Fatal asthma attack duration may be determined by mast cell degranulation
A study at Aristotle University of Thessaloniki using electrogustometry and contact endoscopy appears to have demonstrated how cigarettes decrease taste acuity.
Researchers at the Aristotle University of Thessaloniki (Greece) have discovered the effect of nicotine on fungiform papillae (fPap) – tastebuds located on the dorsal surface of the tongue – using electrical stimulation via electrogustrometry to test taste threshold, and contact endoscopy to examine fPap abundance and morphology.
Electrogustrometry measures taste threshold by applying an electrical current to the tongue in order to generate a metallic taste, and the current at which perception of this taste is established determines the tongue’s taste sensitivity.
In their investigation, which studied the tongues of 62 randomly chosen Greek soldiers, consisting of 28 smokers and 34 nonsmokers, results showed that there was a statistically significant difference (p < 0.05) between the taste thresholds of the two groups, and that 79% of the smokers had reduced numbers of fPap, which were also observed to be flatter in their morphology. The flattened structure is indicative of a reduced blood supply.
“Smoking is an important factor which can lead to decreased taste acuity, as nicotine may cause functional and morphological alterations of fPap,” head researcher Pavlidis Pavlos concludes.
Source: Pavlidis P, Nikolaidis V, Anogeianaki A, Koutsonikolas D, Kekes G, Anogiannakis G. Evaluation of young smokers and non-smokers with electrogustometry and contact endoscopy. BMC Ear Nose Throat Disord. DOI: 10.1186/1472-6815-9-9 (2009) (Epub ahead of print).
Fatal asthma attack duration may be determined by mast cell degranulation
Results of an Australian study suggest a link between mast cell degranulation and the duration of fatal asthma attacks.
Australian researchers have been investigating factors influencing the length of fatal asthma attacks, which have shown to be of either short (less than 3 h) or long (more than 8 h) duration. The varied attack lengths are known to be associated with differing degrees of luminal mucus deposition, smooth muscle contraction and ratios of eosinophils to neutrophils in the airway wall. In addition to these factors, John Elliot and his team have postulated that the bimodal attack length might also be related to airway mast cell degranulation.
Airway tissue samples collected from 29 patients, aged between 10 and 46 years, who died from asthma attacks were studied. Within the sample population studied, 20 patients had died from short-duration attacks and nine had died from long-duration attacks. Examination of the samples focused on the abundance of tryptase-positive mast cells, airway dimensions and the numbers of intact and granulated mast cells.
Analysis of results revealed a similar total number of mast cells in both short- and long-duration cases; however, the ratio of degranulated to intact mast cells was significantly increased in the outer airway wall (p < 0.001) and smooth muscle (p < 0.05) in short-duration attacks compared with long-duration attacks.
Furthermore, results revealed that proportional muscle shortening was significantly increased in patients suffering from short-duration attacks, resulting in an average reduction in smooth muscle of 17%, compared with a decline of only 11% in patients who died from a long-duration attack. It was also noted that airways were larger in patients suffering short-duration fatal attacks than patients who had suffered long-duration attacks.
From their investigation, Elliot and his team conclude that “short-duration fatal asthma attacks are accompanied by increased mast cell degranulation compared with long-duration fatal attacks.” Knowledge obtained from this investigation has led them to understand that although a variety of stimuli may provoke a fatal asthma attack, they all act through the mast cells. Elliot stated that “understanding the factors that determine the magnitude of the mast cell response will be important for understanding the causes of fatal attacks and the exacerbations of asthma.”
Source: Elliot J, Abramson M, Drummer O, Walters H, James A. Time to death and mast cell degranulation in fatal asthma. Respirology 14(6), 808–813 (2009).
New internet resource on TB diagnostics
The Stop TB Partnership’s New Diagnostics Working Group (NDWG) recently launched a new website resource called Evidence-based Tuberculosis Diagnosis, available at www.tbevidence.org.
Evidence-based Tuberculosis Diagnosis is a new website resource that aims to be the most comprehensive single source of evidence syntheses, policies, guidelines and research agendas on TB diagnosis. The website also provides detailed guidance on how to conduct and report diagnostic research on TB, guidance on how to perform systematic reviews of diagnostics, tools on guideline development, and documents on improvement of laboratory quality and practice. Up-to-date information on the current TB diagnostics pipeline is also provided, along with SOPs for several tests, and specimen and data banks. All information is provided as open access, with no registration, restrictions or fee requirements.
Information from a wide range of sources has been compiled to produce this extensive resource; the website allows access to all published systematic reviews on TB diagnostics as well as all the relevant policies, guidelines and research agendas. This high quality resource on evidence-based TB diagnostics aims to aid the development of new tools into TB control activities and therefore help to achieve the goal of eliminating TB as a public health problem and, ultimately, to obtain a world free of TB.
Source: Stop TB’s New Diagnostics Working Group (NDWG): www.tbevidence.org
Research into flu vaccination strategies reveals optimal targets to minimize disease spread
Researchers from Yale University (CT, USA) suggest that target groups most likely to transmit infection should be vaccinated first in order to dramatically reduce numbers affected by the swine flu or seasonal flu virus.
Jan Medlock and Alison Galvani from Yale University used a model parameterized with survey-based contact data and mortality data from previous influenza pandemics to determine an optimal vaccine allocation. Their vaccination strategy, published in the journal Science, considers five outcome measures: deaths, infections, years of life lost, contingent valuation and economic costs.
Current vaccination guidelines given by the Advisory Committee on Immunization Practises (ACIP) and the US CDC prioritize people at high risk from swine flu and seasonal flu complications for vaccination. This grouping includes children under 5 years of age, adults over 65 years of age, pregnant women and patients with respiratory, cardiovascular and other disorders.
However, Medlock and Galvani’s research into optimal vaccination highlights different target groups as being first priority to receive the vaccine, owing to these groups consisting of people most likely to transmit the viruses. Their investigation suggests that if vaccination priority was given to school children who are responsible for transmission and their parents who serve as ‘bridges’ to the rest of the population, there would be fewer cases of infection and improved survival rates.
Using mathematical models to measure the five specified outcomes, based on data from previous influenza epidemics, Medlock and Galvani compared their optimal strategy with the ACIP recommendations. They calculated that following ACIP guidelines would result in 1.3 million infections, 2600 deaths and US$28 billion in economic costs to the USA, whereas their optimal strategy, targeting school children and adults aged 30–39 years, predicted 113,000 infections, 242 deaths and US$1.6 billion in costs. “Our results illustrate the importance of considering transmission when allocating vaccines,” commented Galvani.
With fears of swine flu cases increasing in the winter months, this optimal vaccination strategy could be key to minimizing the numbers of individuals infected by the virus. Galvani concludes, “the optimal allocation of vaccines is paramount to minimizing mortality and morbidity in the population, particularly when there is a supply shortage.”
Source: Metlock J, Galvani A. Optimizing influenza vaccine distribution. Science DOI: 10.1126/science1175570 (2009) (Epub ahead of print).
Attack mechanism of respiratory syncytial virus is uncovered
New research at West Virginia University has revealed the mechanism that makes the respiratory syncytial virus such a severe and persistent illness.
Respiratory syncytial virus (RSV) is the most common respiratory infection in childhood, affecting approximately half of all infants during their first year of life. RSV causes inflammation of the airways, resulting in wheezing, coughing and difficulty in breathing. It may also predispose children to health problems later in life such as asthma.
Giovanni Piedimonte and his team’s breakthrough has revealed how the infection is so persistent, discovering that when the RSV invades a cell it releases a specific molecule, which keeps the invaded host cell alive despite the infection. “Viruses must find a way of surviving inside the host, and on this case RSV has found a way of keeping alive the bronchial epithelial cells that they infect,” Piedimonte explained. He continued, “RSV invades the cell which then produces a nerve growth factor (NGF). The NGF allows the cell to survive while the virus reproduces itself. Finally, the cell explodes releasing new viral particles ready to infect the neighboring cells.”
The team also discovered that the virus induces NGF production within an hour of coming into contact with the human cells, before the virus even starts to multiply. This explains how the infection takes hold so quickly and can become very severe.
Exposing the virus’s NGF mechanism that causes the life of the infected cell to be prolonged may act as a blueprint for viral infection, and would be used to aid the development of new antiviral drugs. These would aim to inhibit NGF action and therefore allow apoptosis to occur in the infected bronchial epithelium.
The team continues to focus on this mechanism in other diseases such as the common cold and influenza viruses, in order to establish whether other viruses act in a similar manner.
Source: Othumpangat S, Gibson L, Samsell L, Piedimonte G. NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection. PLoS ONE DOI:10.1371/journal.pone.0006444 4(7), e6444 (2009) (Epub ahead of print).
Stem cell therapy may be able treat chronic obstructive pulmonary disease
Entest BioMedical unit, the wholly-owned research subsidiary of the Bio-Matirix Scientfic Group Inc., has identified chronic obstructive pulmonary disease (COPD) as a disease believed to be treatable through stem cell therapy and has filed a patent application for its use.
COPD is a combination of lung inflammatory disorders including both chronic bronchitis and emphysema that result in narrowed airways, leading to restricted air flow and shortness of breath. The condition, which is projected to be the third leading cause of death worldwide, is not easily reversible and gets progressively worse over time.
Current treatment methods include using inhalers and/or oxygen therapy, similar to the treatment of asthma; however, these procedures do not provide a cure for the disease and are only able increase the patient’s comfort.
Steven Josephs, who is working on the project, explained “the approach is intended at the very least to alleviate the chronic inflammation in COPD. This is done by using agents known to coax adult stem cells that are delivered to the diseased lung tissue to release cytokines, which in addition to the anti-inflammatory effects, may actually promote the regeneration of functional lung tissue.”
Identifying this major health disorder as a disease able to be treated by adipose-derived stem cell therapy is a huge breakthrough, and Entest BioMedical Inc’s main objective is to develop a stem cell therapy able to reverse the effects of COPD on the respiratory system. Feng Ling, Entest BioMedical’s scientific director, and Josephs continue to work on the development of this treatment.
Source: Entest BioMedical Inc.: www.entestbio.com/