Discover the causes of idiopathic pulmonary fibrosis

31 10 2013

Researchers from the Vall D'hebron University Hospital and the Group of Pneumology of the Vall D'hebron Research Institute (VHIR) they have shown that causes of pulmonary fibrosis idiopathic in half of the cases can be determined following the completion of a clinical study in depth, that includes an exhaustive and systematic interrogation, determination of antibodies against the causative substances, inhalation tests, crops and environmental measurements where the patient attends (home and work) to detect antigens that may cause this serious disease.

 

De izquierda a derecha: Dra. Maria Jesús Cruz, Dr. Ferran Morell y la neumóloga Ana Villar

From left to right: DRA. Maria Jesus Cruz, Dr. Ferran Morell and Ana Villar neumologa

The importance of this trial, made with patients from the outpatient service of Pneumology Hospital, It is showing that assisted a systematized and in depth and with techniques appropriate, advances for our health care system can also be”, says Dr. Ferran Morell, the study's lead author.

 

The study, published in The Lancet Respiratory Medicine, was conducted between 2004 and 2011 in 60 patients with this disease and it will open a new Avenue in the diagnosis and treatment of this pathology, Since the identification of the causes will prevent this disease and this will prevent disease to evolve towards advanced or severe phases.

 

Researchers have found that one of the main causes of idiopathic pulmonary fibrosis is exposure to quilts and cushions of feathers, as well as exposure to birds and fungi in minimal but persistent amounts. In short, It's the disease called chronic Hypersensitivity Pneumonitis, disease in which the Hospital Universitari Vall D'hebron is world reference.

To be able to timely diagnose this pathology, Dr. Ferran Morell ensures that “is essential for the diagnosis of the patients study have ready the techniques for the detection of antibodies against the causative substances and inhalation tests (broncoprovocacion), as well as the realization of soluble extracts from substances, etc.”.

 

Idiopathic pulmonary fibrosis is a recognized disease from 1940, in which both lungs gradually is fibrosan (heal); Like this, the lung loses elasticity, making it difficult to inspiration, gradually losing the patient breathing capacity. This disease affects one 10.000 patients in Spain (2.000 in Catalonia) and has an incidence of between 10 and 20 new cases for each 100.000 inhabitants per year.

 

 

 

 

Vhir.org [en línea] Barcelona (ESP): vhir.org, 31 de octubre de 2013 [REF. 18 October of 2013] Available on Internet: http://www.vhir.org/ salapremsa/mitjans/mitjans_detall.asp?any = 2013&NUM = 269&MV1 = 5&MV2 = 1&Language = is&title = researchers of Vall d' Hebró



What happens in the head of young children?

28 10 2013

The two to four years the brain opens an important window for the development of the language. This was the conclusion of a study by British and American scientists.

 

A los 6 años, el niño tiene un vocabulario de unas 5.000 palabras.

To the 6 years, the child has a vocabulary of some 5.000 words.

According to the experts, environmental influences have the greatest impact before the four years, While developing the brain circuitry for processing new words.

The research published in The Journal of Neuroscience It suggests that the disorders that cause learning difficulties in language should be addressed early.

It also explains why young children are so good to learn more than one language.

The scientists of the King ’ s College London and Brown University in the United States studied to 108 children with normal development between the ages of one to six years.

They used brain scan to look at the myelin, thermal insulation that develops from birth in brain circuitry.

To his surprise, they discovered that the distribution of myelin is fixed from the four years, which suggests that the brain is most plastic at an early age.

Experts predict that any environmental influence on the development of the brain will be strongest during childhood.

In addition to facilitating children to be bilingual, These findings also suggest there is a critical time during the development when the environmental influence on cognitive abilities may be higher.

Dr. Jonathan O ’ Muircheartaigh, of King ’ s College London and head of the study, He told the BBC that “due to our work it seems to indicate that the circuits in the brain associated with language are more flexible before the four years, early intervention for children with language delays should be started before this critical age”.

“This can be critical for many disorders of development, as Autism, Since the language problems are a common early feature”, added.

 

Increasing vocabulary

 

Early childhood is the time in which language develops more quickly. To the 12 months, babies can say simple words like “Mama” and “Pope”, a vocabulary that is enriched exponentially to the 6 years, that the child has knowledge of a few 5.000 words.

Language skills are located in the left frontal region of the brain.

The researchers hoped that more myelin was developed in that area, to the extent that children learned more words.

What they discovered is that it remains constant, suggesting that there is a crucial window to intervene in development disorders.

“This work is important because it is the first one that investigates the relationship between the structure of the brain and language in early childhood, It also shows how this relationship changes with age”, explained Dr. Sean Deoni of the Brown University, study co-author.

“It is important because it is common that the language is altered or delayed in various disorders of development, as Autism”.

For its part, Professor Dorothy Bishop, Department of Neuropsychology at the University of Oxford, He said that the work offers a new important about early development information of the connections in the brain regions that are key to cognitive functions.

“But it is too early to be sure about the functional implications of the result (study)”, added.

The research was funded by the National Institute for Mental Health in the United States.UU., and the Wellcome Foundation, in United Kingdom.

 

Helen Briggs, BBC

 

 

Bbc.co.uk [en línea] London (UK): BBC.co.UK, 28 de octubre de 2013 [REF. 11 October of 2013] Available on Internet: http://mundo/noticias/2013/10/131009_salud_bebe_cerebro_lenguaje_gtg.shtml www.bbc.co.uk/



Discovered one of mechanisms favouring the aggressiveness of Ewing's Sarcoma

24 10 2013

Caveolin-1 is involved in the formation of new blood vessels around the tumor facilitating their growth and their proliferation the finding opens the door to new therapies against this childhood cancer research

 

Grupo de investigación en sarcomas

Research in Sarcoma group

Researchers at the Institute of biomedical research of Bellvitge (IDIBELL) led by the head of the research group in sarcomas, Oscar Martinez-Tirado, they have discovered one of the mechanisms that trigger angiogenesis (formation of new blood vessels) around the tumor cells of Ewing's Sarcoma, a very aggressive childhood cancer.

The results of the study, published in the journal PLoS ONE, they open the door to a new line of research of possible therapies for this tumor. Ewing's sarcoma is the second most common bone cancer and affects children and young people. Currently, If it is diagnosed early and doesn't metastasis, can be cured in the 80% cases between the 25% and the 30% cases are diagnosed when there is metastasis and survival drops to the 30%.

 

Angiogenesis and solid tumors

Angiogenesis is a key process in the growth, proliferation and migration of solid tumours. Tumor cells need new blood vessels that provide them with oxygen and nutrients extras need to be developed at a fast pace.

The Group of Oscar Martinez-Tirado has described in several studies functions of the protein caveolin-1 in Ewing's Sarcoma: “We have seen that it has a tumorogenico role in this type of tumor, to participate in the resistance to chemotherapy, It promotes metastasis and in this work we have shown that it plays a fundamental role in the angiogenic process”.

The researchers found that, in cell lines that are genetically modified to express not the caveolin-1, the tumors were smaller, they had more necrosis and Vascularity index was significantly more lower than in lines with caveolin-1. “It is therefore, a lack of caveolin-1 prevents the angiogenesis” He said Martinez-Tirado.

The researcher explained that although the caveolin-1 seems to be a possible therapeutic target for fighting Ewing's sarcoma, its location, It makes it very difficult to access "so have to find proteins that bind the caveolin-1 and they can take this role”.

In this sense, the study describes how the caveolin-1 interacts with another protein called EphA2 activating a signaling pathway that induces angiogenesis, more specifically the migration of cells that should form the vessels to the tumor. Said Martinez-Tirado “This protein is a membrane receptor that yes could be a good candidate to be therapeutic target”.

 

Possible future therapies

This finding opens the door to future potential therapies. “Now we have to study if in addition to being involved in angiogenesis, the EphA2 protein is tumorogenica per are. If it is not, We have the perfect target. "Our idea of the future is to be able to use this protein as a vehicle to release within the tumor cells toxic substances" explained Oscar Martinez-Tirado.

In this work the Hospital Vall researchers have also participated d ’ Hebron, University Hospital of Salamanca and San Joan de Déu Hospital in Barcelona.

 

The article reference

Sainz-marbled M., Huertas-Martinez J., Lagares-Tena L., Liberal J.M., Mateo-Lozano S., Alava E., C. Torres, Mora J., García del Muro X. and Martinez-Tirado O. EphA2-induced angiogenesis in Ewing sarcoma celles works through bGFG production is dependent on caveolin-1 and. PLoS ONE. August 2013

 

 

Idibell.cat [en línea] Barcelona (ESP): idibell.cat, 24 October of 2013 [REF. 20 in August of 2013] Available on Internet: http://modul/noticies/es/598/descubierto-uno-de-los-mecanismos-que-favorece-la-agresividad-del-sarcoma-de-ewing www.idibell.cat/



Mobile application to cater for people with vision problems

21 10 2013

Only with own a Smartphone hardware, Peek allows physicians to perform visual acuity test, distinction of colours, depth of field and contrast sensitivity. In addition, makes it possible to examine cataract and cornea.

Developed by scientists at the International Centre for eye health, of United Kingdom, Peek (Portable Visual examination) It is a mobile application that works with a smartphone hardware.

According to statistics, estimated by the World Health Organization (WHO) in June of 2012, 285 millions of people in the world are blind or have certain limitations in vision. However, four of every five cases are preventable.

But the 90% those affected come from emerging countries developing and do not have the economic tools to access an ophthalmologist.

In search of a solution, the developers created the application to access remote areas and reduce the inequality gap. In this sense, Peek allows physicians to perform visual acuity test, distinction of colours, depth of field and contrast sensitivity, primarily designed for patients who live away from the specialized centers. In addition, makes it possible to examine cataract and cornea.

It is interesting to note that the application of portable visual examination uses a smart cell phone resources. The camera makes it possible to take pictures that will be then judged in London, a variable-size letter appears on the screen and is used to check the vision, and phone flash illuminates the bottom of the eye and the retina to rule out diseases. In synthesis: low-cost technology, as the value of the equipment does not exceed the 500 $.

Like this, recruited data are recorded on cards that are customized according to each patient. This information, at the same time, It can be Geolocated and consulted by professionals from other regions.

Currently, a research team led by the ophthalmologist Andrew Bastawrous, the Faculty of the London School of Tropical Medicine and hygiene, It is conducting a pilot test in Kenya and Antarctica.

"The patients who need it most never will reach a hospital because they are out of reach. They do not have income to pay for transportation, "so we need a way of reaching them", told the BBC Bastawrous. And then, in reference to the procedure of consultations, added: "We can do using these techniques is to go to the House of patients, to examine them and give them an immediate diagnosis at the gates of their homes".

For its part, Peter Ackland, the International Agency for prevention of blindness, said: "Peek is a tool with a huge potential to change the game."Source: Peek Vision and BBC

 

 

 

Ehealthreporter.com [en línea] Chicago, IL (USA): ehealthreporter.com, 21 October of 2013 [REF. 10 de septiembre de 2013] Available on Internet: http://es/noticia/verNoticia/2770/una-aplicacion-movil-permite-atender-a-personas-de-paises-emergentes-con-problemas-de-vision www.ehealthreporter.com/-



Minicerebros from stem cells

17 10 2013

Scientists develop minicerebros from stem cells

 

Human embryonic stem cell colony phase

Human embryonic stem cell colony phase

 

We have seen coronary tissue that beats, tracheae and bladders developed from stem cells. Now researchers have taken another step forward with the development of minicerebros from these programmable cells.

 

Are not really brains that work - in the same way that a car with the engine on the roof or wheels on the hood is not a vehicle that can lead- but the pieces are there, and is a major scientific advance, According to Juergen Knoblich, senior author of a new study on the use of stem cells for the development of brain tissue.

 

Scientists have created what they call “brain organoid” using stem cells. A pea-sized structures are made of human brain tissue and may help researchers to discuss important questions about development and brain disorders that occur during these early stages of life.

 

The organoid,described in the magazine Nature, they have similar components to the of a brain of an embryo's 9-10 weeks of age, said in a press conference, the lead author of the study, Madeline Lancaster, researcher at the Institute of biotechnology Molecular of the Austrian Academy of the sciences in Vienna. She and her colleagues have created hundreds of these organoids.

 

In this first stage of human development, several key regions of the brain can distinguish already, including the dorsal cortex, the ventral forebrain, choroid Plexus - generated spinal fluid- and regions that are similar to the midbrain and the rear brain. Lancaster and his colleagues claim to have identified some of these regions in these new minicerebros.

 

However, models made from stem cells, these regions are situated in a natural way in the same place to occupy in a normal brain. [Read more about artificial brain]

 

The organoid also lack certain parts that the brains of human embryos of 9 weeks have: the most important thing, the cerebellum, It is involved in the motor movement. In addition to the hippocampus, a structure in the form of seahorse crucial for memory, that rarely was detected in these structures similar to brains.

Source: Edition.CNN.com

 

Progress-tecnologicos.euroresidentes.com [en línea] Alicante (ESP): progress-tecnologicos.euroresidentes.com, 17 October of 2013 [REF. 03 de septiembre de 2013] Available on Internet: http://avances-tecnologicos.euroresidentes.com/

 

 

 



Self-sufficient pacemaker, Thanks to the energy of the heart

14 10 2013

Create a device that transforms heart rate power into electric current to feed indefinitely to implants

 

Traditional pacemakers have a snag: they must be replaced every five to seven years because the batteries run out. Avoid these operations is now possible thanks to a system developed by American scientists: a collector of energy that transforms the heart rate into electric current. This current can be used to feed on the pacemaker, indefinitely.

 

El nuevo dispositivo recoge la energía de los latidos del corazón para destinarla al suministro energético de los marcapasos. Fuente: PhotoXpress.

The new device collects the energy of the heart beat for the energy supply of the pacemaker. Source: PhotoXpress.

U.S. scientists have developed an experimental device that collects the energy of the heart beat for the energy supply of the pacemaker.

The advance, has been presented in the American Heart Association's Scientific Sessions 2012 It held until November 7 in Los Angeles (United States), It could serve for replacing the batteries of the pacemaker in the future, so that these need to be replaced periodically.

In a preliminary study, the researchers tested this device of energy collection that uses the piezoelectricity to generate electricity from the beating of the heart.

Piezoelectricity is the phenomenon whereby a material, When it is subject to mechanical stresses, it gains its mass electric polarization, that is a difference of potential and electrical charges on their surface. The results were promising.

 

An almost eternal pacemaker

According to the American Heart Association published in a press release, This system would be an interesting technological solution for pacemakers, you require only small amounts of energy to function.

But, In addition, piezoelectricity could be used for other cardiac devices in implant, as defibrillators, They also need small quantity of energy, says Amin Karami, lead author of the study and researcher at the Department of aerospace engineering at the University of Michigan in Ann Arbor (United States).

According to Karami, today, the pacemaker must be replaced every five to seven years when its batteries are exhausted, What is expensive and involves a major drawback.

"Many of the patients are children who live for many years with pacemakers. "Imagine how many operations could save themselves if this new technology spreads", explains the scientist.

Tests conducted with the new device were as follows. First of all, the researchers measured the vibrations of the chest, induced by the beating of the heart.

Then, they used a "shaker" to reproduce these vibrations in the laboratory, and they connected it to the prototype of collector of heart energy that had developed.

Measurements on the performance of this prototype, based on a set of 100 heartbeat simulated at different heart rates, They showed that the power collector worked as scientists would have predicted: generating more than 10 times the energy it needs a pacemaker current.

The next step will be to implement this energy collector, whose size is half of the batteries currently used in pacemakers, says Karami. Researchers hope to integrate its technology into commercial pacemaker.

 

Safe mobile phones

Today, There are two types of energy collectors that could supply power to a typical pacemaker: linear and non-linear. Linear collectors work well with a single specific heart rate, so it changes in such frequencies would do that do not collect enough energy.

On the other hand, a non-linear collector - the type used in this study- It uses magnets to increase energy production, and make that the collector is less sensitive to changes in heart rate.

As a result, the developed nonlinear collector generated the necessary energy from heartbeat of between 20 a 600 beats per minute, to feed continuously on a pacemaker.

Karami says that also found that devices such as mobile phones or microwaves do not affect this non-linear device.

 

Other solutions

Karami solution is not the first raised to solve the inconvenience of pacemaker batteries.

Last April of 2012, researchers at the Fraunhofer Institute for ceramic technologies and systems (IKTS) of Germany managed supply power wirelessly from a portable transmitter module to a mobile or "receiver" generator module.

According to scientists, This module will allow feeding distance implants (as a pacemaker), but also systems of dosage of drugs and other medical applications without the need for contact.

On the other hand, nor is this the first time that is achieved to obtain energy from any movement of the body, to take advantage of it to other devices. In this direction, Princeton University engineers (in United States) they developed in 2010 a material able to produce energy from the movements of the human body (career or breathing, for example).

The scientists noted then that this compound, a combination of lead titanate zirconate with silicone rubber (PZT), It could be applied in chips intended for medical devices, as a pacemaker.

 

 

 

By Yaiza Martínez.

 

Tendencia21.NET [en línea] Madrid (ESP): tendencia21.NET, 14 October of 2013 [REF. 05 November of 2012] Available on Internet: http://Marcapasos-autosuficientes-gracias-a-la-energia-del-corazon_a14072.html www.tendencias21.net/



Reducing the size of infarction with early administration of Metoprolol

10 10 2013

  • Metoprolol reduces a 20% the infarct size
  • This follows the study Metocard-Cnic, Since underway thanks to funds from the Ministry of economy and a grant from the IASB
  • The next step is to assess the reduction of the long-term mortality in patients treated early with this drug

 

The early administration of metoprolol is capable of “reduce the size of infarction in a 20 per cent”, as is the Publisher of Circulation, the journal of the American Association of Cardiology, that just published in its edition of the Spanish study results Metocard-Cnic. Results that could now be extended to all over the world, given the great clinical benefit, low cost of the drug (less than two euros) and universal accessibility of this treatment.

 

Parte del equipo investigador coordinador

Part of the research team coordinator

If so, It would change clinical practice before a patient's as infarction, so far, not receiving routinely this medication before undergoing an angioplasty, recommended intervention to open occluded artery causing infarction.

 

To carry out the analysis of efficacy of metoprolol, drug of the family of the beta-blockers prescribed for the treatment of hypertension and other cardiovascular diseases, researchers have received funding from the Ministry of economy and competitiveness, a competitive Fellowship of the national cardiovascular research centre (CNIC) and the distinction Severo Ochoa obtained by this Center in 2011. “The absence of commercial interest makes difficult to perform independent these drugs in clinical research”, underlines Borja Ibanez, Head of the Group's image in experimental Cardiology of the IASC, and one of the principal investigators of this study.

 

In addition to the low cost of the drug, researchers also highlight the greater return on investment from now, Since the Infracted with less necrotic cardiac muscle are less likely to need an implantable defibrillator, with a cost of over of 200.000 EUR, or require costly revenue for heart failure. “By an expenditure of less than two euros, in the future billions of euros will be saved”, aims Ibáñez. Currently, the same team that carried out the study Metocard-IASB is dealing from an analysis of cost-effectiveness.

 

The study, you have participated community emergency services and a total of seven hospitals in Madrid, Galicia, León and Cantabria had a sample of 270 patients with infarction, those who were randomized to receive metoprolol intravenously or to follow the standard protocol. A week of infarction, discussed the State of the patients from a cardiac magnetic resonance, quantifying all the grams of heart which necrotic had resulted after infarction. Like this, It was found that patients with metoprolol had a very reduced infarct size compared to the control group.

 

Once confirmed the clinical benefit, the researchers are now evaluating what is the mechanism by which this therapy works in patients with infarction. In addition, the IASB and the emergency services are already working also in the logistics of another clinical trial of analysis of the reduction of long-term patients treated with metoprolol early mortality, This time at the international level.

 

Link to the article: here

 

Gacetamedica.com [en línea] Madrid (ESP): gacetamedica.com, 10 de octubre de 2013 [REF. 04 October of 2013] Available on Internet: http://Gazette/articulo.aspx www.gacetamedica.com/?idart = 778304&idcat = 797&Type = 2



PASS THROUGH THE TUBE

7 10 2013

It is convenient to have to go through the tube?

El tubo

Tube

 

Pasando por el tubo

Passing through the tube

 

Luz al final del tubo

Light at the end of the tube

 

After which comes an interesting dilemma: is it convenient to, and even more so in these times that run, pass through the tube?

Thank you and happy way!

By Doctopolis.

 



Epidemic Proportions

3 10 2013

The fight against infectious diseases increasingly links discovery with care

 

A WAR WITH LITTLE PEACE: The incidence of extensively drug-resistant tuberculosis continues to grow in Russia. This young man is a patient in a tuberculosis ward in a psychiatric hospital in the North Caucasus region of that nation.

 

When Mycobacterium tuberculosis invades a person’s body, it doesn’t just settle into the lungs and look for a spot from which to eke out a living. It hijacks that person’s macrophages—cells that attack invading bacteria—and uses the mechanisms of inflammation to manipulate the environment around it, remodeling its new home to suit its needs.

 

Salmaan Keshavjee knew about Mycobacterium’s penchant for makeovers, and thought that this knowledge might be useful in the fight against tuberculosis. So he was intrigued when he learned of an unusual approach that researchers at Sweden’s Karolinska Institutet were taking to control these bacteria-orchestrated renovations.

To understand this twist in the body’s normal path of self-defense, and to find ways to get the immune response back on track, the Sweden-based team, led by Markus Maeurer, a professor of clinical immunology at the institute, had cultured the mesenchymal stem cells from patients with extensively drug-resistant tuberculosis (XDR TB), then reinfused the patients with those cultured stem cells. Because mesenchymal stem cells help suppress inflammation, the researchers wanted to see if they could safely dampen and refocus the inflammatory response without  compromising immune function.

“Their preliminary data suggested that the stem cells didn’t suppress immunity in an adverse way, and surprisingly, the patients who received the transplanted cells did much better on their XDR TB treatment than typical patients in their condition,” says Keshavjee, an HMS associate professor in the Department of Global Health and Social Medicine and a physician in the Division of Global Health Equity at Brigham and Women’s Hospital. With the treatments now in use, fewer than a third of patients with XDR TB recover, but in this small initial study, all the participants appeared to recover.

Keshavjee is developing a partnership with the institute’s team, laying a foundation for more-extensive trials of the treatment in Russia and Peru. “Saving lives from a disease that’s killing people—that’s always good,” Keshavjee says. “But this work also opens the door to thinking about tuberculosis differently. If the mycobacterium is manipulating its environment by modulating T cells and other immune cells, we need to ask, ‘What if we unmodulate that environment?’ ”

“Inside our bodies, the bugs are living in an ecosystem,” he adds. “As humans, we also have our own ecology, which plays out in society. Recognizing the complex biosocial nature of infectious diseases moves you toward some crucial insights about how these diseases work and how to fight them.”

To fight infectious diseases worldwide, biomedical researchers and clinicians are joining efforts to apply laboratory-based discoveries to the challenge of saving the lives of people with tuberculosis, cholera, and other age-old ravages. These international collaborations are increasingly considering such diseases in context, as integrated parts of complex interconnected systems that involve humans.

 

“We now have genomic and proteomic platforms that are beginning to have immediate relevance to the challenges of diagnosing and treating infectious disease in poor communities,” says Paul Farmer ’90, the Kolokotrones University Professor at Harvard, head of the Department of Global Health and Social Medicine at HMS, and a cofounder of Partners In Health, an international nonprofit that brings health care to the poor. “Many of these new technologies are more portable, scalable, and affordable than ever before.”

 

In Black and White

Tuberculosis is a global public health issue that is unevenly distributed: the burden of the disease is highest in Asia and Africa, with India and China accounting for almost 40 percent of cases. Africa has 24 percent of the world’s cases and the highest rates of disease and death per capita. In the Russian Federation, XDR TB is a particular concern: it has rapidly spread through prison populations. In Peru, while the incidence of tuberculosis is decreasing, the incidence of multidrug-resistant tuberculosis is on the rise. Overall, according to a 2012 report from the World Health Organization, there were an estimated 8.7 million new cases of tuberculosis and 1.4 million deaths worldwide from the disease in 2011.

Similar sobering statistics can be found for cholera. Although up to 80 percent of cholera cases can be successfully treated with low-cost oral rehydration salts, the WHO estimates that annually more than 100,000 people succumb to the disease.The impact of cholera is most acute in regions with poor sanitation and unsafe supplies of drinking water, conditions that annually spawn three to five million cases worldwide. The entire country of Bangladesh is considered at high risk for this disease, the only country with this designation from the WHO.

 

Delete Buttons

Like tuberculosis, cholera elicits a complex immune response. The infection takes place in the mucosal membrane of the small intestine, where billions of beneficial bacteria live. Our gut microbiota perform welcome chores such as fermenting carbohydrates to release their useful energy. Although our gut mucosa is always on the alert for foreign bacteria, killing every newcomer would be imprudent, as some may be useful in maintaining the health of their human host. Yet when a pathogen is identified, the mucosal cells mount a vigorous immune response.

 

Unfortunately, the basic mechanisms of that response are still poorly understood. This knowledge gap has hindered the development of effective, durable vaccines for diseases such as cholera. In fact, current vaccines offer only partial protection that lasts for just a few years.

To extend this protection, or perhaps even block the disease permanently, researchers, including John Mekalanos, the Adele H. Lehman Professor of Microbiology and Molecular Genetics and head of the Department of Microbiology and Immunobiology at HMS, are tweaking the genetic makeup of Vibrio cholerae. The trick has been determining how to eliminate the genes that turn off the disease without disturbing the ones that elicit an immune reaction. Mekalanos, along with Mike Levine at the University of Maryland, has pioneered the use of a live oral cholera vaccine. This vaccine uses a genetically altered version of the organism that is unable to cause disease.

In addition to learning which genes halt the cholera bacterium, it is necessary to understand which ones are activated during its transmission and infection. Stephen Calderwood ’75, the Morton N. Swartz, M.D. Academy Professor of Medicine (Microbiology and Immunobiology) at HMS and Massachusetts General Hospital,is looking at gene expression at different points in V. cholerae’s life cycle to determine which genes are expressed by the pathogen during infection, as well as which trigger immune responses in the human host.

For this research, Calderwood is collaborating with clinicians and researchers at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh. Calderwood’s team has collected thousands of samples from patients who have been hospitalized with severe cholera.

 

The Sniff Test

The insights from such molecular biology studies can also lead to some surprising diagnostic tools for infectious disease. The tubercle bacterium, for example, can be insidious; it can lurk in the lungs of a mildly infected patient for years. Active infections of the bacterium, however, release a detectable signature of volatile organic compounds. This airborne fingerprint may be useful in diagnosing the disease, particularly in children; not only is it difficult for them to produce sufficient sputum for analysis, their sputum contains relatively few of the organisms.

“A baby’s exhalation could be captured,” says Ed Nardell, an HMS associate professor of medicine at Brigham and Women’s, “so she wouldn’t need to produce a sputum sample.”

 

Nardell is part of a team that’s investigating the effectiveness of a new gas chromatography technology that can detect the chemical signature of M. tuberculosis in a few puffs of human breath. In some parts of the world, giant Gambian rats, trained to sniff out the bacterium’s signature compounds, are already being used to detect M. tuberculosis in sputum samples. Unlike humans using microscopes, these trained rats accurately examine specimen after specimen without fatigue—and all for the fee of a sweet treat.

 

Phase Shifts

Another complicating factor in the fight against these diseases is that the causal agents change throughout their life cycles. The tubercle bacterium modifies its environment to suit its needs. By contrast, the cholera bacterium acclimates itself to the environment it inhabits. Many cholera microbes spend their lives in water, feeding on plankton to derive energy. During this aquatic phase, the adaptations that help them survive in water make them much less infectious in humans. Calderwood and his team, however, have discovered that the cholera microbes found in the fecal matter of infected humans—before the microbes adapt to the aquatic environment—are hyperinfectious for a brief period following their evacuation from the host.

Because this human ecology is important to the transmission of the disease, Calderwood’s collaborators in Bangladesh dispatch research teams to patients’ homes. To study disease transmission in a household, the team invites all family members, sick or well, to participate. While visiting, the team can survey a patient’s living conditions and, if needed, provide medical care to other family members.

 

“These diseases are perfect examples of how knowing the social context of an infection can be crucial,” says Mercedes Becerra, an HMS associate professor of global health and social medicine. “It’s not some vague notion of social context; it’s actually seeing the physical setting where people live and testing the strains that have infected different members of a family or community. The household is a really important unit for analysis and for medical interaction.”

Just as it is crucial to see how the bacteria operate—at the chemical and genetic levels—in human hosts, it is important to understand how the illness plays out in the context of specific human populations, according to Becerra.

 

Knit One, World View

These diseases also interact in another key ecosystem: the community of HMS researchers working on global health and infectious disease. Some may be community health workers with knowledge of the lives of their neighbors. Some are social scientists measuring the clinical effectiveness of different approaches to preventing and treating these diseases, or mapping the social, political, and historical aspects of health. Geneticists, immunologists, engineers, and architects—each play a role in teasing out the intricacies of these diseases and the pathogens that cause them.

“To beat these diseases, somebody has to understand the immune system and the bugs at different levels,” Becerra says, “while others have to work on understanding the impact on patients and families. That’s why it’s so important to work together from multiple angles, linking discovery with care delivery—and then turn around to look for new discoveries.”

Jake Miller is a science writer in the HMS Office of Communications and External Relations.

 

by Jake Miller

 

 

 

Hms.harvard.edu [en línea] Cambridge, MA (USA)

hms.harvard.edu, 03 October of 2013 [REF. Summer 2013] Available on Internet: http://hms.harvard.edu/news/harvard-medicine/harvard-medicine/how-bugs-are-built/epidemic-proportions