Sudden Decline in Testosterone May Cause Parkinson's Disease Symptoms in Men

From ScienceDaily website (see original article)

 July 26, 2013 — The results of a new study by neurological researchers at Rush University Medical Center show that a sudden decrease of testosterone, the male sex hormone, may cause Parkinson's like symptoms in male mice.
The findings were recently published in the Journal of Biological Chemistry.

One of the major roadblocks for discovering drugs against Parkinson's disease is the unavailability of a reliable animal model for this disease.

"While scientists use different toxins and a number of complex genetic approaches to model Parkinson's disease in mice, we have found that the sudden drop in the levels of testosterone following castration is sufficient to cause persistent Parkinson's like pathology and symptoms in male mice," said Dr. Kalipada Pahan, lead author of the study and the Floyd A. Davis endowed professor of neurology at Rush.
"We found that the supplementation of testosterone in the form of 5-alpha dihydrotestosterone (DHT) pellets reverses Parkinson's pathology in male mice."

"In men, testosterone levels are intimately coupled to many disease processes," said Pahan.
Typically, in healthy males, testosterone level is the maximum in the mid-30s, which then drop about one percent each year.
However, testosterone levels may dip drastically due to stress or sudden turn of other life events, which may make somebody more vulnerable to Parkinson's disease.

"Therefore, preservation of testosterone in males may be an important step to become resistant to Parkinson's disease," said Pahan.

Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson's disease.
Nitric oxide is an important molecule for our brain and the body.

"However, when nitric oxide is produced within the brain in excess by a protein called inducible nitric oxide synthase, neurons start dying," said Pahan.

"This study has become more fascinating than we thought," said Pahan.
"After castration, levels of inducible nitric oxide synthase (iNOS) and nitric oxide go up in the brain dramatically.
Interestingly, castration does not cause Parkinson's like symptoms in male mice deficient in iNOS gene, indicating that loss of testosterone causes symptoms via increased nitric oxide production."

"Further research must be conducted to see how we could potentially target testosterone levels in human males in order to find a viable treatment," said Pahan.

Migraines Associated With Variations in Structure of Brain Arteries

From ScienceDaily website (see original article)

July 26, 2013 — The network of arteries supplying blood flow to the brain is more likely to be incomplete in people who suffer migraine, a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania reports.
Variations in arterial anatomy lead to asymmetries in cerebral blood flow that might contribute to the process triggering migraines.

The arterial supply of blood to the brain is protected by a series of connections between the major arteries, termed the "circle of Willis" after the English physician who first described it in the 17th century.
People with migraine, particularly migraine with aura, are more likely to be missing components of the circle of Willis.

Migraine affects an estimated 28 million Americans, causing significant disability.
Experts once believed that migraine was caused by dilation of blood vessels in the head, while more recently it has been attributed to abnormal neuronal signals.
In this study, appearing in PLOS ONE, researchers suggest that blood vessels play a different role than previously suspected: structural alterations of the blood supply to the brain may increase susceptibility to changes in cerebral blood flow, contributing to the abnormal neuronal activity that starts migraine.

"People with migraine actually have differences in the structure of their blood vessels -- this is something you are born with," said the study's lead author, Brett Cucchiara, MD, Associate Professor of Neurology.
"These differences seem to be associated with changes in blood flow in the brain, and it's possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches."

In a study of 170 people from three groups -- a control group with no headaches, those who had migraine with aura, and those who had migraine without aura -- the team found that an incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent).
The team used magnetic resonance angiography to examine blood vessel structure and a noninvasive magnetic resonance imaging method pioneered at the University of Pennsylvania, called Arterial spin labeling (ASL), to measure changes in cerebral blood flow.

"Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located.
This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines," said the study's senior author, John Detre, MD, Professor of Neurology and Radiology.

Both migraine and incomplete circle of Willis are common, and the observed association is likely one of many factors that contribute to migraine in any individual.
The researchers suggest that at some point diagnostic tests of circle of Willis integrity and function could help pinpoint this contributing factor in an individual patient.
Treatment strategies might then be personalized and tested in specific subgroups.

Esagerare con il pesce grasso può far male al cuore

Dalla rubrica Salute - Corriere della Sera (vedi articolo originale)


Il pesce fa bene al cuore, su questo ci sono ormai ben pochi dubbi.

Eppure se si esagera e se ne mangia troppo anche salmone e compagnia possono far male, aumentando il rischio di aritmie gravi come la fibrillazione atriale.

Lo dimostra una ricerca danese presentata a EHRA EUROPACE 2013, secondo cui l'ideale sarebbe un apporto “medio” dei preziosi acidi grassi omega-3 del pesce: introdurne troppi o troppo pochi è ugualmente dannoso per la funzionalità del cuore.

STUDIO – I dati sono stati raccolti da Thomas Rix dell'ospedale universitario danese di Aalborg su oltre 57mila persone dai 50 ai 64 anni che facevano parte del Danish Diet, Cancer and Health Study, un'indagine nata per indagare il ruolo della dieta nello sviluppo dei tumori.

Attraverso questionari si sono raccolte informazioni precise sull'alimentazione dei partecipanti, ricostruendo il consumo di pesce e da questo l'introito quotidiano medio di acidi grassi omega-3; tutti sono stati poi seguiti per oltre 13 anni registrando i casi di fibrillazione atriale occorsi nel frattempo, poco meno di 3500 nell'arco del periodo di osservazione.

Quindi, si sono confrontate le diete di chi si era ammalato e degli altri, scoprendo che rispetto a chi non mangiava mai o pochissimo pesce (da zero a 0,38 grammi al giorno di omega-3) chi lo consumava in quantità moderate (da 0.39 a 0.53 grammi o da 0.54 a 0.73 grammi al giorno) aveva un rischio di fibrillazione atriale dal 9 al 13 per cento inferiore.

All'aumentare degli omega-3, però, non si è visto un progressivo ridursi del pericolo di aritmie, anzi: i partecipanti con un consumo elevato (oltre 0.73 ma entro 0.99 grammi al giorno) avevano un rischio ridotto di appena il 4 per cento, quelli che mangiavano moltissimo pesce (oltre 1 grammo al giorno di omega-3) avevano addirittura una probabilità di aritmie del 3 per cento superiore a chi non lo consumava mai o pochissimo.

PESCE – La «dose» di pesce che garantisce il minimo rischio è quella che apporta circa 0.63 grammi di omega-3 al giorno, ovvero circa due porzioni a settimana di pesci ricchi di grassi “buoni” come salmone, acciughe, sgombri e simili.

«La riduzione del 13 per cento del rischio di aritmia con questi livelli di consumo si può spiegare con effetti diretti antiaritmici degli omega-3, a cui si aggiungono proprietà antinfiammatorie e di riduzione del pericolo di ischemia cardiaca che contribuiscono alla salute del cuore – osserva Rix –. Questo dato conferma osservazioni precedenti secondo cui mangiare pesce da una a quattro volte a settimana riduce di quasi un terzo il pericolo di fibrillazione atriale rispetto a consumarlo meno di una volta al mese.

Più difficile spiegare i meccanismi biologici connessi all'incremento del rischio di aritmia in chi mangia molto pesce, invece: possiamo solo supporre che il bilancio fra gli effetti di inibizione o al contrario di promozione della fibrillazione atriale si modifichi in base alle altre patologie eventualmente presenti, ma non abbiamo idea del motivo reale.

Saranno necessari ulteriori ricerche per capire perché troppi omega-3 possano essere deleteri; tuttavia, questi dati potrebbero spiegare perché l'uso di questi composti per la prevenzione delle patologie cardiovascolari abbia dato risultati contraddittori, in passato».

Cancer Risks Double When Two Carcinogens Present at 'Safe' Levels, Epigenetics Study Finds

From ScienceDaily website (see original article)

June 28, 2013 — Science knows that arsenic and estrogen can cause cancer. At certain very low levels, the chemicals offer little to no threats to human health.

However, new research conducted by Texas Tech University scientists has found that low doses of both chemicals together -- even at levels low enough to be considered "safe" for humans if they were on their own -- can cause cancer in prostate cells.

The combination of the two chemicals was almost twice as likely to create cancer in prostate cells, the research found.
The study published online in the peer-reviewed journal The Prostate.

Kamaleshwar Singh, an assistant professor at The Institute of Environmental and Human Health (TIEHH) at Texas Tech said the findings could have an impact on health regulations regarding the "safe" doses of these chemicals and others.
Most regulations are set by testing one chemical at a time on cells. Very few if any have looked at multiple chemicals at the same time.

"The majority of cancers are caused by environmental influences," Singh said.
"Only about 5 to 10 percent of cancers are due to genetic predisposition. Science has looked at these chemicals, such as arsenic, and tested them in a lab to find the amounts that may cause cancer.
But that's just a single chemical in a single test. In the real world, we are getting exposed to many chemicals at once."

Singh said he became interested in studying two chemicals at once after looking at arsenic's carcinogenic properties in a previous paper.

Because cigarette smoke and well water in some areas, including India, Mexico and even Lubbock county, can contain arsenic, Singh and his doctoral student, Justin Treas, wondered how the carcinogenic properties might change when paired with the presence of another carcinogenic chemical.

The two focused on estrogen because of the chemical's abundance. Many plastics, such as food can liners and bisphenol A (BPA), release small amounts of chemicals that mimic estrogen in the body.

"Co-exposure was creating a greater impact," Singh said. "That was one of the important findings of our study.
The next thing we wanted to know is how these two chemicals are creating a greater effect."

Unlike stronger chemicals that do major damage to the DNA in a cell, such as benzene, arsenic and estrogen aren't major mutagens Singh said.
Instead, their presence tends to stop certain genes from expressing. The process is called DNA hypermethylation.

In the experiment, human prostate cells were treated about once a week for six months with arsenic, estrogen and a combination of the two.
Many of the tests involved levels of arsenic, estrogen or both at levels considered safe by the Environmental Protection Agency.

Treas said the two chemicals stopped the MLH1 gene, which is responsible for sending the signal to start the self-destruct sequence when a cell is damaged. Because the self-destruct couldn't activate, the cells became cancerous after exposure.

"With the lower dose not killing the cell, it's causing damages that go under the cell's radar," Treas said. "We found when you have two compounds together, lower doses could be more serious problem."

Dietary Fructose Causes Liver Damage in Animal Model

From ScienceDaily website (see original article)

June 19, 2013 — The role of dietary fructose in the development of obesity and fatty liver diseases remains controversial, with previous studies indicating that the problems resulted from fructose and a diet too high in calories.

However, a new study conducted in an animal model at Wake Forest Baptist Medical Center showed that fructose rapidly caused liver damage even without weight gain.
The researchers found that over the six-week study period liver damage more than doubled in the animals fed a high-fructose diet as compared to those in the control group.

The study is published in the June 19 online edition of the American Journal of Clinical Nutrition.

"Is a calorie a calorie? Are they all created equal? Based on this study, we would say not," said Kylie Kavanagh, D.V.M., assistant professor of pathology-comparative medicine at Wake Forest Baptist and lead author of the study.

In a previous trial which is referenced in the current journal article, Kavanagh's team studied monkeys who were allowed to eat as much as they wanted of low-fat food with added fructose for seven years, as compared to a control group fed a low-fructose, low-fat diet for the same time period.
Not surprisingly, the animals allowed to eat as much as they wanted of the high-fructose diet gained 50 percent more weight than the control group.
They developed diabetes at three times the rate of the control group and also developed hepatic steatosis, or non-alcoholic fatty liver disease.

The big question for the researchers was what caused the liver damage.
Was it because the animals got fat from eating too much, or was it something else?

To answer that question, this study was designed to prevent weight gain.
Ten middle-aged, normal weight monkeys who had never eaten fructose were divided into two groups based on comparable body shapes and waist circumference.
Over six weeks, one group was fed a calorie-controlled diet consisting of 24 percent fructose, while the control group was fed a calorie-controlled diet with only a negligible amount of fructose, approximately 0.5 percent.

Both diets had the same amount of fat, carbohydrate and protein, but the sources were different, Kavanagh said. The high-fructose group's diet was made from flour, butter, pork fat, eggs and fructose (the main ingredient in corn syrup), similar to what many people eat, while the control group's diet was made from healthy complex carbohydrates and soy protein.

Every week the research team weighed both groups and measured their waist circumference, then adjusted the amount of food provided to prevent weight gain.
At the end of the study, the researchers measured biomarkers of liver damage through blood samples and examined what type of bacteria was in the intestine through fecal samples and intestinal biopsies.

"What surprised us the most was how quickly the liver was affected and how extensive the damage was, especially without weight gain as a factor," Kavanagh said.
"Six weeks in monkeys is roughly equivalent to three months in humans."

In the high-fructose group, the researchers found that the type of intestinal bacteria hadn't changed, but that they were migrating to the liver more rapidly and causing damage there.
It appears that something about the high fructose levels was causing the intestines to be less protective than normal, and consequently allowing the bacteria to leak out at a 30 percent higher rate, Kavanagh said.

One of the limitations of the study was that it only tested for fructose and not dextrose.
Fructose and dextrose are simple sugars found naturally in plants.

"We studied fructose because it is the most commonly added sugar in the American diet, but based on our study findings, we can't say conclusively that fructose caused the liver damage," Kavanagh said.
"What we can say is that high added sugars caused bacteria to exit the intestines, go into the blood stream and damage the liver.

"The liver damage began even in the absence of weight gain.
This could have clinical implications because most doctors and scientists have thought that it was the fat in and around tissues in the body that caused the health problems."

The Wake Forest Baptist team plans to begin a new study using the same controls but testing for both fructose and dextrose over a longer time frame.

Phthalates -- Chemicals Widely Found in Plastics and Processed Food -- Linked to Elevated Blood Pressure in Children and Teens

From ScienceDaily website (see original article)

May 22, 2013 — Plastic additives known as phthalates (pronounced THAL-ates) are odorless, colorless and just about everywhere: They turn up in flooring, plastic cups, beach balls, plastic wrap, intravenous tubing and -- according to the Centers for Disease Control and Prevention -- the bodies of most Americans.
Once perceived as harmless, phthalates have come under increasing scrutiny.
A growing collection of evidence suggests dietary exposure to phthalates (which can leech from packaging and mix with food) may cause significant metabolic and hormonal abnormalities, especially during early development.

Now, new research published this Wednesday in The Journal of Pediatrics suggests that certain types of phthalates could pose another risk to children: compromised heart health.
Drawing on data from a nationally representative survey of nearly 3,000 children and teens, researchers at NYU Langone Medical Center, in collaboration with researchers at the University of Washington and Penn State University School of Medicine, have documented for the first time a connection between dietary exposure to DEHP (di-2-ethyhexylphthalate), a common class of phthalate widely used in industrial food production, and elevated systolic blood pressure, a measure of pressure in the arteries when the heart contracts.

"Phthalates can inhibit the function of cardiac cells and cause oxidative stress that compromises the health of arteries.
But no one has explored the relationship between phthalate exposure and heart health in children" says lead author Leonardo Trasande, MD, MPP, associate professor of pediatrics, environmental medicine and population health at NYU Langone Medical Center.
"We wanted to examine the link between phthalates and childhood blood pressure in particular given the increase in elevated blood pressure in children and the increasing evidence implicating exposure to environmental exposures in early development of disease."

Hypertension is clinically defined as a systolic blood-pressure reading above 140 mm Hg.
It's most common in people over 50 years old, although the condition is becoming increasingly prevalent among children owing to the global obesity epidemic. Recent national surveys indicate that 14 percent of American adolescents now have pre-hypertension or hypertension.
"Obesity is driving the trend but our findings suggest that environmental factors may also be a part of the problem," says Dr. Trasande.
"This is important because phthalate exposure can be controlled through regulatory and behavioral interventions."

Researchers from NYU School of Medicine, the University of Washington and Penn State University School of Medicine examined six years of data from a nationally representative survey of the U.S. population administered by the National Centers for Health Statistics of the Centers for Disease Control and Prevention.
Phthalates were measured in urine samples using standard analysis techniques.
Controlling for a number of potential confounders, including race, socioeconomic status, body mass index, caloric intake and activity levels, the researchers found that every three-fold increase in the level of breakdown products of DEHP in urine correlated with a roughly one-millimeter mercury increase in a child's blood pressure.
"That increment may seem very modest at an individual level, but on a population level such shifts in blood pressure can increase the number of children with elevated blood pressure substantially," says Dr. Trasande.
"Our study underscores the need for policy initiatives that limit exposure to disruptive environmental chemicals, in combination with dietary and behavioral interventions geared toward protecting cardiovascular health."

Melanoma Succumbs To Natural Plant Substance Gossypin In Lab Tests

For the first time, using lab tests on cell cultures and mice, researchers in the US have shown that gossypin, a naturally-occurring substance found in plants, may be an effective treatment against melanoma, the deadliest form of skin cancer.

Hareesh Nair of the Texas Biomedical Research Institute, and colleagues, write about their findings in the April issue of Molecular Cancer Therapeutics.

In their background information they explain that previous studies have shown gossypin, a flavone originally isolated from the hibiscus plant (H. vitifolius), suppresses inflammation and cancer.
However, the underlying molecular activity has not been clear.

In this study, they show that the substance inhibits the action of two gene mutations that commonly occur in people with melanoma, as Nair explains in a press statement:

"Our results indicate that gossypin may have great therapeutic potential as a dual inhibitor of mutations called BRAFV600E kinase and CDK4, which occur in the vast majority of melanoma patients."

According to the American Cancer Society, every year, about 76,000 people are diagnosed with melanoma, the least common form of skin cancer, but the one responsible for the most deaths.

There is currently no single drug or combination that treats all types of melanoma.

For their study, Nair and colleagues tested the effect of gossypin on melanoma in cell cultures and also in live mice.

In the cell culture experiments they found that gossypin stopped cancer cell growth in melanoma cell lines that contained the two gene mutations and stopped the growth of various human melanoma cells.

They suggest gossypin stunted the activity of the mutations by binding with them directly "as confirmed by molecular docking studies".

Gossypin treatment also reduced tumor volume and increased survival rate in mice transplanted with human melanoma tumors containing the two mutated genes.

The authors conclude that:

"In summary, this study identified gossypin as a novel agent with dual inhibitory effects for BRAFV600E kinase and CDK4 for treatment of melanoma."
Nair says the findings "open a new avenue for the generation of a novel class of compounds for the treatment of melanoma".
He and his team now plan to do further studies to understand how the body absorbs and metabolizes gossypin.
The study was funded by the Texas Biomedical Forum and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation.