Best and Worst in Health and Healthcare – May 2016by Sara Adaes, PhD | June 20, 2016
May was full of promising news in glioblastoma research, one of the deadliest forms of brain cancer. But as usual, there were also not-so-good news, with the side-effects of drugs being on the spotlight.
Nanotechnology applied to glioma treatment
Glioblastoma multiforme is a rare but highly lethal disease with no effective treatment options. One of the main difficulties in glioblastoma therapy is the delivery of chemotherapeutic agents into the tumor across the blood–brain barrier.
A new study published in Nanomedicine describes a new drug nanocarrier capable of crossing the blood-brain barrier and delivering chemotherapeutic drugs into the brain, thereby increasing the local availability of the drug. It was shown that these nanostructures selectively accumulated in glioma cells, increasing the targeted death of these cells. These targeted drug nanocarrier systems hold great potential for the delivery of drugs that would otherwise be unable to reach the brain.
A new use for an old drug in glioblastoma treatment
Glioblastoma is characterized by a high cellular metabolic rate with a high expenditure of glucose that drives the fast proliferation of new tumor cells and blood vessels. The cellular metabolism of glioblastoma cells may therefore be a key therapeutic target. Flavopiridol is a synthetic flavonoid that can target glucose metabolism and that has previously been used in cancer treatment.
Research published in the Journal of Cellular Physiology assessed whether flavopiridol could decrease the proliferation of glioblastoma cells by targeting their glucose metabolism. The results were promising: it was shown that flavopiridol could indeed reduce glycolysis in glioblastoma cells and inhibit their proliferation. This study, carried out in vitro, therefore brings promise for a possible new use of flavopiridol in glioblastoma patients.
Vitamin E is a risk factor biomarker for glioblastoma
Besides the poor treatment options, the biological risk factors are another poorly understood aspect of glioblastoma. Aiming to identify new potential glioblastoma risk factors, a study published in Oncotarget investigated changes in metabolite concentrations in serum samples from glioblastoma patients that had been obtained prior to the diagnosis of the disease.
The study identified nine metabolites as potential biomarkers for glioblastoma, all involved in antioxidant metabolism. The serum concentrations of Vitamin E were a particularly relevant serum indicator of an increased risk of glioblastoma development. Although additional studies may be necessary to confirm this association, these results provide strong indications of a probable applicability of Vitamin E serum levels measurements to the determination of the risk of developing glioblastoma.
How green light sooths migraine headaches
Migraine sufferers know how headaches can be exacerbated by light. But apparently not all light has the same impact. According to a study published in Brain, green light is much less impactful in migraine headaches than white, blue, amber or red lights. It was shown that green light activates retinal pathways to a lesser extent than white, blue and red lights, that neurons in the thalamus are most responsive to blue and least responsive to green light, and that the cerebral cortex responds to green light to a lesser extent that to blue, amber and red lights.
These results reveal a mechanisms for migraine associated photofobia, which may originate in cone cells (the light receptors in the retina responsible for color vision), modulated by thalamic neurons, and maintained by the cerebral cortex. This study also indicates a possible mechanism for the headache soothing effects of green light.
Fasting as a therapy for multiple sclerosis
A fasting mimicking diet may be effective in the treatment of multiple sclerosis. This was the main conclusion of a study published in Cell Reports where it was shown that periodic cycles of fasting decrease demyelination and other multiple sclerosis symptoms in an experimental model of autoimmune encephalomyelitis. The fasting mimicking diet was able to reduce multiple sclerosis severity in all animals tested, and to completely reverse symptoms in 20% of animals, indicating that this dietary approach may hold great therapeutic potential.
Pregabalin may induce birth defects
Pregabalin is a widely used antiepileptic drug. Aiming to determine whether pregabalin could affect pregnancy outcomes following maternal use, a new study published in Neurology collected data from exposed pregnancies and found that the administration of pregabalin after the first trimester significantly increased the risk of major birth defects. The rate of live births due to elective and medically indicated pregnancy terminations was also lower in the pregabalin group.
Although further confirmation is still required, the results of this work should be kept in mind when treatment with pregabalin is required during pregnancy.
The fractionation of radiation therapy may not reduce its side-effects
Radiation therapy for the treatment of brain tumors can have a number of undesired side-effects. A common approach to reduce them is to fractionate radiation therapy instead of delivering a single, larger dose of radiation.
Research published on the International Journal of Radiation Oncology assessed whether fractionation was indeed effective in reducing radiation side-effects; it was found that although fractionation could reduce weight loss associated with the treatment, it was not effective in reducing the loss of support cells in the brain. These cells, called oligodendrocytes, are responsible for the synthesis of myelin, an insulating molecule that is fundamental for the proper functioning of neurons. The loss of myelin can be associated with cognitive deficits, a common side-effect of radiation therapy. These results therefore indicate that fractionation may not be as effective in protecting the brain as believed.
The consequences of shift work on cognitive performance
There have been some studies on the effects of shift work linking it to the development of cognitive issues, but there is still a lot of conflicting information regarding this topic.
A new study published in Neurobiology of Aging assessed data from over 7000 middle-aged and elderly Swedish individuals to investigate if shift work could be associated with cognitive performance. The collected data indicated that shift workers performed worse on cognitive tests evaluating executive cognitive function, known to decrease with age. These results indicate that shift work can induce an accelerated cognitive loss in middle-aged and elderly humans.
A paradoxical effect of morphine
Neuropathic pain, arising from disease or damage of the nervous system, is predominantly treated with opioids. However, these are known to induce various side-effects.
Research published in the Proceedings of the National Academy of Sciences now indicates that the opioid morphine may have a paradoxical effect: short course administration of morphine after nerve injury actually doubled the duration of neuropathic pain. This study indicates that although opioids can reduce neuropathic pain, they may also end up prolonging it. This adds another concern to the abundant clinical use of opioids to treat chronic pain.
Traumatic brain injury outcome is negatively affected by anemia
According to an article published in World Neurosurgery, outcome after traumatic brain injury is worse in patients with anemia.
After reviewing records of patients with brain injury and studying their levels of hemoglobin in the blood, it was determined that lower concentrations of hemoglobin were predictors of poor outcome after brain injury. For each 1 g/dL higher hemoglobin levels, the likelihood of a good post-injury outcome increased by 33%. According to these findings, blood transfusion for traumatic brain injury patients with low levels of hemoglobin may significantly improve their recovery.
Begolly, S., Shrager, P., Olschowka, J., Williams, J., & O’Banion, M. (2016). Fractionation spares mice from radiation-induced reductions in weight gain but does not prevent late oligodendrocyte lineage side effects International Journal of Radiation Oncology*Biology*Physics DOI: 10.1016/j.ijrobp.2016.05.005
Björkblom, B., Wibom, C., Jonsson, P., Mörén, L., Andersson, U., Børge Johannesen, T., Langseth, H., Antti, H., & Melin, B. (2016). Metabolomic screening of pre-diagnostic serum samples identifies association between ?- and ?-tocopherols and glioblastoma risk Oncotarget DOI: 10.18632/oncotarget.9242
Choi, I., Piccio, L., Childress, P., Bollman, B., Ghosh, A., Brandhorst, S., Suarez, J., Michalsen, A., Cross, A., Morgan, T., Wei, M., Paul, F., Bock, M., & Longo, V. (2016). A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms Cell Reports, 15 (10), 2136-2146 DOI: 10.1016/j.celrep.2016.05.009
Cimini, A., d’Angelo, M., Benedetti, E., D’Angelo, B., Laurenti, G., Antonosante, A., Cristiano, L., Di Mambro, A., Barbarino, M., Castelli, V., Cinque, B., Cifone, M., Ippoliti, R., Pentimalli, F., & Giordano, A. (2016). Flavopiridol: An old drug with new perspectives? Implication for development of new drugs Journal of Cellular Physiology DOI: 10.1002/jcp.25421
Grace, P., Strand, K., Galer, E., Urban, D., Wang, X., Baratta, M., Fabisiak, T., Anderson, N., Cheng, K., Greene, L., Berkelhammer, D., Zhang, Y., Ellis, A., Yin, H., Campeau, S., Rice, K., Roth, B., Maier, S., & Watkins, L. (2016). Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation Proceedings of the National Academy of Sciences, 113 (24) DOI: 10.1073/pnas.1602070113
Litofsky, N., Martin, S., Diaz, J., Ge, B., Petroski, G., Miller, D., & Barnes, S. (2016). The Negative Impact of Anemia in Outcome from Traumatic Brain Injury World Neurosurgery, 90, 82-90 DOI: 10.1016/j.wneu.2016.02.076
Miller, K., Dixit, S., Bredlau, A., Moore, A., McKinnon, E., & Broome, A. (2016). Delivery of a drug cache to glioma cells overexpressing platelet-derived growth factor receptor using lipid nanocarriers Nanomedicine, 11 (6), 581-595 DOI: 10.2217/nnm.15.218
Noseda, R., Bernstein, C., Nir, R., Lee, A., Fulton, A., Bertisch, S., Hovaguimian, A., Cestari, D., Saavedra-Walker, R., Borsook, D., Doran, B., Buettner, C., & Burstein, R. (2016). Migraine photophobia originating in cone-driven retinal pathways Brain DOI: 10.1093/brain/aww119
Titova, O., Lindberg, E., Elmståhl, S., Lind, L., Schiöth, H., & Benedict, C. (2016). Association between shift work history and performance on the trail making test in middle-aged and elderly humans: the EpiHealth study Neurobiology of Aging, 45, 23-29 DOI: 10.1016/j.neurobiolaging.2016.05.007
Winterfeld, U., Merlob, P., Baud, D., Rousson, V., Panchaud, A., Rothuizen, L., Bernard, N., Vial, T., Yates, L., Pistelli, A., Ellfolk, M., Eleftheriou, G., de Vries, L., Jonville-Bera, A., Kadioglu, M., Biollaz, J., & Buclin, T. (2016). Pregnancy outcome following maternal exposure to pregabalin may call for concern Neurology, 86 (24), 2251-2257 DOI: 10.1212/WNL.0000000000002767
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