Aldolase: A Myositis Biomarker

Aldolase: A Myositis Biomarker

29 May 2019

Aldolase: A Myositis Biomarker

The month of May is devoted to myositis awareness, a muscle-wasting disease resulting in reduced muscle strength and fatigue. The term ‘myositis’ is an umbrella term referring to the “general inflammation or swelling of the muscle”.  However, myositis is more often referred to as a disease involving chronic inflammation of the muscles which does not improve with rest. This condition is also known as idiopathic inflammatory myopathy (IIM) 1.

Myositis is an autoimmune disease characterised by pain, muscle weaknesses, swelling and extreme fatigue which often gradually appear. Myositis can be potentially life-threatening, especially dermatomyositis which affects the heart muscle and lungs. Whilst a rare disease, it is estimated that 75,000 Americans suffer from myositis, however, many are undiagnosed or misdiagnosed with more common autoimmune diseases. Most physicians are unfamiliar with the disease and symptoms and so the consequences of this can be catastrophic in terms of long-term physical muscle damage, disability and even death 1, 2, 3.

Did you know?

5,000 to 6,000 people in the UK have a form of myositis 3.

Table 1 reviews the different forms of myositis

A table comparing the different types of Myositis

Table 2 reviews complications with or due to myositis

Complications with or due to Myositis

It is vital that physicians are educated to include myositis despite it being a rare disease as it is essential that myositis patients are diagnosed quickly to ensure appropriate treatment plans are implemented.

Aldolase Testing

Aldolase testing has been recognised as a marker in the differential diagnosis of muscle weakness as aldolase levels remain consistent where weakness is caused by neurological problems such as multiple sclerosis (MS). Aldolase is an enzyme specifically found in skeletal muscle and the liver. When either the muscle or liver are damaged, aldolase is released into the bloodstream 13 . A few studies support aldolase testing in the diagnosis of myositis:

 1.  Arthritis Research & Therapy (2012): Aldolase predicts subsequent myopathy occurrence in systemic sclerosis 14

Objective:

A French monocentric 4-year study prospectively evaluated n=137 systemic sclerosis (SSc) patients without proximal muscle weakness to assess the risk of myopathy related systemic sclerosis (Myo-SSc) according to the European Neuro Muscular Centre criteria. Aldolase, creatine kinase (CK), C-reactive protein (CRP), alanine transaminase (ALT) and aspartate transaminase (AST) were evaluated.

Conclusion:

Aldolase is a valuable diagnostic tool in the identification of SSc patients at a high risk of developing subsequent Myo-SSc. This enables clinicians to monitor at-risk patients as well as identifying Myo-SSc in its earliest stages, enabling the effective and swift implementation of an appropriate treatment plan when the muscle damage is still in a reversible stage.

Findings:

2.  Clinical and Experimental Rheumatology (2013): Isolated elevation of aldolase in the serum of myositis patients: a potential biomarker of damaged early regenerating muscle cells 15

Objective:

The in vitro analysis of the gene and protein expression levels of aldolase and CK during muscle cell differentiation.

Conclusion:

Aldolase A is expressed in the absence of CK in undifferentiated muscle cells and in the early differentiation process. Isolated elevated serum aldolase A in myositis patients reflects preferential immune-mediated damage of early regenerative cells. Aldolase is a biomarker of damaged early regenerating muscle cells.

Findings:

Myositis can be a potentially life-threatening disease when undiagnosed or misdiagnosed. Aldolase is recognised as a biomarker in the diagnosis and monitoring of myositis. Randox are one of the only in-vitro diagnostic manufacturers to offer the aldolase assay in an automated and manual biochemistry format. Not only does the Randox methodology have an excellent correlation coefficient to r=0.9917 when compared against standard methods, the Randox assay is lyophilised for enhanced stability with an excellent measuring range of 1.73 – 106U/l. Moreover, applications are available detailing instrument-specific settings for the convenient use of the Randox aldolase assay on a wide range of clinical chemistry analysers.

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Rare Disease Day: 28th February 2019

28th February 2019

Rare Disease Day: 28th February 2019

Rare Disease Day raises awareness of rare diseases and how patients’ lives are affected. Many rare diseases remain incurable and many go undiagnosed. 1 in 20 people will live with a rare disease at some point in their life and this is why it is so important to raise awareness.1

What is a rare disease?

There is no single definition for a rare disease, as many countries identify them differently. In the United States, the Rare Diseases Act of 2002 defines a rare disease by its prevalence: “any disease or condition that affects fewer than 200,000 people in the United States”. However, the EU defines a rare disease as a condition that affects less than 5 in 10,000 of the population. There are approximately 7000 rare diseases and disorders and 50% of people affected by rare diseases are children.2,3

Hyperlipoproteinemia type III

This rare disease day, Randox will be raising awareness of hyperlipoproteinemia type III.  Hyperlipoproteinemia type III, also known as dysbetalipoproteinemia or broad beta disease, is a rare genetic disorder characterised by improper breakdown of lipids, specifically cholesterol and triglycerides.  The condition is caused by mutations in the Apo-E gene, however the inheritance of this condition is complicated due to the development of symptoms having to be triggered by a secondary factor to raise lipid levels. These factors include diabetes, obesity or hypothyroidism.

It is unknown exactly what the prevalence of the condition is, but it is estimated to affect approximately 1 in 5,000 – 10,000 of the general population and it has been found that it affects males more often than females, with women rarely being affected until after menopause.4,5

Figure A. Example of cholesterol and lipid build-up [6] 

Symptoms

Symptoms for hyperlipoproteinemia type III will vary for each individual and some people may even be asymptomatic. The most common symptom is the development of xanthomas which are deposits of fatty material, the lipids, in the skin and underlying tissue. Xanthomas may appear on the palms of the hands, eyelids, soles of the feet or on the tendons of the knees and elbows.

> Chest pain or other signs of coronary artery disease

> Cramps in the calves when walking

> Sores on toes

> Stroke-like symptoms such as trouble speaking, dropping on one side of the face, weakness in an arm or a leg and a loss of balance6

Complications can arise if the condition is left untreated and these can include: myocardial infarction, ischemic stroke, peripheral vascular disease, intermittent claudication and gangrene of the lower extremities.7

Diagnosis

Although there is no specific diagnostic test for hyperlipoproteinemia type III, diagnosis is based on clinical evaluation and identification of symptoms. Research has indicated that an algorithm comprising a number of dysbetalipoproteinemia indices may be helpful in the diagnosis of the disease.  These include:

> Low apolipoprotein B to total cholesterol ratio

> Elevated levels of triglycerides

> Elevated levels of total cholesterol8

Managing the condition

The condition cannot be cured but treatment is to control conditions such as obesity, hypothyroidism and diabetes. Most patients will go through dietary therapy to control their intake of cholesterol and saturated fat. This prevents xanthomas, high levels of lipids in the blood, exercise will also help to lower lipid levels. However, dietary changes may not be effective for some individuals and this is where drugs may be used to lower lipid levels instead.

How Randox can Help

Randox offer a range of routine and niche assays within the lipid testing panel to monitor lipid levels and to identify associated complications.  Some of these tests include:

Apolipoprotein B

The Randox Apolipoprotein B tests utilises an immunoturbidimetric method, offers a wide measuring range and is available liquid ready-to-use for convenience and ease of use.

Learn more about the Randox Apolipoprotein B Test

Total Cholesterol

The Randox Total Cholesterol test utilises the CHOD-PAP method and offers an extensive measuring range with a wide range of kits available to suit a wide range of laboratory sizes.

Learn more about the Randox Total Cholesterol test

Triglycerides

The Randox Triglycerides test utilises the GPO-PAP method while offering an extensive measuring range with both liquid and lyophilised formats available offering choice and flexibility.

Want to know more?

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  • References

    [1] Rare Disease Day. What is Rare Disease Day? Rare Disease Day. [Online] 2019. [Cited: February 21, 2019.] https://www.rarediseaseday.org/article/what-is-rare-disease-day

    [2] Genetic Alliance UK. What is a Rare Disease? Rare Disease UK. [Online] 2018. [Cited: February 21, 2019.] https://www.raredisease.org.uk/what-is-a-rare-disease/

    [3] NZORD. Rare Disease Facts and Figures. NZORD. [Online] 2019. [Cited: February 21, 2019.] https://www.nzord.org.nz/helpful-information/rare-disease-facts-and-figures.

    [4] NORD. Hyperlipoproteinemia Type III. NORD. [Online] 2019. [Cited: February 21, 2019.] https://rarediseases.org/rare-diseases/hyperlipoproteinemia-type-iii/

    [5] GARD. Hyperlipidemia Type 3. National Centre for Advanciing Translational Sciences. [Online] December 29, 2016. [Cited: February 21, 2019.] https://rarediseases.info.nih.gov/diseases/6703/hyperlipidemia-type-3

    [6] Falck, Suzanne. Everything you need to know about hyperlipidemia. Medical News Today. [Online] December 21, 2017. [Cited: February 21, 2019.] https://www.medicalnewstoday.com/articles/295385.php

    [7] Medline Plus. Familial Dysbetalipoproteinemia. Medline Plus. [Online] May 16, 2018. [Cited: February 21, 2019.] https://medlineplus.gov/ency/article/000402.htm.

    [8] Dysbetalipoproteinemia: Two cases report and a diagnostic algorithm. Kei, Anastazia, et al. 4, s.l. : World Journal of Clinical Cases, 2015, Vol. 3.


Obesity and Kidney Disease: What is the Connection?

30th January 2019

Obesity and Kidney Disease: What is the Connection?

The month of January has forever been the month of resolutions with many choosing to ditch the sweets and join the gym. However, for many these efforts are limited to January and bad habits are quick to remerge. Obesity has been a burden on the health service for many years with the problem, like many people’s waist lines, only continuing to expand.

Recent findings have shown that this problem is no longer just increasing in developed countries but also in developing countries. In fact, worldwide obesity has tripled since 1975. In 2016, more than 1.9 million adults were classed as overweight, of which over 650 million were obese.1 These are shocking statistics for a condition that is preventable. As a global concern, it is important to assess all the potential risks of this problem.

The most common diseases associated with obesity are cardiovascular disease (CVD) and diabetes. However, the associated risks are much greater than this. Being overweight may also increase the risk of certain types of cancer, sleep apnea, osteoarthritis, fatty liver disease and kidney disease.2

Obesity is now recognised as a potent risk factor for the development of renal disease.3 Excess weight has a direct impact on the development and progression of chronic kidney disease (CKD). Globally, the prevalence of diabetic kidney disease rose by 39.5% between 2005 and 2015, coinciding with the increased CKD prevalence.4 In obese individuals, the kidneys have to work harder, filtering more blood than normal to meet the metabolic demands of increased body weight, increasing the risk of kidney disease.

The traditional diagnostic test for renal impairment is creatinine. This test is carried out through the measurement of creatinine levels in the blood to assess the kidneys ability to clear creatinine from the body. This is called the creatinine clearance rate which helps to estimate the glomerular filtration rate (GFR), which is the rate of blood flow through the kidneys.5

Problems arise when using creatinine for CKD testing as a number of factors need to be taken into consideration including age, gender, ethnicity and muscle mass. For this reason, black men and women exhibit higher creatinine levels than white men and women, raising concern over the accuracy of this test for certain patient groups.6 In addition, serum creatinine is not an adequate screening test for renal impairment in the elderly due to their decreased muscle mass.7

The main disadvantage of using creatinine to screen for renal impairment is that up to 50% of renal function can be lost before significant creatinine levels become detectable as creatinine is insensitive to small changes in GFR. Consequently, treatment is not provided at the appropriate time which can be fatal, therefore, an earlier and more sensitive marker for renal function is vital.8

These disadvantages have not only been highlighted in research but also by the national institute for health and care excellence (NICE).  NICE updated the classification of CKD in 2004 to include the albumin: creatinine ratio (ACR). They split chronic kidney disease patients into categories based on GFR and ACR. Figure 1 highlights the different categories and risk of adverse outcomes. NICE recommend using eGFR Cystatin C for people in the CKD G3aA1 and higher.9

Figure 1 Classification of Chronic Kidney Disease using GFR and ACR categories.9

Despite these suggestions, Creatinine is still being used for G3a1 and increasing risk levels.

The utility of cystatin C as a diagnostic biomarker for kidney disease has been documented to show superiority of traditional CKD tests. There is no ‘blind area’ making it very sensitive to small changes in GFR and capable of detecting early reductions.  Furthermore, this marker is less influenced by diet or muscle mass and has proven to be a beneficial test in patients who are overweight.8

A number of studies support the statement: ‘Cystatin C levels are higher in overweight and obese patients’. This is important because when cystatin c levels are too high, it may suggest that the kidneys are not functioning properly. One study conducted, using a nationally representative sample of participants, found that overweight and obesity maintained a strong association with elevated serum cystatin C. This suggests that weight can affect the levels of cystatin C and therefore the likelihood of developing kidney disease.10

How Randox can Help

The Randox automated Latex Enhanced Immunoturbidimetric Cystatin C tests offers an improved method for assessing CKD risk, combined with a convenient format for routine clinical use, for the early assessment of at risk patients. Randox is currently one of the only diagnostic manufacturers who offer an automated biochemistry test for Cystatin C measurement, worldwide.

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World Diabetes Day: The Biggest Burden on the NHS

14 November 2018

World Diabetes Day

Diabetes

Approximately 400,000 people in the UK are living with type 1 diabetes, with over 29,000 being children and young people [1]. Type 1 diabetes affects 96% of all children with diabetes in England and Wales, with incidences increasing by approximately 4% each year.

Globally, the UK has the fifth highest rate of type 1 diabetes diagnosis in children (aged up to 14) with 85% of these children having no family history of the condition. Whilst the condition isn’t fatal and can be managed, it cannot be cured. Type 1 diabetes increases the risk of developing other health problems such as heart disease, stroke, foot and circulation problems, sight problems including blindness, nerve damage and kidney problems. However, many of these related conditions are preventable and it is recommended to stabilise blood sugar levels, attend diabetes appointments regularly and complete a diabetes course to educate patients and family members and prevent the risk of further help complications[2].

Diabetes in children

Children under five are at the highest risk of developing diabetic ketoacidosis due to a late diagnosis and it is also thought to be due to of lack of public knowledge of the signs and symptoms attributed to type 1 diabetes. Such symptoms include:

  • Frequent urination as the kidneys are trying to expel excess sugar in the blood, resulting in dehydration which leads to extreme thirst.
  • Increased hunger or unexpected weight loss because the body is unable to attain enough energy from food
  • Slow healing cuts as high blood sugar levels can affect blood flow which can cause nerve damage.
  • Fatigue as the body is unable to convert sugar into energy
  • Irritable behaviour combined with other symptoms can be a means of concern

Diabetes and the NHS

Diabetes costs the NHS approximately £9.8 billion per year, an estimate of 10% of total expenditures. Hospital admissions of children and young people with diabetes presents a considerable burden on themselves, their families and the NHS. It is estimated that approximately 80% of these cases are potentially avoidable.

A report produced by the National Paediatric Diabetes Audit found that although the numbers of admissions didn’t significantly differ year to year, it highlighted differences in terms of socio-economic risk factors:

  • Living in a deprived area increases the risk of hospital admissions which can be attributed to lack of education in the community about diabetic symptoms and the management of diabetes.
  • Children below 5 years of age have a 35% increased risk of hospitalisation compared to those aged 5-9
  • Females have a 33% increased risk of developing type 1 diabetes compared to males.
  • Children with poor diabetes control have a twelve-fold increased risk of hospital admission
  • Insulin pump users have a 27% increased risk of hospital admission compared to those who use insulin injections.
Figure A. Number of preventable paediatric diabetes admissions  [3] 

Prevention

There are campaigns in place to aid in the early diagnosis of type 1 diabetes which mainly focus on raising awareness of the signs and symptoms of diabetes. On this World Diabetes Day, it is important to know that it is not just simply the responsibility of the diabetic patient to prevent admission but the main responsibility lies with the diabetic teams that inform the families with children who are diagnosed with type 1 diabetes.

Paediatric diabetes teams should ensure that the families and the children receive structured education for self-management when diagnosed and throughout the illness. In doing so, the diabetic teams should implement blood ketone testing from diagnosis and utilise the nationally agreed hypoglycaemia management guidelines. It is also important that diabetic teams are fully aware of the patient characteristics associated with a greater risk of admission and that they use this knowledge to develop anti-admission strategies specifically tailored to the needs of each individual group.

Primary care practitioners should seek access to a specialist diabetic team who they can refer to when deciding if a patient requires admission to hospital. Furthermore, they should access blood glucose and ketone testing to identify patients at risk of diabetic ketoacidosis that require hospital admission.

How Randox can Help

Randox offer a range of assays to diagnosis and monitor diabetes and to monitor associated complications.  Some of these tests are unique to Randox, including:

Fructosamine

The Randox fructosamine assay employs the enzymatic method which offers improved specificity and reliability compared to conventional NBT-based methods. The Randox enzymatic method does not suffer from non-specific interferences unlike other commercially available fructosamine assays.

Learn more about the Randox Fructosamine test

D-3-Hydroxybutyrate (Ranbut)

The Randox D-3-Hydroxybutyrate (Ranbut) assay detects the most abundant and sensitive ketone in the body, D-3-Hydroxybutyrate. The Randox Ranbut assay is used for the diagnosis of ketosis, more specifically diabetic ketoacidosis. Other commercially available tests, such as the nitroprusside method, are less sensitive as they only detect acetone and acetoacetate, not D-3-Hydroxybutyrate.

Learn more about the Randox D-3-Hydroxybutyrate test

Adiponectin

The Randox adiponectin assay is a biomarker in diabetes testing as adiponectin is a protein hormone responsible for regulating the metabolism of lipids and glucose and influences the body’s response to insulin. Adiponectin levels inversely correlates with abdominal visceral fat levels.

Want to know more?

Contact us or visit our Diabetes panel page to learn more.




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  • References

    [1] National Paediatric Diabetes Audit and Royal College of Paediatrics and Child Health, National Paediatric Diabetes Audit Report 2012-15: Part 2, 2017

    [2] NHS, “Avoiding Complications” – Type 1 Diabetes, Available at: https://www.nhs.uk/conditions/type-1-diabetes/avoiding-complications/ [Accessed on 24th October 2018].

    [3] “Potentially Preventable Pediatric Hospital Inpatient Stays for Asthma and Diabetes, 2003-2012”, www.hcup-us.ahrq.gov, 2015. [Online] Available: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb192-Pediatric-Preventable-Hospitalizations-Asthma-Diabetes.jsp [Accessed 08-Nov-18]


Iron Deficiency Anaemia during Pregnancy

On a global scale, 1.62 billion people are affected by anaemia which is equivalent to 24.8% of the population . According to a review carried out by WHO of various national surveys, anaemia affects approximately 42% of pregnant women worldwide and it is also estimated that at least 50% of all anaemia cases are due to iron deficiency.

Anaemia caused by iron deficiency is usually expected during pregnancy. This is due to several reasons: the increased demand for iron by a pregnant woman’s body from increased total blood cell volume, requirements of the foetus and placenta as well as mass blood loss during labour₂. Although iron cost is unbalanced by the lack of loss of menstrual blood during pregnancy, the net cost is still high enough that iron recommendations are higher than in non-pregnant women. Also, iron is critical during pregnancy considering its involvement in foetal growth: 600-800mg of iron is required during pregnancy with around 300mg needed just for the foetus, a minimum of 25mg for the placenta and almost 500mg due to the increase in volume of red blood cells. ₃

Iron deficiency is the most common micronutrient deficiency in pregnant women leading to iron deficiency anaemia if left untreated. However, iron deficiency can be difficult to measure in some populations due to the lack of availability of field-specific biomarkers. For example, anaemia can affect up to 56% of pregnant women in developing countries, which suggests a high prevalence of iron deficiency anaemia: around 25%. In settings with endemic malaria, such as certain countries in Africa, the number of pregnant women with anaemia is much higher: around 65%.

There are various factors that may increase the risks of iron deficiency anaemia. For example, a diet influenced by religious beliefs can cause a lack of iron in the diet, such as vegetarianism which is common in countries such as India where religious beliefs dictate this. Iron levels can also be affected by consumption of nutrients which inhibit proper absorption of iron, such as calcium or ones that promote iron absorption, such as vitamin C. Other circumstantial risks include infections, multiple pregnancies and adolescent pregnancy while socioeconomic factors and access to healthcare mean some women won’t have access to anaemia control programs, iron supplements or even access to information about iron deficiency anaemia during pregnancy.

To prevent iron deficiency, international guidelines state that iron supplementation to manage iron deficiency is recommended during pregnancy. ₄ However, this is not always available, especially in developing countries.

Iron deficiency anaemia during pregnancy can cause several complications for the mother including:

  • Increased fatigue
  • Short-term memory loss
  • Decreased attention span
  • Increased pressure on the cardiovascular system due to insufficient haemoglobin and blood oxygen levels
  • Lower resistance to infections
  • Reduced tolerance to significant blood loss and surgical implications during labour.

As expected, neonates with mothers who suffered from iron deficiency anaemia during pregnancy will also be confronted with risks and, even if iron deficiency is only mild to moderate, can result in a premature birth, complications with foetal brain development, low birth weight and even foetal death. Additionally, it has been proven that cognitive and behavioural abnormalities can be seen in children for up to ten years after iron insufficiency in the womb.

Randox Soluble Transferrin Receptor (sTfR) Reagent

Randox Reagents offer a Soluble Transferrin Receptor assay to expand upon our current iron testing offering.

In iron deficiency anaemia, soluble transferrin receptor levels are significantly increased, however, remain normal in acute phase conditions including: chronic diseases and inflammation.  As such, sTfR measurements are useful in the differential diagnosis of anaemia: anaemia of chronic disease or iron deficiency anaemia.

In iron deficiency anaemia, increased sTfR levels have also been observed in haemolytic anaemia, sickle cell anaemia and B12 deficiency.

The benefits of the Randox Soluble Transferrin Receptor (sTfR) Reagent include:

  • Latex enhanced immunoturbidimetric method facilitating testing on biochemistry analysers and eliminating the need for dedicated equipment.
  • Liquid ready-to-use reagents for convenience and ease-of-use
  • Stable to expiry date when stored at +2 to +8 °C
  • Excellent measuring range of 0.5 – 11.77mg/L, comfortably detecting levels outside of the normal health range of 0.65 – 1.88mg/L
  • Excellent correlation coefficient of r=0.977 when compared against other commercially available methods
  • Applications available detailing instrument-specific settings for a wide range of clinical chemistry analysers

Find out more at: https://www.randox.com/stfr/

References:

  1. de Benoist B et al., eds.Worldwide prevalence of anaemia 1993-2005WHO Global Database on Anaemia Geneva, World Health Organization, 2008.
  2. Harvey et al, Assessment of Iron Deficiency and Anemia in Pregnant Women: An Observational French Study, Women’s Health, Vol 12 Issue 1, 2016
  3. Burke et al, Identification, Prevention and Treatment of Iron Deficiency during the First 1000 Days, Nutrients, Vol 6 Issue 10, 2014
  4. Guideline: Daily Iron and Folic Acid Supplementation in Pregnant Women. World Health Organization; Geneva, Switzerland: 2012

If you are a clinician or laboratory who are interested in running assays to test iron status, Randox offer a range of assays, including: Iron, Total Iron-Binding Capacity (TIBC), Transferrin and Ferritin .  These assays can be run on most automated biochemistry analysers.

Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

For more information, visit: https://www.randox.com/stfr / or email: reagents@randox.com 


The Keto Diet: Are the risks worth the benefits?

Diet trends have continued to evolve throughout the years with a strong influence from celebrities. Beginning in the 1930s the grapefruit diet aka the “Hollywood diet” started which encouraged eating a grapefruit with every meal. More recently an increasing amount of extreme diet trends have emerged. In 2004, Beyoncé started the master cleanse involving a concoction of hot water, lemon juice, maple syrup and cayenne pepper and even crazier was Reese Witherspoon’s “baby food diet”. The newest trend to materialise is the keto diet favoured by celebrities including Halle Berry and the Kardashians. However, the results for long term weight loss and the safety of the diet is still questioned.

What is the ketogenic diet?

The ketogenic diet is a low carb diet which involves drastically reducing carbohydrate intake and replacing it with fat. Initially, the purpose of the ketogenic diet was not to aid weight loss but was prescribed to aid in the treatment of tough-to-control epileptic seizures that were unresponsive to drugs. In the 1920s the diet was found to significantly reduce the frequency of seizures in children. However, the benefits for weight loss have also been realised as the carbohydrate reduction kicks the body into a natural fat burning state called ketosis. By starving the body of carbohydrates and sugars, the first fuel the body burns, the body looks for another source of fuel to retrieve its energy. The body becomes efficient at burning fat for energy whilst also turning fat into ketones in the liver which can supply the brain with energy.

Ketosis

The metabolism of fatty acids in the liver results in the production of ketone bodies. These comprise of three chemicals consisting of acetone (2%), acetoacetate (20%) and D-3-Hydroxybutyrate (78%) and this production is called ketogenesis. The ketone bodies are produced by the chemical acetyl-CoA predominantly in the mitochondrial matrix of liver cells. This process is necessary in small amounts particularly when carbohydrates are scarce, and glucose is not available as a fuel source.  

The ketone bodies are water soluble allowing for the transportation across the inner mitochondrial membrane as well as across the blood brain barrier and cell membranes. This allows them to source the brain, heart and muscle with fuel. Interestingly, during starvation they are the major energy source for the brain, providing up to 75%.

The excess production of ketones can accumulate in the body creating a state of ketosis. This stage, although abnormal, is not considered harmful, which is why it is being promoted as a diet craze. However, due to the acidic nature of the ketone bodies, particularly D-3-Hydroxybutyrate, larger amounts of ketone bodies can cause the pH levels in the body to drop to dangerously acidic levels creating a state of ketoacidosis.

Ketoacidosis

The benefits of the keto diet have been well advertised and received a lot of celebrity support. With powerful celebrities such as Halle berry ‘swearing by it’ as it allows her to manage her diabetes, it is easy to see why so many are keen to try it. However, with little to no information about the long-term effects, should we be finding out more before trying it ourselves?

In 2006, a study was conducted reviewing the influence of a low-carbohydrate diet can have on ketoacidosis. In this study the patient who had no history of diabetes was placed on a strict low carbohydrate diet for four years. Although the patient showed a significant decrease in weight on the diet, they also experienced four episodes of ketoacidosis. Each time an episode occurred the patient was administered intravenous fluids and insulin which lead to their recovery, however each time they returned to the diet it wasn’t long before another ketoacidosis episode occurred. When the patient was placed on a diet containing normal amounts of carbohydrates their glucose levels returned to normal, preventing a ketoacidosis episode from occurring again. The more ketones in the blood, the more ill a person with ketoacidosis will become. Left untreated ketoacidosis can cause potentially fatal complications such as severe dehydration, coma and swelling of the brain.

Randox D-3-Hydroxybutyrate (Ranbut) Reagent

Randox Reagents offer a D-3-Hydrobutyrate assay designed to measure the major ketone lvels in the body, D-3-Hydroxybutyrate, allowing for an efficient diagnosis to be implemented. The superior methodology provides more accurate, reliable and specific results compared to the traditional dipstick method of ketone body measurement.

The benefits of the Randox D-3-Hydroxybutyrate (Ranbut) assay include:

  • Excellent precision of less than 3.5% CV
  • Exceptional correlation coefficient of r=0.9954 when compared against other commercially available methods.
  • A wide measuring range of 0.100 – 5.75mmol/l, comfortably detecting levels outside of the healthy range, 0.4 – 0.5mmol/l.
  • Enzymatic method for accurate and reliable results
  • Reconstituted stability of 7 days when stored between +2 to +8⁰C

References

  1. Ketoacidosis during a low-carbohydrate diet. Shah, Panjak and Isley, William. s.l. : The new england journal of medicine, 2006, Vol. 354.

Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

For more information, visit: https://www.randox.com/homocysteine or email: reagents@randox.com  


The Correlation Between Liver Cirrhosis and Lactic Acidosis

Lactic acid is an organic compound which produces the conjugate base lactate through a dissociation reaction. Due to it being a chiral compound, two optical isomers of lactate exist; D-Lactate and L-Lactate. The lactate dehydrogenase (LDH) enzyme can produce and metabolise both isomer forms to pyruvate, however due to the isomer-specific nature of LDH different forms of the enzyme are required. D-Lactate requires a D-LDH form whereas L-Lactate requires L-LDH. As a result of this requirement, combined with the fact that mammalian cells only contain L-LDH, the lactate produced in humans is almost exclusively L-Lactate.

One of the roles of L-Lactate is its involvement in the Cori Cycle, a metabolic pathway involved in the production of glucose. The cycle involves the rotatory transportation of lactate and glucose from the liver and the muscle. Lactate is produced in the muscle through glycolysis which is then transported to the liver through the blood stream. In the liver, the lactate is oxidised to pyruvate and then converted to glucose by gluconeogenesis, which is then transported back to the muscle for the process to start again. 1500 mmol of lactate is produced daily by the body and is cleared at a constant rate via the liver.

Cori Cycle

Problems can arise if the liver fails to regulate the lactate produced. Hyperlactamia is the name given to elevated levels of lactate in the body, as a result of the rate of production exceeding the rate of disposal. This is due to a lack of oxygen that reduces blood flow to the tissues. If levels continue to rise a patient is at risk of lactic acidosis.

The liver is an important tissue in the regulation of lactate, it is therefore no surprise that liver damage can prevent this process resulting in a further diagnosis of lactic acidosis. A healthy liver is a vital part of lactate regulation as it acts as the main consumer of lactate and contributes to 30-40% of lactate metabolism. Potential victims are patients who suffer with cirrhosis, a complication of liver disease, which is commonly caused by alcohol abuse and viral Hepatitis B and C.

Patients with liver cirrhosis have a higher risk of increased lactate levels. Increased levels of the lactate ions disturbs the acid-base equilibrium, causing a tilt towards lactic acidosis. The mortality rate of patients who develop lactic acidosis is high, prompt recognition and treatment of the underlying cause remain the only realistic hope for improving survival.

The Randox L-Lactate reagent allows for a prompt and accurate diagnosis of lactic acidosis.

Randox L-Lactate Reagent

The Randox L-Lactate key benefits include:

  • Excellent working reagent stability of two weeks when stored at + 15 – +25°C
  • Exceptional correlation of r = 0.99 when compared against other commercially available methods
  • A wide measuring range of 0.100 – 19.7 mmol/l and so is capable of detecting abnormal levels in a sample

Other features:

  • Colorimetric method
  • Lyophilised reagents for enhanced stability
L-Lactate

If you are a clinician or laboratory who are interested in running assays for Lactic Acidosis or Liver Disease, Randox offer a range of high-quality routine and niche assays including:L- Lactate, Ethanol, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Albumin which can be used to diagnose conditions commonly affecting the liver.  These assays can be run on most automated biochemistry analysers.

Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

For more information, visit: https://www.randox.com/lactate/ or email: reagents@randox.com 


Securing the future with in vitro diagnostic tests

The aim of Biomedical Science Day is to raise the public’s awareness of the importance of biomedical science and the vital role it plays in the world.  Randox are dedicated to improving healthcare worldwide through placing a major focus on research and development.  The Randox scientists work in pioneering research into a range of common illnesses such as cancer, cardiovascular disease and Alzheimer’s disease.

A recent blog from Doris-Ann Williams, the Chief Executive at BIVDA, explains how “increased funding is not enough to sustain the NHS” and how “we need to make better use of in vitro diagnostics to ensure a successful future”.

The National Health Service (NHS) is a publicly funded, primarily taxation, national healthcare system in the United Kingdom.  It was first set-up on July 5th, 1948 by Aneurin Bevan as he believed that everyone, regardless of wealth, should have access to good healthcare.  Whilst the NHS is an extremely important aspect of healthcare in the UK, in vitro diagnostics are the heart and soul of the healthcare system as healthcare professionals not only rely on blood tests to diagnose and treat patients, but also to rule out the different contributing causes to a disease state.  In vitro diagnostics also plays a key role in monitoring chronic disease states.  In vitro diagnostics can also aid in reducing hospital stays, reduce misdiagnosis and support patients in looking after their own health and to deliver personalised treatment plans.

The Randox scientists have developed several niche assays to improve patient diagnosis, monitor treatment and eliminate misdiagnosis.

Adiponectin

Adiponectin is a protein hormone secreted by adipocytes with anti-inflammatory and insulin-sensitising properties.  It plays an important role in a number of metabolic processes including glucose regulation and fatty acid oxidation.  Adiponectin levels are inversely correlated with abdominal visceral fat which have proven to be a strong predictor of several pathologies, including: metabolic syndrome, type 2 diabetes mellitus (T2DM), cancers and cardiovascular disease (CVD).  For more information on the importance of testing Adiponectin levels, check out our Adiponectin Whitepaper.

Cystatin C

Cystatin C is an early risk marker for renal impairment.  The most commonly run test for renal impairment is Creatinine.  Creatinine measurements have proven to be inadequate as certain factors must be taken into consideration, including age, gender, ethnicity etc.  The National Institute for Health and Care Excellence (NICE) have updated their guidelines, which now recommends Cystatin C as a more superior test for renal impairment due to its higher specificity for significant disease outcomes than those based on Creatinine.  For more information on the importance of testing Cystatin C levels, check out our Cystatin C Whitepaper.

Small-dense LDL Cholesterol (sdLDL-C)

LDL Cholesterol (LDL-C) consists of two parts: the large and buoyant LDL Cholesterol and the small and dense LDL Cholesterol.  Whilst all LDL-C transports triglycerides and cholesterol to bodily tissues, their atherogensis varies according to their size.  As sdLDL-C is small and dense, they can more readily permeate the arterial wall and are more susceptible to oxidation.  Research indicates that individuals with a predominance of sdLDL-C have a 3-fold increased risk of myocardial infarction.  It has been noted that sdLDL-C carries less Cholesterol than large LDL, therefore a patient with predominately sdLDL-C particle may require nearly 70% more sdLDL-C particles to carry the same amount of cholesterol as the patient with predominately LDL-C particles.  For more information on the importance of testing sdLDL-C levels, check out our sdLDL-C Whitepaper.

These three niche in vitro diagnostics tests developed by Randox scientists can aid in reducing NHS costs due to their higher performance compared to the traditional tests.  Randox are constantly striving to improve healthcare worldwide.

For more information on the extensive range of Randox third-party in vitro diagnostic reagents, visit: https://www.randox.com/diagnostic-reagents/ or contact reagents@randox.com.

diagnostic tests

Homocysteine & Women’s Health

Homocysteine is a thio-containing amino acid produced by the intracellular demethylation of methionine.  Elevated levels of homocysteine (hyperhomocysteinemia) is more common in women than in men and is associated with a wide array of illnesses.  It has also been proven to cause several problems in women including: cardiovascular disease (CVD), colon cancer, pregnancy complications, and birth defects. 

Cardiovascular Disease

Elevated levels of circulating homocysteine correlates with an increased risk of vascular occlusion (blockage of a blood vessel).  Hyperhomocysteinemia can cause inflammation of the endothelium (thin layer of cells linking the interior blood vessels).  Failure to lower homocysteine levels can cause further inflammation of the arteries, veins, and capillaries causing atherosclerosis.  Consequently, blood and oxygen supply to tissues is reduced, increasing the risk of cardiovascular disease.  Elevated levels correlates with higher diastolic and systolic blood pressure, hypertension.  However, this correlation is stronger in women than in men.  Women with elevated levels of homocysteine have a 3-fold increased risk of CVD, whereas men have a 2-fold increased risk.

Colon Cancer

Women with hyperhomocysteinemia have an increased risk of colorectal cancer than women with lower levels.   Women who present with the highest levels of homocysteine have more than a 70% increased colorectal cancer risk.  A correlation between reduced levels of folate and increased levels of homocysteine have been found in women with colorectal adenoma.  It is recommended that women with hyperhomocysteinemia and reduced levels of folate should increase their intake of fruit and vegetables to reduce their levels of homocysteine and increase their levels of folate.

Pregnancy Complications and Birth Defects

Homocysteine levels should decline during pregnancy, however, in some cases, levels increase.  Hyperhomocysteinemia is associated with foetal neural tube defects which causes various conditions, characterised by placental vasculopathy, including pre-eclampsia, abruption, and recurrent pregnancy loss.  It has been identified that folate supplementation can half the risk of foetal neural tube defects.  One study found that hyperhomocysteinemia was associated with a 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abrupyio placentae, and intrauterine growth restriction.

Randox Homocysteine Reagent

The Randox Homocysteine assay offers a few unique features:

  • Limited interference from Bilirubin, Haemoglobin, Triglycerides, and Intralipid, producing more accurate and precise results.
  • Two-reagent format for convenience and ease of use
  • Calibrator provided with kit, simplifying the ordering process

Other features include:

  • Liquid ready-to-use reagents – for optimum user experience
  • Excellent linearity – 47. 9 μmol/L, ensuring abnormally high levels of homocysteine are detected.
  • Enzymatic method
  • Tri-level cardiac control available
Homocysteine

If you are a clinician or laboratory who are interested in running assays for women’s health, Randox offer a range of high-quality routine and niche assays including: Adiponectin, Cystatin C, Lipoprotein (a), and Zinc which can be used to diagnose conditions commonly affecting women.  These assays can be run on most automated biochemistry analysers.

Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

For more information, visit: https://www.randox.com/homocysteine or email: reagents@randox.com  


Rheumatoid Arthritis and Women’s Health

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterised by pain, swelling and stiffness in joints which commonly affects the hands, wrists and feet.  Whilst both men and women can suffer from rheumatoid arthritis, it is more commonly seen in women than men.

Rheumatoid arthritis is the most common autoimmune disease with a higher prevalence rate compared to lupus, multiple sclerosis, type 1 diabetes, Crohn’s disease and psoriasis.

(Simmons, 2013)

The incidence rates of rheumatoid arthritis differ between men and women.  The onset of RA occurs much earlier for women, for most, during their 30’s and 40’s.  In an American study, it was noted that the incidence rates peak for women around the ages of 55 to 64, compared to 75 to 84 years of age for men.

(Simmons, 2013)

As most women are diagnosed with rheumatoid arthritis in their 30’s and 40’s, a study found that the diagnosis negatively impacts both the body and mind of women, as indicated in their pain, disease activity, and quality of life scores.  This is due to women being diagnosed at a time when their burdens are the heaviest as this is the time when women are most likely to have children or are raising children combined with work and socialising.

Changes in hormone levels also impacts women.  It has been noted that before a menstrual period, women find the symptoms of rheumatoid arthritis to be more severe, but settles during their cycle.  Also, due to the changes in hormone levels during pregnancy, 50 – 60% of women with rheumatoid arthritis noticed that their symptoms improved.

The key to managing rheumatoid arthritis is to start the treatment as early as possible as it can halt or slow the disease, preventing joint damage and complications, including: osteoporosis and cardiovascular disease.  Rheumatoid arthritis increases the risk of heart attack by 60%.  To start treatment as early as possible, it is important that it is diagnosed as early as possible.

Randox offer a number of key assays for the diagnosis of rheumatoid arthritis.

Rheumatoid factor is the most routinely run test to diagnose rheumatoid arthritis as 80% of rheumatoid arthritis patients test positive for rheumatoid factor.  The Randox Rheumatoid Factor reagent offers the following benefits:

  • Wide measuring range of 6.72 – 104lU/ml for the accurate measurement of clinically important results
  • Accurate assessment of rheumatoid factor titre (calibrant standardised against primary WHO material; 1st British Standard 64/2)
  • No interference from complement C1q
  • Automated immunoturbidimetric assay
  • Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings

It has been found that complement C4 and CRP upregulation indicates the middle to late stages of rheumatoid arthritis.

The Randox Complement C4 reagent offers the following benefits:

  • Wide measuring of 3.41 – 152mg/dl for the accurate measurement of clinically significant results
  • Limited interferences from Bilirubin, Haemoglobin, Intralipids, and Triglycerides, producing more accurate results
  • Automated immunoturbidimetric assay
  • Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings

The Randox High-Sensitivity CRP reagent offers the following benefits:

  • Wide measuring of 0.477 – 10mg/l fir the accurate measurement of clinically significant results
  • Liquid ready-to-use reagents for convenience and ease of use
  • Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings

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