As well as announcing the launch of a new global diagnostics business unit at Medica last month, Avantor Performance Materials also announced the creation of a new diagnostics product brand: BeneSpheradiagnostics solutions, which will include a broad and expanding range of reliable, affordable diagnostic technologies and easy-to-use products, focused on three segments: in vitro reagents and instruments for clinical chemistry, immunology, haematology, microbiology, histology and cytology and genetic testing; instruments for in vivo diagnostics, currently sold under the Diagnova name in India; and consumables and instruments for life sciences research in academia, government and pharmaceutical labs, also currently sold under the Diagnova name in India.
At the moment Avantor’s performance diagnostics solutions include J.T.Baker clinical reagents, which have provided world-class solutions for haematology and histology applications for over 30 years, and BeneSphera diagnostics solutions built on Diagnova, the company’s Indian-based diagnostics business with a 25-year legacy offering products, engineering and application support for immunology, clinical chemistry, haematology, microbiology, endoscopy and life science needs.
Avantor’s plans are to grow the new global diagnostics business through organic development and the strategic acquisition of R&D-backed manufacturing and distribution companies in targeted locations to support a strong global brand and supply chain.
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Researchers have identified a genetic signature for a severe, often painful food allergy – eosinophilic esophagitis – that could lead to improved diagnosis and treatment for children unable to eat a wide variety of foods.
The scientists, from Cincinnati Children’s Hospital Medical Center that they have pinpointed a dysregulated microRNA signature for eosinophilic esophagitis (EoE), a disease that also may cause weight loss, vomiting, heartburn and swallowing difficulties.
Interestingly, the dysregulated microRNA was reversible with steroid treatment, according to the study’s senior investigator, Marc E. Rothenberg, MD, PhD, director of Allergy and Immunology and the Center for Eosinophilic Disorders at Cincinnati Children’s. MicroRNAs are short segments of RNA that can regulate whether genetic messengers (mRNAs) are degraded or translated into protein.
‘The identification of biomarkers specific to EoE is a significant advancement for both the diagnosis and treatment of the disease,’ explains Rothenberg. ‘The microRNA signature provides an opportunity for more precise analysis of oesophageal biopsies.’
Rothenberg said children with EoE now undergo anaesthesia and invasive endoscopy to diagnose and monitor the allergy. The ability to determine the presence and status of EoE with a non-invasive method, such as blood test that measures microRNAs, would have a positive impact on individuals and families.
In the current study, investigators analyzed esophageal microRNA expression of patients with active EoE, steroid-induced EoE remission, patients with chronic (non-eosinophilic) esophagitis and of healthy individuals. Additionally, they assessed plasma microRNA expression of patients with active EoE, remission of EoE remission and of healthy individuals.
The researchers found that EoE was associated with 32 differentially regulated microRNAs and distinguishable from the non-eosinophilic forms of esophagitis (such as reflux disease). Esophageal eosinophil levels correlated significantly with expression of the most increased microRNAs, miR-21 and miR-223, and most decreased, miR-375. MiR-223 was also one of the most increased microRNAs in the plasma, along with miR-146a and miR-146b.
Notably, the expression of microRNAs dysregulated in patients with active EoE was normalised in patients with EoE who responded to steroid treatment. This suggests a significantly specific microRNA signature for disease activity points to its promise for use as a biomarker for EoE.
EurekAlert
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The discovery of a gene that causes a form of hereditary spastic paraplegia may provide scientists with an important insight into what causes axons, the stems of our nerve cells, to degenerate in conditions such as multiple sclerosis.An international team of scientists led by Dr Evan Reid at the University of Cambridge and Dr Stephan Zuchner from the University of Miami reports that mutations in the gene known as reticulon 2 on chromosome 19 cause a form of hereditary spastic paraplegia (HSP). HSP is characterised by progressive stiffness and contraction (spasticity) of the legs, caused by selective and specific degeneration of axons.
The team identified three mutations in the reticulon 2 gene as causing a type of HSP – in one case, this mutation included an entire deletion of the gene. In addition, the researchers showed that reticulon 2 interacts with another gene, spastin. Mutations in this gene cause the most common form of hereditary spastic paraplegia.
Reticulon 2 provides the genetic code for a reticulon protein that is a member of a family of proteins recently shown to have a key role in shaping the endoplasmic reticulum. The endoplasmic reticulum is a network of interconnected sheets and tubules that extends throughout the cytoplasm in nearly all cells.
The endoplasmic reticulum has several functions, including protein synthesis, calcium signalling and the regulation of other components of the cell. Recent data suggest the sheets are involved in protein synthesis, whereas the tubules are specialised to carry out the other functions.
This new study provides the most direct evidence to date that defects in how the endoplasmic reticulum is shaped and formed could underlie axon degeneration. When axons degenerate, signals are unable to pass through the nerve cells, leading to a breakdown of communication within the central nervous system. This is common in degenerative diseases of the nervous system, such as multiple sclerosis.
‘Our work highlights important new disease mechanisms, which may provide a platform for us to study how axons are damaged in devastating illnesses such as HSP, and perhaps even in multiple sclerosis, which in some cases is very similar to HSP,’ explains Dr Reid, a Wellcome Trust Senior Research Fellow in Clinical Science. ‘But we must not forget how this work may immediately directly benefit families affected by HSP, for whom the discovery now opens up the possibility of genetic counselling and testing.’
Wellcome Trust
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Siemens Healthcare Diagnostics and Illumina have entered into a partnership aimed at setting new standards in the use of next-generation sequencing for the rapid, accurate identification of patients’ infectious disease states and potential treatment paths. Through this agreement, the companies plan to make existing Siemens molecular HIV tests compatible with the recently launched Illumina MiSeq next-generation sequencing platform, with the ultimate goal of introducing breakthrough sequencing-based infectious disease assays for the clinical diagnostics market.
Ten years ago the TRUGENE HIV-1 Genotyping Assay, the first DNA sequencing-based test for HIV to be cleared by the FDA, was launched to a worldwide market. This laid the foundation for Siemens to become a leader in infectious disease testing solutions that employ DNA sequencing technology. Since then, TRUGENE has become one of the market’s leading DNA sequencing tests for infectious disease testing. By making this test compatible with Illumina’s MiSeq analyser, Siemens expects to be well positioned to help even more clinical laboratories leverage next-generation sequencing for their infectious disease testing with the fastest turnaround time and highest accuracy possible.
Roche Accu-Chek® Inform II test strips chosen by CEGA Air Ambulance requirements for accuracy and ease-of-use
CEGA Air Ambulance has recently upgraded its blood glucose monitoring system to use the advanced Accu-Chek Inform II test strips from Roche. Ensuring accurate and reliable results across a wide range of glucose levels, these easy to use blood glucose test strips provide the performance criteria necessary for monitoring critically ill patients prior to, during and after emergency flight transfers.
“We require a reliable, easy to use, professional tool for blood glucose measurement,” comments CEGA Senior Flight Nurse, Stuart Cox. “After reviewing all the kits that are available on the market, we felt that the Roche Accu-Chek Inform II test strips best met our requirements for high quality patient care in the air ambulance environment. The user interface is very simple and straightforward to use anywhere and by any of our trained staff. In addition, the strips have a very good range compared to other systems, giving accurate results at both high and low glucose levels, which is essential for patient safety.”
Stress-induced insulin resistance and hyperglycaemia is common in critically ill patients [1,2,3] and so close monitoring of blood glucose levels is an important part of their care. Studies have shown that maintenance of appropriate glycaemic control in such patients improves morbidity and mortality [1,4,5].
“Providing international medical assistance, including the transportation of critical care patients around Europe, we use the Accu-Chek Inform II glucose strips to assess patients prior to the flight to make sure they are stable; during the transfer to monitor them and guide any necessary treatment; and then after the flight to assess their status before handing them over to the next medical team. The accuracy of the Accu-Chek Inform II strips ensures that patients get the right care at the right time, and we can have confidence in the results.”
The Accu-Chek Inform II test strips have undergone extensive evaluation, including studies at over 30 external sites as well as thorough internal testing [6]. The results of these evaluations demonstrate that the Accu‑Chek Inform II strips provide accurate and reliable blood glucose measurements under a variety conditions, including wide haematocrit and environmental ranges and in presence of maltose. Furthermore, the strips require a minimal sample volume of just 0.6µl and deliver accurate results from alternative sampling sites, such as the palm and forearm.
“The Accu-Chek Inform II strips mirror our needs for air ambulance work,” concludes Stuart. “They are well researched, with evidence-based performance. We also value the after sales and technical support we have received from Roche, which has been invaluable in the training of our staff.”
www.roche.co.ukwww.cega-air-ambulance.com.
1. Van den Berghe, G., Wouters, P., Weekers, F. et al (2001) N Engl. J. Med. 345: 1359-67 2. Van den Berghe, G. (2004) J. Clin. Invest. 114: 1187-1195 3. Mizock, B.A. Best Pract. Res. Clin. Endocrinol. Metab. 2001,15(4): 533 – 551. 4. Krinsley, J.S. (2004) Mayo Clin. Proc. 79:992-1000 5. Insulin in Intensive Care – The Leuven Protocol. Intensive Care Society website: http://www.ics.ac.uk/icmprof/pubsother.asp?menuid=86. Information available on request, Roche Diagnostics, Burgess Hill, UK.
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Roche sets up co –marketing agreement with private laboratory to support greater access to HPV testing
In an innovative commercial agreement, leading healthcare company Roche and foremost private cellular pathology laboratory Unilabs-IHS, are collaborating to help make state-of-the art testing for signs of cervical cancer more accessible to thousands of women in London and throughout the UK.
Roche’s leading-edge and fully automated cobas® HPV test which runs on the acclaimed cobas 4800 system, will provide a fast turn-around of cervical smear samples from potentially thousands of women per year, sent to the London based laboratory from clinicians from all over the country. The testing at Unilabs-IHS, will not only be conducted as a follow up to the traditional “Pap” cervical smear method to check ambiguous results, it will also be used upon request in primary screening for cervical pre cancer, giving a greater chance to avoid disease progression.
The ultra-high reliability of the cobas HPV test will be of huge benefit for clinicians and patients alike, due to the test’s unique genotyping that individually identifies genotypes 16 and 18, the highest risk types associated with the development of cervical cancer and its precursor lesions, while simultaneously identifying 12 other high risk HPV types. Such technology provides better risk stratification of patients enabling a more sensitive and efficient approach to cervical screening.
Dr Glen Dixon, Medical Director of Cytopathology at Unilabs-IHS from Unilabs-IHS said “We are delighted to have come to this agreement with Roche. Using the cobas HPV test on the cobas 4800 platform for our HPV testing work load, means that clinicians will not only have the fastest ever turnaround times, but will also have enhanced and incontrovertible HPV results, with no need to re-test – and all at no extra cost.”
Paul Eros, Director of Molecular Diagnostics at Roche said: “HPV testing provides earlier identification of those women at risk of developing cervical cancer. The agreement that we have struck with Unilabs-IHS for cervical screening with the cobas HPV test, is a significant step forward towards spreading access to HPV testing at the primary screening stage. Given the clear benefits of this technology to patients as well as the NHS, we look forward to seeing the technology’s timely introduction at the primary screening stage, across the country via the national cervical screening programme – promising a better deal for women and a more efficient approach to cervical screening.”
www.roche.com
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The hormone oxytocin—often referred to as the ‘trust’ hormone or ‘love hormone’ for its role in stimulating emotional responses—plays an important role in Williams syndrome (WS), according to a study.
The study, a collaboration between scientists at the Salk Institute for Biological Studies and the University of Utah, found that people with WS flushed with the hormones oxytocin and arginine vasopressin (AVP) when exposed to emotional triggers.
The findings may help in understanding human emotional and behavioural systems and lead to new treatments for devastating illnesses such as WS, post-traumatic stress disorder, anxiety and possibly even autism.
‘Williams syndrome results from a very clear genetic deletion, allowing us to explore the genetic and neuronal basis of social behaviour,’ says Ursula Bellugi, the director of Salk’s Laboratory for Cognitive Neuroscience and a co-author on the paper. ‘This study provides us with crucial information about genes and brain regions involved in the control of oxytocin and vasopressin, hormones that may play important roles in other disorders.’
WS arises from a faulty recombination event during the development of sperm or egg cells. As a result, virtually everyone with WS has exactly the same set of genes missing (25 to 28 genes are missing from one of two copies of chromosome 7). There also are rare cases of individuals who retain one or more genes that most people with the disorder have lost.
To children with WS, people are much more comprehensible than inanimate objects. Despite myriad health problems they are extremely gregarious, irresistibly drawn to strangers, and insist on making eye contact. They have an affinity for music. But they also experience heightened anxiety, have an average IQ of 60, experience severe spatial-visual problems, and suffer from cardiovascular and other health issues. Despite their desire to befriend people, they have difficulty creating and maintaining social relationships, something that is not at all understood but can afflict many people without WS.
In the new study, led by Dr. Julie R. Korenberg, a University of Utah professor and Salk adjunct professor, the scientists conducted a trial with 21 participants, 13 who have WS and a control group of eight people without the disorder. The participants were evaluated at the Cedars-Sinai Medical Center in Los Angeles. Because music is a known strong emotional stimulus, the researchers asked participants to listen to music.
Before the music was played, the participants’ blood was drawn to determine a baseline level for oxytocin, and those with WS had three times as much of the hormone as those without the syndrome. Blood also was drawn at regular intervals while the music played and was analysed afterward to check for real-time, rapid changes in the levels of oxytocin and AVP. Other studies have examined how oxytocin affects emotion when artificially introduced into people, such as through nasal sprays, but this is one of the first significant studies to measure naturally occurring changes in oxytocin levels in rapid, real time as people undergo an emotional response.
There was little outward response to the music, but when the blood samples were analysed, the researchers were happily surprised. The analyses showed that the oxytocin levels, and to a lesser degree AVP, had not only increased but begun to bounce among WS participants while among those without WS, both the oxytocin and AVP levels remained largely unchanged as they listened to music.
Korenberg believes the blood analyses strongly indicate that oxytocin and AVP are not regulated correctly in people with WS, and that the behavioural characteristics unique to people with WS are related to this problem.
‘This shows that oxytocin quite likely is very involved in emotional response,’ Korenberg says.
To ensure accuracy of results, those taking the test also were asked to place their hands in 60-degree Fahrenheit water to test for negative stress, and the same results were produced as when they listened to music. Those with WS experienced an increase in oxytocin and AVP, while those without the syndrome did not.
Salk Institute
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Certain proteins, such as 14-3-3, conserve their basic functions of cell cycle control in diverse organisms, from worms to humans. In a study led by Julián Cerón and Simó Schwartz Jr, researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the Research Institute of Vall d’Hebron (VHIR) respectively, have described germ line functions of par-5, which is one of the two 14-3-3 proteins existing in Caenorhabditis elegans, worms used as experimental model in genetic studies. The overexpression of the 14-3-3 proteins is related to the resistance of tumours to chemotherapy, which could have implications for clinical practice.
Researchers found that par-5 gene, as its human homologues, is required for DNA damage response in C. Elegans validating the model to investigate chemotherapies and genetic modifications since 14-3-3 proteins are therapeutic targets in cancer
The powerful genetic tools of C. elegans have allowed a precise functional dissection of the single 14-3-3 protein present in their germline. The researchers have discovered that par-5 is not only necessary for proper cell cycle regulation, but also to prevent the accumulation of endogenous DNA damage and genomic instability.
Moreover, this study reveals that par-5 is required for DNA repair response when it is damaged by chemicals or ionizing radiation. In such response, the researchers propose a model where PAR-5 regulates CDK-1 phosphorylation to stop the cell cycle and repair the damage induced by chemotherapeutic agents.
The overexpression of the 14-3-3 protein has been related to chemotherapy resistance in cancer cell lines while its downregulation sensitises cells to therapy-induced cell death. Therefore, this study in C. elegans provides the basis for a model to study chemotherapy response in the context of a whole living organism.
Regulators proteins 14-3-3, evolutionarily conserved, bind to signalling proteins and affect their stability, activity or cellular localisation. So, they are involved in the regulation of various cellular processes, including apoptosis, the cell cycle and stress response.
In addition, the researchers found that par-5 is required for cell cycle arrest in response to replicative stress and ionizing radiation.
IDIBELL-Bellvitge Biomedical Research Institute
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Scientists from the University of Liverpool’s School of Environmental Sciences are working with computer modelling specialists from C-MMACS in India to predict areas of the country that are at most risk of malaria outbreaks, following changes in monsoon rainfall. The number of heavy rainfall events in India has increased over the past 50 years, but research has tended to focus on the impact this has on agriculture rather than the vector-borne diseases, such as malaria and Japanese encephalitis. The model could help inform early intervention methods to prevent the spread of malaria at key points in the seasonal monsoon cycle, reducing the economic and health impacts of the disease. It is already known that an anomalous season of heavy rainfall, when heat and humidity are high, allows mosquitoes to thrive and spread infection to humans. In order to prepare health services and prevent epidemics there is need for a way of predicting when these events are likely to occur in areas that are not accustomed to annual outbreaks of malaria. C-MMACS is rapidly developing its computer modelling capabilities using technology that can address the impacts of climate variability on agriculture and water systems. This knowledge, together with the Liverpool models of vector-borne diseases, will help develop systems to predict when changes in the monsoonal rain may occur and which areas are most likely to see an increase in malaria.
http://tinyurl.com/cscnsro
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Retinoic acid (vitamin A) and steroids are hormones found in our body that protect against oxidative stress, reduce inflammation and are involved in cellular differentiation processes. One of the characteristics of tumours is that their cells have lost the ability to differentiate; therefore these hormones have useful properties to prevent cancer. Currently, retinoic acid and steroids are being used to treat some types of leukemia.
A study led by the research group on Genes and Cancer of the Bellvitge Biomedical Research Institute (IDIBELL) has shown that loss of BRG1 gene implies a lack of response of cells to these hormones, and therefore the tumour may continue growing.
The IDIBELL research group on Genes and Cancer led by Montse Sanchez-Cespedes discovered some years ago that the BRG1 gene, a tumour suppressor, is inactivated in non-small cell lung cancer by genetic mutations. ‘The BRG1 protein is part of a chromatin remodelling complex that regulates the expression of several genes,’ said the researcher, ‘and is related to the differentiation of lung cells, allowing cells response to certain hormones and environment vitamins like vitamin A or steroids.’
When BRG1 is mutated and therefore inactive, tumour cells do not respond to the presence of these hormones and they continue growing and spreading. For this reason, these types of tumours are refractory to treatment with these substances.
‘At the moment,’ says Montse Sanchez-Cespedes, ‘we are not able to restore the functionality of a tumour suppressor gene as BRG1 in patients. Therefore, we are still far from a therapeutic application but the discovery enables us to better understand the biology of tumours. What we will try to do in the immediate future is to look for agents that specifically destroy the cells with mutated BRG1, following the strategy of lethal synthetics’.
In any case, this finding it can be useful in advancing personalised medicine, because ‘it explains why lung cancer patients are resistant to these treatments and may serve to rule out therapies with lipid-derived hormones in patients with BRG1 mutations, not just in lung cancer but also in breast and prostate, among others. ‘
IDIBELL
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