Scientific paper recognised as a JBC Classic

Published on Monday, March 6th, 2017

The Journal of Biological Chemistry (JBC) recognised one of our scientific papers published in 1985 as a JBC Classic. A link to this announcement can be be seen at http:/www.jbc.org/content/ 292/1/80.full.html.

The actual paper is: “Isolation and Properties of Recombinant DNA Produced Variants of Human alpha-1-Proteinase Inhibitor (= alpha-1-antitrypsin)” by  James Travis, Maurice Owen, Peter George, Robin Carrell, Stephen Rosenberg, Robert Halliwell and Philip Barr and published in the  Journal of  Biological  Chemistry  Vol 260 No 7, 4384-4389, 1985.

This work followed on from an earlier paper by Maurice Owen, Stephen Brennan,  Jessica Lewis and Robin Carrell, “Mutation of antitrypsin to antithrombin. Alpha -1-antitrypsin Pittsburgh (386 Met to Arg), a Fatal Bleeding disorder” published in the New England Journal of Medicine 1983: 309:694-698. This showed how a single change at the active site of antitrypsin dramatically changed the protein from an inhibitor of elastase to an inhibitor of thrombin which resulted in a fatal bleeding disorder.

Professor Jim Travis, from the University of Georgia  USA, spent a few months with us in Christchurch NZ in 1984 where he worked on modifying the active site amino acid of alpha-1-antitrypsin from the native Methionine, which is susceptible to oxidation, to a Valine, which is resistant to oxidation. This resulted in a non-oxidisable form of the protein.  Antitrypsin protects the lungs from emphysema. However it loses its protective activity if it is oxidised – which can occur in subjects that are heavy smokers.

This work was done when recombinant DNA technology was in its infancy. It was one of the first demonstrations of the ability to tailor-make therapeutics.

Canterbury Scientific News – May 2016

Published on Monday, May 16th, 2016

In this special announcement, we share news of senior staff farewells and welcomes, and our recent KiwiNet award recognition. Read the newsletter.

Article: Not All Calories Are Equal

Published on Tuesday, December 15th, 2015

Advance diabetes feature Dec15b

Explore the common pathways linking obesity and type 2 diabetes

Feature Article in ADVANCE for Laboratory by Maurice Owen, PhD, FACB

It is estimated that,by 2030, 550 million people will have type 2 diabetes (T2DM) and about half will be unaware of this fact. A similar number are estimated to be at future risk of developing T2DM.1,2 The majority of new cases are due to an increase in affluence leading to chronic energy imbalance with increasing energy intake and decreasing levels of exercise, resulting in obesity. However, recent evidence suggests that the type of calories (energy) consumed can result in vastly different outcomes. The epidemic of T2DM worldwide has been correlated with a dramatic rise in obesity, but the link between the two may be more complex than it seems.

Read the article

Media Article: Diabetes Trends

Published on Monday, December 7th, 2015

Examining some of the emerging options for diabetes testing in the clinical laboratory

Advance diabetes feature Nov15From the clinical laboratory to the diagnosing physicians, there are few areas that represent such a group effort in the healthcare industry as the prevention of type 2 diabetes. The importance of a lifestyle change in pre-diabetic patients cannot be understated, but the need for increased presence in clinical screening for warning signs is paramount.

In a recent interview with ADVANCE for Administrators of the Laboratory, Chris Florkowski, MD(Lond), MRCP(UK), FRCPA, FRACP, consultant with Canterbury Scientific and chemical pathologist at Canterbury Health Laboratories in Christchurch, NZ, discussed the role of the laboratory in helping patients with pre-diabetes.  Read the article

Article: The glucose vs. HbA1c controversy

Published on Wednesday, November 4th, 2015

This article written by Dr Maurice Owen is published in the Future Buzz section of the November 2015 issue of MLO magazine.

The glucose vs. HbA1c controversy

MLO article Nov15Which test should be used for the diagnosis of diabetes: glucose or HbA1c? Over the last few years, an increasing number of countries have moved from fasting plasma glucose to HbA1c as the method of choice. The measurement of glucose, which goes back more than 100 years, far pre-dates HbA1c, and it can be argued that it measures the analyte that is widely known as being central to diabetes. Hemoglobin does not have so strong a pedigree as a diabetes diagnostic. The red protein that transports oxygen from the lungs to the tissues and carbon dioxide back to the lungs is an artifact, or at most an indirect measure, of average glucose. HbA1c testing has historically been recommended only to determine glucose control in those who already have been diagnosed as diabetic. Why, then, are we seeing an increasing move toward measuring HbA1c rather than fasting plasma glucose as the diagnostic test for diabetes?

Some relevant background

The red blood cell has an average circulating life of some 120 days. The cell membrane allows some reagents to cross into the cell. These so-called penetrating solutes include glucose, urea, bicarbonate, phosphate, and water. Hemoglobin, which is highly concentrated within the cell, reacts with free glucose to form glycated hemoglobin. The main glycation site is at the N-terminal valine of the beta chain. The term HbA1c refers to glycation at this specific site. Hemoglobin is also glycated at a number of €-amino lysines such as ß-66, α-16, and ß-17, and also on the alpha N-terminal valine.1

In 1969 Samuel Rahbar, an Iranian scientist, was the first to report the linkage between diabetes and HbA1c.2 He showed a band migrating ahead of HbA (toward the cathode) using agar gel electrophoresis at pH 6.2. This band had the same chromatographic mobility as the HbA1c peak on a Bio-Rex 70 column. He reported that normal, non-diabetic subjects had HbA1c levels in the range of four percent to six percent of the total hemoglobin, whereas patients with diabetes showed levels from 7.5 percent to 10.6 percent.

The Diabetes Complications and Control Trial (DCCT)3 and the UK Prospective Diabetes Studies4 on type 1 and type 2 diabetic subjects respectively showed the value of intensive treatment to maintain blood glucose levels close to the normal range, as opposed to conventional treatment. The intensively treated group had a significantly reduced risk of developing complications such as retinopathy, nephropathy, and neuropathy compared with the conventionally treated group. Furthermore, the intensively treated group showed a drop in median HbA1c from 9.1 percent to 7.4 percent in the DCCT study and from 7.9 percent to 7.0 percent in the UK Prospective Diabetes Study.

Since the mid-1990s the NGSP5 has focused its efforts on standardizing the measurement of HbA1c and has seen dramatic improvements in the assay. The IFCC6 has overseen the development of a primary reference material against which calibrators can be standardized.

Arguments in favor of HbA1c

There are real concerns about the accuracy of blood glucose measurements. The test needs to be performed promptly after collection since glucose will decrease up to 10mg/dL per hour unseparated at room temperature. Frequently there are delays in the blood sample reaching the testing laboratory, often with samples not having been kept chilled. There are also significant day-to-day variations in fasting blood glucose from the same subject, with a coefficient of variation up to 8.3 percent.7 In contrast, the coefficient of variation for HbA1c measurements is now consistently below 3.5 percent.

Patients may also fast for a few days prior to their appointment to give a non-representative average of fasting glucose level. Whether or not patients try to cook the results that way, it is argued that HbA1c is more convenient since it does not require a fasting sample and there is less day-to-day variation.

Selvin et al8 looked at the prognostic value of HbA1c compared with fasting glucose in a population of non-diabetic adults to identify those at risk for diabetes or cardiovascular disease. They found that a fasting glucose in the pre-diabetic range of 100 mg/dL to 125 mg/dL had no predictive value for coronary heart disease, but an HbA1c between 6.0 percent and 6.4 percent showed an 88 percent risk of developing coronary heart disease. In other words, HbA1c was found to be a better predictor of cardiovascular disease than glucose.

Arguments in favor of glucose

Skeptics of HbA1c point out that all HbA1c assay methods have some bias. This means that reliance on a particular instrument or method may consistently give values that are higher or lower than the actual level. Potentially a diagnosis for diabetes using HbA1c could be missed or falsely given with levels near the critical decision point.

The presence of hemoglobinopathies also may give a false result.5 Instruments using boronate affinity methods are largely unaffected by the common variants HbC, HbS, HbE, and HbD. Newer HPLC instruments are generally unaffected, although HbE remains a problem with some.

Any condition that decreases erythrocyte age will lower the HbA1c independently of glycemia. Iron deficiency has been shown to shift HbA1c levels slightly upward.9 Again, this may be a problem with lower HbA1c levels where diagnostic decisions are made.

It has been proposed that some individuals have HbA1c values that are higher or lower than expected from measurements of average blood glucose or fructosamine concentrations. This has been termed the glycation gap. However, this is probably more an issue of the limitations of the fructosamine assay, including its dependence upon the albumin level, and the problems in determining an average glucose level, rather than a glycation issue.10

The verdict?

If it were an easy question, it would have an easy answer; in fact, the controversy continues. But the general trend has been a shift from glucose to HbA1c for the diagnosis of diabetes, and signs are the trend will continue

The main problem with glucose relates to it being a fasting sample that needs to be transported on ice to the laboratory and tested promptly. In contrast, HbA1c does not require a fasting sample and is stable during transportation to the laboratory. The analyzers, thanks to the efforts of NGSP and IFCC, have very good CVs.

As with any laboratory diagnostic test, the result must be interpreted in light of the subject’s clinical situation. This may mean other tests may be required to confirm the diagnosis. In many cases, glucose and HbA1c may work together for the diagnosis of diabetes.

References

1. Shapiro R, McManus MJ, Zalut C , Bunn HF. Sites of nonenzymatic glycosylation of human hemoglobin A. J. Biol. Chem. 1980;255(7):3120-3127.

2. Rahbar S, Blumfield O, Ranney HM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Comm. 1969;36(5)838-843.

3. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. 1993; NEJM 329(14):977-986.

4. American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Diabetes Care.2002; Vol 25 Supplement 1:28-32.

5. NGSP: Harmonizing HbA1c testing. www.ngsp.org. Accessed September 18, 2015.

6. International Federation of Clinical Chemistry and Laboratory Medi6.cine. www.ifcchba1c.net. Accessed September 20, 2015.

7. Paxton A. Diabetes debate: HbA1c or glucose. www.captodayonline.com/diabetes-debate-hba1c-or-glucose. Accessed September 20, 2015.

8. Selvin E, Steffes MW, Zhu H et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. NEJM. 2010;362(9):800-811.

9. Ahmad J, Rafat D. HbA1c and iron deficiency: a review. Diabets Metab Syndr. 2013;7(2):118-122.

10. Sacks DB, Nathan, DM, Lachin JM. Gaps in the glycation gap hypothesis. Clin Chem. 2011;57(2):150-152.

Maurice Owen

Maurice Owen

 

Maurice Owen, BSc(Hons), PhD, BD, FACB, serves as Scientific Director for New Zealand-based Canterbury Scientific. He has published in the fields of hemoglobin, α1-antitrypsin and antithrombin-3 with a focus on the molecular pathology of variants.

Canterbury company leading global medical market

Published on Tuesday, September 22nd, 2015

Article written by the Canterbury Employers Chambers of Commerce, September 2015

Built on a solid foundation of world-class innovation, local company Canterbury Scientific is celebrating 30 years of success in the international medical community this year, while continuously striving to maintain its leading market position.

Established in 1985, the company develops and produces the highest quality freeze-dried and ready-to-use liquid haemoglobin controls available. Its major product, the haemoglobin A1c (HbA1c) control, is relied on by tens of thousands of people around the world to help manage their diabetes.

“We have close to 30 per cent of the global market within this HbA1c space – that’s a pretty remarkable position to be in for a little Christchurch-based operation,” says Canterbury Scientific CEO Neil Pattinson. “But we don’t want to rest on our laurels; we want to continue to grow and diversify.”

Diabetes is a serious global issue, particularly as emerging markets take on a more Westernised diet, he says. “However, it’s those emerging markets that are not very well serviced. In China, for example, there are 90 million diabetics – and more than half of those individuals are undiagnosed at this stage.

“If you don’t manage your diabetes, you end up with really severe secondary complications, such as circulatory disorders, renal dysfunction, retinopathy, and cardiovascular disease. Obviously, if you can prevent those conditions, that’s a huge saving – both to the individual and the health sector.”

Neil says the HbA1c control’s stability and shelf life are unrivalled in the international market. “Haemoglobin is a particularly unstable molecule. We went from developing freeze-dried controls – because the compounds are a lot more stable if they are in a dehydrated state – then moved on to a liquid product. Our liquid product has the same shelf life as freeze-dried. So, basically, you can have controls that are up to three years old, and they behave as freshly drawn blood.

“Obviously the liquid product is a lot easier to handle. At a hospital lab, for example, when you’ve got thousands of samples coming through – you don’t want to spend half an hour re-solubilising the product, making sure it’s well mixed and homogenous. It’s a huge advantage to have it in liquid form.”

Neil says continuous innovation and quality science is key to maintaining the company’s leading market position. “Canterbury Scientific’s motto is ‘quality science – quality product’. Everything we do is built upon a strong foundation of good quality science. Unless you have good science to support a product, you won’t end up with a market-leading product.

Read more

Canterbury Scientific finalist in NZ Bio Awards 2015

Published on Wednesday, September 16th, 2015

We’re very excited to announce that Canterbury Scientific has been nominated one of three finalists in the Company of the Year category of the NZ Bio Awards 2015.

The awards will be announced at the NZ Bio conference on 23 September at the St James Theatre in Wellington, NZ. We wish all the very best of luck to all the finalists.

Canterbury Scientific is a finalist in the 2015 New Zealand International Business Awards

Published on Wednesday, February 25th, 2015

We’re excited to announce that Canterbury Scientific achieved finalist recognition in two categories of the 2015 New Zealand International Business Awards: the ANZ Best Business Operating Internationally category and the Excellence in Innovation category supported by AJ Park.

The awards are run by New Zealand Trade and Enterprise (NZTE) and Strategic Partner ANZ, and celebrate the passion, vision and new approaches that New Zealand businesses are taking to achieve international success.

Congratulations to all the finalists and winners.

Read the NZTE press release.

NZIBA 2015 image

Holiday dates – closed 24 Dec, reopen 5 Jan 2015

Published on Monday, November 24th, 2014

Please note that our last working day before the holiday season commences will be Tuesday 23 December. We will reopen the office on Monday 5 January. Wishing you all a wonderful festive season and very happy holidays.

Canterbury Scientific News – July 2014

Published on Wednesday, July 9th, 2014

Our latest edition is out, with updates on our Board of Directors, NZBIO, our 5S workplace organisation method and Health & Safety updates. <read the newsletter>

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