments to try to culture human cell lines. HeLa cells were able to quickly grow in established conditions, differentially from other cells tested. Dr Gey sent his cells to many laboratories around the world and shared information about culture conditions and so on. This generosity allowed important scientific advances, especially in vaccination field because HeLa cells were firstly used to test and produce the Polio vaccine. Unfortunately, giving their ability to grow also in unfavorable conditions, HeLa cells became one of the most dangerous contaminant agents of other cell lines. The doubt that scientists were using HeLa cells in their experiments rather than breast, prostate or placental cells made necessary further analyses to figure out the true identity of cell lines used. Thus, after almost thirty years from her death, the Hopkins Hospital contacted Henrietta’s children and familiar to invite them donate some blood or tissue samples.
Genetic analyses and blood type were information required by scientists to complete the Henrietta’ profile and recognize HeLa cells from others. Even if the scientific purpose was correct, Henrietta’ family didn’t have all explanation needed to well understand physicians’ operations. This was only one of dark points from an ethical point of view present in this story. Fortunately after Henrietta’s experience, ethical question has acquired great importance in experimental medicine and now informed consent is required for every medical action. Another important issue of this story were the moral and legal questions that arose about the commercial value of something derived from human body. Who may have the copyright of HeLa cells? With these cells several billions of dollars have been gained by pharmaceutical companies, research institutes and so on, but Henrietta’s family haven’t had any benefit. But on other hand, what has been the role of Henrietta in whole story? She was just a poor mother who died too soon.
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