Sleep keeps brain fit by clearing waste

Disease-causing waste that builds up during the day is cleaned out from our brain as we sleep at night, say researchers.

Their findings, published today in the journal Science, could help explain why people spend a third of their lives asleep, and may help in developing treatments for Alzheimer's disease and other neurological disorders.

"This study shows that the brain has different functional states when asleep and when awake," says study leader Dr Maiken Nedergaard from the University of Rochester Medical Center in New York.

"In fact, the restorative nature of sleep appears to be the result of the active clearance of the by-products of neural activity that accumulate during wakefulness."

In lab experiments on mice - whose brains are remarkably similar to humans - Nedergaard and colleagues observed how cellular waste was flushed out via the brain's blood vessels into the body's circulatory system and eventually the liver.

These waste products included amyloid beta, a protein that, when accumulated, is a driver of Alzheimer's disease.

Plumbing system

The researchers say waste is removed from brain tissue by cerebral spinal fluid (CSF) flushed through a 'plumbing system' called the glymphatic system, which appears to be nearly 10 times more active during sleep than while awake.

In their study Nedergaard and colleagues first injected dye into the CSF of mice and watched it flow through their brains, while simultaneously monitoring electrical brain activity. They found the dye flowed rapidly when the mice were unconscious, either asleep or anesthetised, but when the same mice were awake it barely flowed at all.

"We were surprised by how little flow there was into the brain when the mice were awake," says Nedergaard. "It suggested that the space between brain cells changed greatly between conscious and unconscious states."

To test this idea, the researchers used electrodes inserted into the brain to directly measure the space between brain cells.

They found that during sleep, the brain's cells shrink by about 60 per cent, opening up the brain's interstitial space and allowing the fluid to move faster and more freely through it.

Energy use

Nedergaard and colleagues say the amount of energy consumed by the brain does not decrease dramatically while we sleep.

Because pumping CSF demands a great deal of energy, they speculate that the process of cleaning may not be compatible with the functions the brain must perform when we are awake and actively processing information.

"The brain only has limited energy at its disposal," says Nedergaard. "You can think of it like having a house party. You can either entertain the guests or clean up the house, but you can't really do both at the same time."

During the study the researchers also injected labelled amyloid beta proteins into the brains of the mice and found that during sleep CSF cleared away this dirt outside of the cells twice as quickly.

"These findings have significant implications for treating 'dirty brain' disease like Alzheimer's," says Nedergaard. "Understanding precisely how and when the brain activates the glymphatic system and clears waste is a critical first step in efforts to potentially modulate this system and make it work more efficiently."

Tomado de ABC science at abc.net.au

Gold-plated nano-bits find, destroy cancer cells

Comparable to nano-scale Navy Seals, Cornell scientists have merged tiny gold and iron oxide particles to work as a team, then added antibody guides to steer the team through the bloodstream toward colorectal cancer cells. And in a nanosecond, the alloyed allies then kill the bad guys – cancer cells – with absorbed infrared heat.

This scenario is not science fiction – welcome to a medical reality.

“It’s a simple concept. It’s colloidal chemistry. By themselves, gold and iron-oxide alloys are benign and inert, and the infrared light is low-power heating,” said Carl Batt, Cornell’s Liberty Hyde Bailey Professor of Food Science and the senior author on the paper. “But put these inert alloys together, attach an antibody to guide it to the right target, zap it with infrared light and the cancer cells die. The cells only need to be heated up a few degrees to die.”

Batt and his colleagues – Dickson K. Kirui, Ph.D. ’11, a postdoctoral fellow at Houston Methodist Research Institute and the paper’s first author; Ildar Khalidov, radiology, Weill Cornell Medical College; and Yi Wang, biomedical engineering, Cornell – published their study in Nanomedicine (print edition, July 2013).

For cancer therapy, current hyperthermic techniques – applying heat to the whole body – heat up cancer cells and healthy tissue, alike. Thus, healthy tissue tends to get damaged. This study shows that by using gold nanoparticles, which amplify the low energy heat source efficiently, cancer cells can be targeted better and heat damage to healthy tissues can be mitigated. By adding the magnetic iron oxide particles to the gold, doctors watching MRI and CT scanners can follow along the trail of this nano-sized crew to its target.

When a near-infrared laser is used, the light penetrates deep into the tissue, heating the nanoparticle to about 120 degrees Fahrenheit – an ample temperature to kill many targeted cancer cells. This results in a threefold increase in killing cancer cells and a substantial tumor reduction within 30 days, according to Kirui. “It’s not a complete reduction in the tumor, but doctors can employ other aggressive strategies with success. It also reduces the dosage of highly toxic chemicals and radiation – leading to a better quality of life,” he explained.

Tomado de: news.cornell.edu

Prueba automatizada para detectar la tuberculosis en pacientes pediátricos

Un equipo de investigadores sudafricanos comparó la efectividad de una nueva prueba automatizada, que detecta simultáneamente la tuberculosis (TB) y la resistencia a la rifampicina y la compararon con la microscopía clásica y los métodos de cultivo en pacientes pediátricos.

La Organización Mundial de la Salud (OMS), calculó que, solamente en 2011, aparecieron más de 500.000 casos nuevos de TB, con casi 64.000 muertes entre los menores de 15 años de edad.

Los autores de este estudio recopilaron casi 1.500 muestras pareadas de esputo y nasofaríngeas de 354 niños que se presentaron en una clínica de atención primaria con síntomas de tuberculosis. Las muestras fueron analizadas con la prueba Cepheid (Sunnyvale, CA, EUA) Xpert MTB/RIF, y se comparó la exactitud diagnóstica de los resultados con los patrones de referencia del cultivo y la baciloscopia.

La prueba Xpert MTB/RIF detecta la tuberculosis y la resistencia a la rifampicina, con alta sensibilidad, incluso en muestras negativas por frotis o muestras positivas por cultivo. La prueba produce resultados en dos horas y no requiere instrumentos diferentes al Sistema GeneXpert.

El sistema GeneXpert de Cepheid es una plataforma cerrada, autónoma, totalmente integrada y automatizada que combina la preparación de muestras a bordo con la amplificación de la PCR (reacción en cadena de la polimerasa), en tiempo real, y las funciones de detección para el análisis de ácidos nucleicos totalmente integrado y automatizado. El sistema está diseñado para purificar, concentrar, detectar, e identificar secuencias de ácidos nucleicos específicos, suministrando de este modo respuestas directamente a partir de muestras sin procesar.

Los resultados revelaron que cinco niños (1%) dieron resultados positivos para tuberculosis en la baciloscopia, 26 (7%) dieron un resultado positivo por Xpert MTB/RIF, y 30 (8%) dieron positivo mediante el cultivo. Entre los niños que en realidad no tienen la enfermedad, los resultados de la prueba Xpert, informaron un resultado negativo para TB con un 99% de exactitud. Estos hallazgos sugieren que la prueba Xpert MTB/RIF, en las secreciones respiratorias, es una prueba útil para el diagnóstico rápido de la tuberculosis pulmonar pediátrica en atención primaria.

El Dr. Fred Tenover, director jefe de asuntos científicos de Cepheid, dijo: “Si se va a inocular una prueba Xpert MTB/RIF, al mismo tiempo que usted comienza la preparación de sus frotis acidorresistentes, en el momento en que termina de leer las láminas, el resultado de la prueba Xpert MTB/RIF estaría listo, diciéndole si su coloración ácido-alcohol resistente positiva era tuberculosis y si la cepa era resistente a la rifampicina, que es un excelente marcador sustituto de la TM-MDR (TB resistente a múltiples fármacos). Estoy seguro de que Koch y Pasteur no sólo estarían muy complacidos con el avance tecnológico; probablemente dirían: ‘Ya es hora’”.

“Ha habido una percepción, entre los trabajadores de la salud, de que el diagnóstico rápido de la tuberculosis en los niños no era posible en la atención primaria, pero este estudio refuta esa opinión, dijo la primera autora, Dra. Heather Zar, profesora de pediatría en la Universidad de Ciudad del Cabo (Sudáfrica). “Teniendo en cuenta nuestros resultados, la adopción generalizada de las pruebas rápidas para la tuberculosis y la resistencia a los medicamentos en los niños puede mejorar sustancialmente la salud pública, sin aumentar considerablemente los costos”.

Los resultados del estudio sudafricano fueron publicados en la edición de agosto de 2013, de la revista Lancet Global Health.

Tomado de Labmedica.es

High dependency predicts BMI increase during smoking cessation

Smokers who are heavily addicted to nicotine are significantly more likely to gain weight when they try to quit, researchers report.

Investigators studying 186 patients who successfully quit smoking after receiving nicotine replacement therapy at an outpatient clinic found that mean body mass index increased significantly from 23.5 kg/m² at an initial consultation to 23.9 kg/m² at 3 months after the start of therapy. A high Fagerstrom Test for Nicotine Dependence (FTND) score, indicating severe dependency, was found on multivariate analysis to be the strongest predictor of increase (using a gender-adjusted standardized coefficient).

Dr. Maki Komiyama of Kyoto (Japan) Medical Center and colleagues reported their findings online Aug. 21 in the open access journal PLoS One (PLoS One 2013 Aug. 21[doi:10.1371/journal.pone.0072010]).

The findings are important because, while smoking cessation is known to reduce cardiovascular and cancer risk and to reduce all-cause mortality, associated weight gain is linked with greater risk of glucose intolerance and a reduction in the beneficial effects that quitting has on pulmonary function. Concerns about weight gain also can lead to a failure to quit smoking, they said.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk. However, there is also a possibility that if one can prevent post-cessation weight gain, then this will further reduce the cardiovascular risk due to having ceased smoking," they wrote

Thus, they continued, the ability to predict which patients are likely to gain weight during smoking cessation therapy – and performing weight control accordingly at the outset – could lead to improved outcomes, and the findings of this study may be useful for discriminating such patient groups.

Study participants were 132 men and 54 women with a mean age of 59.6 years who visited the smoking cessation clinic at the National Hospital Organization Kyoto Medical Center between July 2007 and November 2011 and successfully quit smoking.

Other factors found on univariate analysis to be significantly associated with BMI increase included triglyceride level, high-density lipoprotein cholesterol, and daily cigarette consumption. "To further investigate ... we performed multivariate analysis. The results demonstrated that the triglyceride level and FTND score were factors determining the post-cessation BMI increase, and that the FTND score was the strongest one," the investigators wrote.

An FTND score of 8 or more (on a scale of 1-10) was associated with larger postcessation BMI increase, and the increase was statistically significant when compared with the level of BMI increase in those with a score of 7 or less, they noted.

"The result that a high FTND score was the most important determinant of a BMI increase supports the hypothesis that post-cessation weight gain is one of the nicotine withdrawal symptoms," they said.

As for the association between triglyceride elevation and weight gain, the mechanism is not clearly understood and requires further study, they noted.

With the exception of two patients who did not receive medical treatment, study participants were treated with either oral varenicline (95 patients) or nicotine patch (89 patients). No difference was seen between the varenicline and nicotine patch groups with respect to BMI increase, but the varenicline group had higher nicotine dependency.

They also noted that, in their study, "although a significant increase in BMI was confirmed after smoking-cessation therapy, the BMI increase was only 0.4 kg/m² (1.1 kg), which is much smaller than reported in previous studies for people who quit smoking on their own initiative (2.8-3.8 kg)."

Additional study is needed to determine the appropriate timing for initiating interventions against post–smoking cessation weight gain, they noted.

This study was supported by a grant-in-aid for clinical research from the National Hospital Organization and the Pfizer Health Research Foundation. The authors reported that one study drug (varenicline) is manufactured by Pfizer but confirmed "that this does not alter their adherence to all the PLoS One policies on sharing data and materials."

Tomado de:familypracticenews.com

Yeast infection four times as likely with penicillin use

 Only certain classes of antibiotics increased the risk of yeast infections in a study of 650 women followed for 18 months to see what factors were associated with new-onset vulvovaginal candidiasis.

Penicillins increased the risk the most (adjusted hazard ratio, 4.1), followed by cephalosporins (aHR, 3.3) and metronidazole (aHR, 2.8), compared with women who did not report antibiotic use. Other classes of antibiotics were not associated with yeast infections.

"Many women and physicians believe that if you take an antibiotic, you’re just bound to get yeast. The message is that not all antibiotics are associated with yeast vaginitis; it’s certain classes of antibiotics that carry the highest risk," said senior investigator Sharon L. Hillier, Ph.D., a professor of obstetrics and gynecology and reproductive sciences at the University of Pittsburgh.

"When women are given antibiotics, I think it’s useful to help them understand they have some likelihood of getting a yeast infection with these three, and less so with quinolones or tetracyclines or something else," she said at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The 650 subjects – 18-40 years old, not pregnant, and with no signs or symptoms of yeast at baseline – were followed at 2-month intervals during the investigation, and had a total of 4,934 follow-up office visits. Each time, they were asked what antibiotics they had been on, if any, among other questions.

There were 82 clinical yeast vaginitis diagnoses and 58 self-diagnosed infections with documented antifungal use. The results were largely similar when the team limited analysis to just clinically diagnosed cases.

A total of 312 women used an antibiotic at least once. Macrolides, metronidazole, and penicillins were used most often among the nine classes of reported antibiotics. The most common indications were upper respiratory tract infections, bacterial vaginosis, urinary tract infections, and sexually transmitted infections.

Having two or more male sexual partners was also a strong predictor of yeast vaginitis (aHR, 5.0), "and that was something that was a little bit surprising because it’s not a sexually transmitted infection. It’s useful maybe to tell women that limiting their numbers of sex partners will also decrease their risk," Dr. Hillier said.

Using depot medroxyprogesterone acetate (Depo-Provera), meanwhile, had a protective effect (aHR, 0.3), compared with women not using hormonal contraceptives. "Depo-Provera has a very strong progestin; some women who get the shot actually have estrogen depletion in the vaginal epithelium. The finding suggests that when you remove the estrogen from the [vaginal] epithelium, it can reduce your risk for yeast vaginitis," Dr. Hillier said.

Other forms of hormonal contraception were not associated with yeast vaginitis. Although "many women believe oral contraceptives and other hormonal methods increase the risk, there was no evidence of increased risk in this study," she said.

Tomado de: familypracticenews.com