Obesity - symptom of a viral infection?

Type the search terms "obesity, adenovirus-36" into PubMed, the U.S. National Library of Medicine's online database of biomedical research, and you get 21 hits. In fact, the first report of a link between adenovirus infection and increased body fat was published in 2000 by Dhurandar et al¹. This report not only showed that infection with adenovirus-36 increased body fat, but also highlighted the fact that cholesterol and triglycerides were decreased in animals infected with adenovirus-36.

By 2004 this research group had shown that neutralizing antibodies to adenovirus-36 are associated with obesity in humans and showed that infection with the virus seemesto enhance differentiation of pre-adipocytes² (i.e. encouraged the formation of fat cells).

In 2007 Durhandar and co-workers showed that infection with adenovirus-36 not only enhanced differentiation of fat cells, but also decreased leptin levels and increased glucose uptake by fat cells. ³ Leptin is a hormone that regulates appetite and is secreted by fat cells. The group also suggested that infection could increase insulin sensitivity.

In 2010 and 2011 two studies reported no link between the presence of adenovirus-36 and body fat in individuals:

Goossens and co-workers found that adenovirus-36 does not play a role as a direct cause of BMI increase and obesity in humans in the Netherlands and Belgium.⁴ This iwas s in contrast to the United States, where Adenovirus-36 significantly correlates with obesity as illustrated by an Ad-36 seroprevalence of 30% in obese individuals and 11% in nonobese individuals. (Dr Atkinson replies here to the Goossens et al. study)

Broderick and co-workers showed no relationship between Ad-36 presence and obesity or serum cholesterol levels among US military personnel. ⁵ However, they did find a correlation between Ad-36 exposure and age, race and gender.

Recently, Waye has proposed a mechanism that involves oxidative stress in the pathology of Adenovirus-36 induced obesity. ⁶

At present there is still a lot of questions to be answered about the theory of viral-induced obesity. However, if obesity is caused by a virus it would be possible to prevent it by vaccinating humans against it. Obetech LLC is a company already investigating this possibility.

Image: human adenovirus



¹ Dhurandhar NV, Israel BA, Kolesar JM, Mayhew GF, Cook ME, Atkinson RL.(2000) Increased adiposity in animals due to a human virus. Int J Obes Relat Metab Disord. 24: 989-96.

² Vangipuram SD, Sheele J, Atkinson RL, Holland TC, Dhurandhar NV. (2004) A human adenovirus enhances preadipocyte differentiation. Obes Res. 12: 770-7.

³ Vangipuram SD, Yu M, Tian J, Stanhope KL, Pasarica M, Havel PJ, Heydari AR, Dhurandhar NV. (2007) Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. Int J Obes (Lond). 31: 87-96. Epub 2006 May 16.

⁴ Goossens VJ, deJager SA, Grauls GE, Gielen M, Vlietinck RF, Derom CA, Loos RJ, Rensen SS, Buurman WA, Greve JW, van Baak MA, Wolffs PF, Bruggeman CA, Hoebe CJ. (2011) Obesity (Silver Spring). 19: 220-1. Epub 2009 Dec 10.

⁵ Broderick MP, Hansen CJ, Irvine M, Metzgar D, Campbell K, Baker C, Russell KL. (2010) Adenovirus 36 seropositivity is strongly associated with race and gender, but not obesity, among US military personnel. Int J Obes (Lond). 34: 302-8. Epub 2009 Nov 10.

⁶ Waye MM. (2011) New insights into how adenovirus might lead to obesity: An oxidative stress theory. Free Radic Res. May 26. [Epub ahead of print]

Controversies

There are a few popular idease that I am skeptical about. As an ex-scientist I'm well aware that data can be massaged to tell you exactly what you want to hear. However, when research that sounds controversial is published, it still makes for interesting reading and should be given due consideration.

There are many controversial issues around food. For example, the theory that artificial colours cause hyperactivity. In the April issue of Clinical Pediatrics, Dr Laura Stevens and co-workers reflect on 35 years of research looking for a causative link between artificial food colours and attention deficit hyperactivity disorder (ADHD).¹ It has been shown that a small subgroup of children respond to artificial colours, when challenged with at least 100mg. [Note: Typically just 10 - 50 mg is used in a kg of food ²] The authors note that recently, 2 large studies demonstrated behavioral sensitivity to artificial food colourings and benzoate in children both with and without ADHD. However, the study does start off stating that artificial food colors have not been established as the main cause of attention-deficit hyperactivity disorder.

At the University of Osnabrück in Germany, Dr Bodo Melnik has suggested a relationship between milk and type 2 diabetes. ³ This is a proposed mechanism only and is based on the idea that drinking milk after weaning may cause signalling in the pancreas. This might overstimulate β-cell proliferation in the pancrease, and ultimately will speed up β-cell senescence. Both β-cell proliferation and sensecence are hallmarks of type 2 diabetes. The author also mentions a link with Alzheimer's Disease - this is because type 2 diabetes has been linked to an increased risk of Alzheimer's disease. ⁴ Of course, milk has also been shown to be an exceptional recovery drink for sportsmen, giving even better results than special sports drinks. ^5,6

The latest sports-superfood is cherries. Researchers at London South Bank University have shown that Montmorency cherry juice consumption improves the recovery of isometric muscle strength after intensive exercise. ⁷ The researchers suggest that the cherries might have an anti-oxidative effect due to polyphenolic compounds including flavonoids and anthocyanins. [Interestingly, blueberries, chokeberries, European blackcurrants, elderberries and black raspberries contain significantly more flavonoids and anthocyanin than cherry ⁸]

On a non-food note, some researchers in China and the USA have published a case-control study investigating the link between breast cancer and sleeping with the light on.⁹ Subjects were identified in Connecticut, USA, and questioned with respect to their sleeping patterns and bedroom light environment. A non-significantly increased risk of breast cancer was observed among postmenopausal women for those keeping lights on while sleeping. This non-significant increased risk was also observed in women who reported mainly sleeping in the daytime and those not drawing the curtains while sleeping at night. The researchers conclude that this study suggest a potential increased risk of breast cancer associated with domestic exposure to light at night. Another group in Israel found a positive relation between breast cancer and light at night, and suggest that this may be due to disruption of the body's circadian clock.¹⁰ This correlation has not been found with lung cancer. <sup>11





1</sup> Stevens LJ, Kuczek T, Burgess JR, Hurt E, Arnold LE. (2000) Dietary Sensitivities and ADHD Symptoms: Thirty-five Years of Research. Clin Pediatr (Phila). 50: 279-93. Epub 2010 Dec 2.

² http://www.understandingfoodadditives.org/pages/Ch2p1-3.htm

³ Melnik BC. (2011) Milk signalling in the pathogenesis of type 2 diabetes. Med Hypotheses. 76: 553-9. Epub 2011 Jan 19.

⁴http://www.nature.com/nrneurol/journal/v2/n3/full/ncpneuro0124.html

⁵ Pritchett K, Bishop P, Pritchett R, Green M, Katica C. (2009) Acute effects of chocolate milk and a commercial recovery beverage on postexercise recovery indices and endurance cycling performance. Appl Physiol Nutr Metab. 34:1017-22.

⁶ Cockburn E, Stevenson E, Hayes PR, Robson-Ansley P, Howatson G. (2010) Effect of milk-based carbohydrate-protein supplement timing on the attenuation of exercise-induced muscle damage. Appl Physiol Nutr Metab. 35: 270-7.

⁷ Bowtell JL, Sumners DP, Dyer A, Fox P, Mileva KN. (2011) Montmorency Cherry Juice Reduces Muscle Damage Caused By Intensive Strength Exercise. Med Sci Sports Exerc. Jan 12. [Epub ahead of print]

⁸ http://www.mivelle.hu/sambucol/Flavonoid%20and%20Anthocyanin%20Content.pdf

⁹ Li Q, Zheng T, Holford TR, Boyle P, Zhang Y, Dai M. (2010) Light at night and breast cancer risk: results from a population-based case-control study in Connecticut, USA. Cancer Causes Control. 21: 2281-5. Epub 2010 Oct 7.

¹⁰ Kloog I, Portnov BA, Rennert HS, Haim A. (2011) Does the modern urbanized sleeping habitat pose a breast cancer risk? Chronobiol Int. 2: 76-80.

¹¹ Kloog I, Haim A, Stevens RG, Barchana M, Portnov BA. (2008) Light at night co-distributes with incident breast but not lung cancer in the female population of Israel. Chronobiol Int. 25: 65-81.

Taurine protects a donor heart

Some of us may know taurine in the following forms:

















However, recent research has shown that taurine can protect donor hearts from being damaged by blood deprivation.¹ Hearts from rats that were fed taurine showed less damage compared to hearts from rats fed a normal diet, when hearts were removed and kept on ice for 5 hours.

This study also pointed out that taurine infusion can protect the heart muscle if supplied before coronary artery bypass surgery and that dietary taurine can protect the heart from damage caused by heart attack.

Please note: energy drinks also have other ingredients which may not be good for your heart, so they definitely can't be considered a medicine!


¹Mehmet A Sahin, Orhan Yucel, Adem Guler, et al. (2011) Is there any cardioprotective role of Taurine during cold ischemic period following global myocardial ischemia? Journal of Cardiothoracic Surgery 6: 31

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More good bacteria

Not all bacteria are bad, as we know. There are "good bacteria" that live in our gut and help us to digest our food. Now, bacteria have been harnessed to help doctors and clinicians as a vector to treat or prevent disease. This bacterial gene therapy is known as "bactofection".

Peter Celec and his team in the Slovak Republic researched the usage of bacteria to treat inflammatory bowel disease.¹ The Salmonella bacteria carried genes for an antioxidant (superoxide dismutase) and a protein that stimulates the immune response (monocyte chemoattractant protein-1). Bactofection was applied to mice suffering from inflammatory bowel disease (colitis), and alleviated colitis symptoms in these mice when compared to untreated mice.

Listeria has been tested as a vector to deliver therapeutic genes and proteins to cancer cells and immune cells.² Listeria is a particularly good candidate as it is very efficient at entering host cells, and can move from cell to cell without having to exit it anywhere. Moreover it is safe and effective in clinical trials. Anti-cancer genes can be targeted to tumours by packaging them inside this pathogen.


Salmonella has also been used as a vehicle to treat cancer. ³ Both Listeria and Salmonella infect and can survive in antigen presenting cells (cells that form part of the immune system). They can be engineered to express tumour-like proteins which stimulates the body's immune system to break tolerance against tumour cells that look a lot like "self" to the body.



Image: Salmonella enterica serovar typhimurium



¹Palffy R, Gardlik R, Behuliak M, Jani P, Balakova D, Kadasi L, Turna J, Celec P. Salmonella-mediated gene therapy in experimental colitis in mice. Exp Biol Med (Maywood). (2011) 236:177-83.

²Tangney M, Gahan CGM. Listeria monocytogenes as a Vector for Anti-Cancer Therapies. Current Gene Therapy (2010) 10: 46-55.

³Paterson Y, Guirnalda PD, Wood LM. Listeria and Salmonella bacterial vectors of tumor-associated antigens for cancer immunotherapy. Seminars in Immunology (2010) 22: 183-189.

Gold nanocages

Prof. Younan Xia and his team invented gold nanocages (see below) for therapeutic applications. In a review¹ published in 2010, he explained how gold nanoparticles have gained an increasing interest due to their plasmonic characteristics. In particular, the metal can convert light into heat. This heat can be used for different applications, such as selectively releasing the drug contents of the nanocarriers once they have reached their target, or for photothermal therapy, where the heat generated by the nanoparticles destroy the cancer cells to which they are targeted.










¹Cobley CM, Au L, Chen J, Xia Y. Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery. Expert Opin Drug Deliv. 7: 577-87 (2010)

The spirit is willing but the flesh is weak

If you're struggling to lose weight, it might actually be due to a chemical imbalance in your brain.

Researchers at the National Institutes of Health have shown that some obese individuals might have differences in the reward areas of the brain, compared to non-obese individuals.¹ The ability to resist the urge to eat needs to be stronger than the expected feeling of reward when we do eat. Some people seem to have an impairment in the brain area associated with reward sensitivity, and therefore their willpower is overwhelmed by the need to get that food reward.

[I wish this paper were open access as I'd love to know whether the researchers think one could break the conditioned response!]


¹Volkow ND, Wang GJ, Baler RD. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci. 15:37-46 (2011).

Placebos as medicine

Did you know that your doctor may be giving you a placebo for your niggle? Well they very well may be. Antibiotics for flu? There you have one example already.

A recent survey was done by Kermen and co-workers¹ to determine how frequently American physicians prescribe placebos.Fifty-six percent (56%) of surveyed physicians reported prescribing or administering placebos in their practices, with younger physicians being a lot more likely to prescribe placebos than older physicians. The most frequently-used placebo was antibiotics (for non-bacterial diagnoses, 40%). The second most frequently prescribed placebo was vitamines (23%), followed by herbal supplements (12%). The most common reasons for prescribing placebos were “unjustified demand for medication” (32%) and “to calm patients” (21%). Most physicians (31%) told their patients that their presription consisted of a substance that will help and not hurt, and a very honest 2% told their patients that what they were given was an actual placebo. Most physicians believe that the placebo effect is beneficial and can have real, positive results.

So, while most physicians "believe" in the placebo effect, only about half would prescribe a substance that they knew had no direct therapeutic ingredient. Of course this was a very small study, but it makes one wonder what's happening in one's own surgery. It also reiterates the strong effect that thoughts can have on health.

¹ Kermen R, Hickner J, Brody H, Hasham I. Family physicians believe the placebo effect is therapeutic but often use real drugs as placebos. Fam Med. 42:636-42 (2010)
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Christmas special: the weird and the wonderful

In the process of looking for hot new research topics (or just in the course of my daily working day) I find a fair amount of curious papers. So, as a final entry for the year I thought I'd post a special edition, listing a few of my favourites.

From the department of Advanced Medical Science (literally)¹:

"Obesity significantly increases the difficulty of patient management in the emergency department."

With the objective to "... determine which aspects of ED management are adversely affected by patient obesity, to determine the level of obesity above which management is made more difficult and to make recommendations on how these effects might be mitigated...", this study showed that patient obesity makes it difficult to manage an emergency department. And offered no solutions.


Ever wondered if watching TV or working on your computer late at night affects your sleep? So did a couple of researchers in Brazil who investigated the "Quality of sleep among university students: effects of nighttime computer and television use."²

The internet lost out in this study as it seems to affect sleep a lot more than television. Interestingly, if you manage to use the internet untill 3am, you sleep a bit better. This blogger wonders how much of the "affected sleep" is due to online arguing...



The title of this paper says it all, really: PMS: premenstrual storm? An unusual cause of electrical storm in a young woman with vasospastic angina. ³
Never underestimate how hard it is to be a girl...



Apparently "Hearing loss in stranded odontocete dolphins and whales" ⁴ is a big problem. Researchers speculate that this may have somethig to do with the actual stranding. How do you measure hearing in a dolphin? Well, with great difficulty, but apparently "in all cases, a jawphone consisting of an ITC-1042 piezoceramic transducer embedded in a RTV silicone suction cup was placed on the lower jaw fat pad to deliver sound stimuli." If a response could be detected from the dolphin or whale, then that was marked as the level at which the animal could "hear". There was a strong correlation between stranding and hearing loss in some of the species. (Picture below: a hydrophone)




The brushtail possum is a major pest species of New Zealand. Some researchers are investigating a nanoparticle system containing a chemical sterilitant which could be used orally to control their numbers.⁵ Poor little possums.




Our last two entries are shamelessly of a scatological nature:

A woman with a history of depression presents with abdominal bloating. Her doctor sends her for a colonoscopy. It turns out she's fine, but they do find something odd. A cockroach. ⁶


And finally... Apparently "robotic assisted laparoscopic radical prostatectomy" is a fairly uncomfortable procedure used in prostate cancer. So a few researchers in Seattle wondered whether a suppository containing belladonna (that's deadly nightshade to me and you) and opium would help.⁷ And indeed it did! With no adverse events noted either!





¹ Kam J, Taylor DM. Emerg Med Australas. 2010 Aug;22(4):316-23. Source

² Mesquita G, Reimão R. Arq Neuropsiquiatr. 2010 Oct;68(5):720-5. Source

³ Li J, Zitron E, Katus HA, Becker R. Clin Res Cardiol. 2010 Nov 30. [Epub ahead of print] Source

⁴ Mann D, Hill-Cook M, Manire C, Greenhow D, Montie E, Powell J, Wells R, Bauer G, Cunningham-Smith P, Lingenfelser R, DiGiovanni R Jr, Stone A, Brodsky M, Stevens R, Kieffer G, Hoetjes P. PLoS One. 2010 Nov 3;5(11):e13824. Source

⁵ Kafka AP, McLeod BJ, Rades T, McDowell A. J Control Release. 2010 Oct 31. [Epub ahead of print] Source

⁶ Kumar AR, Perez JA, Miick R, Govil YK Endoscopy. 2010;42 Suppl 2:E209-10. Epub 2010 Sep 15. Source - INCLUDES FULL ARTICLE PLUS PHOTO!

⁷ Lukasewycz S, Holman M, Kozlowski P, Porter CR, Odom E, Bernards C, Neil N, Corman JM. Can J Urol. 2010 Oct;17(5):5377-82. Source

New skins for old wine

Curcumin is the metabolite that's responsible for the yellow colour of the spice, tumeric. It can be used for food colouring (it's E number is E100), to quantify boron ¹, and to treat a number of ailments.

The first research on curcumin looked at its antibacterial properties ², and since then researchers have looked at its antioxidant properties ³, its use as an antirheumatic ⁴, a potential cholesterol-lowering role for it ⁵ and many other medicinal applications.

Recently a group in Canada investigated the effect of tumeric on cancer treatment.⁶ Previous research showed that curcumin also has an anti-cancer effect, but these researchers wanted to know if curcumin given in addition to standard chemotherapy could improve the efficacy of the treatment while keeping side-effects to a minimum. The researchers found that the combined treatment worked at lower doses than monotherapy; that non-cancerous cells remained unaffected; and that cancer cells still responded to the treatment even after the drugs were removed.

Many people scoff at the idea of "natural therapies", but it is important to remember that aspirin was originally made from willow bark. Tumeric might be the next aspirin!


¹Roth HJ, Miller B. On the color reaction between boric acid and curcumin. I. Boric acid-curcumin complexes. Arch Pharm (Weinheim)297:617-23 (1964)

²SCHRAUFSTATTER E, BERNT H. Antibacterial action of curcumin and related compounds. Nature. 164(4167):456 (1949)

³ Sharma OP. Antioxidant activity of curcumin and related compounds. Biochem Pharmacol. 25:1811-2 (1976)

⁴Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res. 71:632-4 (1980)

⁵Soudamini KK, Unnikrishnan MC, Soni KB, Kuttan R. Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin. Indian J Physiol Pharmacol. 36:239-43 (1992)

⁶
Chatterjee SJ, Pandey S. Chemo-resistant melanoma sensitized by tamoxifen to low dose curcumin treatment through induction of apoptosis and autophagy. Cancer Biol Ther. 2011 Jan 29;11(2). [Epub ahead of print]

Nanobots!

In Star Trek: The Next Generation episode Evolution (1989), Wesley Crusher creates Nanobots called “nanites” which unexpectedly evolve to the point of sentience.

According to the Futurama Wiki "The Nanobots were a model of Robots created by Professor Hubert J. Farnsworth that inhabited the Robo-Planetoid during August of 3010."

Recently, Prof Joseph Wang and his team at UCSD published a paper on fuel free nanomotors¹. These nanomotors or nanoshuttles are designed to pick up, transport, and deliver drugs to their target more efficiently than current nanotherapy strategies.

Each nanoshuttle has a polypyrrole-cadmium nanowire containing a diode, which allows an electric current to flow in only one direction.² In order to get the nanoshuttles to move, an alternating current electric field is applied to the nanowires - this propels the shuttle by converting electrical energy into movement. The nanoshuttles are propelled a distance equivalent to seven times their body length in one second.


¹ Kagan D et al. Small Oct 27 (2010) E-pub
² Burch H. Nanomotors go fuel-free. Chemical Science 09 February 2010. (Source) This article includes a video.

Nanotherapy for targeted cancer treatment

Many researchers are currently investigating more effective, targeted ways of delivering cancer drugs and therapies to patients.

Two such innovative studies have looked at the use of wheat germ agglutinin and folic acid, respectively, as a conjugate to target tumors.

A team in Singapore have modified the nano-encapsulated drug, paclitaxel, with wheat germ agglutinin (WGA) to target colon cancer cells.¹ These cells express a greater amount of WGA-binding glycoproteins. Nanoparticles modified with WGA showed greater uptake into cancer cells when compared to unmodified particles. The WGA-modified particles also showed an enhanced anti-proliferative activit.

In India, a research team have modified nanoparticles loaded with grape seed extract(active as a neutraceutical), in order to target them to folate receptor over-expressing cancers.² The nanoparticles were conjugated with folic acid in order to target them to these cells. Folate receptor positive cancer cells readily took up the nanoparticles, showing enhanced bioavailability to tumor cells, sparing the normal ones.

Both these reports underline the application of modifications to target cancer therapies - strategies that may greatly improve the side-effects of chemotherapy.

¹ Wang C, Ho PC, Lim LY. Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells. Int J Pharm 400:201-10 (2010).

² Narayanan S, Binulal NS, Mony U, Manzoor K, Nair S, Menon D. Folate targeted polymeric 'green' nanotherapy for cancer. Nanotechnology 21:285107 (2010).

Neurorehabilitation - gaming systems

In a marriage of medicine and gaming culture, virtual reality games have been investigated in the rehabilitation of stroke patients.¹

Researchers in Barcelona have investigated novel technology-based neurorehabilitation techniques in the treatment of strokes. A special aspect of this technique was the fact that the game could be adjusted and personalized for each patient.

While a stroke causes massive damage, brain cells can reorganize themselves. Therefore the aim of rehabilitation is to maximize the effect of this plasticity. The Spanish research team developed the Rehabilitation Gaming System (RGS), a virtual reality-based neurorehabilitation program .

The RGS tracks arm and finger movements and maps them onto a virtual environment. The user controls the movement of two virtual limbs that are viewed on a screen. The RGS "game" that the researchers used was called Spheroids (see figure below). In this game the user has to catch and place spheres that move towards them. The idea behind this is that, when the patients use their limbs and observe the virtual limbs move in a way that is controlled by them, conditions are created that stimulate the reorganization of neurons involved in motor functions.


The researchers also tried to make the tasks just challenging enough to remain engaging for the patients. The RGS automatically adjusts the difficulty of the task with respect to the measured performance of a subject in order to keep them encouraged and to maximize effect.

The researchers concluded that the RGS is a promising neurorehabilitation tool that can be used to alleviate the deficits brought on by lesions to the central nervous system as the ones caused by stroke.

¹ Cameirão MS, Bermúdez i Badia S, Oller ED, Verschure1 PFMJ. Neurorehabilitation using the virtual reality based Rehabilitation Gaming System: methodology, design, psychometrics, usability and validation. Journal of NeuroEngineering and Rehabilitation 7:48 (2010).
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Stem cell therapy for cardiovascular disease

Stem cell therapy is controversial, mostly for the application of foetal stem cells in a large proportion of research.

A new type of stem cell has been developed by researchers in Japan, called induced pluropotent stem (iPS) cells. These cells derive from somatic (body) cells, and therefore are a lot less morally questionable than foetal cells.

A recent study has investigated the usage of iPS cells in the treatment of ischemia ¹ - the restriction of blood supply to a specific body part that can lead to tissue damage. Hind limb ischemia in mice was treated with iPS cells specifically treated to produce a protein called fetal liver kinase-1 (Flk-1). This protein plays an important role in the formation of blood vessels.

Transplantation of stem cells producing Flk-1 into the damaged limbs of mice accelerated the formation of new blood vessels, showing that this therapy could potentially rescue tissues that have suffered restricted blood flow. This could potentially be applied after events such as heart attacks.

¹ Suzuki et al. Therapeutic angiogenesis by transplantation of induced pluripotent stem cell-derived Flk-1 positive cells. BMC Cell Biology 11:72 (2010)

Rubbish! Chilis don't make you lose weight! ...or do they?!

Research on the effect of chili peppers on metabolic rate, continues.

In a study done at McMaster University in Canada, researchers tested the effect of capsinoids (substances present in chili peppers, and related to the more famous compound capsaicin) on energy expenditure, fat burning, and levels of certain molecules in the blood.¹

Twelve healthy male subjects were observed before and after a 90 minute stationary bike ride. During two separate experiments all subjects took (randomly) either a placebo or a treatment containing 10mg capsinoid, so that each subject had results that represented the effect of capsinoids and the effect of placebo. The subjects were tested with respect to oxygen consumption, respiratory exchange ratio (RER), heart rate, perceived exertion, and blood metabolites. Previous research on other andrenergic agonists (like caffeine) showed that these variables are changed by the treatment both during rest and during exercise. However, in the current study effects were mainly significant during rest. The main findings in this study were that, versus a placebo, 10 mg of capsinoids induced a rise in resting oxygen consumption, a decline in RER, an increase in plasma norepinephrine, and a decline in serum free fatty acids at rest. 10 mg of capsinoids also blunted the small but significant rise in blood lactate observed at the onset of exercise seen in the placebo group (0 mg).

This means that capsinoids raise the resting metabolic rate (shown as an increase in oxygen consumption) without increasing resting heart rate (none were observed in the study). Furthermore, the increase in norepinephrine and decline in RER suggest that the body burns more fat at rest. However, the effect of capsinoids on metabolism didn't carry over into exercise, where both groups showed similar metabolic states.

Capsinoids, therefore, represent a useful treatment for patients who want to lose weight, regardless of their level of physical activity.

¹ Josse et al. Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise. Nutrition & Metabolism 7: 65 (2010).

Aspirin as a treatment for schizophrenia

Based on research that suggested that inflammation plays a role in schizophrenia (see below), further research has been done to investigate whether aspirin could improve existing anti-psychotic treatment.¹

Seventy patients in total took part in the randomized, placebo-controlled trial. One group of patients received their normal anti-psychotic treatment plus placebo, while the other group received their normal anti-psychotic treatment along with 1000mg of aspirin per day. During a 3-month follow up, patients were assessed according to the Positive and Negative Syndrome Scale (PANSS) - a medical scale used for measuring symptom severity of patients with schizophrenia. Researchers also tested the patients' cognitive function and changes in their immune systems.

Patients who took aspirin showed greater improvement in their PANNS scores, and therefore reduced the symptoms of schizophrenia. The reduction was greater in patients who have a more altered immune function. The researchers concluded that inflammation may be a potential new target for antipsychotic drug development.

¹ Laan W et al. Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 71: 520-7 (2010).
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Inflammation linked to metabolic syndrome and mental disorders

Recent results provide evidence that link inflammation with an increased risk of metabolic syndrome and schizophrenia.¹ Metabolic syndrome is characterised by central obesity, raised blood pressure, sub-optimal cholesterol and triglyceride profiles, and raised blood glucose.

In the study, white blood cell count (WBC) was determined in 199 patients. Increased WBC strongly predicted the condition of metabolic syndrome. Further significant correlations were found between high WBC and the Brief Psychiatric Rating Scale (BPRS) - a rating scale which is used to measure psychiatric symptoms such as depression, anxiety, hallucinations and unusual behaviour.

The researchers concluded that WBC can be used as a marker to predict an increased risk for metabolic syndrome and more severe psychiatric symptoms in patients with schizophrenia.

¹ Fan X et al. Higher white blood cell counts are associated with an increased risk for metabolic syndrome and more severe psychopathology in non-diabetic patients with schizophrenia. Schizophrenia Research 118: 211-217 (2010).
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An effective treatment for Alzheimer's disease

Alzheimer's disease reduces the number of nerve cells in the brain, causing it to shrink. Nerve cells can't be replaced naturally, and no cure has yet been discovered, therefore this is irreversible. Alzheimer's disease also leads to a decrease in the number of neurotransmitters, particularly acetylcholine, therefore transmission of neural messages is decreased. The disease leads to deterioration of brain function, resulting in memory loss, reduced language skills and behavioural and emotional problems.

Alzheimer's disease can be treated with acetylcholinesterase inhibitors, although they aren't very effective and most people get little benefit from them.¹ A couple of years ago the first steps were made to investigate the usage of a new drug in the treatment of Alzheimer's disease. Etanercept is an inhibitor that regulates the transmission of signals between neurons in the brain. It regulates the function of a protein called TNF-alpha that is usually involved in inflammation.² A number of investigations have related excess TNF-alpha to the progression of Alzheimer's disease, as it seems to also act as a neural transmitter in the human body.²

Etanercept has previously been used in the effective relief of pain, through perispinal administration (injection around the spine, but not into the spinal column).² This indicated that etanercept crosses the blood-brain membrane barrier, and suggested that the veins around the spine can be used to transport drugs to the spine and the brain.

In a case study, two patients were treated with perispinal etanercept.² The first patient had impairments in attention, linguistic processing, and memory. After treatment with a non-effective drug, he had become effectively mute before his treatment regime was changed to include perispinal etanercept. The patient's speech, as well as his movement, increased significantly after treatment, with the greatest improvement seen in the week after treatment.

The second patient was an 80 year-old who had a history of increasing word-finding difficulty, and worsening memory and handwriting. Even just 8 minutes after treatment with etanercept, the patient showed improvement, being able to recite the days of the week backwards, something he was incapable of doing before treatment. His conversational ability, attention span, and forgetfulness all improved in the weeks post-treatment, with the greatest effect being seen in the first week.

Since the greatest effect was observed one week after etanercept treatment, weekly treatments might be the most effective. Although this study has limitations, it adds to the range of treatments available to treat Alzheimer's disease.


¹ http://hcd2.bupa.co.uk/fact_sheets/html/alzheimers_disease.html
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² Tolbinick E and Gross H. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease. BMC Neurology 8:27 (2008)

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Singing therapy for COPD

Chronic obstructive pulmonary disease(COPD) is a term used for a number of lung conditions that all affect ease of breathing, such as bronchitis and emphysema. COPD is a long-term disease that damages the airways, making them increasingly narrow, and thereby further obstructing airflow. Symptoms can be mild, including cough, phlegm, and shortness of breath during the winter or after a cold, to severe, with constant shortness of breath severely affecting daily activities. COPD cannot be cured, but it can be treated.

Patients with COPD often try to compensate for obstructed airways by changing the way they breathe. This may lead to stress on the respiratory muscles, while short, rapid breaths may cause an increased sense of panic, and exacerbate feelings of breathlessness.

A recent randomised controlled trial¹ looked at the effect of a 6-week singing course on the breathing patterns of patients with COPD. Patients who took part in the singing course showed significant improvements in their perceived quality of life as well as anxiety levels when compared to patients who didn't sing. When interviewed, 8 of the patients who took part in singing felt that it had a positive effect on their well-being, community support, achievement, and physical sensation.

In a larger study where a number of open singing workshops were offered, almost all of the 150 patients experienced the workshop as very enjoyable, and thought it had taught them how to breathe in a different way. The vast majority felt a marked physical difference after the workshop.

Therefore singing classes can improve the lives of patients with COPD, with a number of positive effects and no negative effects.

¹ Lord VM et al. Singing teaching as a therapy for chronic respiratory disease - a randomised controlled trial and qualitative evaluation. BMC Pulmonary Medicine 10:41 (2010)
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If you develop it, they will use it

Research from the department of "why didn't we think of that?": in research sponsored by Reckitt Benckiser Healthcare International Ltd, the treatment of pain with a tablet containing both paracetamol and ibuprofen was investigated.¹ These pain killers (analgesics) work in different ways, and therefore can be used together safely without causing overdose. Paracetamol, in contrast to ibuprofen, can accumulate in the liver when overdose occurs, and cause massive damage.

Volunteers were given either a combination paracetamol-ibuprofen tablet, or the two analgesics seperately. The combination pill showed a more rapid absorption of paracetamol, compared to paracetamol taken on its own. The mean blood concentrations of both paracetamol and ibuprofen were higher, earlier, than when the drugs were taken individually.

When the combined paracetamol-ibuprofen tablet was taken after a meal, absorption of ibuprofen was delayed by 25 minutes, and that of paracetamol was delayed by 55 minutes. The maximal blood concentration of both was also decreased when the tablet was taken after a meal. The study also determined that the combination tablet causes therapeutic dose levels of ibuprofen and paracetamol for approximately 12 hours when given three times per day. Therefore a combination paracetamol-ibuprofen treatment could provide enhanced pain relief for more severe pain.

Or, of course, you could just buy the two seperately, and take them together.




¹Tanner T, Aspley S, Munn A, Thomas T. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol. BMC Clinical Pharmacology 10:10 (2010).
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The effect of drug use on pain tolerance

Research has shown that former opiate addicts that have been treated with methadone, and thereafter systematically taken off the methadone treatment, show decreases in brain function and abnormal pain thresholds.¹

A recent study tested the mental acuity of former opiate-dependent subjects before and after being exposed to a treatment that caused pain. The subjects were treated with a heat stimulus at their pain threshold. Their mental acuity was tested with a Stroop test. In this test you are instructed to name the colour that a word has been written in, when the word itself describes a colour (see image right).

Control subjects performed better than former opiate-dependent subjects in the Stroop test, when no pain was experienced. (Controls were never opiate-dependent and weren't exposed to methadone treatment either. ) In general, females performed better than males under these conditions. However, under painful conditions, male former opiate-dependent individuals showed a greater improvement in Stroop test scores than male control subjects or females of either group.

Therefore previous opiate dependence affects brain function, with males seemingly being more affected than females. However, response to pain is also altered, with males who were previously opiate dependent showing greater improvements in Stroop scores than females and control subjects.

¹Aniskin DB, MD; Fink E, MD; Prosser J, MD; Cohen LJ, PhD; Boda N, MD; Steinfeld M, MS; Galynker II, MD, PhD. The Effect of Pain on Stroop Performance in Patients With Opiate Dependence in Sustained Remission. Journal of Addiction Medicine doi: 10.1097/ADM.0b013e3181d77c07
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