Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson’s disease

Highlights

• The CBD treatment decreases hyperalgesia and allodynia in experimental parkinsonism.

• The inverse agonist of the CB1 receptor prevents the antinociceptive effect of CBD.

• FAAH inhibitor or TRPV1 antagonist potentiates the CBD antinociceptive effect.

Abstract

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson’s disease (PD). Pain is a prevalent PD’s non-motor symptom with a higher prevalence of analgesic drugs prescription for patients.

However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception.

Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine.

Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD.

Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.

ScienceDirect: Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson’s disease

More than 100 million Americans have diabetes or prediabetes

Diabetes growth rate steady, adding to health care burden

 

More than 100 million U.S. adults are now living with diabetes or prediabetes, according to a new reportCdc-pdf released today by the Centers for Disease Control and Prevention (CDC).

The report finds that as of 2015, 30.3 million Americans – 9.4 percent of the U.S. population –have diabetes. Another 84.1 million have prediabetes, a condition that if not treated often leads to type 2 diabetes within five years.

The report confirms that the rate of new diabetes diagnoses remains steady. However, the disease continues to represent a growing health problem: Diabetes was the seventh leading cause of death in the U.S. in 2015. The report also includes county-level data for the first time, and shows that some areas of the country bear a heavier diabetes burden than others.

“Although these findings reveal some progress in diabetes management and prevention, there are still too many Americans with diabetes and prediabetes,” said CDC Director Brenda Fitzgerald, M.D. “More than a third of U.S. adults have prediabetes, and the majority don’t know it. Now, more than ever, we must step up our efforts to reduce the burden of this serious disease.”

Diabetes is a serious disease that can often be managed through physical activity, diet, and the appropriate use of insulin and other medications to control blood sugar levels. People with diabetes are at increased risk of serious health complications including premature death, vision loss, heart disease, stroke, kidney failure, and amputation of toes, feet, or legs.

The National Diabetes Statistics Report, released approximately every two years, provides information on diabetes prevalence and incidence, prediabetes, risk factors for complications, acute and long-term complications, mortality, and costs in the U.S.

Key findings from the National Diabetes Statistics Report

The report finds that:

  • In 2015, an estimated 1.5 million new cases of diabetes were diagnosed among people ages 18 and older.
  • Nearly 1 in 4 four adults living with diabetes – 7.2 million Americans – didn’t know they had the condition. Only 11.6 percent of adults with prediabetes knew they had it.
  • Rates of diagnosed diabetes increased with age. Among adults ages 18-44, 4 percent had diabetes. Among those ages 45-64 years, 17 percent had diabetes. And among those ages 65 years and older, 25 percent had diabetes.

Rates of diagnosed diabetes were higher among American Indians/Alaska Natives (15.1 percent), non-Hispanic blacks (12.7 percent), and Hispanics (12.1 percent), compared to Asians (8.0 percent) and non-Hispanic whites (7.4 percent).

 

Source: https://www.cdc.gov/media/releases/2017/p0718-diabetes-report.html

 

Pediatric Metabolic and Bariatric Surgery: Evidence, Barriers, and Best Practices

Severe obesity among youth is an “epidemic within an epidemic” and portends a shortened life expectancy for today’s children compared with those of their parents’ generation. Severe obesity has outpaced less severe forms of childhood obesity in prevalence, and it disproportionately affects adolescents. Emerging evidence has linked severe obesity to the development and progression of multiple comorbid states, including increased cardiometabolic risk resulting in end-organ damage in adulthood. Lifestyle modification treatment has achieved moderate short-term success among young children and those with less severe forms of obesity, but no studies to date demonstrate significant and durable weight loss among youth with severe obesity.

Metabolic and bariatric surgery has emerged as an important treatment for adults with severe obesity and, more recently, has been shown to be a safe and effective strategy for groups of youth with severe obesity. However, current data suggest that youth with severe obesity may not have adequate access to metabolic and bariatric surgery, especially among underserved populations. This report outlines the current evidence regarding adolescent bariatric surgery, provides recommendations for practitioners and policy makers, and serves as a companion to an accompanying technical report, “Metabolic and Bariatric Surgery for Pediatric Patients With Severe Obesity,” which provides details and supporting evidence.

This policy statement uses the term “pediatric” in reference to a person under 18 years of age. The term “adolescent” may be defined differently in various studies and clinical settings on the basis of age or developmental stage. When making specific recommendations, this policy statement uses “adolescent” to refer to a person from age 13 years to age 18 years. “Severe” obesity (class 2 obesity or higher) is defined as having a BMI ≥35 or ≥120% of the 95th percentile for age and sex.1 Recent data from the NHANES (2014–2016) report the prevalence of severe obesity in youth at 7.9% overall, 9.7% in 12- to 15-year-olds, and 14% in 16- to 19-year-olds. These numbers represent a near doubling since 1999 and equate to 4.5 million children in the United States affected by severe obesity.2 These children are at high risk for developing chronic and progressive diseases, including hypertension, dyslipidemia, obstructive sleep apnea, polycystic ovarian syndrome, type 2 diabetes mellitus, fatty liver disease, bone and joint dysfunction, depression, social isolation, and poor quality of life.37

Roux-en-Y gastric bypass (RYGB) is often referred to as the gold standard for surgical management of severe obesity in adults8,9 and adolescents7 and is performed by using minimally invasive, laparoscopic surgical techniques. RYGB results in significant weight loss as a result of its effects on appetite, satiety, and regulation of energy balance.9

Vertical sleeve gastrectomy (VSG) leads to weight loss through similar effects on appetite, satiety, and regulation of energy balance and may reduce appetite through delayed gastric emptying and altered neurohormonal feedback mechanisms.10 VSG is the most common bariatric procedure performed in adults and is becoming more common among adolescents.11,12

Laparoscopic adjustable gastric band (LAGB), a reversible procedure that accounted for approximately one-third of all bariatric operations in the United States a decade ago,12 has experienced a significant decline in use among adults because of limited long-term effectiveness and higher-than-expected complication rates.13,14 Disappointing outcomes in the context of few prospective studies in the pediatric population have resulted in a similar decline in use of LAGB among adolescents.11 At present, LAGB is limited by the US Food and Drug Administration to people 18 years or older.

Pediatrics : Pediatric Metabolic and Bariatric Surgery: Evidence, Barriers, and Best Practices

Scientists reveal the relationship between sugar and cancer

A nine-year joint research project conducted by VIB, KU Leuven and VUB has led to a crucial breakthrough in cancer research. Scientists have clarified how the Warburg effect, a phenomenon in which cancer cells rapidly break down sugars, stimulates tumor growth. This discovery provides evidence for a positive correlation between sugar and cancer, which may have far-reaching impacts on tailor-made diets for cancer patients.

The research has been published in the leading academic journal Nature Communications. This project was started in 2008 under the leadership of Johan Thevelein (VIB-KU Leuven), Wim Versées (VIB-VUB) and Veerle Janssens (KU Leuven). Its main focus was the Warburg effect, or the observation that tumors convert significantly higher amounts of sugar into lactate compared to healthy tissues. As one of the most prominent features of cancer cells, this phenomenon has been extensively studied and even used to detect brain tumors, among other applications. But thus far, it has been unclear whether the effect is merely a symptom of cancer, or a cause.

Sugar awakens cancer cells

While earlier research into cancer cell metabolism focused on mapping out metabolic peculiarities, this study clarifies the link between metabolic deviation and oncogenic potency in cancerous cells.

Prof. Johan Thevelein (VIB-KU Leuven): “Our research reveals how the hyperactive sugar consumption of cancerous cells leads to a vicious cycle of continued stimulation of cancer development and growth. Thus, it is able to explain the correlation between the strength of the Warburg effect and tumor aggressiveness. This link between sugar and cancer has sweeping consequences. Our results provide a foundation for future research in this domain, which can now be performed with a much more precise and relevant focus.”

Yeast as an advantageous model organism

Yeast cell research was essential to the discovery, as these cells contain the same ‘Ras’ proteins commonly found in tumor cells, which can cause cancer in mutated form. Using yeast as a model organism, the research team examined the connection between Ras activity and the highly active sugar metabolism in yeast.

Prof. Johan Thevelein (VIB-KU Leuven): “We observed in yeast that sugar degradation is linked via the intermediate fructose 1,6-biophosphate to the activation of Ras proteins, which stimulate the multiplication of both yeast and cancer cells. It is striking that this mechanism has been conserved throughout the long evolution of yeast cell to human.

“The main advantage of using yeast was that our research was not affected by the additional regulatory mechanisms of mammalian cells, which conceal crucial underlying processes. We were thus able to target this process in yeast cells and confirm its presence in mammalian cells. However, the findings are not sufficient to identify the primary cause of the Warburg effect. Further research is needed to find out whether this primary cause is also conserved in yeast cells.”

 

Source: https://www.sciencedaily.com/releases/2017/10/171013103623.htm

Sugar – the elephant in the kitchen

Robert H. Lustig is an American pediatric endocrinologist at the University of California, San Francisco (UCSF) where he is a Professor of Clinical Pediatrics. Dr. Lustig assesses the health dangers of sugar and its link to Type-2 diabetes and the global obesity epidemic. He is the author of several books and many articles on childhood obesity, including the recent “Obesity Before Birth.”

Effect of carbohydrate rich versus fat rich loads on gas exchange and walking performance in patients with chronic obstructive lung disease.

High calorie intakes, especially as carbohydrate, increase carbon dioxide production (VCO2) and may precipitate respiratory failure in patients with severe pulmonary disease. Energy obtained from fat results in less carbon dioxide and thus may permit a reduced level of alveolar ventilation for any given arterial blood carbon dioxide tension (PaCO2). 

Ten patients with stable severe chronic obstructive lung disease underwent a six minute walk before and 45 minutes after taking 920 kcal of a fat rich drink, an isocalorific amount of a carbohydrate rich drink, and an equal volume of a non-calorific control liquid on three separate days, in a double blind randomised crossover study. Borg scores of the perceived effort to breathe were measured at the beginning and end of each six minute walk. Minute ventilation (VE2), VCO2, oxygen consumption (VO2), respiratory quotient (RQ), arterial blood gas tensions, and lung function were measured before and 30 minutes after each test drink. 

Baseline measurements were similar on all three test days and the non-calorific control drink resulted in no changes in any of the measured variables. The carbohydrate rich drink resulted in significantly greater increases in VE, VCO2, VO2, RQ, PaCO2, and Borg score and a greater fall in the distance walked in six minutes than the fat rich drink (mean fall after carbohydrate rich drink 17 m v 3 m after fat rich drink and the non-calorific control). The increase in VCO2 correlated significantly with the decrease in six minute walking distance and the increase in Borg score after the carbohydrate rich drink. The only significant change after the fat rich drink when compared with the non-calorific control was an increase in VCO2.

Comparatively small changes in the carbohydrate and fat constitution of meals can have a significant effect on VCO2, exercise tolerance, and breathlessness in patients with chronic obstructive lung disease.

PMC: Effect of carbohydrate rich versus fat rich loads on gas exchange and walking performance in patients with chronic obstructive lung disease.

 

Can we beat T2 Diabetes? HOPE on the horizon

Dr. David Unwin is GP based in Southport in the United Kingdom. After 25 years of attempting to treat diabetes by conventional methods, Dr. Unwin was introduced to low carb nutrition through one of his patients and the website www.diabetes.co.uk From this revelation, Dr. Unwin now ignores official advice and treats his patients with a low-carbohydrate diet. Since adopting the approach, his practice now spends £50,000 less each year on drugs for diabetes than is average for his area. Dr. Unwin is the RCGP National Champion for Collaborative Care and Support Planning in Obesity & Diabetes, as well as a Clinical Expert in diabetes. In 2015 he won the North West NHS ‘Innovator of the Year Award’ and in 2016 he won the National NHS ‘Innovator of the Year Award’ for his work in treating diabetes with a low carbohydrate approach.

 

On the keto diet? Ditch the cheat day

“The ketogenic — or keto — diet has become very common for weight loss or to manage diseases like type 2 diabetes,” says Jonathan Little, associate professor in the School of Health and Exercise Sciences at UBCO and study senior author. “It consists of eating foods rich in fats, moderate in protein, but very low in carbohydrates and it causes the body to go into a state called ketosis.”

Little says the diet can be very effective because once the body is in ketosis and starved for its preferred fuel glucose, the body’s chemistry changes and it begins to aggressively burn its fat stores. This leads to weight loss and can reverse the symptoms of diseases like Type 2 diabetes.

“We were interested in finding out what happens to the body’s physiology once a dose of glucose is reintroduced,” says Cody Durrer, UBC Okanagan doctoral student and study first author. “Since impaired glucose tolerance and spikes in blood sugar levels are known to be associated with an increased risk in cardiovascular disease, it made sense to look at what was happening in the blood vessels after a sugar hit.”

For their test, the researchers recruited nine healthy young males and had them consume a 75-gram glucose drink before and after a seven-day high fat, low carbohydrate diet. The diet consisted of 70 per cent fat, 10 per cent carbohydrates and 20 per cent protein, similar to that of a modern ketogenic diet.

“We were originally looking for things like an inflammatory response or reduced tolerance to blood glucose,” says Durrer. “What we found instead were biomarkers in the blood suggesting that vessel walls were being damaged by the sudden spike in glucose.”

Little says the most likely culprit for the damage is the body’s own metabolic response to excess blood sugar, which causes blood vessel cells to shed and possibly die.

“Even though these were otherwise healthy young males, when we looked at their blood vessel health after consuming the glucose drink, the results looked like they might have come from someone with poor cardiovascular health,” adds Little. “It was somewhat alarming.”

The researchers point out that with only nine individuals included in the study, more work is needed to verify their findings, but that the results should give those on a keto diet pause when considering a cheat day.

“My concern is that many of the people going on a keto diet — whether it’s to lose weight, to treat Type 2 diabetes, or some other health reason — may be undoing some of the positive impacts on their blood vessels if they suddenly blast them with glucose,” he says. “Especially if these people are at a higher risk for cardiovascular disease in the first place.”

“Our data suggests a ketogenic diet is not something you do for six days a week and take Saturday off.”

ScienceDaily: On the keto diet? Ditch the cheat day

The True Causes of Heart Disease are Not What You Think!

Finally got hold of the man who more than anyone, has deep-dived into the root causes of heart disease – without bias – just fixated with finding the truth. I’m of course referring to Dr. Malcolm Kendrick, who has created the 65-part (and growing) series “What Causes Heart Disease?“.
See index below for a gist of what we covered (hint – it was A LOT!)

INDEX/CONTENTS:

00:00:40 Are the causes we talk about “necessary and sufficient”?

00:04:45 What does Sickle Cell Disease prove about heart disease cause?

00:09:33 Kawasaki Disease illuminates the true causes of heart disease

00:14:45 Vein/artery differences, blood pressure & turbulence – speak volumes

00:20:14 Damage and repair – it’s the imbalance that is the problem

00:24:34 Steroids, inflammation and …Cushing’s Disease – what do they say?

00:28:12 Blood glucose, insulin resistance and their effects – a pivotal axis

00:31:54 Pollution, leaded petrol – and the surprising effect of Chelation

00:35:50 Bias, homocysteine, drug treatments – and the research world behaving badly

00:46:01 LDL importance…versus blood clotting factors

00:49:40 Atherosclerosis is the result of endothelial damage & blood clotting processes –root mechanisms

00:53:08 Sun, Nitric Oxide – and taking Viagra…!

00:56:53 Magnesium, salts, nitric oxide – and why your arteries fail you

01:02:06 Blood clotting is at the very core of heart disease – deep-dive

01:09:05 LDL, Lp(a) – and what cholesterol crystals in plaque really say!

01:15:05 Lp(a0, Vitamin C and Plasminogen – putting it all together

01:22:45 Familial Hypercholesterolemia….and what’s actually occurring all along

01:25:39 The mechanisms of statins and other drugs – beyond the old LDL story

01:34:48 “Well, they can’t all be wrong, can they?” – but history has shown how often this has been the case

Source: https://thefatemperor.com/ep40-dr-malcolm-kendrick-the-true-causes-of-heart-disease-are-not-what-you-think/

01:43:04 We’re building a cathedral of wisdom – at least on the root causes of heart disease!

Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a)

Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals.

Better understanding of the evolutionary advantage of this molecule should elucidate its physiological role. We developed a new mouse model with two characteristics of human metabolism: the expression of Lp(a) and the lack of endogenous ascorbate (vitamin C) production.

We show that dietary deficiency of ascorbate increases serum levels of Lp(a). Moreover, chronic hypoascorbemia and complete depletion of ascorbate (scurvy) leads to Lp(a) accumulation in the vascular wall and parallels atherosclerotic lesion development. The results suggest that dietary ascorbate deficiency is a risk factor for atherosclerosis independent of dietary lipids.

We provide support for the concept that Lp(a) functions as a mobile repair molecule compensating for the structural impairment of the vascular wall, a morphological hallmark of hypoascorbemia and scurvy.

PMC: Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice