Positive Health Online

New Pulsed Electric Field Technology Could Allow for Less Invasive Tumour Molecular Profiling

Electroporation bears less of the negative consequences of biopsies, say TAU, IDC, Technion researchers.

Current cancer treatment courses often begin with tissue biopsies. Biopsies, however, which involve the physical resection of a small tissue sample, can lead to localized tissue injury, bleeding, inflammation, and stress, as well as increased risk of metastasis.

New technology developed by a team of researchers from Tel Aviv University (TAU), Herzliya Interdisciplinary (IDC), and Technion–Israel Institute of Technology may soon offer an alternative means of profiling tissues. The research finds that electroporation – the application of high voltage pulsed electric fields to tissues – enables minimally invasive extraction of RNA and proteins that reveal tissue-specific differential expression critical to molecular profiling.

"Our new method can enhance the information surgeons obtain from biopsy, for example," explains Prof. Alexander Golberg of TAU's Porter School of Environment and Earth Sciences, a lead author of the study. "By harvesting molecules from suspicious areas, this method enables improved diagnostics of the site and produces information pertinent to treatment decisions, including molecular biomarkers."

Research for the study was conducted by TAU graduate student Julia Sheviryov, Dr Oz Solomon of IDC, Leon Anavy of the Technion, and Prof Zohar Yakhini from IDC and the Technion. The research was published in Scientific Reports on October 31.[1]

By extracting tissue-specific molecules using a combination of high-voltage and short pulses applied to specific sites, the technology enables profiling RNA, proteins, or metabolites in tissue and tissue environments. This can improve the accuracy of tumor diagnostics, including the potential response to different therapies.

For the research, the scientists used electroporation to extract proteins and RNA from several normal human tissues, including liver tissues, and from a liver cancer model in mice. They then used advanced bioinformatics tools to demonstrate that tissue types can be distinguished by identifying specific molecules in the extracted samples.

"Further in vivo development of extraction methods based on electroporation can drive novel approaches to the molecular profiling of tumours and tumor environments, and thereby to related diagnosis practices," Prof. Golberg concludes. "Now we have a new method with which to sample tissue in vivo. We can sample molecules without extracting cells and without the risky excision of tissue parts."

The researchers now plan to develop a device for local extraction, thus enabling tumor heterogeneity mapping and the in vivo probing of tumor environment molecular composition.

References

1. Golberg, A., Sheviryov, J., Solomon, O. et al. Molecular harvesting with electroporation for tissue profiling. Sci Rep 9: 15750  https://doi.org/10.1038/s41598-019-51634-7. 2019.

https://www.nature.com/articles/s41598-019-51634-7

Source and Further Information

https://www.aftau.org/weblog-medicine--health

George Hunka ghunka@aftau.org

Jordan Isenstadt jisenstadt@marinopr.com

Fibromyalgia Patient Update – Sept 2019 – Update after 10 Months Treatment

Recovery from Fibromyalgia; CFS, Fibromyalgia & Arthritis Patient Update

Published Positive Health PH Online Issue 255 June 2019

Letter from Patient to Dr Amir

Dear Dr Amir,

It is now 10 months since I started my course of treatment with you so here is my long overdue update.

Following the initial and dramatic improvements to my health that were a result of improved breathing bought upon by wearing the first braces that you provided me the following months have seen slower but noticeable further improvements to my situation.
Having worn your braces continually for the last 10 months, I have gradually begun to feel Stronger and Stronger with much less Fibromyalgia pain and a feeling that I was beginning to feel much more myself and not a dumbed-down version of who I had been so many years before.

I finally felt ready to start reducing some of the prescription medications that my rheumatologist had prescribed me as I really felt that I no longer needed them. The following list is the drugs that I managed to STOP in the months that followed:

• Naproxen (anti inflammatory)
• Dosulepin (anti depressant)
• Zopiclone (sleeping pill)
• Hydroxychloroquine (immune suppressant)
• Ventolin inhaler (asthma)

As the summer grew nearer I was feeling brighter so we booked a week away in Wales with our daughter and grandson, this was a major milestone for me as previously my health had only allowed for very short breaks with them. I am pleased to say that despite my anxiety I managed the whole week without needing to rest and was able to enjoy the holiday so much more than on previous occasions.

I did however return home very exhausted and decided to discuss my continued lack of energy with you Dr Amir. You were adamant that a major barrier to further improvements to my health and energy levels were the strong opioid painkillers that I continued to take.

With new found enthusiasm I was determined to start reducing my Tramadol that I felt I no longer needed for pain relief. I had been taking them for 10 years so was worried about possible withdrawals and side effects so with the help of my husband and some empty pill capsules bought of the internet we started splitting the Tramadol pills into reduced doses, gradually lowering the amount of drug in each pill every few weeks. When I got it down to taking just one reduced dose pill per day I began to feel a flicker of energy inside me.

Dr Amir was again right and I was so excited to tell him that my energy was returning. I took my last Tramodol three weeks ago. I did have some withdrawal symptoms, most noticeably hot flushes and what can only be described as a strange feeling that worms were crawling underneath my skin. Not pleasant but these are now beginning to fade. I would recommend to anyone this slow method of withdrawal from using opioid pain killers.

My mind is now clearer and my emotions less dulled down, this brings a sadness that for so many years such heavy medication has been stopping much needed energy from coming through.

I am still on Morphine patches for pain relief which I intend to start reducing in the coming weeks and a low dose anti-depressant that was prescribed to relax my muscles at night. I am sure that with your continued help and as your treatment of me continues in the coming months that I will finally be free from all prescription drugs.

My visits to you continue to be the highlight of my month and I remain hopeful that your treatment has set me on the road to full recovery from serious long term health problems.

Source: M Amir <amir2647@msn.com>

Dr M Amir BDS MSc(U. London) Dental Surgeon

Cranio-dental & Skeletal Symmetry Centre

50B Lower Richmond Road, Putney, London SW151JT

Tel: 0208 780 3433

RIP Dr Bocci

With a saddened heart, I write about the loss of Dr Velio Bocci, the Father of Ozone Therapy. 

Dr Bocci pioneered the scientific foundation of a treatment that has helped millions.  Without his work, millions of people would continue to suffer.  He dedicated his intellect, passion, and life to the study of ozone therapy.

I, among countless others, have been impassioned and inspired by Dr Velio Bocci's work. 

"Really, we do not want to compete with official medicine, but only help patients to regain health."

His single minded focus was the benefit of the patient and not the prestige of politics or the enticement of money.

Dr. Bocci leaves us with a work that is not yet finished,

"We are certainly not blinded by ozone therapy but the great strides of molecular biology and gene therapy during the last decade have not yet been paralleled by comparable advances in therapeutic innovations and many unforeseen difficulties still have to be overcome"

As Dr Lamberto Re put it, "Ozone is the medicine of the future."  Dr Bocci gives us the opportunity to stand on his shoulders and make that a reality. 

Rest in peace Dr Bocci. 

Source

Micah Lowe - The Ozonaut  info@simplyo3.com

Genotyping Service to Improve Cancer Patient Treatment

by Dr Peter H Kay

There are a number of different approaches to treatment of cancer. They include the use of long standing conventional treatments of chemotherapy, surgery and radiotherapy. In recent times, newer approaches have been developed. These include immune based treatments such as the use of monoclonal antibodies, immune checkpoint therapy, CAR T cell therapy and electrochemotherapy. Interestingly, based on the understanding of why some cancers disappear without any treatment at all, the application of certain viruses that can kill cancer cells is showing promise as an exciting new approach to cancer treatment.

I offer an information clinic for cancer patients. Even though there are a number of different approaches to cancer treatment, one of the most common questions asked is "Why do some chemotherapeutic drugs help some people but harm others?”.

To explain. The effectiveness of most chemotherapeutic drugs depends on a number of factors including the inherited genetic profile of the patient as well as the genetic profile of their cancer cells.

Most chemotherapeutic drugs work by entering cancer cells that are rapidly dividing. On entry, they usually kill the cancer cell by damaging its genetic machinery. Chemotherapeutic drugs also kill rapidly dividing healthy cells. That is why there may be hair loss, gastro-intestinal and bone marrow problems following chemotherapy.

Some chemotherapeutic drugs are administered in an inactive form, as a prodrug. Inactive prodrugs are metabolized to an active form usually when they have entered the bloodstream. Other drugs are administered in an already active form. Different genetic factors are needed to optimise the effectiveness of each of these two different types of drug.

With respect to the activation of prodrugs, the body has a wide range of anti-toxin defence mechanisms. One of them, the cytochrome P450 enzyme system chemically alters and neutralises the many toxic substances that we are exposed to on a daily basis. The same detoxifying system recognises chemotherapeutic drugs (and other drugs) as toxic substances.

When prodrugs enter the bloodstream, they are broken down by members of the cytochrome P450 system. The breakdown or metabolism of a prodrug releases an active drug which can then help destroy cancer cells. Many prodrugs are activated by one of the cytochrome P450 enzyme family members called CYP2D6.

The problem is that there are four different heritable types of cytochrome P450 enzymes such as CYP2D6. Each type activates prodrugs at different rates.  They are classified as 1) poor metabolizers with little or no enzymatic activity; 2) intermediate metabolizers that metabolize drugs at a rate somewhere between the poor and extensive metabolizers; 3) extensive metabolizers with normal enzymatic activity and 4) ultra-rapid metabolizers. People who inherit an ultra-rapid metabolizing enzyme type have greater than normal enzyme activity.

Most prodrugs are designed to work optimally when administered to people who are extensive metabolizers, those with normal enzyme activity.

Patients who are poor metabolizers may not benefit from administration of chemotherapeutic prodrugs because too little of the active drug is generated. By contrast, those who are ultra-rapid metabolizers may suffer unwanted side effects because of the formation of too much active drug.

With regard to administration of active chemotherapeutic drugs, those who are ultra-rapid metabolizers may remove the active drug too quickly before any beneficial effect can be achieved. On the other hand, serious side effects may be caused in poor or intermediate metabolizers because cell destroying drug activity is maintained for too long.

Some commonly used active chemotherapeutic drugs within the fluoropyrimidine group may cause serious side effects or even death when administered to patients who have inherited a particular form of a gene called DPYD.

The effectiveness and safety of any particular drug may be pre-determined by reference to genetic typing of appropriate cytochrome P450 encoding genes, particularly that which encodes CYP2D6 as well as the DPYD gene.

The body has another important cellular protection mechanism, toxic substances can be pumped out of or effluxed from a cell by a series of molecules encoded by multi-drug resistance genes.

Many cancer cells develop increased activity of their multi-drug resistance genes. When they do, chemotherapy drugs are rendered harmless because they are pumped out of the cancer cell before they can be of benefit. Multi-drug resistance is considered the main obstacle limiting the success of anti-cancer chemotherapy because almost half of all cancers may develop resistance to commonly used anti-cancer drugs.

Intensive work is underway to find ways of combating development of cancer cell specific multi-drug resistance. Interestingly, scientists at the Institute of Zoology, Beijing have recently discovered that the anti-parasitic drug ivermectin may help to reduce multi-drug resistance in cancer cells. Drug entry into cancer cells may also be helped by exposing tumours to pulses of electricity. This treatment is called electrochemotherapy.

Clearly, for improvement of patient safety, there is a need for the availability of standard laboratory tests to determine the genetic status of genes that encode factors that determine whether certain chemotherapeutic drugs are likely to help or harm the patient. I would like to hear from anyone interested in establishment of this much needed service.

I also offer talks, workshops and consultations on these and many other relevant matters for cancer patients, health carers, students of science and other interested parties.

Further Information

Dr Peter H Kay  may be contacted at peterhkay@gmail.com or telephone 01772 691 443 for more information.

Simple Blood Test Could Better Predict Kidney Disease and Cardiovascular Risk

Researchers have found a better way to test for kidney disease using a simple blood test that is affordable and although it is available in NHS laboratories is not yet widely used.

In a study, published today in Nature Medicine[1] and led by the University of Glasgow, researchers have highlighted that a simple blood test - which could easily be adopted routinely in the NHS – is a better way of measuring both kidney and cardiovascular disease risk, as it offers a more precise diagnosis and could lead to better patient outcomes.

Chronic kidney disease characterized by gradual loss of kidney function over time, is common, affecting around 10% of the population. It is also associated with premature cardiovascular disease and mortality and more rarely progresses to the point where patients need dialysis or a kidney transplant. 

Amongst patients with Chronic Kidney Disease reducing the risk of cardiovascular disease relies on accurate diagnosis, recognition of risk and early identification and treatment of risk factors.

Dr Jennifer Lees, from the University of Glasgow’s Institute of Cardiovascular and Medical Sciences, said: “Our study emphasises how important renal function is for our general health, given that suboptimal renal function can lead to an increased risk of a cardiovascular event.

“Our findings indicate that patients would benefit from the added predictive value of using a test called the cystatin C test. We would hope to see it adopted as the primary method for diagnosis of Chronic Kidney Disease – particularly for those patients with cardiovascular disease risk factors such as diabetes, hypertension or obesity.”

Paddy Mark, Professor of Nephrology, added: “For a relatively low cost – about £2.50 per test – doctors can use this test to gain a much clearer understanding of a patient’s kidney health, as well as cardiovascular risk. With this knowledge, doctors can identify and treat risk factors earlier and, hopefully, save more lives in the process.”

The study used data from over 400,000 patients in the UK Biobank and looked at three different kidney function tests for eGFR – estimated glomerular filtration rate – to determine which was the most clinically informative for predicting cardiovascular disease and mortality.

Using statistical models to compare the results, the researchers determined the cystatin C formula to be the best at predicting cardiovascular risk as compared to the traditionally-used serum creatinine method. 

Cystatin C testing has been available in the NHS for over 10 years, and has a number of potential advantages over serum creatinine and is thought to be a more sensitive measure to estimate kidney function.  However, cystatin C is around 10 times more expensive than serum creatinine at £2.50 per test, compared with £0.25 for serum creatinine. Currently cystatin c is only used in highly specialized settings and is not available in all hospitals.

Dr Lees added: “Despite being recommended by the National Institute for Health and Care Excellence (NICE), measurement of cystatin C has not been widely adopted in clinical practice, presumably relating to uncertainty around the added value of a more expensive test.

“We hope our study shows that the adoption of this simple test would provide doctors with a precision medicine diagnosis for kidney disease and cardiovascular risk.”

The study, ‘Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease’, is published in Nature Medicine.[1] The work was funded by Chest, Heart and Stroke Association Scotland, The British Heart Foundation and Kidney Research UK.

1. Lees JS, Welsh, CE, Celis-Morales CA et al. Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nat Med 25, 1753–1760. doi:10.1038/s41591-019-0627-8. 2019. https://www.nature.com/articles/s41591-019-0627-8#citeas

Further Information

For more information contact Elizabeth McMeekin or Ali Howard in the University of Glasgow Communications and Public Affairs Office on 0141 330 4831 or 0141 330 6557; or email Elizabeth.mcmeekin@glasgow.ac.uk  or ali.howard@glasgow.ac.uk 

Exotic Tick-borne Parasite Detected in UK

Scientists have detected an exotic tick-borne parasite within sheep in the North of Scotland, according to a new study.

The research, by scientists at the University of Glasgow’s School of Veterinary Medicine and Institute of Biodiversity, Animal Health and Comparative Medicine, was published today in Emerging Infectious Diseases, the journal of the Centre for Disease Control (CDC).[1] The study reports that this is the first time this organism, called Babesia venatorum (B. venatorum), has been identified in animals in the UK, and the first time it has been found in sheep anywhere in the world.

The identification of this parasite in the UK raises concerns for European public health and farming policy, according to the study’s authors. Although some evidence suggests this parasite may be more virulent than the species of Babesia usually found in the UK, the risk of people contracting this infection is believed to be low.

The parasite causes babesiosis, an economically important tick-transmitted animal disease, which is recognised as an emerging infection in humans. In the last two decades, the parasite has been recorded extensively in the Far East (China) and also in Europe with two confirmed human infections in Italy. Fortunately, babesiosis is treatable in most cases, although this depends on rapid and accurate diagnosis.

 To conduct the study, scientists collected blood from sheep, cattle and deer in the northeast of Scotland, in areas where tick-borne diseases have previously been detected. DNA from the B. venatorum parasite was detected in the blood of a large number of sheep, which were not showing any signs of disease, and which therefore can be considered as carrier animals.

 The scientists believe that B. venatorum may have been carried by migratory birds coming to the UK from Scandinavia, where the parasite has previously been found in ticks collected from the environment and migratory birds.

Dr Willie Weir, Senior University Clinician in Veterinary Pathology, Public Health & Disease Investigation, said: “The presence of B. venatorum in the UK represents a new risk to humans working, living, or hiking in areas with infected ticks and livestock, particularly sheep. Although we believe the threat to humans to be low, nevertheless local health and veterinary professionals will need to be aware of the disease if the health risk from tick-borne disease in the UK is to be fully understood.

“Our findings follow the recent report of the detection of tick-borne encephalitis virus in the UK. Taken together, these findings signify a change in the landscape of tick-borne pathogens in the UK, and the underlying causes for this need to be investigated.”

First author Dr Alex Gray added: “Our study reveals that sheep can be a natural host for B. venatorum in the UK, which is surprising since we believed roe deer to be the main mammalian host for this parasite in Europe.

“Given our findings, ongoing active surveillance of this parasite in UK livestock would be useful to fully understand the prevalence and transmission of the disease, as such information may be critical for controlling the spread of babesiosis. As sheep are routinely transported large distances, including across international borders, we would also suggest the role that livestock play in transmission of the B. venatorum parasite in continental Europe be re-assessed.”

The paper, ‘Discovery of sheep as a host species for zoonotic Babesia venatorum in the United Kingdom’ is published in the December edition of Emerging Infectious Disease. The work was funded by The Scottish Government’s Strategic Partnership for Animal Science Excellence (SPASE).

A link to the study can be found here https://wwwnc.cdc.gov/eid/article/25/12/19-0459_article

Reference

1. Gray, A., Capewell, P., Loney, C., Katzer, F., Shiels, B. R., & Weir, W. Sheep as Host Species for Zoonotic Babesia venatorum, United Kingdom. Emerging Infectious Diseases, 25(12), 2257-2260. https://dx.doi.org/10.3201/eid2512.190459. 2019. https://wwwnc.cdc.gov/eid/article/25/12/19-0459_article

Further Information

For more information contact Elizabeth McMeekin or Ali Howard in the University of Glasgow Communications and Public Affairs Office on Tel: 0141 330 4831 or 0141 330 6557; or email Elizabeth.mcmeekin@glasgow.ac.uk  or ali.howard@glasgow.ac.uk