Oxytocin hormone inhibits fear center in brain, shows study

In continuation of my update on oxytocin...

Frightening experiences do not quickly fade from memory. A team of researchers under the guidance of the University of Bonn Hospital has now been able to demonstrate in a study that the bonding hormone oxytocin inhibits the fear center in the brain and allows fear stimuli to subside more easily. This basic research could also usher in a new era in the treatment of anxiety disorders. The study has already appeared in advance online in the journal "Biological Psychiatry". The print edition will be available in a few weeks.

Significant fear becomes deeply entrenched in memory. Following a car accident, for example, it is difficult to manage street traffic once again - even screeching tires can evoke significant anxiety. Scientists refer to this as "conditioning". Certain images or noises are very closely intertwined in the brain with the experience of pain or fear. Only gradually does one learn that not every screeching tire means danger. This active overwriting in the memory is known as "extinction". "In this process, however, the original contents of the memory are not erased but instead merely overlaid with positive experiences," explains Prof. Dr. Dr. René Hurlemann from the Department of Psychiatry and Psychotherapy of the University of Bonn Hospital. If there are dangerous situations once again, the fear, which was believed to have been already overcome, frequently flares up once more.

Extinction is often used in therapy for anxiety disorders. For example, a person suffering from a spider phobia will gradually and increasingly come face to face with spiders. First the patient has to view photos of spiders and then look at living examples until finally he holds a tarantula in his hand. When people with an anxiety disorder experience as frequently as possible the fact that they do not need to fear the trigger, their fear is reduced. "However, this can take a very long time, because this confrontation with the fearful situation frequently has to be experienced. In addition, there may be relapses because the original trace of fear is still anchored in the memory," reports Prof. Hurlemann. This is why therapists seek a possibility for "overwriting" the fearful memory in a faster and longer-lasting way.

Oxytocin hormone inhibits fear center in brain, shows study

New anti-cancer drug may protect normal cells against radiation

Although radiation treatments have become much more refined in recent years, it remains a challenge to both sufficiently dose the tumor while sparing the surrounding tissue. A new anti-cancer drug, already in clinical development, may help address this issue by protecting normal cells - but not the cancer - from the effects of radiation. The research, published November 14th in Molecular Cancer Therapeutics, further suggests this drug may also be useful in treating accidental exposure to radiation.

"It was a stroke of luck that the drug that most effectively protected normal cells and tissues against radiation also has anti-cancer properties, thus potentially increasing the therapeutic index of radiation therapy," says Ulrich Rodeck, M.D., Ph.D., Professor of Dermatology and Cutaneous Biology and Radiation Oncology at Thomas Jefferson University, and senior author on the study.

Together with first author Vitali Alexeev, Ph.D., Assistant Professor, Dermatology and Cutaneous Biology, Dr. Rodeck and colleagues tested five compounds that were shown to have radiation-protective properties in earlier studies. The researchers gave the mice one of the five compounds a day before and for several days after radiation treatment. A compound called RTA 408 emerged from this screen as a robust radiation protector and its effect was comparable to the only drug currently approved by the FDA for that purpose. (The approved drug, called amifostine, however, has a number side effects including severe nausea or vomiting that make it an unappealing choice for clinicians.) Sites that are usually most susceptible to radiation damage including the gut and blood cells in the bone marrow were both protected in mice treated with RTA 408.

Ref : http://mct.aacrjournals.org/content/early/2014/11/12/1535-7163.MCT-14-0354.abstract?sid=22fc8faf-65af-4c60-8a08-265701e2f6ad

New anti-cancer drug may protect normal cells against radiation

New active substance effectively combats Philadelphia chromosome-positive leukaemia

New active substance effectively combats Philadelphia chromosome-positive leukaemia

Bacterial protein flagellin can prevent and cure rotavirus infection

Activation of the innate immune system with the bacterial protein flagellin could prevent and cure rotavirus infection, which is among the most common causes of severe diarrhea, says a Georgia State University research team that described the method as a novel means to prevent and treat viral infection.

The team's findings are to be published in Science on Nov. 14.

Rotavirus is most problematic in infants and young children, who can become severely dehydrated and require hospitalization. Rotavirus causes about 500,000 deaths annually worldwide in children younger than five years of age, according to the Centers for Disease Control and Prevention.

The research, performed in mice, was led by Dr. Andrew Gewirtz and Dr. Benyue Zhang of the Institute for Biomedical Sciences at Georgia State, and included collaborators at Emory University School of Medicine, Baylor College of Medicine, Vanderbilt University School of Medicine, Genentech Inc. and the Pennsylvania State University.

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The researchers expect the specific method used in their work, using flagellin or the IL-22 and IL-18 proteins it elicits, might be effective against a range of chronic viral infections of the digestive system such as norovirus and hepatitis C virus. The team is now planning studies in humans to test this hypothesis. The general model of activating innate immunity to combat viral infection should prove an effective means of slowing down most any virus and could be a temporary means to deal with a broad range of viral infections until more specific solutions could be developed, Gewirtz said.

Bacterial protein flagellin can prevent and cure rotavirus infection

Smart drug Modafinil can impair cognitive performance in healthy students

It is claimed one in five students have taken the 'smart' drug Modafinil to boost their ability to study and improve their chances of exam success. But new research into the effects of Modafinil has shown that healthy students could find their performance impaired by the drug. 

The study carried out by Dr Ahmed Dahir Mohamed, in the School of Psychology at The University of Nottingham Malaysia Campus, and published today, Wednesday 12 November 2014, in the open access journal PLOS ONE, showed the drug had negative effects in healthy people.

Dr Mohamed said: "We looked at how the drug acted when you are required to respond accurately and in a timely manner. Our findings were completely opposite to the results we expected."

In a randomised double blind study, 'Modafinil increases the latency of response in the Hayling Sentence Completion Test in Healthy Volunteers: A Randomised Controlled Trial', they administered 32 participants with the drug and 32 with a placebo. All the participants were given a famous neuropsychological task known as the Hayling Sentence Completion Test in which they were asked to respond both quickly and accurately. Dr Mohamed found the drug slowed down reaction times, impaired their ability to respond in a timely manner and failed to improve their performance of the task.

Smart drug Modafinil can impair cognitive performance in healthy students

Breakthrough in flexible electronics enabled by inorganic-based laser lift-off

A research team led by Prof. Keon Jae Lee of KAIST provides an easier methodology  to  realize  high  performance flexible electronics by using the  Inorganic-based Laser  Lift-off  (ILLO),  which  enables    nanoscale processes  for   high   density   flexible   devices and    high temperature processes that were previously difficult to achieve on plastic substrates.

Breakthrough in flexible electronics enabled by inorganic-based laser lift-off  

Chaetocin synergistic with TKIs against CML cells

Chaetocin (structure below), a mycotoxin that increases oxidative stress, can complement the activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) by overcoming innate resistance mediated by secreted bone marrow stromal cytokines and growth factors (BMSFs), researchers report.

The authors explain that CML–leukaemic stem cells (CML–LSCs), which exhibit innate resistance to TKIs, are crucial for the maintenance of CML. And add that BMSFs are implicated in this innate resistance, and are also known to increase the levels of reactive oxygen species (ROS).

“Higher ROS levels in CML-LSCs exposed to BMSFs might render them susceptible to ROS-mediated damage by exogenous ROS-generating agents”, hypothesises the team inOncogenesis.

Chaetocin significantly reduced the viability and colony forming capacity of CML–LSK cells, and increased apoptosis. These effects of chaetocin were enhanced in the presence of BMSFs.

Moreover, treatment with both chaetocin and imatinib overcame BMSF-mediated imatinib resistance, and resulted in increased cytotoxicity and apoptosis induction as well as a complete loss of colony formation.

Although treatment with either chaetocin or BMSFs resulted in increased ROS levels in CML–LSKs, when the two were used in combination, ROS levels were significantly higher than when either was used alone. Interestingly, chaetocin-mediated cytotoxicty was inhibited when the cells were pretreated with an antioxidant, N-acetyl-cysteine.

This “strongly suggested” that chaetocin activity against CML–LSKs, and its potentiation by BMSFs, was mediated by the increased ROS, say the researchers.

Chaetocin synergistic with TKIs against CML cells

Isis Pharmaceuticals announces initiation of ISIS-SMN Rx Phase 3 study in children with SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced  the initiation of a pivotal Phase 3 study evaluating ISIS-SMNRx in approximately 120 non-ambulatory children with spinal muscular atrophy (SMA). SMA is a severe and rare genetic neuromuscular disease characterized by muscle atrophy and weakness. The Phase 3 study, CHERISH, is the second Phase 3 study Isis has initiated in a global late-stage clinical development program for ISIS-SMNRx. Isis earned a $27 million milestone payment from its development partner, Biogen Idec, for the dosing of the first patient in this study. Isis is also evaluating ISIS-SMNRx in the Phase 3 study, ENDEAR, in infants with SMA. Isis is conducting both Phase 3 studies with agreement from the U.S. Food and Drug Administration (FDA) for special protocol assessments, or SPAs.

Isis Pharmaceuticals announces initiation of ISIS-SMN Rx Phase 3 study in children with SMA

University of Leeds researchers make new synthetic anti-cancer molecule

Researchers at the University of Leeds have made a new synthetic anti-cancer molecule that targets two key mechanisms in the spread of malignant tumours through the body. A study published in the journal PLOS ONE today reports that the synthetic molecule JK-31 blocks the signalling of a "growth factor" chemical that promotes the creation of networks of blood vessels to feed tumours.

But the researchers also found that the new molecule intervened directly in the growth of the cancer itself, inhibiting a protein that controls the division and proliferation of malignant cells.

Dr Vas Ponnambalam, Reader in Human Disease Biology in the University of Leeds' Faculty of Biological Sciences, said: "The ability to mount this two-pronged attack on cancerous growths is exciting. There is a great need for better drugs against cancer than what we currently have and JK31 may represent an important addition to the toolkit for drug makers developing the next generation of drugs."

The researchers observed the effect of the synthetically produced molecule, JK-31, on the growth and proliferation of a model human breast cancer cell line and found that it effectively blocked the protein cyclin-dependent kinase 1 (CDK1), which plays a key part in the process of the division of cancer cells, and therefore inhibited the proliferation of the cells.

In a separate laboratory experiment, they found the same JK-31 molecule also blocked a specific growth factor (VEGF-A) produced by the cancer to attract the growth of blood vessels.

Other molecules exhibiting similar dual effects are known but JK-31 is the only compound so far shown to successfully target CDK1 and block VEGF-A.

University of Leeds researchers make new synthetic anti-cancer molecule

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

A new drug combination for rheumatoid arthritis treats the disease just as well as other intensive treatment strategies but with less medication and fewer side effects at a significantly lower cost. Doctoral researcher Diederik De Cock (KU Leuven) describes the strategy in a new study published in Annals of Rheumatic Diseases.

Rheumatoid arthritis (RA) is a chronic auto-immune disease that causes pain and stiffness in the joints, fatigue, bone damage and, eventually, loss of mobility. RA afflicts around 1% of people in the western world; in Belgium, 80,000 to 100,000 people currently live with the disease.

Because there is no known cure for RA, physicians focus treatment on suppressing disease activity. Therapies have improved in recent years, and clinical studies show that intensive treatment of early RA can prevent joint damage and improve patients' quality of life.

In the two-year study, called 'CareRA' (Care in early RA), researchers and clinicians in the rheumatology unit at University Hospitals Leuven examined various therapies for early RA. Their goal: to find the optimal combination and dosage of three commonly prescribed antirheumatic drugs (methotrexate, sulfasalazine and leflunomide) in combination with glucocorticoids (a class of steroid hormones).

The researchers divided 290 early RA patients into three treatment groups. Each group received a different combination therapy: 'COBRA Classic' (methotrexate, sulfasalazine and a high first dose of glucocorticoids), 'COBRA Slim' (methotrexate and a moderate dose of glucocorticoids) or 'COBRA Avant-Garde' (methotrexate, leflunomide and a moderate dose of glucocorticoids).

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

Sulindac drug can protect against oxidative damage due to AMD

In continuation of my update on Sulindac

Scientists at Florida Atlantic University's Charles E. Schmidt College of Science, as well as the Charles E. Schmidt College of Medicine, have found that sulindac, a known anti-inflammatory drug, can protect against oxidative damage due to age-related macular degeneration (AMD), one of the primary causes of vision loss in the elderly. Their findings were released today in an article titled "Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α" in the prestigious Proceedings of the National Academy of Sciences.

Sulindac drug can protect against oxidative damage due to AMD

FDA Approves Olysio (simeprevir) in Combination with Sofosbuvir for Genotype 1 Chronic Hepatitis C Infection

In continuation of my update on sofosbuvir

Janssen Therapeutics, Division of Janssen Products, LP (Janssen) announced the U.S. Food and Drug Administration (FDA) has approved Olysio (simeprevir), a hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination withsofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C (CHC) infection in adult patients as part of a combination antiviral treatment regimen. Sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

FDA Approves Olysio (simeprevir) in Combination with Sofosbuvir for Genotype 1 Chronic Hepatitis C Infection

New treatment regimen for hepatitis C in transplant patients produces promising results

The investigational three-drug regimen, which produced hepatitis C cure rates of 97 percent, is an oral interferon-free therapy. Previously, the typical treatment for hepatitis C after a liver transplant was an interferon-based therapy, usually given for 48 weeks. It had a much lower response rate, had a risk of organ rejection and was poorly tolerated because of the immunosuppressants required to prevent rejection. The new oral regimen -- ABT-450, ombitasvir and dasabuvir (with or without ribavirin) -- produces significantly fewer side effects and is prescribed for 24 weeks.

New treatment regimen for hepatitis C in transplant patients produces promising results

Study reports anti-cancer activity in mice treated with experimental drug TAK-733

Study reports anti-cancer activity in mice treated with experimental drug TAK-733

TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc.

Ref: http://www.heemd.com/news/?md=1510006/
http://www.medchemexpress.com/TAK-733.html

Eribulin drug has minor added benefit in one patient group, indication of lesser benefit in others

In continuation of my update on Eribulin

Eribulin (trade name: Halaven) is approved for women with locally advanced or metastatic breast cancer in whom the disease has progressed despite prior drug therapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether the drug offers an added benefit over the appropriate comparator therapy in these patient groups.

According to the findings, there are both positive and negative effects. There is proof of minor added benefit for one group of patients. For other groups, there are hints or indications of lesser benefit.

Second assessment of eribulin

IQWiG already presented a dossier assessment of eribulin in February 2012. The subsequent decision on the added benefit made by the Federal Joint Committee (G-BA) was limited until April 2014. In addition, the drug manufacturer meanwhile obtained approval for an expanded therapeutic indication: In March 2011 eribulin was only available for patients who have progressed further after at least two chemotherapeutic regimens. Since June 2014, however, the drug can already be used after one unsuccessful treatment attempt. Hence there were two reasons ─ independent from each other ─ for the reassessment of eribulin.

G-BA specified appropriate comparator therapies

When the G-BA specified the appropriate comparator therapy, it distinguished between several treatment situations: The first one refers to patients who are not eligible for further chemotherapy with a taxane or an anthracycline. In this situation, eribulin was to be compared with individual chemotherapy containing the drugs capecitabine or vinorelbine.

In patients for whom taxanes or anthracyclines are principally still an option, eribulin was to be compared with an individual chemotherapy containing a taxane or an anthracycline.

Eribulin drug has minor added benefit in one patient group, indication of lesser benefit in others