Myasthenia Gravis – Causes And Symptoms

Myasthenia gravis is an autoimmune disease that affects 5 in 100,000 individuals and is more common in women, sex ratio being 2/1 for women. The disease has two peaks of incidence: between 20 and 30 years  and a second peak between 50 and 70 years. Excepting congenital form, onset in adolescence is rare.

Myasthenia Gravis Causes

Myasthenia gravis is an immunologically mediated disease in which antibodies are directed against the acetylcholine receptor, causing disturbances in the functionality of acetylcholine receptors and in neuromuscular transmission, leading to muscle fatigue. Anti-acetylcholine antibodies are considered essential in the development of the disease.

Anti-acetylcholine antibodies levels are increased in 80% -90% of patients with myasthenia gravis, while 10% -20% of patients do not present elevated levels of these antibodies.

Increased levels of anti-acetylcholine antibodies are correlated with disease severity. The form of disease with ocular onset is correlated with low levels of these antibodies.

Anti-acetylcholine antibodies are highly specific for the disease and essential for diagnosis. Their biological significance is not fully known, but it is considered that they may not be the only causative factors of the disease, knowing that are absent in 10% of patients with myasthenia gravis  and in 40% of patients with ocular form of the disease anti-acetylcholine antibodies are not present.

The mechanism by which anti-acetylcholine antibodies produce the disease is not fully known. In myasthenia gravis, there is a reduction in the number of acethilcholine receptors available at the muscle endplate and flattening of the postsynaptic folds. Due to this events, even if a normal amount of acethylcholine is released, fewer endplate potentials will be produced, being insufficient to generate an action potential. The result of this process is inefficient neuromuscular transmission, explaining the muscle fatigue seen in myasthenia gravis patients.

Myasthenia Gravis

Myasthenia gravis symptoms appear when the number of acethlycoline receptors is reduced to approximately 30% of normal. Due to the fact that cholinergic receptors of cardiac muscle have a different antigenicity than skeletal muscle, cardiac symptoms are not specific for the disease.

The decrease in the number of acethylcoholine receptors is the result of  an autoimmune process that produce  anti-acthylcholine antibodies against this receptors, causing an increase turnover of  actehylcholine receptors.

Stimulus for anti-acetylcholine antibodies formation is uncertain, but however, the thymus seems to have an important role because most patients with myasthenia gravis present a thymic abnormality in the form of thymoma or thymic hyperplasia. Thymoma is detected in 9% -16% of patients and between 47% -81% of patients have thymic hyperplasia.

Autoimmune mechanism of the disease is supported by the fact that myasthenia gravis is frequently associated with other autoimmune diseases such as rheumatoid arthritis, lupus, polymyositis and autoimmune thyroiditis.

Myasthenia Gravis Symptoms

Myasthenia gravis is a neuromuscular disorder characterized by excessive fatigue of skeletal muscle at normal physical activity. The characteristics of the disease are:

• Deficits restoration at rest;
• Diurnal fluctuation of symptoms;
• Affecting a certain muscle group;
• Evolution with intermittent remissions.

Muscle fatigue can become pseudo-paralytic, with transient paresis which improve at rest and anticholinesterase medication. The two important clinical aspects of myasthenia gravis are distribution and fluctuation character of muscle fatigue. Muscle fatigue is more pronounced in the second part of the day.

Myasthenia Gravis

There are two clinical forms, cephalic or superior form and generalized form. In most cases, the disease begins at the cephalic muscles, especially in the eye muscles, and for 15% of patients symptoms are limited to this level (ocular myasthenia). Bulbar muscles is then affected and generally within about three years disease spreads to other muscle groups.

Onset is usually insidious over 4-6 months, with a slowly progressive symptomatology, that is affecting, over time, all muscle groups. There are forms of disease with rapid evolution, within a few days with respiratory failure, which occurs most often after a respiratory infection or psychological trauma. The disease can also debut in pregnancy.

Symptoms may be exaggerated after administration of certain drugs: nondepolarizing skeletal muscle relaxants, quinidine, procainamide, benzodiazepines, beta blockers, corticosteroids, etc..

Hypocalcemia, hypokalemia, hypothyroidism and hyperthyroidism can aggravate the symptoms.

Superior or cephalic form of myasthenia gravis

Ocular symptoms occur at onset in 50% of cases and in evolution are present in over 90% of patients. Most commonly occurs palpebral ptosis and diplopia. Palpebral ptosis is bilateral, unequal, alternate, asymmetric and is caused by upper eyelid levator muscle weakness. Diplopia and strabismus, with limited eye movements, are caused by extrinsic eye muscle weakness. Symptoms  are more pronounced in the second part of the day.

Myasthenia Gravis Ocular Form

Bulbar or facial form of myasthenia gravis

Facial muscles involved in chewing, swallowing and speaking are affected in 80% of cases. Approximately 60% of patients can not smile and thus appear myasthenic snarf, in which the upper lip rises vertical (horizontal laughter). Myasthenic facies is characterized by a tired expressions, poor gestures, with tight lips, half-closed eyes and the disappearance of physiological folds. Nasal twang to the voice and nasal regurgitation of food,especially liquids, appear due to palatal muscle weakness. Chewing may become difficult and severe jaw weakness may cause the jaw to hang open (the patient may support  his chin with the hand ). Fluid aspiration may occur, causing coughing or choking while drinking. Tongue mobility disorders occur rarely and may cause the appearance of  furcus myasthenicus (three longitudinal grooves on the tongue surface). Fasciculations are not characteristic for the disease.

Severe symptoms of  bulbar form may announces, or sometimes may accompany, the appearance of myasthenic crisis.

Autoimmune Disease

Generalized form of myasthenia gravis

In generalized form, first are affected neck muscles, then in evolution are affected proximal limb muscles and finally back muscles. Muscle fatigue occur at a minor physical effort. Weakness is most often in proximal limb muscle, patient being unable to  stand up from a chair and to raise his arms above his head. Over time, most affected muscles may suffer atrophies. In severe cases of myasthenia gravis, diaphragm and intercostal muscles may be affected.

Generally, pain is not characteristic for  myasthenia gravis and if pain occurs is due to extreme muscle fatigue of neck, back and trunk muscles.

The evolution of the disease is different, depending on the affected muscles, severity of the disease and age of onset. The disease is often unpredictable, with remission, but there is the possibility of rapid decompensations, with the occurrence of acute respiratory failure. Decompensation of a patient with myasthenia gravis occurs due to infection, high temperature environment, surgery, trauma and stress. In the first years after onset, decompensations are more frequent.

New Study Allows Fetal Genome Sequencing From Maternal Blood Samples

Scientists from the Stanford University School of Medicine have managed to sequence the genome of a fetus through the use of a blood sample taken from the mother for the first time. The new discovery has been published on the 4th of July, in the journal Nature. The new discovery is based on research done by scientists at the University of Washington, who were able to sequence the genome of the unborn child by using DNA samples of the parents and the mother’s blood sample.

One of the breakthroughs made by the researchers at Stanford was that DNA from the father was no longer required for the genome sequencing. This is especially useful if the father of the child is unknown or if the father doesn’t want to give a DNA sample. “We’re interested in identifying conditions that can be treated before birth, or immediately after”, said Professor Stephen Quake, Ph.D., who is also the lead author of the study.

Scientists say that because the costs of this new technology will probably continue to drop, thus allowing researchers to discover genetic disorders within the first trimester of pregnancy. Through this new study, researchers have also shown that sequencing the exome, which is only the coding part of the genome, can be relevant to further clinical studies.

In their research, scientists managed to sequence the exome and genome of an unborn child, thus discovering it suffered from a syndrome called DiGeorge. This is caused by a deletion of the chromosome 22 and cause various symptoms, the most common symptoms being neuromuscular and cardiac problems. The severity of the manifestations can vary from patient to patient.

“In this paper, Quake’s group elegantly shows how sequencing of the exome can show that a fetus has inherited DiGeorge syndrome from its mother”, said Dr. Diana Bianchi, the director of the Mother Infant Research and also member of the Verinata Health Inc., the company that had already provided genetic testing by using earlier technology also developed by Professor Stephen Quake.

Close View of a DNA Strand

Prenatal diagnosis is not a new technology. Women have been undergoing different tests, such as amniocentesis and chorionic villus sampling, as an attempt to early diagnose if their children suffer from genetic disorders. These sort of tests involved obtaining cells from the unborn child through the use of a needle inserted in the uterus. This procedure is dangerous and can lead to miscarriage rather often, whilst also being able to detect only a small number of genetic disorders.

The new technology developed by Dr. Quake is based on the fact that the pregnant woman’s blood also contains the DNA of her fetus. Back in 2008, Dr. Quake’s laboratory managed to pioneer the use of fetal DNA levels in maternal blood in order to diagnose conditions such as Down syndrome or other genetic disorders caused by missing or extra chromosomes. This test is currently being marketed by four companies in the United States. However, these tests do not offer a full genetic profile, thus not being able to discover more subtle genetic disorders.

 The new study has taken blood sampling a step further. By comparing the relative levels of DNA from regions containing both maternal and paternal DNA, scientists managed to identify and isolate the fetal DNA. Maternal DNA can be found in both the mother and the fetus whilst paternal DNA can only be found in the fetus. The new method has been tested on a number of two pregnancies. One of the mothers was suffering from the DiGeorge syndrome whilst the other didn’t. The sequencing of the genome and exome of the mother suffering from the DiGeorge syndrome showed that her unborn child would also suffer from the same genetic disorder.

“We always knew that detecting fetal chromosomal abnormalities was just the tip of the iceberg, and that diagnosing individual gene defects was the future. This important study confirms our ability to detect individual fetal gene defects simply by testing mom’s blood”, said Dr. Yair Blumenfeld, the co-author of the study, who is also an assistant professor.

Scientists from the Stanford University School of Medicine are already planning on developing this new technique in order to provide it for clinical use.

Myeloproliferative Disorders

Myeloproliferative disorders are clonal hematopoietic neoplastic diseases that originate from an abnormal stem cell.  In all myeloproliferative disorders the proliferation capacity of abnormal stem cell is not adequately controlled and for this reason an excessive and ineffective hematopoiesis occurs. One of the neoplastic stem cell characteristic is to maintain its differentiation capacity and therefore, in peripheral blood is an increased number of  mature and immature neoplastic cells.

Detection of chromosomal abnormalities by cytogenetic techniques continues to be a major instrument in the investigation of malignant hematological disorders because can provide important information about diagnosis, evolution and prognosis of the disease.

These molecular cytogenetic tests can detect chromosomal anomalies and hybrid oncogenes and can also determine the exact percentage of malignant cell clones.

Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes are considered preleukemic syndromes, situated at the boundary between refractory anemia and acute myelogenous leukemia. MDS occur more frequently in adults, over the age 50 years.

According to FAB classification (French American British) myelodysplastic syndromes are divided into:

• Refractory anemia;
• Refractory anemia with ringed sideroblasts;
• Refractory anemia with excess blasts;
• Refractory anemia with excess blasts and in transformation;
• Chronic myelomonocytic leukemia (CMML).

Clonal chromosomal abnormalities (monosomies, trisomies or structural abnormalities) can be seen at the initial cytogenetic analysis of bone marrow or as a result of karyotype evolution during disease progression.

Main karyotype changes refer to a loss of genetic material:

• Deletions of long arm of chromosome 5 or chromosome 7;
• Partial monosomy of chromosome 5 or chromosome 7;
• Total monosomy of chromosome 5 or chromosome 7.

Myelodysplastic Syndrome

Chromosomes 5 and 7 are known as carriers of various oncogenes and deletions at their level may lead to their alteration and consecutive appear neoplastic growth factors that lead to abnormal clones proliferation.

Chromosomal abnormalities are not specific associated with a particular group of FAB classification, except for deletion of long arm of chromosome 5 that is associated with refractory anemia.

Evolution of patients with MDS to acute myeloid leukemia occurs mostly in cases where there are total monsomy of chromosomes 5 and 7 or in the case of multiple chromosomal abnormalities. Increased complexity of genetic abnormalities was correlated with a short survival and probably reflects the expansion of unstable genetically clones.

In children with myelodysplastic syndromes most commonly encountered are trisomy 8, monosomy 7, deletions of the long arm of chromosome 20 and deletions of the long arm of X chromosome. Total monosomy of chromosome 7 is specific for children with myelodysplastic syndromes and indicate a poor prognosis.

Patients with myelodysplastic syndromes and a normal karyotype have a better survival. Highlighting an unstable karyotype indicates a poor prognosis.

Acute Myeloid Leukemia (AML)

Most patients present clonal chromosomal abnormalities, along with cells with normal karyotype. Chromosomal abnormalities observed at disease onset disappear in complete remissions and reappear shortly before relapse.

FAB (French American British) classification of acute myeloid leukemia includes 8 subtypes and it is conceived upon morphological, enzymatic and immunological criteria. Due to constant and specific association of certain chromosomal abnormalities with morphological subtypes, some of the chromosomal abnormalities are assigned as complementary quality criteria for the classification of acute leukemia.

Subtype M0 (minimally differentiated acute myeloblastic leukemia): most patients present a single cytogenetic abnormality, of which the most common is trisomy 7 or total monosomy of chromosome 7. Prognosis of these patients is reserved, compared with other subtypes of FAB classification.

Subtype M1 (acute myeloblastic leukemia, without maturation): most are secondary leukemias with very severe prognosis and the most commonly encountered type of cytogenetic abnormalities are the loss of genetic material, for example total monosomy of chromosome 7. Philadelphia chromosome can be identified in some cases of M1 subtypes and indicate a very severe prognosis.

Subtype M2 ( acute myeloblastic leukemia, with granulocytic maturation): most patients have translocations between chromosomes 8 and 21. At the breaking point on chromosome 21 is located AML1 gene(acute myeloid leukemia 1), and at the breaking point of chromosome 8 is located MTG8 gene (myeloid translocation on 8). After translocation of these two chromosomes appear a hybrid gene called AML1/MTG8 which product seems to be the critical event in cancer cell proliferation. Among numerical chromosomal abnormalities found in AML, the most common is trisomy 8, which is correlated with this subtype and indicate a good prognosis. Other chromosomal abnormalities are represented by translocations between chromosomes 22 and translocations between chromosomes 6 and chromosome 9.

Acute Myeloid Leukemia

Full remission is achieved in 90% of cases and average survival is about 2 years.

Subtype M3 ( promyelocytic or acute promyelocytic leukemia ): translocation between chromosome 15 and chromosome 17 is considered to be the most specific chromosomal abnormality and is associated exclusively with M3 subtype, being present at about 100% of patients. Genes isolated from the breaking points are PML (promyelocytic leukemia) on chromosome 15 and RARA (retinoic acid receptor alpha) on chromosome 17. Protein encoded by hybrid gene PML / RARA inhibit cellular differentiation and determine clonal expansion of promyelocytes. Translocation between chromosomes 15 and 17 indicate a good prognosis because it was identified a specific therapy with retinoic acid that induces cell differentiation process, thus overcoming the stage of promyelocytes.

Subtype M4 (acute myelomonocytic leukemia): presents different structural abnormalities on chromosome 16, such as inversions, deletions and translocations between chromosomes 16. Patients with structural abnormalities of chromosome 16 have a better prognosis compared with patients in which chromosome 16 is normal.

Subtype M5 subtype (acute monocytic- monoblastic leukemia): among cytogenetic abnormalities found in this subtype most commonly are observed changes in the long arm (q) of chromosome 11, region 23 (translocations involving 11q23 and another chromosome, followed by interstitial or terminal deletions).

Molecular studies have isolated in the region 11q23, gene MLL (myeloid-lymphoid leukemia), which encodes  “zinc finger” domains that bind DNA, which requires its inclusion in the category of genes that are regulating cell differentiation process.

In order of frequency, translocations involving 11q23 region are:

• Translocations between chromosomes 9 and 11;
• Translocations between chromosomes 11 and 19;
• Translocations between chromosomes 6 and 11;
• Translocations between chromosomes 1 and 11.

Structural rearrangements in the 11q23 region are associated with a poor prognosis.

Subtype M6 (acute erythroid leukemia) is a rare form of AML, characterized by the presence in the bone marrow of dysplastic erythroblasts. This subtype is characterized by complex cytogenetic abnormalities and by chromosomal karyotype instability.

Subtype M7 (acute megakaryoblastic leukemia): although chromosomal abnormalities in this subtype are nonspecific, were observed aberrations of chromosome 3, inversions or deletions of this chromosome have a higher incidence when there is present an abnormal megakaryocytopoiesis.

Sleep Apnea Harmful Effects Noticeble After Just One Moth Of Onset

According to a study conducted by researchers from Texas, sleep apnea, a breathing disorder, can lead to impaired cerebral blood vessels as quick as 30 days after onset of symptoms.

Sleep Apnea

Sleep apnea is a breathing disorder characterized by repeated pauses in breathing during sleep. There are three types of sleep apnea, obstructive form , central form, and mixed form. It should be noted that such episodes last 10 seconds each, and the number of periods of apnea varies from 5 to 50 per hour of sleep. Depending on the severity of sleep apnea, it can be mild, moderate or severe. In terms of obstructive sleep apnea, there are several causes such as obesity, tonsilar hypertrophy , scoliosis, alcohol consumption etc. Patients with sleep apnea snore, present a restless sleep, daytime sleepiness, irritability and decreased concentration. Also, due to decreased oxygenation during sleep, morning headache frequently occurs.

Sleep Apnea

The mechanism underlying sleep apnea consists of airway collapse, which translates to snoring followed by periods of apnea. The patient wakes up from sleep, falls asleep again and the episode occurs again dozens of times each night. Cessation of breathing causes decreased oxygen and increased carbon dioxide in the blood stream. Decreased oxygen leads to  nervous system and cardiovascular overload. Gradually  patients may develop coronary artery disease, hypertension and other complications. Therefore, effects of sleep apnea can be very serious. According to Mr. Crossland “OSA Can have a detrimental impact on a person’s body and off their life. It is a Serious, yet treatable, disorder should not be taken that lightly”.

Although the link between sleep apnea and stroke has been established, the consequences of episodes of apnea on cerebral circulation has not been documented. Therefore, researchers in Texas have developed an animal model to study the effects on cerebral circulation. The researchers induced 30 episodes of apnea lasting 10 seconds, during an 8 hour sleep on laboratory animals. The experiment lasted one month. The interesting fact is they have found that after only 30 days, they were able to observe changes of the cerebral vessels. Dilatory function was reduced by 22%. Researcher Randy Crossland  remarks that there are two important aspects of this experiment. The first is that based on these animal models scientists can study disease in more detail. The second is the observation made by researchers, namely that after 30 days of sleep apnea, changes in the cerebral vessels occur, which increases the risk of stroke.

Sleep apnea effects on average 1 in 5 Americans, but estimated that the incidence of this syndrome will increase. Also, be taken into account that some patients with sleep apnea have not been diagnosed.

Vitamin D Does Not Improve Brain Activity in Teenagers

A new research published in the online Journal of Epidemiology and Community Health reveals that the brain activity of teens is not positively influenced by higher levels of vitamin D. According to precedent studies, higher levels of vitamin D directly influence the brain activity of adults.

The main goal of this current study was to investigate if vitamin D has the same effects on teenagers as it has on adults. Scientists have tested the effects of two different types of vitamin D: ergocalciferol (Vitamin D2 – sourced from plants) and cholecalciferol (Vitamin D3 – sourced from sunlight).

Their results are based on testing a little over 3000 children which had their D2 and D3 levels measured at approximately the age of nine. All of the tested children are part of a long-term health program called  the Avon Longitudinal Study of Parents and Children, which tracks numerous children that were born in the early 90s.

The academic level of the children was tested twice. The first time it was tested was at the age of 13, the second time being later, at the age of 16, when scientists evaluated the results the children had at the General Certificate of Secondary Education (GCSE) exams. The tested domains included English, science and mathematics.

Vitamin D

Children originating from disadvantaged backgrounds were found to have higher levels of Vitamin D2 whilst higher levels of Vitamin D3 was found amongst children originating from  less disadvantaged backgrounds. The study shows that high levels of Vitamin D3 is not linked to increased brain activity and better academic performance.

Poor English  skills has been observed in children aged 13 to 14 that had higher levels of D2. The study revealed that children aged 15 to 16 also received fewer high grades at the GCSE exams.

The leading authors of the study suggest that the study suggests that the beneficial effects of Vitamin D on the brain activity and academic performance might only surface later in life. They also note that the results might indicate that Vitamin D is more beneficial to the aging brain rather than the younger brain.

The authors point out that there have been many studies that indicate that there is an important link between the neurological functions of the brain and vitamin D. Because of these results, several changes regarding the protection against UV have been made in the public health guides.

“However, our results suggest that protection of children from UVB exposure, which has been associated with low levels of vitamin D, but which protects against skin damage and skin cancer, is unlikely to have any detrimental effect on academic achievement”, conclude the authors of the study.

 Smoking and Barrett’s Esophagus

New research conducted by the National Cancer Institute shows that smoking is a risk factor for Barrett’s esophagus, among gastroesophageal reflux disease.
Barrett esophagus is a lesion characterized by the appearance of islands of intestinal cells in the esophagus. Normally, the esophagus  is covered inside by a lining composed of squamous epithelium. Intestinal epithelium is usually caused by gastroesophageal reflux after repair response due to more rapid regeneration of epithelial ulceration with columnar epithelium. Therefore, Barrett’s esophagus occurs mainly in lower level near the gastroesophageal junction. It is important to notice that Barrett esophagus can be the cause of esophageal cancer.

Barrett’s Esophagus

However, new studies show that smoking is a major risk factor for Barrett’s esophagus. Michael B. Cook, Ph.D., of the National Cancer Institute in Bethesda, Md., nd associates have investigated five case control studies and found that Barrett’s esophagus is more common in people who  smoke. Researchers analyzed the cases of 1059  patients with Barrett’s esophagus , 1332 controls with gastroesophageal reflux disease (GERD), and 1143 population-based controls. Moreover, the risk of developing this disease is even greater as the number of cigarettes is greater.

Smoking is considered a risk factor for development of several cancers, most notably is lung cancer. The risk of lung cancer in smokers is 20-30 times higher than in nonsmokers. Besides the action of carcinogenic substances in tobacco smoke, the smoke causes bronchial cell metaplasia which in turn can progress to malignancy. Also, smoking is considered a risk factor for several cancers such as bladder cancer and kidney cancer or oropharyngeal cancer. Regarding the involvement of smoking in Barrett’s esophagus, it  is a well-known fact that smoking lowers the alkaline pancreatic secretion and cancel mechanisms of acid secretion inhibitors, leading to gastroduodenal ulcers. These changes are expressed clinical appearance of heartburn, which is a heartburn that disappears  to antacids.

The involvement of smoking in the Barrett esophagus is important because Barrett esophagus is one of precancerous lesions. Therefore, American College of Gastroenterology recommends endoscopy of all patients with reflux disease. If damage is found in the esophagus, the doctor can take biopsy for histopathological examination. In case of severe dysplasia, endoscopic mucosal resection is recommended. However, any patient with Barrett’s esophagus should be carefully monitored and evaluated.
Symptoms are similar to gastroesophageal reflux disease, chest pain that is burning nature,   that may increase in pain  when lying down, etc. Also, it is important to remember that Barrett’s esophagus to cancer is advancing early. Chromosomal aberrations or gene mutations can lead to inactivation of tumor suppressor genes. Once inactivated these genes, cancer cells divide, they begin to grow erratically, causing cancer.

Epilepsy-Like Symptoms Attributed To Stress And Poor Coping Skills

Doctors and psychologists at Johns Hopkins have noticed that more than one-third of patients admitted with the presumptive diagnosis of epilepsy do not actually have epilepsy and their seizures are actually caused due to stress. Doctors call these crises that mimic epilepsy psychogenic non-epileptic seizures (PNES). But unlike epilepsy, there is no discharge in the brain such as in epilepsy. Epilepsy is a neurological disorder characterized by sudden and intense electrical discharges in the brain This electrical activity is manifested clinically by seizures that affect control of movement, of speech, of vision and sometimes even consciousness. Keep in mind that not all people who have seizures also have epilepsy, because seizures can be caused by brain injury, aggression. In this case, seizures disappear when the triggering cause disappear. In children, for example, seizures may occur due to fever.

Epilepsy Seizures

Two types of seizures are described , generalized and partial. It is important to differentiate between the two types because the treatment options are different. The generalized discharges are due to electrical discharges on all surface of the brain, and can affect the entire body. The partial start from a specific area of the brain and affects only the body. There are several conditions that are similar but they’re not  seizures, such as strong headaches, muscle spasms, apnea, etc.. These events do not go with AEDs, which as proving that no seizure etiology. The psychiatrists called in the past these events “hysteria”. Doctors believed that crises were due to emotional distress converted into  physical symptoms.

The study conducted by a  team of neuropsychologists and neurologists at the Johns Hopkins University School of Medicine and published in the online journal ‘Seizures’, notes that people with epilepsy-like symptoms are not able to cope with stressful situations. “These patients behave as if they have organic brain disease year, But they do not,” says Jason Brandt, Ph.D., the study’s senior investigator and a professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine.

Researchers have tried to find out why some people are more likely to develop psychogenic non-epileptic seizures. therefore, The researchers analyzed more patients, including 40 with PNES, 20 epilepsy and 40 healthy individuals. When asked how often they experience stressful situations in their lives, patients with PNES reported a greater number of stressful situations. The researchers also found that those with PNES have difficulty getting out of a stressful situations,  have unstable relationships and high health care expenditures.

Marijuana-Like Compound Found Effective Against Late Stage HIV Infection

According to a new study published in the journal PloS ONE, researchers from Mount Sinai School of Medicine discovered that marijuana-like compounds can inhibit the multiplication of human immunodeficiency virus (HIV) in late-stage AIDS by acting on viral receptors.

Medical marijuana is prescribed in diseases which are accompanied by appetite suppression or by sever weight loss also for management of chronic pain, symptoms that are usually present in late stages of AIDS. Through this study, scientists found out that on the surface of immune cells a type of receptors called cannabinoid receptors, CB1 and CB2, are triggered by marijuana-like compounds and can inhibit the dissemination of human immunodeficiency virus throughout the body. It is very important for scientists to understand what are the effects of activated CB1 and CB2 receptors, because in the future they hope to be able to develop new drugs that can slow the progression of HIV infection to AIDS.

“We knew that cannabinoid drugs like marijuana can have a therapeutic effect in AIDS patients, but did not understand how they influence the spread of the virus itself. We wanted to explore cannabinoid receptors as a target for pharmaceutical interventions that treat the symptoms of late-stage AIDS and prevent further progression of the disease without the undesirable side effects of medical marijuana.”, leader of the study said.

HIV Infected Cell

When it enters the body, the HIV virus infects T helper lymphocytes (cells that are expressing CD4 receptor), making them ineffective in fighting infection. In order to disseminate, human immunodeficiency virus needs that inactive T helper lymphocytes to be activated by the immune system. In late-stages of AIDS, in viral genome mutations are produced in order to penetrate inactive T helper lymphocytes, action that is mediated by a signaling receptor called CXCR4. By using marijuana-like chemicals, cannabinoid receptor agonists which are able to activate CB2 receptors, researchers observed that activated CB2 receptor can block CXCR4 receptor, thus suppressing the spread of viral infection to inactive T helper lymphocytes.

By triggering CB1 receptors it was observed that marijuana-like compounds have the same effects as marijuana, causing unwanted side effects. Scientists want to develop marijuana-like compounds that are only triggering CB2 receptors, because this CB2 agonist reduce the infection of inactive T helper cells.

“Developing a drug that triggers only CB2 as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading,” researchers added.

It has been observed that HIV infects inactive T helper lymphocytes by using CXCR4 receptor only in advanced stages of AIDS, so marijuana-like compounds seem to be effective only in advanced stages of the disease.

Due to the fact that the results of this study were very promising in vitro, researchers want to develop a lab mouse model with late-stage of AIDS to test the effectiveness of marijuana-like compounds that are triggering CB2 receptors in vivo.

Study Links Antibiotic Use To More Severe Allergic Asthma Cases

A study conducted by researchers at University of British Columbia found out that the increased incidence and severity of allergies asthma in early life is correlated to the wide use of antibiotics. The study was published today in the journal EMBO reports.
The prevalence of allergic asthma is increasing by 5 per cent every decade, particularly in industrialized countries, and it affects nowadays more that 100 million people worldwide. The Asthma Society of Canada estimates that 12 per cent of children in Canada have been diagnosed with allergic asthma.

Antibiotic Drugs

The antibiotics that are active against intestinal bacteria also influence allergic asthma. UBC microbiologist Brett Finlay, the study’s author said “It has long been suspected that kids exposed to more antibiotics “ like those in developed countries “ are more prone to allergic asthma. Our study is the first experimental proof that shows how.”

The antibiotics studied by Finley’s team at UBC’s Dept. of Microbiology and Immunology and Michael Smith Laboratories were vancomycin and streptomycin. There are two widely used antibiotics that also act against the intestinal bacteria. They found that vancomycin aggravates the asthma symptomatology in mice models, but it does not  increase the mice’s susceptibility to develop asthma. This proves that the immune system established in early life is a critical factor that protects the individual from developing asthma.

There are approximately 1,000 species of  bacteria in the human intestine with a total of 100 trillion of individual bacterial cells that form the intestinal flora. These bacteria are very important in performing multiple functions in the body. “Modern societal practices, such as improved sanitation methods and widespread antibiotic use, are causing the disappearance of ancestral species of bacteria in our gut that may be critical to a healthy immune system,” says Finlay.

“Our study shows this is the case with certain antibiotics and allergic asthma, and the gut-lung connection is also consistent with observations that incidence of asthma has not increased significantly in developing countries where antibiotic use is less prevalent “ and in turn, the gut flora is permitted to fully develop.”

“It has been recognized that microbes play an important role in human health “ and we are discovering that a disruption of these bugs is associated with a number of chronic health conditions. The important results from Prof. Finlay’s team confirm that giving antibiotics to young children, which disturb their normal bacterial flora, should not be taken lightly” added Marc Ouellette, Scientific Director of CIHR’s Institute of Infection and Immunity.

Scientists Can Stop Bladder Cancer To Metastasize To Lungs

According to new study conducted at the University of Colorado and published today in the Journal of Clinical Investigation, researchers were able to demonstrate the way in which bladder cancer metastasizes to the lungs and to develop a method that can stop bladder cancer dissemination into the lungs. This study is very important because patients with localized forms of bladder cancer present an 80 percent five-year survival rate, unlike patients with metastasizing forms of bladder cancer who present 20 percent survival rate at three years.

With this study scientists demonstrated that a protein that is involved in cancer cell migration, called versican is responsible for lung metastasis and high levels of this protein are associated with aggressive forms of bladder cancer and with poor prognosis. Researchers also observed that cancer cells synthesize a protein called RhoGDI2 which blocks the production of versican, thus stopping the migration of cancerous cells into the lungs and the capacity of bladder cancer to produce lung metastasis.

“For a decade, we’ve known that the major challenge of treating bladder cancer is treating or preventing the metastatic form of the disease. This study represents an advance in the latter “ by preventing the spread of bladder cancer to the lungs, we could improve patient survival,” says Dan Theodorescu, MD, PhD, the study’s senior author.

In their process of metastasis, cancer cells dose not become suddenly mobile and start to float through bloodstream or lymphatic flow to other organs. Instead, it was observed that cancer cells present the capacity to float through bloodstream for a long period of time and to metastasize only when are able to grow in an organ where this cells are attached, in this case the lungs.

Cancer Cells

When cancerous cells are attaching to an organ and start to metastasize they are distressed and become weaker. Cancer cells distress is expressed by the secretion of versican, a protein which has the ability to attract macrophages, cells that are part of the body’s immune system and participate to the immune response.  Process by which macrophages are attracted by cancer cells into organs presents both advantages and disadvantages. Advantages are represented by the fact that macrophages are immune system cells which have the ability to destroy cancer cells by phagocytosis. The big disadvantage is that in their process of helping healthy cells to survive, macrophages also promote the development of cancerous cells that reached other organs, thus promoting metastasis of cancer.

In conclusion, the more versican is secreted by cancer cells , a greater number macrophages are attracted, which in addition to their protective effects on healthy cells, enhance the growth of cancerous cells and the appearance of metastasis, in this case in the lungs.

But scientists observed that a protein secreted by cancer cells called RhoGDI2 can reduce the secretion of versican, because in organs were cancer cells secrete more RhoGDI2 the levels of versican are lower and the number of macrophages is lower, which make cancer cells to become sensitive and to be destroyed by the immune system. When researchers added RhoGDI2 to metastatic tumor, the level of versican became lower and metastases began to shrink.

“We believe this study provides an important contribution to the scientific literature by delineating for the first time a new mechanism of metastasis suppression, namely that suppression of metastasis is possible by altering the tumor microenvironment, including reducing the presence macrophages,” Dan Theodorescu added.

This study shows an other important step in cancer research because it was demonstrated that versican can attract macrophages only by the secretion of some proteins called CCL2, for which were discovered drugs that inhibit their activity, drugs that are now tested in clinical trials for other diseases.

Scientists hope that in the future CCL2 inhibitors to become a part of bladder cancer treatment scheme, especially for bladder cancer that express increased levels of versican and decrease levels of RhoGDI2. By inhibiting CCL2 proteins, the capacity of versican to attract macrophages can be reduced, thus can be stopped metastasis development, fact that improve the outcome of patients with aggressive forms of bladder cancer.