Studies Cast Doubt on Cancer Drug as Alzheimer’s Treatment.


studies-cast-doubt-cancer-drug-alzheimers_1

Four labs can’t replicate finding that showed large-scale clearance of disease-related plaques. Some hope remains for improving memory

Bexarotene, a cancer drug touted as a potential treatment for Alzheimer’s disease, may not be the blockbuster remedy scientists were hoping for, according to several analyses published in Science on 24 May. Four independent research groups report that they failed to fully replicate striking results published in the journal last year by Gary Landreth, a neuroscientist at Case Western Reserve University School of Medicine in Cleveland, Ohio, and his colleagues.

Landreth’s team reported that the drug bexarotene could lower brain concentrations of the β-amyloid protein that has long been suspected as a key contributor to Alzheimer’s disease, and could even reverse cognitive impairments in diseased mice. But the study garnered particular attention for its claim that the drug could clear 50% of amyloid plaques — sticky clumps of the protein thought to interfere with brain function — in as little as 72 hours.

“That attracted a lot of folks to try to replicate these studies,” says Philip Wong, a neuroscientist at Johns Hopkins University in Baltimore, Maryland. “No drug at the present moment can do things like that.”

None of the follow-up studies published this week replicated the effects of bexarotene on plaques. Two groups did, however, confirm Landreth’s finding that the drug reduced levels of a soluble, free-floating form of β-amyloid, which can aggregate in plaques.

Not all of the papers examined memory in mice, but one group led by Radosveta Koldamova, a neuroscientist at the University of Pittsburgh in Pennsylvania, found that bexarotene treatment led to cognitive improvements.

Sticking points
“It was our expectation other people would be able to repeat this,” says Landreth about the results of the studies. “Turns out that wasn’t the case, and we fundamentally don’t understand that.” He suggests that the other groups might have used different drug preparations that altered the concentration of bexarotene in the brain or even changed its biological activity.

In a response published alongside the comment articles, Landreth emphasizes that some of the studies affirm two key conclusions of the original paper: the lowering of soluble β-amyloid levels and the reversal of cognitive deficits. He says that the interest in plaques may even be irrelevant to Alzheimer’s disease. In the past ten years, some neuroscientists have begun to question whether it is plaques or soluble β-amyloid proteins that are most dangerous to brain health.

As the debate over plaques continues, Koldamova says that the cognitive improvement she and Landreth observed suggests that bexarotene is still very promising. “Patients don’t go to the doctor because they have plaques. They go because they have memory decline,” she says.

Ethical dilemma
Other researchers say the contradictory results suggest that much more basic research is needed before bexarotene is used to treat Alzheimer’s. “The mechanism of action behind bexarotene has not been proven,” says Kevin Felsenstein, a neuroscientist at the University of Florida College of Medicine in Gainesville, and a co-author of one of the dissenting papers. Felsenstein’s group found no evidence that bexarotene lowered levels of soluble or plaque forms of β-amyloid protein.

Felsenstein worries that interest in Landreth’s original results could lead to misuse of the drug because, unlike many experimental treatments, it is already on the market. The US Food and Drug Administration has approved bexarotene to treat skin cancer.

In August 2012, The New England Journal of Medicine published an article anticipating growing demand for unauthorized prescriptions of bexarotene as an Alzheimer’s treatment and urging physicians to wait for evidence from human clinical trials.

Physicians and researchers may get some answers soon: Landreth’s group has begun an early clinical trial to test the drug in healthy participants.

Source: scientificamerican.com

 

Rare View of Ancient Galaxy Crash Revealed.


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Astronomers caught a glimpse of two star-forming galaxies as they collided 11 billion light-years away. The smashup could eventually produce one giant elliptical galaxy, researchers say

Astronomers have caught two big ancient galaxies in the act of colliding, shedding new light on the role such megamergers played in galactic evolution during the universe’s youth.

The colossal smashup will eventually produce one giant elliptical galaxy, researchers said, suggesting that most such behemoths formed rapidly in this manner long ago, rather than growing slowly over time by gobbling up a series of relatively small galaxies.

“I think at least 90 percent of elliptical galaxies at this mass were formed through this channel,” study lead author Hai Fu, of the University of California, Irvine, told SPACE.com. [Photos of Great Galactic Crashes]

Two galaxies becoming one

The merger is occurring 11 billion light-years away, meaning that astronomers are seeing the two colliding galaxies as they were about 3 billion years after the Big Bangthat created the universe. During this epoch, “red and dead” elliptical galaxies full of old stars were common.

Fu and his colleagues initially thought the two merging galaxies were a singleton, dubbed HXMM01, when they saw it with the European Space Agency’s infraredHerschel space telescope.

But follow-up observations with a variety of other instruments, both on the ground and in space, revealed that HXMM01 is actually two galaxies on a collision course, separated by about 62,000 light-years at the moment.

The gas-rich two-galaxy system contains the stellar equivalent of about 400 billion suns and is churning out new stars at a fantastic clip — about 2,000 per year, researchers said. For comparison, just two to three new stars are born every year in our own Milky Way.

At this rate, the newly forming elliptical galaxy will exhaust its gas reservoirs and cease birthing stars in just 200 million years, going red and dead in what researchers describe as a surprisingly short period of time.

“The common thought was that massive galaxies form by accreting smaller galaxies and the growth, though rapid, would last more than 200 million years,” co-author Asantha Cooray, also of UC-Irvine, told SPACE.com via email.

“And the formation was expected to not be as efficient as we have observed,” Cooray added. “The 40 percent efficiency of star formation, the efficiency at which gas is converted to stars in one rotation of the system, was unexpected.”

Fu and his colleagues report their results online today (May 22) in the journal Nature.

Star-formation mystery

The HXMM01 system’s startling efficiency explains how elliptical galaxies can go red and dead so fast, Fu and Cooray said. Ellipticals’ quick transformation had been a mystery, with some astronomers suggesting that their star-forming raw materials had been ejected by superpowerful phenomena such as quasars.

But this efficiency raises intriguing new questions, which Fu and his colleagues hope to tackle by further studying these ancient galaxies and their merging progenitors.

They want to “truly understand what is going on in those galaxies — why the star-formation efficiency is 10 times higher than normal star-forming galaxies,” Fu said. “That part is a total mystery right now.”

Source: http://www.scientificamerican.com

 

Why Stress Is Good for You.


http://www.scientificamerican.com/video.cfm?id=why-stress-is-good-for-you2013-05-21&WT.mc_id=SA_CAT_BS_20130524

Source: Scientific American

Gamma Knife surgery for the treatment of patients with asymptomatic meningiomas.


Abstract

OBJECT

Increasingly, meningiomas are detected incidentally, prior to symptom development. While these lesions are traditionally managed conservatively until symptoms develop or lesion growth occurs, it is conceivable that patients at high risk for symptom development may benefit from earlier intervention prior to the appearance of symptoms. However, little research has been performed to determine whether Gamma Knife surgery (GKS) can alter the rate of symptom development in such patients.

METHODS

A retrospective case study was performed by screening the University of Virginia GKS database for patients treated for asymptomatic meningiomas. From the patient’s medical records, pertinent demographic and treatment information was obtained. Yearly follow-up MRI had been performed to assess tumor control and detect signs of radiation-induced injury. Clinical follow-up via neurological examination had been performed to assess symptom development.

RESULTS

Forty-two patients, 33 females (78.6%) and 9 males (21.4%), with 42 asymptomatic meningiomas were included in the analysis. The median age at GKS was 53 years. The most common lesion location was the cerebral convexities (10 lesions [23.8%]), and the median lesion size was 4.0 ml. The median duration of imaging and clinical follow-ups was 59 and 76 months, respectively. During the follow-up period, 1 tumor (2.4%) increased in size, 2 patients (4.8%) demonstrated symptoms, and 1 patient (2.4%) exhibited possible signs of radiation-induced injury. Thus, actuarial tumor control rates were 100%, 95.7%, and 95.7% for 2, 5, and 10 years, respectively. Actuarial symptom control at 5 and 10 years was 97% and 93.1%, respectively. Overall progression-free survival was 91.1% and 77.8% at 5 and 10 years, respectively.

CONCLUSIONS

Compared with published rates of symptom development in patients with untreated meningiomas, results in this study indicated that patients with asymptomatic lesions may benefit from prophylactic radiosurgery prior to the appearance of symptoms. Additionally, GKS is a treatment option that offers low morbidity.

Source: :  journal of neurosurgery

 

 

Use of the intrathoracic pressure regulator to lower intracranial pressure in patients with altered intracranial elastance: a pilot study.


Clinical article

Abstract

OBJECT

The intrathoracic pressure regulator (ITPR) is a novel noninvasive device designed to increase circulation and blood pressure. By applying negative pressure during the expiratory phase of ventilation it decreases intrathoracic pressure and enhances venous return, which increases cardiac output. It is possible that the ITPR may both decrease intracranial pressure (ICP) and increase cerebral perfusion pressure (CPP) in brain-injured patients by decreasing cerebral venous blood volume and increasing cardiac output. The authors conducted an open-label, “first-in-humans” study of the ITPR in patients with an ICP monitor or external ventricular drain and altered intracranial elastance.

METHODS

This prospective randomized trial commenced July 2009. Baseline hemodynamic variables and ICP were recorded prior to inserting one of the two ITPRs into the ventilator circuit based on a randomization scheme. Depending on the device selected, activation provided either −5 or −9 mm Hg endotracheal tube pressure. Hemodynamic and ICP data were recorded sequentially every 2 minutes for 10 minutes. The first device was turned off for 10 minutes, then it was removed and the second device was applied, and then the procedure was repeated for the second device.

RESULTS

Ten patients with elevated ICP secondary to intracranial hemorrhage (n = 4), trauma (n = 2), obstructive hydrocephalus (n = 2), or diffuse cerebral processes (n = 2) were enrolled. Baseline ICP ranged from 12 to 38 mm Hg. With device application, a decrease in ICP was observed in 16 of 20 applications. During treatment with the −5 mm Hg device, there was a mean maximal decrease of 3.3 mm Hg in ICP (21.7 vs 18.4 mm Hg, p = 0.003), which was associated with an increase in CPP of 6.5 mm Hg (58.2 vs 64.7 mm Hg, p = 0.019). During treatment with the −9 mm Hg device, there was a mean maximal decrease of 2.4 mm Hg in ICP (21.1 vs 18.7 mm Hg, p = 0.044), which was associated with an increase in CPP of 6.5 mm Hg (59.2 vs 65.7 mm Hg, p = 0.001).

CONCLUSIONS

This pilot study demonstrates that use of the ITPR in patients with altered intracranial elastance is feasible. Although this study was not powered to demonstrate efficacy, these data strongly suggest that the ITPR may be used to rapidly lower ICP and increase CPP without apparent adverse effects. Additional studies will be needed to assess longitudinal changes in ICP when the device is in use and to delineate treatment parameters.

Source:  journal of neurosurgery

Fish oil increased adiponectin in humans


Fish oil consumption may improve insulin sensitivity and adipocyte function, according to data from a meta-analysis of randomized controlled trials

Using data from 14 trials, Jason Wu, PhD,and colleagues at the Harvard School of Public Health, along with the University of Western Australia, Brigham and Women’s Hospital and Harvard Medical School, aimed to determine the effects of consuming long-chain polyunsaturated omega-3 fatty acids (n-3 PUFA) on circulating adiponectin in humans.

Participants in the 14 trials received fish oil at a median dose of 1.3 g/day for a median of 8 weeks (n=682) or placebo (olive and sunflower oil were most commonly used; n=641).

Fish oil was associated with a 0.37-mcg/mL (95% CI, 0.07-0.67) increase in adiponectin. According to the study results, statistical heterogeneity was evident but unexplained by n-3 PUFA dose or duration, study quality score, study location or baseline BMI (P>.05 each).

Two trial arms in one study examined the effect of fish meal feeding on adiponectin, but it was not statistically significant (–0.01 mcg/mL; P=.99).

“These findings support potential beneficial effects of fish oil supplementation on pathways related to adipocyte health and adiponectin metabolism,” Wu and colleagues wrote.

Source: Endocrine today

 

 

 

Calcium intake may protect against mortality among women.


Calcium supplements, up to 1,000 mg daily, and increased dietary calcium intake may reduce the risk for mortality among women, according to data from a recent Canadian study. Researchers also studied vitamin D intake but found no evidence of harm or benefit associated with daily doses.

In the Canadian Multicentre Osteoporosis Study, 9,033 men and women were followed for 10 years, during which time 1,160 people died.

Among women, per 500 mg increase in total daily calcium intake, the HR for mortality was 0.95 (95% CI, 0.89-1.01). Additionally, the risk for mortality was lower among women who used calcium supplements vs. those who did not (HR=0.78; 95% CI, 0.66-0.92), although the researchers reported no dose-response effect.

Among men, there were no statistical benefits.

“Our study found daily use of calcium supplements was associated with a lower risk of death among women,” study researcher David Goltzman, MD,professor in the department of medicine at McGill University in Montreal, said in a press release. “Higher amounts of calcium were potentially linked to longer life spans in women, regardless of the source of the calcium.”

Based on their findings, including a lack of evidence that vitamin D intake affects the association between calcium and mortality, Goltzman and colleagues recommend assessing dietary intake to meet calcium and vitamin D needs for bone health and to consider supplements, when necessary, to meet these requirements.

Source: Endocrine today

FDA allows marketing for HbA1c assay to diagnose diabetes.


The FDA has announced they will allow the marketing of the COBAS INTEGRA 800 Tina-quant HbA1cDx assay for the diagnosis of diabetes by health care professionals, according to a press release.

Investigators analyzed 141 blood samples and found a difference of <6% in accuracy between the Tina-quant HbA1cDx assay (Roche) and results from standard reference for HbA1c analysis, according to the release.

Clinical laboratories will be permitted to use the Tina-quant HbA1cDX assay to diagnose patients with diabetes and monitor glucose control. The assay should not be used to diagnose diabetes during pregnancy or used to diagnose or monitor diabetes in patients with hemoglobin variant hemoglobin F. Furthermore, it should not be used to monitor diabetes in patients with hemoglobinopathy, hereditary spherocytosis, malignancies, or severe chronic, hepatic and renal disease, according to the release.

Source: Endocrine today

Ibuprofen with or without an antiemetic for acute migraine headaches in adults.


This is an updated version of the original review published in Issue 10, 2010 (Rabbie 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers do not seek professional help, relying instead on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce symptoms commonly associated with migraine headaches.

OBJECTIVES: To determine efficacy and tolerability of ibuprofen, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. SEARCH
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, ClinicalTrials.gov, and reference lists for studies through 22 April 2010 for the original review and to 14 February 2013 for the update.
SELECTION CRITERIA: We included randomised, double-blind, placebo- or active-controlled studies using self-administered ibuprofen to treat a migraine headache episode, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and number needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment.
MAIN RESULTS: No new studies were found for this update. Nine included studies (4373 participants, 5223 attacks) compared ibuprofen with placebo or other active comparators; none combined ibuprofen with a self-administered antiemetic. All studies treated attacks with single doses of medication. For ibuprofen 400 mg versus placebo, NNTs for 2-hour pain-free (26% versus 12% with placebo), 2-hour headache relief (57% versus 25%) and 24-hour sustained headache relief (45% versus 19%) were 7.2, 3.2 and 4.0, respectively. For ibuprofen 200 mg versus placebo, NNTs for 2-hour pain-free (20% versus 10%) and 2-hour headache relief (52% versus 37%) were 9.7 and 6.3, respectively. The higher dose was significantly better than the lower dose for 2-hour headache relief. Soluble formulations of ibuprofen 400 mg were better than standard tablets for 1-hour, but not 2-hour headache relief.Similar numbers of participants experienced adverse events, which were mostly mild and transient, with ibuprofen and placebo.Ibuprofen 400 mg did not differ from rofecoxib 25 mg for 2-hour headache relief or 24-hour headache relief.
AUTHORS’ CONCLUSIONS: We found no new studies since the last version of this review. Ibuprofen is an effective treatment for acute migraine headaches, providing pain relief in about half of sufferers, but complete relief from pain and associated symptoms for only a minority. NNTs for all efficacy outcomes were better with 400 mg than 200 mg in comparisons with placebo, and soluble formulations provided more rapid relief. Adverse events were mostly mild and transient, occurring at the same rate as with placebo.

Source: Cochrane

 

 

Fluoride Loosens Bacterial Enamel Grip.


Rather than significantly hardening tooth enamel, fluoride may cut cavities by making it harder for oral bacteria to stick around. Karen Hopkin reports

Fluoride helps fight cavities. That’s why it’s in our drinking water and toothpaste. But how this mineral works its dental magic is still somewhat mysterious. Now, researchers offer an incisive solution. They find that fluoride treatment can loosen bacteria’s grip on tooth enamel. The study is in the journal Langmuir. [Peter Loskill et al.,Reduced Adhesion of Oral Bacteria on Hydroxyapatite by Fluoride Treatment]

Scientists used to think that fluoride could harden tooth enamel, helping it retain the minerals that protect teeth from the acid produced by our oral flora. But recent work has shown that fluoride doesn’t really penetrate past the tooth’s thinnest outer layer, suggesting that something other than hardening is going on.

To drill deeper into this toothsome mystery, researchers whipped up a set of artificial choppers, made of the same stuff as teeth. And they used atomic force microscopy to take a closer look at how bacteria interact with this dental material. They found that three different strains of cavity-causing bugs cling less tightly to enamel that’s been rinsed with fluoride.

The bacteria carry a net negative charge on their surfaces. So the negatively charged fluoride ions in the treated enamel may be literally repulsive to the bacteria. Which causes them to bite the dust.

Source: scientificamerican.com