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3066

Marijuana Use Could Be Related to Higher Stroke Risk, Study Says

According to a new paper presented during the International Stroke Conference of 2013 held by the American Stroke Association, marijuana could double the risk of stroke in young adults. The study, led by a research team from New Zealand, reveals that patients who had been tested positive for marijuana were 2 times more likely to suffer from transient ischemic attacks or even ischemic strokes, when compared to patients of the same sex and age.

The study, led by professor Alan Barber, is the first case-control study that links marijuana to an increased risk of ischemic stroke. “Cannabis has been thought by the public to be a relatively safe, although illegal substance. This study shows this might not be the case; it may lead to stroke”, noted Barber. A total number of 160 patients with a history of ischemic stroke or transient ischemic attacks, aged between 18 and 55, were investigated in the study. Out of the 160 patients, 10 of them had transient ischemic attacks while 150 of them had an ischemic stroke. Almost 16% of the patients tested positive on drug screens upon hospital admission.

Marijuana

Marijuana

A little over 8% of the patients from the control group tested positive for marijuana. The research team discovered that there were no differences in the age and stroke mechanism of the patients, regardless of their marijuana consumption. Previous studies report that both ischemic strokes and transient ischemic attacks can occur a few hours after marijuana use. According to researchers, most of these patients show no history of cardiovascular diseases or other risk factors, excluding alcohol, tobacco and other drugs. The authors of the study mention that it’s almost impossible to conduct prospective studies on marijuana consumers due to the fact that patients might offer unreliable answers.

In order to conduct this study, the research team was allowed to test the urine samples of hospitalized patients. However, the researchers only had access to the urine sample, the sex, the ethnicity and age of the patients. Nonetheless, researchers were able to provide strong evidence towards the link between marijuana usage and stroke. On the other hand, the majority of stroke patients were also tobacco consumers, thus making researchers unable to be sure if the strokes were indeed caused by marijuana. Further research is needed in order to determine if marijuana is connected to stroke, independent of tobacco usage. Barber concluded that although progress will be difficult due to the biases that occur with the study of illegal substances, it is compulsory to continue research to the increasing number of young marijuana consumers.

3319

New Study Identifies Several Inherited Mutations in Autism

Until recently, although researchers observed that autism is somehow related to genetic transmission, only a handful of causes have been found. One of the main reasons why not enough data exists is because of the high variety of mutations that are behind the disease. However, a team of researchers from the Children’s Hospital in Boston managed to pinpoint some mutations through the use of whole-exome sequencing. Theirs studies were done on large Middle Eastern families that suffer from autism. Their study was just published in the journal Neuron.

Autism

Autism

According to the research team, they found that multiple genes that are implicated in different genetic syndromes may also suffer a less sever mutation and become the cause of autism. Tim Yu, Maria Chahrour and Christopher Walsh, the three leaders of the research team, began their study with three large families from the Middle East. Each family had at least two children who suffered from ASDs (Autism Spectrum Disorders). They searched each family for traces of recessive mutations. According to Dr Walsh, they investigated Middle Eastern families due to the fact that US families are usually smaller.The parents from all the three families that were investigated are first cousins. This is a common tradition in Middle Eastern families, and has aided the research greatly. Genetic mapping techniques were used to narrow the search to various specific chromosomal locations. This was followed by the sequencing of protein-coding genes (also known as whole-exome sequencing). The investigators discovered three new mutated genes that weren’t formerly associated with autism. However, one of these genes, the AMT gene, is associated with glycine encephalopathy, a very sever metabolic syndrome with exclusively neurological symptoms. The second gene, known as PEX7, is related to rhizomelic chondrodysplasia punctata, a genetic syndrome that causes seizures, congenital cataracts and death. The third gene, named SYNE1 is associated with severe motor problems and brain malformations. All these syndromes include either intellectual disabilities or autistic behavior, but neither are considered to be the primary symptom.

Maria Chahrour, the first author of the study, notes that their research is the first to link these three genes to autism. She added that “The AMT and PEX7 mutations weren’t picked up by standard tests for metabolic disorders, but when you’re able to sequence the entire exome, you can find them”. A total of 163 Middle Eastern families which had two or more children suffering from autism were included in the study. The scientists searched for different metabolic and genetic syndromes that affect the brain functions. A total of 70 genes were studied, all implicated in different syndromes. They used the same whole-exome sequencing technique in order to analyze the mutations of these genes, thus allowing them to discover several new mutations that can be linked to autism spectrum disorders. Researchers also linked the genes VPS13BPOMGNT1 and MECP2. The first gene is linked to the Cohen syndrome, the second gene is linked to several brain malformations, whilst the third gene is linked to Rett syndrome.

“We have textbook descriptions of all these diseases, but in real life, there can be atypical, milder presentations of the same disease,” says Yu, also a first author in the study. Along with the Middle Eastern families, researchers also investigated data from 612 families from the United States and found at least two gene mutations that were similar in both family cohorts. According to Yu, further studies will allow a rough estimation on the number of autism cases that follow this pattern.

3759

Smoking, high blood pressure and cholesterol increase the mortality rate in stroke patients

According to a Finnish study published in Neurology, patients who had subarachnoid haemorrhage (SAH) have an increased risk of death due to ischemic stroke or hemorrhagic stroke. In addition, it appears that the risk of mortality in these patients is double compared to the general population. The study, led by HUCH, the University of Helsinki, and the Finnish National Institute for Health and Welfare, is one of the largest population-based follow-up study conducted so far on the mortality rate of patients who experienced SAH.

Smoking, high blood pressure and cholesterol increase

images

Neurosurgeon Miikka Korja from the HUCH’s Neurosurgery Department, said that patients who had subarachnoid haemorrhage should be very careful to control cardiovascular risk factors such as smoking, high cholesterol and hypertension. He added that these are primary risk factors for cerebrovascular events, besides age.

The study included 64,000 Finns aged between 25 and 74 years. It was found that, of these, 437 have suffered a subarachnoid haemorrhage during research. Among those who suffered SAH, approximately half of the patients (233) were alive at one year after the episode. After being followed for 8.6 years, 88 (37%) of the 233 died during follow-up.

It was found that the death rate in this group of patients was double compared with the mortality rate calculated in the general population. Regarding the causes of this increased mortality, it was found that the main cause of death was a disturbance of cerebral circulation, that is an ischemic or hemorrhagic stroke. It was also noticed that this mortality rate was  increased by risk factors such as smoking, high cholesterol and hypertension.

“When comparing the continued mortality of SAH survivors to the general population that did not smoke and had low blood pressure and low cholesterol levels, the risk of mortality showed an increase of 31 persons per thousand person-years” Korja mentioned. Therefore, by controlling risk factors, cerebrovascular events, that lead often to premature death, can be prevented. Korja said it is very important that risk factors be controlled since the acute phase of the disease. It is also essential that the patient understand the importance of lifestyle and risk factors (smoking, high cholesterol, hypertension) in secondary prevention of stroke. Another Finnish study published earlier showed that the primary cause underlying SAH is not a genetic predisposition, but the way of life.

Professor Jaakko Kaprio from the University of Helsinki’s Hjelt Institute, pointed out that lifestyle changes can reduce not only the occurrence of SAH but also mortality in those who survive after such an episode.

3468

New treatment options for children with severe juvenile idiopathic arthritis

According to a study published in the New England Journal of Medicine, juvenile idiopathic arthritis children now benefit from new treatment options. Recent studies conducted by the Paediatric Rheumatology International Trials by Organisation (printout) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)  showed that tocilizumab and canakinumab alleviate symptoms in children with juvenile idiopathic arthritis and reduce the dose of oral corticosteroids.

Juvenile idiopathic arthritis is an inflammatory disease that affects the joints and connective tissues of the various organs: blood vessels, pericardium, peritoneum, pleura, iris etc. The disease occurs in children under 16 years and manifests, besides arthritis, through fever, rash, lymphadenopathy, hepatomegaly, splenomegaly, iridocyclitis, etc.. There are three forms of juvenile idiopathic arthritis: oligoarticular type,  polyarticular type and systemic type. Systemic juvenile idiopathic arthritis (SJIA) represents approximately 15% of cases of juvenile idiopathic arthritis.

juvenile idiopathic arthritis

juvenile idiopathic arthritis

The treatment of  this disease consists of corticosteroids (prednisone) as it is an inflammatory disease, but this treatment has many side effects. Corticosteroids cause fluid retention, hypertension, glaucoma, peptic ulcer, impaired phosphocalcic metabolism, impaired growth and development, etc.. It should be noted that this treatment does not target the disease, so it does not cure the disease, it only relieves symptoms.

Now, according to recent studies, it appears that the prognosis of these patients is improving as new therapies proved efficient in relieving symptoms and decreasing the dose of corticosteroids. The two biologic drugs were safe and effective in patients with SJIA according to studies. Dr. Rayfel Schneider, Project Investigator and Staff Physician in the Department of Rheumatology at SickKids, said that these children are very difficult to treat and this research is a big step forward in the treatment of patients with SJIA. He added that no unanticipated side effects were observed in them and that, if there were present, adverse reactions were similar of other drugs of the same class.

These therapies use drugs that block molecules involved in inflammation, namely interleukin 6 and interleukin 1. Tocilizumab is a drug that blocks IL-6 and seems to be highly effective, and safe in children with severe and persistent SJIA. After only one year of treatment, one-third of patients had no active disease and almost half dropped completely to treatment with corticosteroids.

Canakinumab, another drug that inhibits interleukin-1 beta, has been evaluated in two studies. First it was tested whether this drug is effective in controlling fever and arthritis, and in the other study it was evaluated the efficacy and safety of this drug in the management of patients with SJIA. It was found that even a single administration of the drug can inactivate disease and that after 7 months of treatment patients did not need steroid treatment.

5255

Lower birth weights associated with vitamin D deficiency during pregnancy

According to a study published online in the Journal of Clinical Endocrinology & Metabolism, vitamin D deficiency during pregnancy affects baby’s weight at birth. This is the conclusion reached by researchers at the University of Pittsburgh Graduate School of Public Health, after analyzing a sample of 2146 pregnant women. Senior author Lisa M. Bodnar, Ph.D., MPH, RD, assistant professor in Pitt’s Department of Epidemiology Public Health, said that this is one of the largest studies that analyses the vitamin D levels in pregnant women and the relationship with the child’s weight at birth.

Lower birth weights

Lower birth weights

Lead author Alison Gernand, Ph.D., MPH, RD, a postdoctoral associate in Pitt Public Health’s Department of Epidemiology, wanted to mention that vitamin D deficiency in early pregnancy leads to impaired fetal growth later in pregnancy. Also, it appears that low levels of vitamin D in the first trimester is correlated with 2-fold higher risk of growth restriction in utero. It is important to note that vitamin is deficient in people with darker skin. Researchers found that half of black women and 5% of white women in the U.S. have low levels of vitamin D.

 These conclusions were drawn after Dr. Gernand and her colleagues found that women who had vitamin D levels less than 37.5 nmol / L  had children with 46 grams less than their peers at birth. It must be said that study included only children born at term that is between 37 and 42 weeks. In addition, it was also found that women who had in the first trimester, that is during the first 14 weeks, low levels of vitamin D  had children with a lower  weight  for gestational age. These babies are called “small for gestational age. “

Vitamin D is a vitamin hormone and is one of the few vitamins that is formed in our body . Cholecaciferol or vitamin D is synthesized in the skin from cholesterol by sunlight. Therefore, vitamin D supplementation is recommended during the  cold season, when there is no sun. After being transported to the liver and then to the kidney, vitamin D becomes active, that is it may exercise its functions to stimulate calcium absorption. But besides the well-known role in phosphocalcic metabolism, it seems that vitamin D has also a role in immunity, cardiovascular disease, cancer, etc..

Apparently low levels of vitamin D leads to lower birth weights because it affects bone growth in children by preventing the absorption of calcium. It is also likely that  the hormone levels needed to produce fatty acids and glucose for fetal energy needs, are affected too.

 

 

 

3221

 Targeted molecular therapy for untreatable NF1 tumors

A targeted molecular therapy has been used successfully by researchers from Cincinnati Children’s Hospital Medical Center to treat nerve tumours that appear in people with neurofibromatosis type 1. The results of this study were published in the Journal of Clinical Investigation.

Nancy Ratner, PhD, principal investigator and the program leader for the Cancer Biology and Neural tumors Program, said it is the first time researchers could reduce the size of neurofibromas with a molecularly targeted therapy. She added that so far there was no treatment for neurofibromas. Surgery may be a solution to remove neurofibromas that compress organs but resection is sometimes difficult.

 NF1 tumors

NF1 tumors

Neurofibromatosis type 1 is a genetic disorder that is manifested by hyperpigmented skin spots and tumors of the nervous system. Patients with neurofibromatosis type 1 have cafe au lait spots, neurofibromas, speech disorders, epilepsy, optic nerve glioma, bone disorders and others. The disease is progressive, some signs appear at birth while others appear with age. Complications of this disease are chronic pain due neurofibroamas that compress nerves, blindness, chronic hypertension, and other neurological symptoms that occur due to brain tumors.

Neurofibromas are benign tumors localized on peripheral nerves and occur in approximately half of patients with neurofibromatosis. Although initially not cause major symptoms, however there are cases where neurofibromas increase dramatically and cause compression of the surrounding organs. There is a possibility that they turn into malignant tumors and become the cause of death of these people. Mutations of the NF1 are also found in other cancers such as glioblastoma, lung adenocarcinoma and ovarian cancer.

Researchers tested an experimental drug called PD0325901, which inhibits the protein MEK, and it was proved to reduce tumors sizes in neurofibromatosis in 80% of treated mice. MEK is part of a signaling pathway that promotes cell growth and it is involved in tumour formation. PD0325901 is now in clinical investigations in humans to treat cancer.

Researchers found that the drug can reduce tumor size in just 60 days. In addition, it was also showed that PD0325901 can reduce the size of malignant tumors in mice implanted with human MPNSTs (malignant peripheral nerve sheath tumors) and doubled the length of survival, that is to 52 days.  However, the researchers stressed that the size reduction  of malignant tumors compared with benign tumors is modest,  and that it is likely that other signaling pathways are involved. It is possible that in the future PD0325901 to be used in combination with other drugs to treat cancer.

2695

GIST Tumours

Researchers at Dana-Farber Cancer Institute have showed that a new drug can help patients with metastatic GIST tumors. They conducted a worldwide clinical trial, which showed that the oral drug regorafenib may prolong survival by about four months in patients who do not respond to Gleevec and Sutent treatment.

GIST means gastrointestinal stromal tumor and is the most common gastrointestinal mesenchymal tumor. These tumors can be located anywhere in the digestive tract: esophagus, stomach, duodenum, small intestine and colon or rectum, but most are in the stomach. It is important to note that GIST is a non-epithelial tumor. So far studies show that these tumors arise from intertstitial Cajal cells, that is cell of the autonomic nervous system, and that the proliferation of this tumour is linked to a transmembrane receptor tyrosine kinase Kit (CD117). Over 90% of GIST tumors express this marker (CD117 ) but others are also present, such as CD34 or desmin or vimentin.

GIST tumours

GIST tumours

These tumors have nonspecific symptoms: abdominal discomfort, abdominal pain, bleeding, anemia. It may happen that tumors are discovered incidentally on routine examination by palpation of abdominal masses. In terms of diagnosis, imaging can be used (computed tomography, ultrasound, etc.), but the final diagnosis is given by biopsy. Basic treatment consists of surgical excision and cure rate depends on tumor stage, tumor size and the presence of metastases.

Tumours up to 2 cm in size and with low mitotic rate have good prognosis and surgical cure seems to be sufficient, but larger tumors need adjuvant  treatment with imatinib and sunitinib. These two drugs have significantly improved the survival of patients with advanced disease. However 85% of patients become resistant to these treatments after several years and the prognosis gets worse.

According to the study led by researchers at Dana-Farber Cancer Institute, the oral drug regorafenib can prolong survival in patients in which the current treatment has no effect. George Demetri, MD, of Dana-Farber, principal investigator of this clinical trial, said the study results showed that the drug significantly improves overall survival in patients in which other therapies failed.

The study, whose results were published in the Lancet, was conducted on 199 treatment-resistant GIST patients at 57 hospitals in 176 countries. Of these, 133 received regorafenib for three weeks and the rest received placebo. It should be noted that the drug did not result in tumor reduction, it only prolonged the survival. In addition, there have been reported a number of adverse effects such as hypertension, fatigue, diarrhea, redness, peeling of the skin.

 

 

2836

Phase 3 Clinical Trial Confirms Abiraterone Acetate Effectiveness in Metastatic Prostate Cancer

The newest results coming from a phase 3 clinical trial show that the drug marketed as Zytiga (abiraterone acetate) has beneficial effects on the survival rate of patients with metastatic prostate cancer. The study was published in the journal Lancet Oncology and the clinical trial behind the study had investigated patients with castration-resistant prostate cancer.

The action mechanism of the drug involves the blocking of an enzyme that has a  role in the production of testosterone. This hormone is responsible for the proliferation of cancerous cells, thus through its action, the drug can reduce or even stop the growth of the prostate tumor.

This is the first phase 3 clinical trial that is able to show that abiraterone increases the survival rate of prostate cancer patients. The trial involved almost 1200 patients from 13 different countries. Participants were divided into two groups. The first group received abiraterone and prednisone whilst the second group received placebo and prednisone.

Prior to being selected to take part in this trial, all patients underwent at least one round of chemotherapy with Docetaxel. This chemotherapy round showed little to no effect in the stopping of cancer progression. The research team observed that the group that received abiraterone acetate had an average survival time of almost 16 months, compared to a survival time of 11 months in the placebo group.

Zytiga

Zytiga

 Patients that had metastatic prostate cancer have a survival time of less than two years, even after undergoing chemotherapy. Therefore, the increased survival time that is obtained through the use of abiraterone acetate is considered to be a real improvement for patients that continue to experience the growth of the tumor after the treatment with Docetaxel is stopped. Furthermore, the clinical trial has revealed that abiraterone acetate has a good safety profile. All the adverse side effects caused by the use of abiraterone were reversible.

“Our work confirms that abiraterone acetate can be used as an effective and safe treatment for castration-resistant metastatic prostate cancer patients whose disease continues to progress after docetaxel treatment”, said Dr Karim Fizazi from the Gustave Roussy Institute, in France. Dr Fizazi is one of the lead authors of the study. The director of the Urologic Medical Oncology from the University of Alabama, USA, Dr Guru Sonpavde, said that this study represents a major advancement in the treatment of metastatic prostate cancer and castration-resistant prostate cancer. Dr Sonpavde added that further clinical trials are needed in order to improve the survival time of prostate cancer patients.

2846
salt on food

Salt on food

Researchers have found that stress causes the body to retain more sodium and this leads to high blood pressure. Dr. Gregory Harshfield, hypertension researcher at the Institute of Public and Preventive Health at Georgia Health Sciences University, said that sodium retained by the body due to stress is equivalent to the amount of sodium found in a small portion of French fries or a small bag chips.
Sodium, which is found in full in processed foods or fast foods, causes water retention, and this causes, in turn,  high blood pressure. The amount of sodium that body needs daily is about 1500 milligrams. However, the average daily salt consumption is double the daily requirement, that is about 3700 milligrams. Salt increases blood pressure, and this contributes to increased cardiovascular risk. Interestingly, the researchers found that sodium retention caused by stress lead to increased blood pressure for longer periods than usual. In addition, it seems that blood pressure remains high also during the night. Usually sleep must allow the body to recover and it should not be affected by stress.
Dr. Harshfield said that stress causes retention of approximately 160 milligrams of sodium, which leads to increased blood pressure by about 7 points with than normal. In addition, blood pressure remains elevated longer. Studies done by Dr. Harshfield have shown that blacks retain more sodium than whites and for longer period of time. Researchers also found that sodium effects can be blocked by a class of drugs used in cardiology, called angiotensin receptor blockers. This discovery is exciting because it is  known that blacks have high levels of angiotensin and this drug is rarely used in this population. Angiotensin receptor blockers prevent angiotensin to bind to its specific receptors, that is angiotensin is a potent vasoconstrictor agent.

Angiotensin is part of the renin-angiotensin-aldosterone system, which plays a role in controlling blood pressure. Renin is an enzyme secreted by the kidney in response to the action of the sympathetic nervous system, which may be triggered by stressfull situations. Once secreted,  renin activates angiotensin to bind to receptors from the muscle blood vessels causing vasoconstriction. In addition, angiotensin determine also the release of aldosterone, a hormone secreted by the adrenal gland. Aldosterone also leades to  high blood pressure through sodium retention. Angiotensin receptor blockers (ARBs) are found collectively as ARBs: candesartan, valsartan, losartan and others. ARBs are used, as well as converting enzyme inhibitors, for lowering blood pressure, heart failure, and other cardiovascular diseases.

3445

New Therapeutic Target for Parkinson’s Disease Investigated By Scientists At The University Of Houston

Researchers at the University of Houston (UH) have discovered a new therapeutic target against Parkinson’s disease. They are optimistic that with this new therapeutic target, a nuclear receptor called liver X receptor beta (LXRbeta), Parkinson’s disease can not only be prevented but also treated. The study was conducted by researchers from the UH, Center for Nuclear Receptors and Cell Signaling (CNRCS), and published in the Proceedings of the National Academy of Sciences (PNAS).

Parkinson’s disease is a neurological disease that occurs due to insufficient production of dopamine in the brain. The disease is manifested by generalized skeletal muscle hypertonia and hypokinesia. Therefore, symptoms such as stiffness and fine tremor of the extremities appear. In more advanced stages, there are also symptoms regarding cognitive impairment: behavioral disturbances, sensory impairment, dementia. The most striking symptoms in Parkinson’s disease are related to movement. Patients with Parkinson’s disease have a specific walking with the trunk flexed forward and postural instability. Fine tremor of the extremities is also a characteristic symptom. Other signs and symptoms that occur are speech and swallowing impairments, voice changes and others.

Parkinson’s disease is a disease that affects mainly elderly and it is believed that it develops due to dopaminergic neuronal loss in the brain. These dopaminergic neurons play a role in controlling body motility and movement. This hypothesis is confirmed by the fact that blocking dopamine neurons in the brain by certain drugs (neuroleptics) cause a parkinsonian syndrome, similar to Parkinson’s disease.

Parkinson’s disease treatment aims to increase dopaminergic activity in the brain. Therefore, there are used drugs that either increase synaptic dopamine release or inhibit its degradation (selegiline). Another useful drug in Parkinson’s disease treatment is levodopa, which acts as a dopamine precursor. Other useful drugs are dopamine receptor agonist, such as bromocriptine, which allow lower levodopa doses.

Parkinson's Disease

Parkinson’s Disease

Researchers at the University of Houston (UH) have discovered that the nuclear receptor, liver X receptor beta (LXRbeta), which is found in microglia, plays an important role in the survival of dopaminergic neurons. This receptor has been discovered in 1995 and latest experiments showed that this receptor continue to show promise as a potential therapeutic target for this disease, as well as other neurological disorders..

To understand the relationship between LXRbeta and Parkinson’s disease, researchers used a very potent neurotoxin, called MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridina). MPTP is a compound found in street drugs, and it was observed that cause Parkinson’s disease in people who consumed this drugs. In their study, researchers used  MPTP in murine models to simulate the disease and to study its pathology and possible treatments.

The results showed that MPTP had a far more damaging effect on neurons in the absence LXRbeta. Additionally, scientists found that administrating a drug that activates LXRbeta receptors, they can prevented the destructive effects of MPTP and, therefore, may offer protection against midbrain neurodegeneration.

LXRbeta is not expressed in the dopamine-producing neurons, but instead in the microglia surrounding the neurons. Microglia are the police of the brain, keeping things in order. In Parkinson's disease the microglia are overactive and begin to destroy the healthy neurons in the neighborhood of those neurons damaged by MPTP. LXRbeta calms down the microglia and prevents collateral damage. Thus, we have discovered a novel therapeutic target for treatment of Parkinson's disease., Gustafsson, CNRCS director and professor whose lab discovered LXRbeta in 1995, said.

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