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A Blood Test Can Predict Dementia. Trouble Is, There’s No Cure

Nobel prizewinner Koichi Tanaka says the predictive blood test for Alzheimer’s disease he and colleagues spent almost a decade developing is a double-edged sword.

Without medications to stave off the memory-robbing condition, identifying those at risk will do nothing to ease the dementia burden and may fuel anxiety. But used to identify the best patients to enroll in drug studies, the minimally invasive exam could speed the development of therapies for the 152 million people predicted to develop the illness by 2050.

 

“We must be cautious on how the test is used because there’s no curative treatment,” Tanaka said in an interview at Kyoto, Japan-based Shimadzu Corp., where he’s worked for 36 years. The 59-year-old engineer, who shared the Nobel for chemistry in 2002, said he hopes the test he helped pioneer will one day be administered routinely, but right now it belongs in the hands of drug developers and research laboratories.

 
 

More than a century after the telltale signs of Alzheimer’s were first seen under a microscope, and billions of dollars in research spending by Roche Holding AGEli Lilly & Co.Eisai Co. and other companies, there’s still no drug slow down the disease.

 

In the absence of medical breakthroughs, the worldwide cost of dementia is projected double to $2 trillion by 2030.

 

Nature Study

“There are many reasons why drugmakers have failed to develop a cure for Alzheimer’s disease, but it’s too late to start treatment when patients already show symptoms,” Tanaka said.

In a study published in Nature in January last year, Tanaka and colleagues showed it was possible to use a novel biomarker discovered by his lab to accurately quantify minute traces of amyloid-beta from a teaspoonful of blood, and gauge the progression of Alzheimer’s — allowing identification of people likely to develop dementia over the coming decades.

Previously, the brain changes that occur long before Alzheimer’s symptoms appear could only be reliably assessed by magnetic resonance imaging (MRI) and positron-emission tomography (PET) scans, and from measuring amyloid and another errant protein called tau in spinal cord fluid — methods that are expensive and, in the case of a spinal tap, invasive.

“Our finding overturned the common belief that it wouldn’t be possible to estimate amyloid accumulation in the brain from blood,” Tanaka said. “We’re now being chased by others, and the competition is intensifying.”

Roche, Quanterix

About a dozen companies and research groups from around the world, including Roche, Spain’s Araclon Biotech SL, and Lexington, Massachusetts-based Quanterix Corp., are pursuing blood-based diagnostic tools for Alzheimer’s and other neurodegenerative diseases.

“These blood tests are very important to that aim of trying to get these groups identified and ready to go into trials, and make them faster and less expensive,” said Christopher Rowe, a neurologist who heads molecular imaging research at the Austin Hospital in Melbourne. “That, in turn, is the greatest hope for having a significant impact on the epidemic.”

 

Risky Endeavor

Estimated cost of developing a drug through to regulatory approval

The global Alzheimer’s disease diagnostics and therapeutics market is predicted to reach $11.1 billion in 2024 from $7.5 billion last year, ResearchAndMarkets.com said in March.

 
 

‘Exceptional Accuracy’

“You really get exceptional accuracy,” said Bateman, whose lab studies the causes, diagnosis and treatments of Alzheimer’s disease. “I could see that easily becoming a clinical standard.”

Shimadzu Corp.'s Nobel-winning Researcher Koichi Tanaka Interview

Shimadzu’s AXIMA series mass spectrometer.

Photographer: Shoko Takayasu/Bloomberg

Both the Shimadzu and Washington University groups use an analytical technique called mass spectrometry that can search for a particular compound based on its specific molecular weight and charge. The method was found to be 90% accurate when it was checked against brain scans, Tanaka and colleagues said in their Nature paper.

Tanaka likens the approach to fishing with bait that only a specific fish will take. It enabled him to more precisely quantify amyloid in blood than an older, antibody-based method, he said.

New digital technology has bolstered the antibody-based test, with Quanterix using it to detect the errant proteins associated with the start of Alzheimer’s disease, as well as neurofilament light chain — a marker of neurological injury that can be elevated by conditions including concussion, Parkinson’s and multiple sclerosis.

“There’s an incredible opportunity to transform brain health by understanding your neuro baseline,” said Kevin Hrusovsky, Quanterix’s chief executive officer.

‘Game-Changing’

Several drugmakers are trying to get tests for neurofilament light chain validated clinically as a complementary diagnostic tool because they will enable patients’ responses to medications to be monitored in real time, providing an early signal of efficacy, Hrusovsky said. “There’s a lot of evidence that this is going to be game-changing,” he said.

Roche is evaluating the use of Elecsys, which tests cerebrospinal fluid for signs of Alzheimer’s, in blood plasma, the Swiss company said in an emailed response to questions.

Shimadzu Corp.'s Nobel-winning Researcher Koichi Tanaka Interview

Tanaka is a senior fellow at Shimadzu.

Photographer: Shoko Takayasu/Bloomberg

Shimadzu finished analyzing amyloid levels in blood-serum samples from 2,000 patients in March, Tanaka said. The company is preparing to offer the service in the U.S. this year before extending it to Europe and China.

“One thing we are looking into is running prospective cohort studies targeting people who have started to build up amyloid in the brain and see whether anything — food, exercise — can intervene to slow the progression of the disease,” the Nobel laureate said. “There are many things to be done.”

— With assistance by Jason Gale, and Tim Loh

HOW D’OXYVA CAN HELP?

Breathing in additional oxygen improves the function of blood vessels in the brains of people with chronic obstructive pulmonary disease (COPD), according to research published in Experimental Physiology [published online July 5, 2018]. Exp Physiol. doi: 10.1113/EP086994.].  The study revealed that possibly because of lower brain oxygen levels as a result of problems with blood supply from brain blood vessels, patients are at higher risk of dementia. 

Another research published in the Journal of Alzheimer’s & Dementia says improving cerebral microcirculation and metabolism leads to the regression of dementia and cognitive impairment and causes long-term ALZHEIMER’S DISEASE remission. https://www.alzheimersanddementia.com/article/S1552-5260(16)31871-4/fulltext

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation and oxygenation. Based on years of experience, D’OXYVA has continued developing microcirculation therapy. This process, unique to D’OXYVA, has demonstrated triggering protective physiological functions in the body: vasodilation and vasoconstrictions in the vessels, catalyzing vessel structure growth (angiogenesis), autoregulation of local blood supply in tissues and organs, neuroreceptor signaling in the brain and balancing blood pH, among other critical functions.

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Study of Microcirculation of Patients with Varicose Veins of Lower Limbs

Abstract

Varicose veins of lower limbs have always caused, because of their rate, highest social spendings. Those patients who have trophic disturbances often need surgical treatment even after surgical intervention. This condition becomes worse in Southern Europe countries because of environmental and climatic factors.

INTRODUCTION

Varicose veins of lower limbs have always caused, because of their rate,highest social spendings. Those patients
who have trophic disturbances often need surgical treatment even after surgical intervention. This condition becomes worse in Southern Europe countries because of
environmental and climatic factors.
It is therefore necessary to improve diagnostic methods in order to prevent trophic disturbances.
In order to reach this target, our Institute studies all patients affected by varicose disease not only by doppler
c.w. but also by microcirculatory methods, such as Videocapillaroscopy and Reflected Light Rheography on medial malleolus.

MATERIALS AND METHODS

Thirty patients (24 females and 4 males) suffering from varicose veins of lower limbs at 2nd or 3rd stage of Widmer
classification, were studied by Reflected Light Rheography and Videocapillaroscopy on medial malleolus of both legs.
In order to avoid any interference, capillaroscopy was ever made before RLR; in the same way, no drugsduring the
period of study were administered. In the patients with only one affected leg, the other leg gave useful comparison parameters.

RESULTS

In the group of 30 patients the following parameters were evaluated: Venous network, refilling time (TO), venous drain capability (dr), capillaries density and morphology. About rheographic parameters we found TO equal to 12+-3 seconds and dr equal to 100+-50 mV (mean values). In the group of patients at 2nd Widmer stage, TO was equal to 16+-3 seconds and dr was equal to the patients at 3d Widmer stage TO respectively, equal to 8+-2 seconds About capillaroscopic parameters, capillaries density in all subjects; formation” pictures, espectively, (13,3%) patients.

CONCLUSIONS

The study of microcirculation by Capillaroscopy and Rheography, in the patients suffering from varicose veins of lower limbs, was with no doubt useful to demonstrate that any stage of venous disorders causes different microcirculatory alterations. In fact, we found “”halo formation· pictures in patients with more pathological rheographic parameters (TO less than 10 seconds) and nearly all these patients suffered from varicose disease at 3rd stage of Widmer classification. Furthermore, microcirculatory alterations were more evident in patients with trophic disturbances and elder venous disease.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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How does transdermal non-invasive CO2 infusion at the thumb cause improved blood circulation and cellular O2 levels in the foot?

How does transdermal non-invasive CO2 infusion at the thumb cause improved blood circulation and cellular O2 levels in the foot?

ABOUT THE AUTHOR

Judy Delp Ph.D.

Job Description

Professor of Biomedical Sciences

 

Education

B.S. Rockhurst University, Kansas City, Missouri

Ph.D. University of Missouri

 

Memberships

American Physiological Society

American Microcirculatory Society

American Heart Association

Toriyama et al.17 studied the effect of CO2 bathing in 83 limbs with critical ischemia and achieved limb salvage in 83% without surgery. They concluded that peripheral vasodilation from CO2 bathing resulted from an increased parasympathetic and decreased sympathetic activity. In the current study, treatment with transdermal CO2 in a localized area produced a sustained, remote vasodilation, and a lowering of systemic blood pressure.
 
These findings share some similarity with the hemodynamic changes that occur following an acute bout of exercise, in which both neural and vascular components contribute to a sustained decrease in vascular resistance and blood pressure that persists after cessation of exercise18. In the current study, the period of sustained vasodilation seen in response to transdermal CO2 was heightened in diabetic patients.
 
Interestingly, in hypertensive individuals, the period of post-exercise hypotension is of greater magnitude and duration as compared to that of normotensive individuals 18, 19. Paradoxically, the current findings in diabetic patients exposed to transdermal CO2 as well as previous findings in hypertensive patients post-exercise, imply that sensitivity to signals that mediate these cardiovascular responses increases in patients with pre-existing cardiovascular dysfunction19.
 
A sustained decrease in systolic blood pressure occurs post-exercise and here, following application of transdermal CO2, suggesting that neural mechanisms contribute to the observed reduction in systemic vascular resistance. The roles of efferent sympathetic nerve activity18-20, afferent nerve activity from muscle 21-24, and the baroreceptor reflex20, 23 in mediating post-exercise hypotension remain controversial.
 
Neural mechanism(s) could contribute to changes in skin SPP and systolic blood pressure induced by exposure to transdermal CO2. Future studies will need to monitor heart rate, heart rate variability, and sympathetic nerve activity during and after transdermal CO2 in order to more fully assess the role of the autonomic nervous system in mediating the sustained increases in SPP and systolic blood pressure reported in this initial study.
 
Vascular conductance increases in both active muscle and inactive vascular beds following a bout of dynamic exercise 25, 26, suggesting that circulating factors contribute to this period of sustained systemic vasodilation. Vasodilation occuring independently of neural regulation constitutes more than 50% of the increase in systemic vascular conductance that occurs post-exercise; however, the mechanisms that underlie the post-exercise vasodilation have remained elusive.
 
Studies that have employed blockade of nitric oxide or evaluation of circulating nitric oxide metabolites have shown that the post-exercise vasodilatory response does not rely on circulating nitric oxide availability27, 28. A recent study by New and colleagues28 indicates that the nadir of post-exercise hypotension coincides with the peak of appearance of lipid hydroperoxides in venous blood, suggesting that reactive oxygen species with known vasodilatory properties29-32 contribute to the exercise-induced decrease in systemic vascular resistance. In the current study, transdermal CO2 was applied to the thumb, and a significant increase in SPP was measured at the toe.
 
Thus, a similar circulating vasodilatory stimulus may contribute to the remote, sustained vasodilation created by local transdermal application of CO2. Further investigations will need to focus on the identification of the mechanisms involved in both the local and remote factors that contribute to the sustained hemodynamic changes produced by exposure of the skin to CO2.
 
Recently, studies have documented that episodes of brief, non-damaging ischemia occurring in a tissue can induce systemic protection against ischemia-reperfusion injury in a remote organ. This phenomenon, termed remote ischemic conditioning, has been demonstrated to confer protection against ischemic events in the myocardium33-35, brain36, and kidney37, 38.
 
Although shown to be effective in various clinical and pre-clinical models 34, 35, 38-40, the mechanism(s) of remote protection have not been clearly identified. Both neural and humoral mechanisms have been proposed to contribute to the protection against ischemic damage afforded by remote ischemic conditioning38, 39, 41-43.
 
Basalay et al.41 have shown that when remote ischemic conditioning is applied before induction of myocardial ischemia, sensory nerves and recruitment of a parasympathetic neural pathway are involved in reduction of infarct size. In contrast, application of remote ischemic conditioning after myocardial ischemia also afforded protection against infarction, but was not altered by vagotomy or peripheral denervation41.
 
Remote ischemic conditioning has also been demonstrated to improve perfusion of transplanted kidneys, suggesting that remote conditioning confers protection that does not rely on intact neural circuitry38. Recently, Michelsen and colleagues42 have demonstrated that dialysate of human plasma from subjects who underwent either ischemic preconditioning or exercise preconditioning reduced infarct size in rabbit hearts, indicating that release of a humoral factor, possibly acting on opioid receptors, contributes to the cardioprotective effects of ischemic and exercise preconditioning.
 
Other reports in the literature have also shown evidence of a humoral substances that mediate protection against ischemia when remote ischemic conditioning is applied; however, these substance(s) remain to be identified. Application of transdermal CO2 produces a remote vasodilation that may be mediated through release of a circulating humoral agent.
 
Future investigations will need to focus on assessment of plasma samples during and following transdermal CO2 application.
This pilot study demonstrated an increase in measures of remote skin microvascular function with D’OXYVA, a simple commercially-available device to deliver transdermal CO2. The effects of the treatment were evident at all periods up to and including the last test period, 240 minutes post-exposure.
 
Although the sample size was small in this study, a clear increase in SPP and SPP/SBP ratio and a decrease in SBP and DBP continued for 4 hours post-treatment. The differences in skin perfusion and blood pressure responses detected between diabetic and non-diabetic subjects will require further examination in larger studies.
 
Click below to access Prof. Judy Delp’s Presentation on Transdermal Delivery of Carbon Dioxide Boosts Microcirculation.
 

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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“People are dying”: Diabetics rationing insulin amid rising drug prices

Drug manufacturers were grilled Wednesday about the skyrocketing price of insulin, which has doubled in the last five years and led some patients to ration the life-saving drug. One study finds the underuse of insulin could affect nearly 40 million people with diabetes by 2030.

“Nobody cared or nobody understood that without this next vial of insulin, I wouldn’t live to see another week,” said 28-year-old Kristen Whitney Daniels.

She started rationing her insulin after she was kicked off her parents’ insurance plan two years ago.

“I can’t really explain how isolating and how terrifying it is,” she said.

She’s now a patient at the Yale Diabetes Center, where a recent Journal of American Medical Association study found one in four patients reported “cost-related underuse.” Dr. Kasia Lipska treats patients at the clinic, and was the study’s lead author. She testified on Capitol Hill last week.

  • Woman says her son couldn’t afford his insulin – now he’s dead
  • Eli Lilly rolling out half-price insulin. Diabetics say it’s not enough

“This vial of insulin cost just $21 when it first came on the market in 1996. It now costs $275,” she said.

Some drug makers are already reacting to the outrage. On Wednesday, Sanofi announced it will cut the price of insulin for uninsured patients and those who pay cash to $99 per month. But that doesn’t eliminate advocate concerns.

“People are dying from lack of access to a drug that has been around for almost a century. I think it’s unconscionable,” Lipska said.

Insulin manufacturers told CBS News they’ve taken steps to address prices, including offering free medication to people who quality.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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Impaired Tissue Perfusion

What is Impaired Tissue Perfusion?

Ineffective tissue perfusion is a state in which an individual has a decrease in oxygen resulting in failure to nourish the tissues at the capillary level.

Tissue perfusion is a critical parameter for tissue survival and function, and both relative and absolute perfusion assessments are highly relevant for both diagnosis and evaluation of the therapy response.

Sometimes situations occur where this exchange of gases between the blood and the cells is disrupted, meaning the cells (and ultimately the tissues and organs) stop getting adequate oxygen supply. The body can’t function without oxygen, so obviously this is a problem. When tissues don’t receive enough oxygen through the capillaries, this is called ineffective tissue perfusion.

Many conditions can disrupt the exchange of oxygen and carbon dioxide, but diabetes, obesity, anemia, high blood pressure, and coronary artery disease are some of the more common risk factors that can cause ineffective tissue perfusion. We can further classify the type of ineffective tissue perfusion based on the part of the body affected. For example, there’s renal (meaning kidney), cerebral (meaning brain), cardiopulmonary (meaning heart and lungs), gastrointestinal (meaning digestive tract), and peripheral (meaning affecting the extremities) ineffective tissue perfusion.

Common Risk Factors

Small arteries in diabetic subjects, whether hypertensive or normotensive, exhibit severe hypertrophic remodeling, and histological analysis of skeletal muscle biopsy samples reveals capillary rarefaction in subjects with type 2 diabetes. Histological capillary density is inversely related to fasting plasma glucose and fasting insulin levels and positively related to insulin sensitivity in nondiabetic individuals. Microvascular permeability to large molecules such as albumin is increased in diabetes, a process that is linked to hyperglycemia and ROS

In humans, coronary flow reserve is significantly lower in obese than in nonobese subjects, and capillary recruitment is reduced in nondiabetic obese individuals compared with lean control subjects. Even in a sample of healthy children (11 to 14 years of age), microvascular function was negatively correlated with adiposity. Thus, obesity appears to have an independent effect on microvascular function.

Coronary flow reserve decreases progressively with age in subjects without coronary artery disease, from approximately 4 at 30 years to 3 at 65 years of age, largely due to increased basal myocardial blood flow.

Tobacco smoking acutely impairs capillary recruitment, and thus hyperemic blood flow increases in skin and coronary flow reserve is reduced in established smokers. Coronary flow reserve in smokers can be improved by administration of antioxidant vitamin C, which suggests that smoking-related oxidative stress is an important mechanism.

Individuals with hypercholesterolemia without coronary artery disease have reduced coronary flow reserve, and coronary flow reserve is inversely correlated with LDL cholesterol. A reduction in coronary flow reserve can be detected in healthy young men (mean age 31 years) with familial hypercholesterolemia, which suggests that microvascular abnormality is detectable early in the atherosclerotic process.

Given the relationships between individual cardiovascular risk factors with measures of microvascular status, it is not surprising that the overall Framingham risk score is inversely correlated with skin capillary recruitment, maximal skin capillary density, and coronary flow reserve.

Defining Characteristics

Ineffective Tissue Perfusion is characterized by the following signs and symptoms:

  • Abnormal arterial blood gases
  • Altered respiratory rate outside of acceptable parameters
  • Bronchospasms
  • Capillary refill >3 seconds
  • Chest pain
  • Chest retraction
  • Dyspnea
  • Dysrhythmias
  • Nasal flaring
  • Sense of “impending doom”
  • Use of accessory muscles
  • Altered mental status
  • Behavioral changes
  • Changes in motor response
  • Changes in pupillary reactions
  • Difficult in swallowing
  • Extremity weakness or paralysis
  • Speech abnormalities
  • Abdominal distention
  • Abdominal pain or tenderness
  • Hypoactive or absent bowel sounds
  • Nausea
  • Altered sensations
  • Altered skin characteristics (hair, nails, moisture)
  • Cold extremities
  • Dependent, blue, or purple skin color
  • Diminished arterial pulsations
  • Edema
  • Positive Homan’s sign
  • Skin discolorations
  • Skin temperature changes
  • Skin color pale on elevation, color does not return on lowering the leg
  • Slow healing of lesions
  • Weak or absent pulses
  • Altered blood pressure outside of acceptable parameters
  • Elevation in BUN/creatinine ratio
  • Hematuria
  • Oliguria or anuria

Damage, Complications, and Prognosis

Microvascular abnormalities that lead to impaired tissue perfusion appear to represent a generalized condition that affects multiple tissues and organs. For example, in hypertension, coronary flow reserve is correlated with the media:lumen ratios of small arteries in biopsies of subcutaneous fat. Dilatation of venules in the retina independently predicts progression of cerebral small-vessel disease, and in diabetes, reduced coronary flow reserve predicts the occurrence of retinopathy.

Impaired tissue perfusion may be involved in target-organ damage and complications that involve several vascular beds. For the coronary microcirculation, an obvious example associated with both hypertension and diabetes is the occurrence of myocardial ischemia and angina in the presence of angioscopically normal epicardial coronary arteries, also known as cardiac syndrome X. Impaired myocardial perfusion may also be an important factor in the development of hypertensive heart failure and may lead to localized ischemia and disturbed patterns of electrical activity that constitute a substrate for serious arrhythmias. In the case of renal disease, glomerular and peritubular capillary rarefaction has been noted in different animal models and in human progressive renal disease, and it precedes the development of impaired perfusion and chronic hypoxia. It has been suggested that hypoxia may be the common factor linking many forms of progressive renal disease.

Microvascular abnormality is also a predictor of prognosis. In hypertensive patients, the media:lumen ratio of peripheral small arteries is a strong independent predictor of cardiovascular events. Among individuals with normal or minimally diseased coronary arteries, reduced coronary flow reserve is an independent predictor of cardiovascular events within the next decade. Finally, in patients with chest pain and angiographically normal arteries, coronary flow reserve <3 is associated with a 6-fold increase in all-cause mortality risk compared with coronary flow reserve >3 during 8.5 years of follow-up.

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Did you know when used in a regimen, D`OXYVA users have reported a number of health and beauty benefits?

doxyva benefits

OPTIMIZE BLOOD CIRCULATION FOR A WIDE VARIETY OF SIGNIFICANT OUTCOMES

D’OXYVA® (deoxyhemoglobin vasodilator) in various clinical trials has validated leading independent research results and demonstrated above-average results in improving a host of physiological functions at the same time.

People using D’OXYVA® have recorded significant improvements in cardiovascular activity leading to much improved physical activity. As part of a healthy lifestyle, D’OXYVA may help significantly reduce the risk of high blood pressure, hypertension, cholesterol, and diabetes in just two or three months, with an average use of 5 minutes a day and 5 times a week.

Poor circulation is a gateway for a litany of ailments: slow healing, depression, poor complexion, sores, slow metabolism, and more.

D’OXYVA significantly improves sustained oxygen-rich microcirculatory blood flow locally and throughout the body. Its patented method of fully non-invasive, painless, and harmless transdermal delivery is unique only to D’OXYVA.

When used daily, D’OXYVA users have reported a number of health and beauty benefits, including but not limited to:

  • Relief from symptoms of microvascular complications
  • Significantly increased cardiac function, physical fitness, endurance and strength, muscle size, body tone, faster recovery from sports injuries and surgical trauma
  • Improved self-esteem via promoting healthy and radiant skin, complexion, dry skin relief, and acne reduction
  • Significant reduction in downtime from other skin treatments and cosmetic procedures when used in combination, reduction in the appearance of scars, cellulite, fat, spider veins and stretch marks
  • Promoting and maintaining a healthy weight, improving general mobility, deeper, more restful sleep
  • Significant improvement of mental acuity; concentration, problem solving, multitasking, eye-hand coordination, heightened stamina, energy, and focus while managing stress
  • Improved vitals across the board during checkups with zero adverse event reports after years of regular use by people with various health, demographic, and ethnic backgrounds

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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3 Reasons Why Most Wounds Won’t Heal

There are several connected causes for non-healing wounds.

According to figures from the U.S. Centers for Disease Control and Prevention, chronic wounds–injuries that have yet to heal after six weeks–affect some 5.7 American adults. There are many reasons for these non-healing wounds, and understanding each cause is vital to implementing the most effective wound care regimen possible.

 

Here are three of the more frequent explanations for why many wounds just won’t heal:

 

Poor circulation

As Johns Hopkins Medical School pointed out, blood is perhaps the most important component of the entire wound healing process. When an injury occurs, it’s the blood that transports cells to the wound site, which begin rebuilding veins and other important tissue structures.

When you have poor circulation, blood cannot move around as quickly, and as a result, wounds take much longer to begin healing. According to Healthline, there are several medical conditions that cause poor circulation, including varicose veins, obesity and chronic ailments like diabetes, peripheral artery disease and Raynaud’s disease. Fortunately, there are just as many ways to improve circulation, like frequent exercise and elevating wounds or limbs in general.

 

Fluid buildup

According to the Mayo Clinic, edema occurs when fluid leaks from blood vessels, causing these secretions to accumulate in nearby tissue. The result is a large bump or nodule that is painful and sometimes prone to infection. Edema is usually the result of a number of medications, including several drug therapies geared toward diabetes. Edema can also occur due to a reaction to steroids, anti-inflammatory drugs and even estrogen supplements.

Other than being uncomfortable, edema can wreak havoc on the wound-healing process. Due to fluid buildup, the blood vessels and tissue become rigid and immovable, greatly restricting blood flow. This compression cycle can also kill skin patches, which could lead to ulcers.


Infection

As a rule, infections can be quite traumatic to the host. Perhaps the biggest effect–one that might surprise some people–is that infections can all but halt the wound healing process. According to St. Luke’s Clinic, an average infection has a number of methods for preventing healthy tissue regeneration.

For instance, some infections can extend the length of the inflammatory phase, and that can halt the subsequent stages of wound healing. Additionally, there are strains that can interfere with clotting mechanisms, which in turn causes wounds to continue bleeding.

According to a 2010 study from the Journal of Dental Research, the two most damaging strains of bacteria are pseudomonas aeruginosa and staphylococcus.

When it comes to handling chronic wounds, patients need advanced wound care products to prevent infection and create a sustainable healing environment; that’s why so many patients turn to Advanced Tissue when they experience most chronic wounds.

As the nation’s leader in the delivery of specialized wound care supplies, Advanced Tissue ships supplies to individuals at home and in long-term care facilities.

 


Reference: https://advancedtissue.com/2016/02/3-reasons-why-most-wounds-wont-heal/

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Anesthesia, Microcirculation, and Wound Repair in Aging

Abstract

Age-related changes in skin contribute to poor wound healing after surgical procedures. Changes in skin with age include a decline in thickness and composition, a decrease in the number of most cell types, and diminished microcirculation, the process that provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin; however, perioperative management can be modified to minimize damage to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension are examples of adjustable variables that support microcirculation. Anesthetic agents influence microcirculation in a number of ways, including cardiac output, arterial pressure, and local microvascular changes. The authors examined the role of anesthetic management in optimizing microcirculation and potentially improving postoperative wound repair in older persons.

Aged skin is at increased risk of poor postoperative wound healing. Changes in the cutaneous microcirculation with aging contribute to this risk. This review examines the role of anesthesia management in microcirculatory function.

SURGICAL wound repair is a major problem in the older population, who are at increased risk of wound dehiscence and infection. As a specific example, surgical site infections (SSIs) are common (approximately 500,000 cases annually in the United States), lead to worse patient outcome (patients who develop SSI are twice as likely to die), and are an enormous economic burden (1–10 billion dollars annually). Many factors contribute to age-related changes in skin5 and subsequent vulnerability to impaired wound healing and infection. Changes in skin with age (fig. 1) include a decline in epidermal and dermal thickness and composition, as well as a decrease in the number of most resident cell types. The dermal–epidermal junction is flattened and the microcirculation is diminished. The latter is defined as blood flow through arterioles, capillaries, and venules and is the key system that affects the entire skin surface. In the aging patient, the microcirculation in the skin is reduced by 40% between the ages of 20 and 70 yr. The microcirculation provides tissue perfusion, fluid hemostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause disruption of the microcirculation in the skin as manifested by local edema resulting from vasodilation and increased vascular permeability.

Fig. 1.
Numerous changes in skin with age contribute to impaired wound healing.

 

Perioperative management can be modified to optimize the microcirculation. Measures that support the microcirculation include careful use of fluids, normothermia, pain control, and smoking cessation. Factors that can be influenced by intraoperative management (judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension) have been suggested to be beneficial as well. Most anesthetic agents also influence the microcirculation: a reduction in cardiac output and arterial pressure decreases flow in the microcirculation, whereas anesthetic-induced local microvascular changes and vasodilatation can increase perfusion. Optimization of these variables plays an important role in enhancing the microcirculation in all patients, but is especially relevant if modifications could improve postoperative wound healing in the older population.

In this review, we will use skin as a representative organ to describe age-related changes that negatively affect the microcirculation and have subsequent impacts on wound healing and the incidence of postoperative infection. We will then examine the role of anesthesia management in minimizing detrimental effects on the microcirculation. A greater understanding of these variables could promote improvements that lead to better outcomes with respect to wound repair in older patients.

Summary of Wound Repair and Aging

It has been nearly a century since it was noted that the rate of cutaneous scar formation after a wound is inversely related to the age of the patient. Four decades ago, it was observed that older age was associated with an increased risk of postoperative disruption of the surgical wound, leading to higher mortality. Recent data suggest that in patients older than 65 yr, development of SSI is associated with a two-fold increase in cost and a staggering four-fold increase in mortality.

Wound healing ensues via a sequential chain of events (with variable overlap) that includes inflammation, tissue formation, and remodeling (fig. 2). Circulating factors have a pivotal role in each of these phases. Accordingly, as we will discuss below, immediate changes in the microcirculation influence each stages of the wound-healing response in aging. As human data is lacking, we have taken data from established animal models of aging. Although animal models are not uniformly predictive of responses in human tissues, several animal models of wound healing are generally accepted.

Fig. 2.

The stages of wound healing are a sequential chain of events that include: (A) inflammation, (B) proliferation and granulation tissue formation, and (C) extracellular matrix (ECM) deposition and tissue remodeling. PDGF = platelet-derived growth factor; TGF-β1 = transforming growth factor-β1; TNF-α = tumor necrosis factor-α; VEGF = vascular endothelial growth factor.

 

Summary

Nearly every anesthesiologist who provides care to adults will participate in the care of geriatric patients. A growing older population is undergoing surgical procedures that are increasing in number and complexity. Poor healing of surgical wounds is a major cause of morbidity, mortality, and substantial economic burden. Wound healing is dependent on the microcirculation that supplies the incision area. Measures that support the microcirculation during the perioperative period have a profound effect on wound healing. Some measures such as maintenance of normal body temperature and control of postoperative pain are supported by ample evidence and have been implemented in routine clinical care. Other measures, for example, the choice of anesthesia technique and use of opioids are supported by basic research but need further clinical studies. A better understanding of the effect of aging and anesthesia on the microcirculation can potentially assist in improving postoperative wound repair, thereby benefiting a growing older population.

 

The Surgical Context of Wound Repair and Aging

Measures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection.52General preoperative measures such as smoking cessation and optimal management of comorbid medical conditions have been reviewed in other contexts.53,54 For the purpose of this review, we will focus on interventions in the perioperative setting.

Oxygen Administration

Wound healing is dependent upon adequate levels of oxygen.55 Oxygen interacts with growth factor signaling and regulates numerous transduction pathways necessary for cell proliferation and migration.56 It is also an indispensable factor for oxidative killing of microbes.57 Consequently, the effects of oxygen tension on the outcome of surgical wounds have been best studied in the context of postoperative infection. Resistance to surgical wound infection is presumed to be oxygen dependent—with low oxygen tension viewed as a predictor of the development of infection,56 particularly when subcutaneous tissue oxygenation (measured by a polarographic electrode) decreases to less than 40 mmHg.58

In two recent meta-analyses, one found that perioperative supplemental oxygen therapy exerts a significant beneficial effect on the prevention of SSIs,59 whereas the other suggested a benefit only for specific subpopulations.60 Although most authors suggest that supplemental oxygen during surgery is associated with a reduction in infection risk,61,62 others propose it may be associated with an increased incidence of postoperative wound infection.63Notably, in the latter report, the sample size was small and there was a difference in the baseline characteristics of the groups. A prospective trial randomizing patients to either 30 or 80% supplemental oxygen during and 2 h after surgery did not find any difference in several outcome measures including death, pulmonary complications, and wound healing.64 Of note, the administration of oxygen to aged subjects may be limited by the finding that although arterial oxygen tension did not decrease with age, there was reduced steady-state transfer of carbon monoxide in the lungs.65 This indicates that oxygen transport could be diffusion-limited in older subjects, especially when oxygen consumption is increased. Furthermore, longitudinal studies of five healthy men over 3 decades showed impaired efficiency of maximal peripheral oxygen extraction,66 suggesting that tissue oxygen uptake is reduced in the aged subjects.67 This likely reflects a decrease in the number of capillaries as well as a reduction in mitochondrial enzyme activity.68 Animal models (rabbit69 and mouse69,70 ) have suggested that aging and ischemia have an additive effect on disruption of wound healing. Consequently, the potential benefit of increasing tissue oxygen tension during surgical wound repair in older patients should be further evaluated.

 

 

Reference: http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1917910

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Blood, Oxygen & Wound Healing: How It Works

Most of us take our natural wound-healing abilities for granted. You scrape your knee, clean it and wait for it to heal on its own. It seems pretty simple, right? Not exactly. The truth is, what goes on underneath that Band-Aid is a complex process that requires healthy blood flow to deliver the oxygen and nutrients necessary to heal, and if this process is interrupted, it can slow or prevent healing entirely.

 

Wound-Healing Process

Every wound goes through a continuous repair and healing process, which typically takes a few weeks to complete. For a wound to heal properly, the four wound-healing stages must be completed:

Stage 1: Hemostasis

Hemostasis happens immediately after an injury to skin causes bleeding. Your blood vessels constrict and reduce the flow of the blood to the injury site. Blood clots form within the injured blood vessels to prevent further blood loss.

Stage 2: Inflammation

Once a blood clot has closed the wound, the surrounding blood vessels are able to open up to deliver fresh nutrients and oxygen into the wound for healing. This process triggers macrophage, a white blood cell, to enter the wound, fight infection, oversee the repair process and send messengers, called growth factors, needed to heal the wound. Macrophage is the clear fluid you may see in or around the wound.

Stage 3: Proliferation

Proliferation is the growth and rebuilding phase, where blood cells arrive to help build new tissue to replace the tissue and cellular elements that were damaged during the process of wounding the skin. At this point, your body’s cells will produce a protein called collagen, which acts like scaffolding, to support the repair process.

Stage 4: Remodeling

The last wound-healing stage is remodeling, whereby the inflammation is gradually resolved and the collagen is deposited. New tissue takes the form of the original tissue and fills the area of the wound. We call this scar tissue, and while the wound may appear to have healed, it does not have the same strength as the normal tissue previously had. It may take several months to a year for the healed wound to gain full strength.

 

When Wound Healing Is Interrupted

For healthy adults, the four wound-healing stages progress naturally. For others, however, certain factors – especially poor circulation – can interrupt the body’s natural healing process, causing a wound to heal much more slowly, if at all. These wounds are called chronic wounds (wounds that do not heal in six to eight weeks despite normal treatment) and are most common in people with diabetes, high blood pressure, obesity and other vascular diseases. If not cared for or treated by a doctor, chronic wounds can lead to pain, infection, disability and possibly amputation of the affected limb.

 

Tips for Improving Circulation

The oxygen and nutrients that new blood carries to the wound are crucial to the healing process. By improving circulation and blood flow, more healing nutrients and oxygen reach the cells.

 

Eat a healthy diet.

A healthy diet promotes proper blood flow and can even speed up the wound-healing process. Eat the following power foods to make sure you are getting the right nutrients for optimal circulation and wound healing:

Protein: Lean meats, low-sodium beans, low-fat milk and yogurt, tofu, soy nuts and soy products

Vitamin C: Citrus fruits and juices, strawberries, tomatoes, spinach, potatoes, peppers and cruciferous vegetables

Vitamin A: Dark green, leafy vegetables; orange or yellow vegetables; cantaloupe and fortified cereals or dairy products

Zinc: Red meats, seafood and fortified cereals

 

Quit smoking.

There are a number of reasons to quit smoking and better your health. Beyond increasing risk for cancer and heart disease, tobacco can cause poor circulation and delayed wound healing. If you smoke, consult your doctor to devise a smoking cessation plan.

 

Stay hydrated.

Dehydration and poor hydration can greatly reduce circulation of blood and body fluids. Dehydration can also lead to poor oxygen perfusion, a failure to deliver essential nutrients to the wound surface and draining inefficiency. Drink eight 8-ounce glasses of water each day to improve blood flow and wound-healing abilities.

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Why post-menopausal women are prone to heart attack

Why post-menopausal women are prone to heart attack Read more: https://lifestyle.inquirer.net/296431/post-menopausal-women-prone-heart-attack/#ixzz5lzYlOezl Follow us: @inquirerdotnet on Twitter | inquirerdotnet on Facebook

Recently we had a female patient in her early 60s who suffered a heart attack and fortunately survived it.

All the time, she had been accompanying her husband to regular check-ups on his heart problem, without realizing she herself was a walking time bomb.

She has been a smoker most of her adult life. She has a strong family history of cardiovascular disease (CVD), with two male siblings undergoing heart bypass surgery in their early 50s.

Her blood pressure (BP) went on upward trend after menopause, with high cholesterol levels.

She showed no symptoms so she thought she was just fine, until she woke up in the middle of the night with severe chest tightness and shortness of breath.

She was rushed to the hospital, had an immediate declogging of the heart artery through angioplasty, and a small scaffolding-like metal called stent was inserted to keep the culprit coronary artery patent.

The same story happens so many times. Wife is so concerned about her husband with a heart problem and she neglects to have herself checked, or make sure that her lifestyle is not conducive to develop CVD.

Before menopause, women are protected by estrogen, the female reproductive hormone. This hormone has been shown to have a beneficial or cardioprotective effect on the inner layer of artery wall called endothelium.

After age 50

Endothelial dysfunction triggers the start of the atherosclerosis, which is the progressive narrowing of the artery. Estrogen prevents endothelial dysfunction, and helps maintain the flexibility of the blood vessels.

Flexible arteries can relax and expand to accommodate more blood and enhance the blood flow or circulation.

The onset of menopause is usually after the age of 50 (52 to 54 years of age on average). There are some who experience early menopause, signaled by the cessation of the monthly period at a much earlier age, even before age 40.

After menopause, estrogen decreases significantly and the heart protection is almost completely gone around eight to 10 years after menopause. This is usually when women are in their late 50s or early 60s.

Hence, the risk of developing a stroke, or heart attack, may increase and become higher in women compared to men at this age.

For those who have menopause at an early age, the increase in cardiovascular risk may occur at a much earlier age, when the women are just in their late 40s or early 50s.

Ovarian failure

The common cause is premature ovarian failure, but it may also be caused by damage to the ovaries as a result of cancer therapy and/or radiation treatments.

Another cause could be surgical removal of the ovaries if tumors in the female reproductive organs are diagnosed at a younger age.

The symptoms of premature menopause are pretty much the same as regular menopause, and include hot flashes, emotional instability or mood swing, vaginal dryness, decreased memory or comprehension, decreased libido or sex drive, and insomnia.

We have to clarify that menopause, by itself, does not cause CVD. It’s just that the levels of the heart-protective female hormones, particularly estrogen, decrease, and risk factors increase around the time of menopause.

These are increasing BP, high LDL (bad cholesterol) level, and low HDL (good cholesterol level. The triglyceride level, another bad type of fat, also increases after menopause.

A reckless lifestyle in the form of a high-carb and high-fat diet, being sedentary, smoking, and other unhealthy practices —which women could have earlier in life—starts to take its toll after menopause.

Guidelines from various heart associations remind women to really take stock of their health when they’re reaching menopause, so they can avert serious complications.

Since the cardiovascular risk in women peaks around eight to 10 years after the onset of menopause, women who are at high risk could be identified so that they could be treated more aggressively and monitored closely, preventing the complications which could occur years later.

A recently published study suggests that a relatively higher level of the male hormone called androgen or testosterone in postmenopausal women is associated with increased risks of cardiovascular complications.

The study, published in the Journal of the American College of Cardiology, followed up 2,800 postmenopausal women initially free of CVD. The women had their sex hormone levels measured at baseline.

The researchers reported that during an average of 12- year follow-up, CVD was diagnosed in 283 participants, plus clogging of the heart arteries (coronary heart disease or CHD) in 171, and heart failure in 103.

Adjustments were made to discount the effect of conventional risk factors and hormone therapy. The following findings were reported:

Male hormone

Higher total testosterone (male hormone)/estradiol ratio was linked with significantly increased risks for all cardiovascular outcomes.

Higher total testosterone appeared to significantly increase risks for CVD and CHD.
Higher estradiol (female hormone) was associated with significantly lower CHD risk, reaffirming its heart protective effect.

Does this study suggest that we should give post-menopausal women estrogen hormone therapy to prevent CVD or CHD?

I don’t think there’s good data to support that recommendation. There are also potential complications of aggressive hormone therapy which doctors are wary about.

The importance of this study is that we could identify the post-menopausal women who are at risk of suffering potentially serious cardiovascular complications, and implement risk-reducing strategies such as end to smoking, regular exercise and balanced diet.

Which type of diet is really good remains a big issue, in view of various fad diets claiming cardiovascular benefits.

The American Heart Association and Philippine Heart Association recommend eating a balanced diet consisting of: fruits, vegetables, whole grains, low-fat dairy products, poultry, fish and nuts, with less red meat and minimal sugary foods and beverages.

Aside from a healthy diet and lifestyle, adequate control of elevated BP is recommended; as well as the use of cardioprotective drugs like statins even if the cholesterol levels are not that high.

The important thing, too, is to get rid of the misconception that only men are vulnerable to heart disease, and women are spared from them.

A change of this wrong mindset is necessary so that the beloved women in our lives are not deprived of the medical care and attention they need to prevent heart attack, stroke and other cardiovascular complications.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.