Yesterday was Shrove Tuesday, the traditional feast day before the start of Lent. Also known as Pancake Day, many people will have returned to traditional recipes or experimented with the myriad of options available for this versatile treat.
But you may not realise pancakes are helping to advance medicine. Here we revisit some interesting research
The appearance of pancakes depends on how water escapes the batter mix during the cooking process. This is impacted by the batter thickness. Understanding the physics of the process can help in producing the perfect pancake, but also provides insights into how flexible sheets, like those found in human eye, interact with flowing vapour and liquids.
Illustration of a healthy eye, glaucoma, cataract
The researchers at University College London (UCL), UK, compared recipes for 14 different types of pancake from across the world. For each pancake the team analysed and plotted the aspect ratio, i.e. the pancake diameter to the power of three in relation to the volume of batter. They also calculated the baker’s percentage, the ratio of liquid to flour in the batter.
It was found that thick, almost spherical pancakes had the lowest aspect ratio at three, whereas large thin pancakes had a ratio of 300. The baker’s percentage did not vary as dramatically, ranging from 100 for thick mixtures to 175 for thinner mixtures.
Co-author Professor Sir Peng Khaw, Director of the NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology said; ‘We work on better surgical methods for treating glaucoma, which is a build-up of pressure in eyes caused by fluid. To treat this, surgeons create an escape route for the fluid by carefully cutting the flexible sheets of the sclera.’
‘We are improving this technique by working with engineers and mathematicians. It’s a wonderful example of how the science of everyday activities can help us with medicinal treatments of the future.’
Classic american pancakes
Growing in just about the most challenging of locations in the SCIence Garden are a small group of Helleborus niger. They are planted in a very dry and shady location underneath a large tree sized Escallonia and although they struggled to establish when they were first planted (in May 2017) they are now flowering and growing well.
This plant was first featured as a Horticulture Group Medicinal Plant of the Month in December 2011 and as it is now in the SCIence garden I thought a reprise was in order.
Helleborus is a genus of 15 species of evergreen perennials in the buttercup family, Ranunculaceae. In common with most members of the family, the flowers are radially symmetric, bisexual and have numerous stamen.
Helleborus is the Latin name for the lent hellebore, and niger means black – referring in this species to the roots.
This species is native to the Alps and Appenines. Helleborus niger has pure white flowers, with the showy white parts being sepals (the calyx) and the petals (corolla) reduced to nectaries. As with other hellebores, the sepals persist long after the nectaries (petals) have dropped.
All members of the Ranunculaceae contain ranunculin, an unstable glucoside, which when the plant is wounded is enzymatically broken down into glucose and protoanemonin. This unsaturated lactone is toxic to both humans and animals, causing skin irritation and nausea, vomiting, dizziness and worse if ingested.
Protoanemonin dimerises to form anemonin when it comes into contact with air and this is then hydrolysed, with a concomitant ring-opening to give a non-toxic dicarboxylic acid.
Many hellebores have been found to contain hellebrin, a cardiac glycoside. The early chemical literature suggests that this species also contains the substance but later studies did not find it suggesting that either mis-identified or adulterated material was used in the early studies.
It is reported to contain many other specialized metabolites including steroidal saponins.
This plant has long been used in traditional medicine – in European, Ayurvedic and Unani systems and recent research has been aimed at elucidating what constituents are responsible for the medicinal benefit.
Extract of black hellebore is used sometimes in Germany as an adjuvant treatment for some types of tumour.
A recent paper* reports the results of a safety and efficacy investigation. The Helleborus niger extract tested was shown to exhibit neither genotoxic nor haemolytic effects but it was shown to have anti-angiogenetic effects on human umbilical vein endothelial cells (HUVEC), anti-proliferative effects and migration-inhibiting properties on tumour cells thus supporting its use in cancer treatment.
* Felenda, J.E., Turek, C., Mörbt, N. et al. Preclinical evaluation of safety and potential of black hellebore extracts for cancer treatment. BMC Complement Altern Med 19, 105 (2019) doi:10.1186/s12906-019-2517-5
Almost half of world’s adults aged 85 and over have Alzheimer’s Disease.
The amyloid-B precursor protein (APP) plays a key role in the development of the amyloid plaques that are the hallmark of Alzheimer’s disease. Now, researchers claim to have identified thousands of genetic variants of the APP gene that codes for the protein in the brains of patients with the most common form of Alzheimer’s disease, known as late-onset or sporadic AD (SAD).
The study reveals for the first time how this genetic variation occurs – by a mechanism involving the enzyme reverse transcriptase, the same type of enzyme used by HIV to infect cells.
APP forms plaques in the brain, as shown above in a light micrograph.
Our findings provide a scientific rationale for immediate clinical evaluations of HIV antiretroviral therapies in people with AD,’ says Jerold Chun, senior VP of Neuroscience Drug Discovery at Sanford Burnham Prebys Medical Discovery Unit (SBP), an idea that the researchers say is supported by the relative absence of proven AD in ageing HIV patients on antiretroviral medication.
The APP gene variants were created by reverse transcription, the researchers note, when RNA acts as a template to form complementary DNA sequences that are then reinserted back into the original genome.
Discovery of possible Alzheimer’s treatment. Video: Sanford Burnham Prebys Medical Discovery Institute
This process of gene recombination – which occurs each time cells divide to make new ones – has not previously been reported in nerve cells (neurons) in the brain but could also help to explain the complexity and diverse functions of our brain cells.
Psilocybin mushrooms have psychedelic properties. Image: Wikimedia Commons
The psychoactive compound in psychedelic ‘magic mushrooms’ could pave the way for new drugs to treat depression, according to a new study. Patients in the study reported that their mood had lifted, they felt less depressed and were less stressed immediately after taking psilocybin. Nearly half (47%) were still benefiting five weeks after discontinuing treatment.
Robin Carhart-Harris and his team at Imperial College London, UK – the Psychedelic Research Group – gave psilocybin to 19 patients suffering from ‘treatment resistant’ depression, who had failed to benefit from other depression therapies. They were given 10mg initially and 25mg one week later.
The Psychedelic Research Group is the first in 40 years to use LSD in research in the UK since the Misuse of Drugs Act 1971. Image: Pixabay
‘Several of our patients described feeling “reset” after the treatment and often used computer analogies,’ said Carhart-Harris. ’Psilocybin may be giving these individuals the temporary kick start they need to break out of their depressive states.’
Functional MRI scans measuring activity and blood flow in the brain showed marked differences after the treatment. There was reduced blood flow to areas of the brain, including the amygdala, which processes emotional responses, such as stress and fear. Another brain network appeared to ‘stabilise’ after treatment.
‘fMRI scans indicate that the communication within a certain prefronto-limbic circuit known to regulate affective responsiveness, is normalised one day after psilocybin treatment,’ said Imperial College psychologist Tobias Buchborn. ‘This normalisation seems specifically related to the feeling of unity experienced during the psilocybin session.’
The trial didn’t include a control/placebo group for comparison. However, the team plans to compare the effects of psilocybin against a leading antidepressant in a six-week trial in 2018.
Scientists used neuroimaging to track the effectiveness of the treatment.
‘These are exciting, but preliminary findings,’ said Mitul Mehta, professor of neuroimaging & psychopharmacology at King’s College London. ‘It is only a single dose of psilocybin, but this was able to reduce symptoms and produce changes in the same brain networks we know are involved in depression. This impressive study provides a clear rationale for longer-term, controlled studies.’
‘Some of the next challenges are to see if the therapeutic effects hold up in larger groups,’ commented Anil Seth, professor of cognitive and computational neuroscience at Sussex University, UK: ‘And to understand more about how the changes in brain activity elicited by psilocybin underpin both the transient changes in conscious experience the drug produces, as well as the more long-lasting effects on depression.’
Psychedelics: Lifting the veil | Robin Carhart-Harris | TEDxWarwick Video: TEDx Talks
The trial also backs up the results of an earlier study by Robin Carhart-Harris and coworkers in 2016, which found that psilocybin reduced symptoms in 12 treatment resistant patients, five of whom were no longer classed as depressed three months later. Also in 2016, a trial by other researchers in the US demonstrated that a single dose could alleviate the anxiety and depression of people with advanced cancer for six months or longer.
What is paralysis? Video: Doctors’ Circle
Patients suffering from paralysis can at last look forward to a time when their condition is cured, and they can walk, run or move their damaged limbs again, as recent advancements show the possibility of reversal.
‘The environment has never been better for exploring ways to restore neurological function, including paralysis – in fact, there has been a dramatic escalation of the entire research spectrum aimed at functional neurorestoration,’ says Charles Liu, Director of the University of Southern California Neurorestoration Center.
Paralysis comes in many forms: the paralysis of one limb (monoplegia), one side of the body (hemiplegia), below the waist (paraplegia), and all four limbs below the neck (tetraplegia, or also referred to as quadriplegia).
There are many classifications of paralysis. It can be localised or generalised, and can affect most areas of the body. Image: Pixabay
In an able-bodied person, the brain sends a signal as an electrical impulse, known as an action potential, down the spinal cord to the peripheral nerves, which instruct the muscles to contract and move, whereupon sensors in the muscles and skin send signals back to the brain.
In most paralysis cases, the condition occurs as a result of damage to nerves rather than an injury to the affected area. Strokes are the most common cause of paralysis, followed by spinal cord injuries. Multiple sclerosis, cerebral palsy, polio, head injuries and several other rare diseases can also cause paralysis.
‘Long term, we hope to cure paralysis and make the injured walk,’ explains William Sikkema, a graduate student at Rice University, Houston. The challenge is not only to repair cells but to restore connectivity, too. In collaboration with researchers at Konkuk University in South Korea, the team has already made a paralysed rat walk again.
The addition of graphene nanoribbons restored motor and sensory neuronal signals across the previous nerve gap after 24 hours, with almost perfect motor control recovery after a period of healing. ‘Two weeks later, the rat could walk without losing balance, stand up on his hind limbs and use his forelimbs to feed himself with pellets. No recovery was observed in controls,’ the team reported.
‘After a neuron is cut, it doesn’t know where to grow. So, it either doesn’t grow, or grows in the wrong direction,’ says Sikkema. ‘Our graphene nanoribbons act as a scaffolding track, and it tells the neurons where to grow.’
Rats are a common animal model in paralysis studies, as they share similar structure and functions with humans. Image: Pexels
Spinal cord stimulation
Electrical stimulation of the spinal cord could also provide a big breakthrough, says Chet Moritz, Co-Director of the Center for Sensorimotor Neural Engineering at the University of Washington, US.
‘We’re seeing some really impressive results with spinal cord stimulation where people with complete paralysis, who have been unable to function, have regained control of their limbs. We didn’t expect this. It’s the most exciting thing we’ve seen in the last 20 years,’ he says.
Last year, a team led by Grégoire Courtine at the Swiss Federal Institute of Technology inserted an implant in the brains of paralysed monkeys and another over the spinal cord below the injury. The brain-spine interface worked by capturing leg-moving brain signals, decoded by a computer and sent – bypassing the damaged region – to the second implant, which delivered the signals as electrical impulses to the nerves, causing the leg to move.
Grégoire Courtine talks about his pioneering work on paralysis using electrical stimulation. Video: TED
Within six days, the monkeys had regained the use of their lower limbs and improved even more over time. The success of the experiment has led Courtine to launch a human trial of a spinal implant system.
We may be a long way still from restoring full function, as prior to paralysis, but Moritz is optimistic. Even a modest change, such as the movement of a single finger, can have a dramatic effect on quality of life and independence. ‘In five years, we’ve had dramatic improvement in function,’ he says. ‘It’s an exciting trajectory with tremendous potential.’
The next five years will be the most promising in the fight against cancer with immunotherapies – such as CAR-T and moderating T-Cell approaches, and innate immunity therapies – delivering far better patient outcomes.
In the last five years, the industry has rapidly advanced its understanding of the body’s immune response and genetic markers. As a result, combination therapies – chemotherapies will continue to play an important role – are forecast to become an increasingly standardised treatment, with pharma keen to invest.
These newer options are bringing in transformative remission rates, and check-point inhibitors have already been seen to elicit long-term cures in patients, with success rates two-to-three times higher than standard chemotherapy approaches.
Over the next ten years, we will see significant breakthroughs as the industry’s understanding of the immune system improves. There are currently more than 130 biotechs – in addition to 20 big pharma companies – working on new therapies and it is believed the smaller companies are more aggressively bringing newer innovations to market. In the long run, pharma will undoubtedly absorb the most promising players in an effort to become leaders in combination therapy approaches, which many argue will deliver the best outcomes.
The current investor frenzy is comparable to that of the genomics industry at the turn of the century. Experts argue that a more complete understanding of the genome and promise of clinical data of these transformative modalities will create a golden age for cancer therapy over the next few years.
There are, however, a number of immediate challenges. For example, CAR-T, although demonstrating good efficacy in blood cancers, has yet to show enough efficacy in solid tumours. Another challenge is how far towards cures for all patients we can get, particularly for patients with late stage metastatic cancer.
Immunotherapies are moving cancer from treatment options that simply extend life or improve experience to more effective cures. The cost of newer therapies is also coming into focus; however, this is a positive pressure on companies to produce significant, not just incremental, outcomes for patients.