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Archive for category: E-News

E-News

Molecular ‘on switch’ could point to treatments for paediatric brain tumour

, 26 August 2020/in E-News /by 3wmedia

Massachusetts General Hospital (MGH) researchers have identified a mechanism that controls the expression of genes regulating the growth of the most aggressive form of medulloblastoma, the most common paediatric brain tumour. The team also identifies potential targets for future treatments.

“We set out to find the most important regulators of gene expression programs in medulloblastoma,” says senior author Miguel Rivera, MD, of the MGH Department of Pathology and the Center for Cancer Research. “To do that we used a powerful genomic technology called chromatin profiling to map all the genomic elements contributing to transcription regulation in Group 3 medulloblastoma – the most aggressive subtype. This goes beyond measuring gene expression because it tells you how genes are turned on and off.”

Medulloblastoma is a fast-growing tumour that arises in the developing brain and most commonly affects children under the age of 10. Four molecular variants, each with different patterns of DNA alteration and gene expression, have been identified. Subtypes WNT and SSH are the best understood; the other two – Group 3 and Group 4 – are poorly understood and account for 60 percent of tumours.

Cells regulate whether specific genes are transcribed into RNA through the action of transcription factors, proteins that bind to DNA and either stimulate or suppress the expression of their target genes. Rivera’s team used advanced genomic technologies to identify key DNA elements called enhancers that were active in primary Group 3 medulloblastoma samples and cell lines. The transcription factor OTX2, which plays a role in normal brain development and is known to be highly expressed in Group 3 medulloblastomas, was present at the majority of active enhancer sites in tumours, suggesting it may have a role in promoting the expression of tumour-associated genes.

Subsequent experiments revealed that OTX2 can function as a “pioneer factor,” opening up chromatin – which consists of DNA wound around proteins called histones – to activate enhancers and that its function is amplified by a second transcription factor called NEUROD1. The investigators then identified a set of genes the expression of which was significantly reduced when OTX2 was suppressed. Among these genes, they found that expression of the kinase NEK2 responded to OTX2 levels and that its depletion or pharmacologic inhibition strongly reduced the growth and survival of medulloblastoma cells.

“Overall, our findings show that OTX2 is a critical factor in regulating gene expression programs in Group 3 medulloblastoma and possibly in the WNT and Group 4 subtypes, where it is also expressed,” says Rivera, who is an assistant professor of Pathology at Harvard Medical School. “This work points to OTX2 itself and its target genes – including NEK2 – as potential therapeutic targets. Disruption of the relationship between OTX2 and NEUROD1 may also be a potential treatment strategy.

Massachusetts General Hospitalwww.massgeneral.org/about/pressrelease.aspx?id=2063

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Study supports lower cut-off point for defining pre-diabetes

, 26 August 2020/in E-News /by 3wmedia

The health risks and mortality associated with pre-diabetes seem to increase at the lower cut-off point for blood sugar levels recommended by some guidelines, finds a large study published.

Pre-diabetes is a ‘pre-diagnosis’ of diabetes — when a person’s blood glucose level is higher than normal, but not high enough to be considered diabetes. If left untreated, pre-diabetes can develop into type 2 diabetes. An estimated 79 million people in the US and 7 million people in the UK are thought to be affected.

Doctors define pre-diabetes as impaired fasting glucose (higher than normal blood sugar levels after a period of fasting), impaired glucose tolerance (higher than normal blood sugar levels after eating), or raised haemoglobin levels.

But the cut-off points vary across different guidelines and remain controversial.

For example, the World Health Organization (WHO) defines pre-diabetes as fasting plasma glucose of 6.1-6.9 mmol/L, while the 2003 American Diabetes Association (ADA) guideline recommends a cut-off point of 5.6-6.9 mmol/L.

Results of studies on the association between pre-diabetes and risk of cardiovascular disease and all cause mortality are also inconsistent. Furthermore, whether raised haemoglobin levels for defining pre-diabetes is useful for predicting future cardiovascular disease is unclear.

So a team of researchers from the affiliated Hospital at Shunde, Southern Medical University in China analysed the results of 53 studies involving over 1.6 million individuals to shed more light on associations between different definitions of pre-diabetes and the risk of cardiovascular disease, coronary heart disease, stroke, and all cause mortality.

They found that pre-diabetes, defined as impaired fasting glucose or impaired glucose tolerance, was associated with an increased risk of cardiovascular disease and all cause mortality.

The risk increased in people with a fasting glucose concentration as low as 5.6 mmol/L – the lower cut-off point according to ADA criteria.

Raised haemoglobin levels were also associated with an increased risk of cardiovascular disease and coronary heart disease, but not with an increased risk of stroke and all cause mortality.

The authors point to some study limitations that could have influenced their results, and say pulling observational evidence together in a systematic review and meta-analysis is a good way to consider all the evidence at once, ‘but we cannot make statements about cause and effect. We would need to look at experimental evidence for that.’

However, they say their findings ‘strongly support’ the lower cut-off point for impaired fasting glucose and raised haemoglobin levels proposed by the ADA guideline.

And they conclude that lifestyle change — eating a healthy balanced diet, keeping weight under control, and doing regular physical activity — is the most effective treatment.

EurekAlert www.eurekalert.org/pub_releases/2016-11/b-ssl112216.php

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MEDLAB Series expands its presence into Europe

, 26 August 2020/in E-News /by 3wmedia

More than 3,000 medical laboratory industry professionals expected to attend the launch edition of MEDLAB Europe at the Fira Gran Via in Barcelona, Spain. 

After many years of operating successful MEDLAB events around Africa, Asia and the Middle East, Informa Life Sciences Exhibitions has announced that the MEDLAB Series will be expanding its presence into Europe. Taking place at the Fira Gran Via in Barcelona, Spain, from 13-15 September 2017, more than 3,000 industry professionals are expected to attend Europe’s leading event for laboratory management and diagnosis.
With the European medical laboratory market expected to reach USD 15.5 billion (€ 14.2 billion) by 2024[1], a platform such as MEDLAB presents a huge opportunity for global laboratory industry leaders, including manufacturers, dealers and distributors, to make inroads into the European market. Housing international exhibitors and covering 2,000 sqm of exhibition space, MEDLAB Europe will give visitors from across the world an opportunity to access cutting-edge laboratory products, next-generation technology, innovative services and world-class educational content. 
According to Tom Coleman, Group Exhibition Director, MEDLAB Series: “The launch of MEDLAB Europe is in line with our global expansion strategy for our MEDLAB series of events. The increasing prevalence of chronic diseases, rising geriatric population coupled with the rising awareness towards early diagnosis, has positioned the European medical laboratory market as a critical market for manufacturers, services providers, and dealers and distributors from across the globe. MEDLAB Europe will generate substantial value for our customers and partners by driving further product innovation and deeper engagement in these specific markets.”

Over the three-day event, MEDLAB Europe will also offer a multi-disciplinary congress tackling current challenges and developments key to the European market, and leveraging the true potential of laboratory testing to dramatically improve patient outcomes across the continent.

The conference programme covers five main tracks including Point of Care Testing (POCT), Histopathology, Lab Management, Microbiology and Hematology. From new methods of effective lab management to the development of techniques in detecting diseases, the conferences will also review the expanding role of the laboratory medicine and discuss partnership between a clinician and a lab professional in providing delivery of care to every patient.
“The scientific programme at MEDLAB has been carefully designed in collaboration with some of the brightest minds in the medical laboratory industry in order to have a real impact on improving the health and wellbeing of patients across the region,” said Coleman.

1 http://www.grandviewresearch.com/press-release/europe-in-vitro-diagnostics-ivd-market-analysis
 

www.medlabeurope.com

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On the trail of Parkinson’s disease

, 26 August 2020/in E-News /by 3wmedia

The molecular causes of diseases such as Parkinson’s need to be understood as a first step towards combating them. University of Konstanz chemists working alongside Professor Malte Drescher recently succeeded in analysing what happens when selective mutations of the alpha-synuclein protein occur – a protein that is closely linked to Parkinson’s disease. In a complex series of experiments they examined what the effects were of changing a single amino acid in the protein. The physicochemists were able to prove how this tiny change disturbs the binding of alpha-synuclein to membranes. “We hope that the finding of this selectively defective membrane binding will help us to understand how Parkinson’s develops on a molecular level. Ultimately, this will facilitate the devising of therapeutic strategies,” outlines Julia Cattani, a doctoral student, who played a major role in the success of the research.
The human brain contains large quantities of the small alpha-synuclein protein. Its exact biological function is still unknown, yet it is closely linked to Parkinson’s disease; the protein “clumps together” in the nerve cells of Parkinson patients. Alpha-synuclein consists of a chain of 140 amino acids. In rare cases Parkinson’s disease is hereditary; where this occurs one of these 140 components has been replaced. Malte Drescher and his working group in the Department of Chemistry at the University of Konstanz have now found out the influence these selective changes in the protein sequence can have on the behaviour of alpha-synuclein. “We can show that the selective mutations disturb the membrane binding of alpha-synuclein on a local level,” explains Malte Drescher.
To find out more about the influence of selective mutations, the Konstanz-based chemists Dr Marta Robotta and Julia Cattani applied tiny magnetic probe molecules to various places on the alpha-synuclein protein. With the help of electron paramagnetic resonance spectroscopy – a procedure similar in method to magnetic resonance imaging (MRI) used in the medical field – the researchers were able to measure the rotation of these nanomagnets. At every residue at which alpha-synuclein binds to a membrane, the rotation slows down. In this way they were able to find out precisely when and where a binding to the membranes takes place – and when it does not. In the case of the exchanged amino acids the physicochemists from Konstanz discovered a disturbance of the membrane binding of alpha-synuclein – an important clue for the molecular context of Parkinson’s disease.
“We went to great lengths, performing over 200 spectroscopic experiments, the results of which we compared with our models by means of a specially developed simulation algorithm. The outcome certainly compensated our efforts,” says Julia Cattani. Project leader Malte Drescher believes that alongside the huge commitment of his staff, an important prerequisite for the success of the research was, above all, the environment of the Collaborative Research Centre (SFB) 969, “Chemical and biological principles of cellular proteostasis” which formed the basis for sponsoring the project: “By networking on an interdisciplinary level and discussing with colleagues we managed to solve the many problems we faced,” emphasises Malte Drescher.

University of Konstanz
www.uni-konstanz.de/en/university/news-and-media/current-announcements/news/news-in-detail/parkinson-auf-der-spur/

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Technology and innovation on show at MEDLAB 2017

, 26 August 2020/in E-News /by 3wmedia

With the medical laboratory market in the UAE expected to continue on a growth trajectory, innovative products and next-generation technology remains a focus for the region’s medical laboratory and IVD industry

Dubai, UAE, 25th January 2017: As the UAE gears up for a boom in the In-Vitro Diagnostics (IVD) market, expected to reach USD 0.83 billion by the end of 2020[1], the medical community has turned its focus towards exciting new products and technologies to keep up with the demand for new diagnostic capabilities that can have a real impact on improving the health of patients across the region.
MEDLAB Exhibition & Congress, the world’s leading event for laboratory management and diagnostics, which takes place on 6th – 9th February 2017 at the Dubai International Convention & Exhibition Centre, presents a huge opportunity for global laboratory industry leaders, including manufacturers, dealers and distributors, to showcase new innovations and to introduce some cutting-edge products to the UAE market. More than 30,000 visitors are expected to attend the four-day exhibition where they can explore over 400 products and services from more than 700 exhibitors from 38 countries.
A number of companies associated with ABIMO (Brazilian Medical Devices Manufacturers Association) will be at MEDLAB to showcase products and services including diagnosis and laboratory reagents, IVD, devices for medical tests, laboratory tests, laboratory refrigerators and products for hematology.
According to Clara Porto, ABIMO’s marketing and exports manager, “There is almost no national production of the sector and, as such, the region is quite dependent on imports. Generally, there is a great acceptance of Brazilian products so we expect to make good contacts and profitable deals at this year’s show.”
Binding Site, one of the largest independent providers for IVD tests and equipment in the United Kingdom, will be at MEDLAB to launch its latest protein system that can process complex protein assays 40% faster than current systems. Charles de Rohan, CEO from Binding Site commented: “We wanted to bring simplicity to complex analytical processes. The result is Optilite, the latest innovation in special protein testing, which offers laboratories reliable results without compromising speed and efficiency.”
Meanwhile, Sysmex Corporate, one of the leading international providers of solutions for systemising processes for medical laboratories, will be at MEDLAB to showcase their new urinalysis series. For the first time, they are offering an ‘all-in-one’ series of analysers that will allow you to examine both through chemistry and sediment, followed by imaging and validation.
Another exhibitor bringing something new to the market is American Medical Technologists (AMT), an internationally recognised certification agency for allied health professionals, who will promote a set of practice exams for its respected laboratory certifications including Medical Technologists (MTs), Medical Laboratory Technicians (MLTs) and Phlebotomists.
“With a new practice test for those preparing to take the certification exam for medical technologist through AMT, candidates have an important tool to take them a step closer to becoming certified members of the clinical laboratory community,” said Christopher Damon, JD, Executive Director of AMT.
This year at MEDLAB, a selection of free workshops will also be available for all industry professionals offering learning and training opportunities from leading international IVD and laboratory companies. The free workshops are an addition to MEDLAB’s conferences, which will span from blood transfusion medicine, laboratory informatics, clinical diagnostics of cardiology and diabetes, to laboratory management, microbiology, immunology and clinical chemistry.
Dr Mansour Al-Zarouni, Member, General Secretariat Committee at Sultan Bin Khalifa International Thalassemia Award (SITA) and Chair of MEDLAB said: “With new cutting edge innovations having a lifecycle of approximately 24-48 months, it’s crucial for this congress to play a role in connecting and merging pre-existing gaps between clinicians and laboratory professionals, through the conferences, to ensure everything is done to improve patient care outcomes.”
According to Simon Page, Managing Director of Informa Life Sciences Exhibitions, the Organiser of MEDLAB: “It is not enough for our visitors to simply view the new technologies from afar – we want them to get a hand-on experience of these products through the free workshops directly offered by the manufacturers. For example, LabCorp from the USA and National Reference Laboratory in the UAE are coming together to host a workshop on coagulation reference testing to discuss the significance of the coagulation reference laboratory.”
“Another example is Sidra’s workshop, the Pediatric Pathology symposium, which will address anatomical pathology, hematopathology, microbiology and molecular microbiology, clinical chemistry, and genetics, which will be led by international experts and attended by pathologists, lab physicians and scientists in the region, who work with pediatric specimens”, he added.
MEDLAB Exhibition & Congress is supported by the UAE Ministry of Health & Prevention, Health Authority Abu Dhabi, Dubai Health Authority, Dubai Healthcare City Authority, Jebel Ali Free Zone, College of American Pathologists, Clinical and Laboratory Standards Institute and the Saudi Society for Clinical Chemistry.
For more information about MEDLAB Exhibition & Congress, please visit www.medlabme.com

[1] UAE In-Vitro Diagnostics Market – Growth, Trends & Forecast (2015-2020), August 2016

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Single gene encourages growth of intestinal stem cells, supporting “Niche” cells-and cancer

, 26 August 2020/in E-News /by 3wmedia

A gene previously identified as critical for tumour growth in many human cancers also maintains intestinal stem cells and encourages the growth of cells that support them, according to results of a study led by Johns Hopkins researchers. The finding adds to evidence for the intimate link between stem cells and cancer, and advances prospects for regenerative medicine and cancer treatments.
Study leader Linda M. S. Resar, M.D., professor of medicine, oncology and pathology at the Institute for Cellular Engineering at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center, has been studying genes in the high-mobility group (HMG) family for over two decades. Several years ago, while creating a genetically engineered mouse that expresses high levels of the mouse HMGA1 gene to investigate its role in leukaemia, Resar and her colleagues made the chance finding that the intestines of these animals were much larger and heavier than those of “wild-type” animals (or control mice that were not genetically modified). The mouse intestines were also riddled with polyps, abnormal growths projecting from the intestinal lining that can be precursors of cancer.  In fact, polyps in humans frequently progress to colon cancer, which is why they are removed during screening colonoscopies in people over 50 and others at risk for colon cancer.
To better understand how HMGA1 affected the rodents’ intestines, Resar and Lingling Xian, M.D., Ph.D., research associate at the Johns Hopkins University School of Medicine, and their colleagues examined the transgenic animals’ intestinal cells to determine which ones were expressing this gene. Several different experiments localized the active gene and its protein to stem cells buried within the crypts, or deep grooves in the intestinal lining.
After isolating these stem cells from both transgenic and wild-type mice, the researchers found that those carrying the HMGA1 transgene multiplied far more rapidly, forming identical daughter cells in a process called self-renewal, which is a defining property of all stem cells. These transgenic stem cells also readily created intestinal tissues called “organoids” in laboratory dishes. These organoids had more stem cells than those isolated from wild-type mice.
Further investigation, says Resar, showed that these unusual properties arise from the ability of HMGA1 to turn on several genes involved in the Wnt pathway, a network of proteins necessary for embryonic development and stem cell activity.
Stem cells do not function in isolation, explains Resar. They need a “niche” to survive and maintain an undifferentiated state. From the French word nicher, which means to build a nest, a niche is a nest-like compartment comprised of cells that secrete growth factors and other proteins that help stem cells survive. The niche also prevents stem cells from morphing into mature intestinal cells until new intestinal cells are needed.   Intestinal stem cells are particularly important because a new intestinal lining is generated about every 4-5 days.
Looking further into the intestinal crypts of both the transgenic and wild-type mice, the research team made what they consider a surprising finding: Not only was HMGA1 causing the stem cells themselves to self-renew or proliferate more rapidly in the transgenic animals, but it was also increasing the number of Paneth cells, a type of niche cell known to support intestinal stem cells. Additional experiments showed that the protein produced by HMGA1 activates another gene called Sox9, which is directly responsible for turning stem cells into Paneth cells.
“We suspected that HMGA1 might generate new stem cells, but we were extremely surprised that it also helps support these cells by building a niche,” Resar says. “We believe that our experiments provide the first example of a factor that both expands the intestinal stem cell compartment and builds a niche.”
Many genes that are involved in the growth and development of embryos or adult stem cells also play roles in cancer, Resar adds. After scanning the Cancer Genome Atlas, a database of genes expressed in human cancers, the research team discovered that the activity of both HMGA1 and SOX9 genes are tightly correlated in normal colon tissue, and both genes become highly overexpressed in colon cancer. “This tells us that the pathway turned on by HMGA1 in normal intestinal stem cells becomes disrupted and hyperactive in colon cancer,” Resar says.

John Hopkins Hospital
www.hopkinsmedicine.org/news/media/releases/single_gene_encourages_growth_of_intestinal_stem_cells_supporting_niche_cellsand_cancer_

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Discovery of neurotransmission gene may pave way for early detection of Alzheimer’s Disease

, 26 August 2020/in E-News /by 3wmedia
A new Tel Aviv University study identified a gene coding for a protein that turns off neurotransmission signalling, which contributes to Alzheimer’s disease (AD).
The gene, called RGS2 (Regulator of Protein Signalling 2), has never before been implicated in AD. The researchers report that lower RGS2 expression in AD patient cells increases their sensitivity to toxic effects of amyloid-ß. The study may lead to new avenues for diagnosing Alzheimer’s disease — possibly a blood test — and new therapies to halt the progression of the disease.
The research was led by Dr. David Gurwitz of the Department of Human Molecular Genetics and Biochemistry at TAU’s Sackler School of Medicine and Prof. Illana Gozes, the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors; Head of the Elton Laboratory for Molecular Neuroendocrinology at TAU’s Sackler School of Medicine; and a member of TAU’s Adams Super Center for Brain Studies and TAU’s Sagol School of Neuroscience. 
“Alzheimer’s researchers have until now zeroed in on two specific pathological hallmarks of the chronic neurodegenerative disease: deposits of misfolded amyloid-ß (Aß) peptide plaques, and phosphorylated tau protein neurofibrillary tangles found in diseased brains,” Dr. Gurwitz said. “But recent studies suggest amyloid-? plaques are also a common feature of healthy older brains. This raises questions about the central role of A? peptides in Alzheimer’s disease pathology.”
The researchers pinpointed a common suspect — the RGS2 gene — by combining genome-wide gene expression profiling of Alzheimer’s disease blood-derived cell lines with data-mining of previously published gene expression datasets. They found a reduced expression of RGS2 in Alzheimer’s disease blood-derived cell lines, then validated the observation by examining datasets derived from blood samples and post-mortem brain tissue samples from Alzheimer’s patients.
“Several genes and their protein products are already known to be implicated in Alzheimer’s disease pathology, but RGS2 has never been studied in this context,” Dr. Gurwitz said. “We now propose that whether or not Aß is a primary culprit in Alzheimer’s disease, neuroprotective mechanisms activated during early disease phases lead to reduced RGS2 expression.”
The new TAU study furthermore proposes that reduced RGS2 expression increases the susceptibility of brain neurons to the potentially damaging effects of Aß.
“We found that reduced expression of RGS2 is already noticeable in blood cells during mild cognitive impairment, the earliest phase of Alzheimer’s,” Dr. Gurwitz observed. “This supported our theory that the reduced RGS2 expression represents a ‘protective mechanism’ triggered by ongoing brain neurodegeneration.”
The team further found that the reduced expression of RGS2 was correlated with increased Aß neurotoxicity. It acted like a double-edged sword, allowing the diseased brain to function with fewer neurons, while increasing damage to it by accumulating misfolded Aß.
“Our new observations must now be corroborated by other research groups,” Dr. Gurwitz concluded. “The next step will be to design early blood diagnostics and novel therapeutics to offset the negative effects of reduced expression of the RGS2 protein in the brain.”

American Friends of Tel Aviv University 
http://tinyurl.com/h6nz7pf
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Copeptin levels associated with renal and cardiac disease

, 26 August 2020/in E-News /by 3wmedia

Type 1 diabetes patients with elevated albumin in their urine had three times the risk of life-threatening kidney and cardiac disease as those with normal levels, according to researchers at the University of Colorado Anschutz Medical Campus.
The study, led by Dr. Petter Bjornstad, MD, of the Barbara Davis Center for Childhood Diabetes at CU Anschutz, looked at 38 males with type 1 diabetes and albumin in their urine and 38 diabetic males with normal albumin levels. The subjects were recruited across the country from the Type 1 Diabetes Exchange Biobank.
Albuminuria, or the presence of elevated albumin in the urine, is a marker for kidney disease. Bjornstad found that the copeptin was more than three times higher in patients with albuminuria. Copeptin is secreted along with arginine vasopressin or AVP from the pituitary gland and elevated levels appear to predict risk of cardiovascular mortality.
AVP is a hormone that regulates urination, though chronically high levels may cause kidney and vascular damage. But measuring AVP is extremely difficult due to its small size and short half-life. So researchers use copeptin as a surrogate. It is more stable, derived from the same molecule as AVP and can be more easily measured.
In this study, researchers found that the men with type 1 diabetes and albuminuria had significantly greater concentrations of copeptin compared to diabetic males with normal albumin levels.
“High levels of copeptin were associated with greater odds of albuminuria and impaired glomerular filtration rate which measures kidney function and stages of kidney disease,” Bjornstad said.
The findings, he said, could open the door to new ways of treating diabetic kidney disease and other illnesses. Specifically, a family of drugs called vaptans could be used to block excess vasopressin in these patients. “We think that vaptans or therapies targeting vasopressin can delay or stop the development of diabetic kidney disease,” Bjornstad said.
“There are clinical trials undergoing with vaptans in polycystic kidney disease, but to our knowledge no one is looking at vaptans and diabetic kidney disease yet.”
The study has important limitations. The sample size was small and its design prevents determination of causality. It also focused on men and may not apply to young people or women. But the findings support earlier research done by Bjornstad in the Coronary Artery Calcification in Type 1 Diabetes Study (CACTI.)
“We think these findings may have lifesaving implications for those with diabetic kidney and heart disease,” Bjornstad said.

University of Colorado Anschutz Medical Campus http://tinyurl.com/jfsnggz

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Study reverses thinking on genetic links to stress, depression

, 26 August 2020/in E-News /by 3wmedia

For years, scientists have been trying to determine what effect a gene linked to the brain chemical serotonin may have on depression in people exposed to stress. But now, analysing information from more than 40,000 people who have been studied over more than a decade, researchers led by a team at Washington University School of Medicine in St. Louis have found no evidence that the gene alters the impact stress has on depression.
New research findings often garner great attention. But when other scientists follow up and fail to replicate the findings? Not so much.
In fact, a recent study published in PLOS One indicates that only about half of scientific discoveries will be replicated and stand the test of time. So perhaps it shouldn’t come as a surprise that new research led by Washington University School of Medicine in St. Louis shows that an influential 2003 study about the interaction of genes, environment and depression may have missed the mark.
Since its publication in Science, that original paper has been cited by other researchers more than 4,000 times, and some 100 other studies have been published about links between a serotonin-related gene, stressful life events and depression risk. It indicated that people with a particular variant of the serotonin transporter gene were not as well-equipped to deal with stressful life events and, when encountering significant stress, were more likely to develop depression.
Such conclusions were widely accepted, mainly because antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) help relieve depression for a significant percentage of clinically depressed individuals, so many researchers thought it logical that differences in a gene affecting serotonin might be linked to depression risk.
But in this new study, the Washington University researchers looked again at data from the many studies that delved into the issue since the original publication in 2003, analysing information from more than 40,000 people, and found that the previously reported connection between the serotonin gene, depression and stress wasn’t evident.
“Our goal was to get everyone who had gathered data about this relationship to come together and take another look, with each research team using the same tools to analyze data the same way,” said the study’s first author, Robert C. Culverhouse, PhD, an assistant professor of medicine and of biostatistics. “We all ran exactly the same statistical analyses, and after combining all the results, we found no evidence that this gene alters the impact stress has on depression.”
Over the years, dozens of research groups had studied DNA and life experiences involving stress and depression in the more than 40,000 people revisited in this study. Some previous research indicated that those with the gene variant were more likely to develop depression when stressed, while others didn’t see a connection. So for almost two decades, scientists have debated the issue, and thousands of hours of research have been conducted. By getting all these groups to work together to reanalyze the data, this study should put the questions to rest, according to the researchers.
“The idea that differences in the serotonin gene could make people more prone to depression when stressed was a very reasonable hypothesis,” said senior investigator Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry at Washington University. “But when all of the groups came together and looked at the data the same way, we came to a consensus. We still know that stress is related to depression, and we know that genetics is related to depression, but we now know that this particular gene is not.”
Culverhouse noted that finally, when it comes to this gene and its connection to stress and depression, the scientific method has done its job.

Washington University School of Medicine
medicine.wustl.edu/news/study-reverses-thinking-genetic-links-stress-depression/

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Gene find sheds light on growth defects linked to dwarfism

, 26 August 2020/in E-News /by 3wmedia

A new study shows how errors in a specific gene can cause growth defects associated with a rare type of dwarfism.

During the study, an international team of scientists led by the University of Birmingham looked at genetic information from more than 250 people around the world with primordial dwarfism, a group of disorders characterised by short stature and an abnormally small head.

They found that 29 of the individuals had a defective version of a gene called DONSON.

Tests on cells growing in the laboratory revealed that this gene plays a crucial role in ensuring DNA is copied correctly when cells divide and grow.
Cells from patients with mutations in the DONSON gene had difficulty in efficiently replicating their DNA and protecting it from uncontrolled damage, ultimately leading to the growth defects typical of primordial dwarfism.

Most children with primordial dwarfism are not diagnosed until they are around three years old, and doctors are often unable to pinpoint the causes. This research raises the potential of more accurate diagnoses for patients with genetic microcephaly, in addition to providing an insight into how similar rare hereditary diseases are caused.

Professor Grant Stewart, from the Institute of Cancer and Genomic Sciences at the University of Birmingham, says: ‘Despite DNA replication being a process that is fundamental to life, there is still a lot we don’t know. This research sheds new light on the mechanisms underlying DNA replication, and the effect on human health when this process goes wrong.’

Professor Andrew Jackson, of the University of Edinburgh’s Institute for Genetics and Molecular Medicine, says:  ‘Identification of DONSON as a new microcephaly gene has given us new insights into how the genome is protected during DNA replication, and has only been possible through the close collaboration and contributions of clinicians and scientists from many countries around the world.’
Professor Christopher Mathew, from the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ and King’s College London, adds: ‘This is a good example of how unravelling the genetics of rare human disorders can provide profound insight into basic biological processes.’

NIHR Medical Research Institute www.guysandstthomasbrc.nihr.ac.uk/2017/02/14/research-gene-find-sheds-light-on-growth-defects-linked-to-dwarfism/

https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 0 0 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:33:002021-01-08 11:09:40Gene find sheds light on growth defects linked to dwarfism
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