Caring for a stranger: Anjala Devi feeding the stroke patient at Hospital Sultanah Aminah.
Sincerity wins trust of stroke patient
JOHOR BARU: A woman’s act of kindness in feeding a stranger at Hospital Sultanah Aminah here has not only moved the man to tears but also warmed the hearts of Malaysians.
C. Anjala Devi, 63, was at the hospital visiting her nephew on Thursday evening when she noticed the patient in the next bed struggling to eat his dinner.
Despite nurses’ attempts to assist him and urging him to eat, the man was reluctant to accept help.
Recounting the incident, Anjala Devi’s niece K. Jamunahwathy, 28, said they learnt the man is a stroke patient, which made it difficult for him to speak and move.
She said her brother was admitted for heart surgery about a week ago and the man was hospitalised on Thursday.
“We noticed that he did not have any visitors nor did he have a mobile phone with him so my aunt offered to feed him. At first he declined her help, as he was embarrassed and did not want to trouble us.
“But my aunt would not take no for an answer and insisted on spoon-feeding him. She told him, ‘Adik, you will not be able to take your medicine otherwise’,” Jamunahwathy, who works as an audio-visual engineer, said in an interview.
Caring for a stranger: Anjala Devi feeding the stroke patient at Hospital Sultanah Aminah.
The man eventually agreed to be fed and in a spontaneous move, Jamunahwathy whipped out her mobile phone to record the moment and later posted it on social media.
The 26-second video clip captured the man wiping away his tears with a tissue paper as Anjala Devi fed him spoonfuls of food.
The video quickly made the rounds on various social media platforms, drawing praise from Malaysians for the woman’s compassion, with many others also sharing their own experiences of receiving help from strangers.
Jamunahwathy said she uploaded the video with the intention of spreading love, while things like differences in race and religion were far from her mind.
“Judging by the comments on my video, we can see how warm and kind Malaysians are towards each other.
“This is what we should always practise because we would not know what others are going through. A small gesture can make their day at least a little better,” she said.
Jamunahwathy added that her aunt continued to feed “adik” during subsequent visits, even bringing him home-cooked food prepared by her mother.
“My aunt has always been a caring woman and she will not hesitate to visit family and friends who are unwell or hospitalised.
“We told my aunt about her video going viral and she got a bit nervous as she did it from her heart and not for fame,” she said.
The blood vessels that vascularize the central nervous system exhibit
unique properties which control the flow of cells, ions, and molecules from plasma to the brain. Referred to as the blood-brain barrier, it is vital for the protection of the brain and maintains homeostasis. Dysfunction of the blood-brain barrier is linked with a range of neurological conditions.
Blood is carried from the heart to organs and tissue throughout the body via systems of blood vessels. Vessels deliver nutrients and oxygen, whilst removing waste products and carbon dioxide and regulating how the immune system interacts with each tissue. This vascular system includes arteries, venules and veins and capillaries. Capillaries comprise the smallest segments of the vascular system, known as the microvasculature and have varying properties depending on the requirements of the area they vascularize.
There are three structural classes of capillaries: discontinuous, continuous fenestrated, and continuous non-fenestrated.
Discontinuous capillaries are found only in the liver and have intercellular gaps which allow for large molecules and cells to be transported between the blood and tissue, supporting metabolism.
Continuous fenestrated capillaries have small perforations in their cell walls which allows for molecular exchange. This is important in the areas that require frequent exchanges between blood and tissue, such as the filtration of waste products by the kidneys, or absorption of nutrients by the small ntestine.
Continuous non-fenestrated capillaries have a complete plasma membrane with no perforations, allowing only small molecules to pass between their intercellular clefts, such as water or ions.
The microvasculature of the central nervous system
The blood-brain barrier (BBB) is a term used to describe the unique properties of the microvasculature of the central nervous system (CNS). Blood vessels of the CNS are continuous non-fenestrated vessels but have additional distinct properties which tightly govern the movement of small molecules and ions. The BBB is highly selective, allowing only certain substances to travel from the bloodstream to the brain, providing the CNS with protection from pathogens, toxins, and neurochemical imbalance.
Cells of the blood-brain barrier
The interior surface of blood vessels is lined with endothelial cells, which form a one-cell thick layer referred to as the endothelium. Throughout other areas of the body, the endothelium is fenestrated. The endothelial cells of the blood-brain barrier however are securely fused together by tight cell junctions, a class of cellular structure that provides adhesion between neighboring cells, restricting diffusion of solutes between the blood and the brain.
Astrocytes, a type of glial cell
in the CNS, perform specialized functions called astrocytic end-feet, a projection from the cell body of the astrocyte to the membrane surrounding the endothelium. Astrocytic end-feet are thought to play a critical role in the formation and regulation of the BBB by interacting with endothelial cells and influencing the signaling to tight cell junctions.
Although primarily to maintain the BBB, astrocytic end-feet may also influence the transient opening of the BBB under certain physiological circumstances. Examples may include the passage of antibodies or cytokines that stimulate cell growth from plasma to the brain.
Blood Brain Barrier, Animation
Drug Transport Across the Blood Brain Barrier with Dr. Sadhana Jackson
Dysfunction of the blood-brain barrier
Functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) and post-mortem analysis of brain samples have identified pathological dysfunction of the blood-brain barrier in many neurological disorders.
Although BBB pathology is typically a functional symptom of a primary neurological disorder, in some diseases including Alzheimer's Disease and Muscular Sclerosis, it has been hypothesized as a cause.
Multiple sclerosis (MS)
Multiple sclerosis is an autoimmune disorder whereby inflammation of the brain and spinal cord disrupts nerve signaling between the brain and body. Although the etiology of MS is unclear and likely to include multiple epigenetic factors, the breakdown of the blood-brain barrier is observed in the early stages of the disease. Recent research suggests that in MS, an abnormal immune response damages the myelin (the protein and lipid-rich substance surrounding cell axons) of the CNS. Myelin-producing cells, known as oligodendrocyte precursor cells (OPCs), however, are unable to cross the BBB to repair areas of damage. Thus,the BBB plays a role in both the initiation and maintenance of the inflammatory disorder.
Hypoxia and cerebral ischemia
Among the different stressors which induce disruption to the blood-brain barrier, hypoxic and ischemic challenges (reduced oxygen and/or reduced glucose delivery to the brain) are acutely injurious to brain function and can trigger the death of neuronal cells within minutes. Cerebral ischemia (stroke) induces severe brain injury and substantive disruption to the BBB.
Although the mechanisms by which hypoxia and ischemia disrupt the BBB remain unclear, oxidative stress is thought to be contributory. Oxidative stress is an imbalance of pro and anti-oxidants resulting in elevated reactive oxygen species (ROS) and may affect the integrity of the endothelium, breaking down the BBB.
Alzheimer’s Disease (AD)
Dysfunction of the blood-brain barrier has been well documented in post-mortem studies of individuals with established AD. However, recent studies which have imaged the brains of people with mild cognitive impairment (MCI) and early Alzheimer’s disease have shown the breakdown of the BBB prior to brain atrophy or dementia, suggesting it occurs at an early stage of the disease. Although the extent of BBB dysfunction and its causal role in Alzheimer’s disease continues to be debated, one theory suggests that BBB leakage caused by aging, illness, or injury could cause an inflammatory response leading to Alzheimer’s disease
pathology.
References
Abbott, N., Rönnbäck, L. & Hansson, E. Astrocyte–endothelial interactions at the blood–brain
Al Ahmad, A., Gassmann, M., & Ogunshola, O. O. (2012).
Involvement of oxidative stress in hypoxia-induced blood-brain barrier
breakdown. Microvascular research, 84(2), 222–225. https://doi.org/10.1016/j.mvr.2012.05.008
Caterina P. Profaci, Roeben N. Munji, Robert S. Pulido, Richard
Daneman; The blood–brain barrier in health and disease: Important
unanswered questions. J Exp Med 6 April 2020; 217 (4): e20190062. doi: https://doi.org/10.1084/jem.20190062
Daneman R. (2012). The blood-brain barrier in health and disease. Annals of neurology, 72(5), 648–672. https://doi.org/10.1002/ana.23648
Griffin, C. T., & Gao, S. (2017). Building discontinuous liver sinusoidal vessels. The Journal of clinical investigation, 127(3), 790–792. https://doi.org/10.1172/JCI92823
While this barrier functions to keep harmful organisms and substances out of our brain, it can also prevent useful drugs from crossing over.
WHAT is the most complex organ in the human body?
Undoubtedly, most of us will think of the brain.
Powered by energy-rich glucose and oxygen through the blood circulatory system, the brain is one of the biggest and most complex organs in our body.
This amazing organ, physically soft with a spongy mixture of protein and fat, weighs only approximately 2% of our total body weight, but utilises about a fifth of our energy!
The brain is composed of more than a hundred billion brain cells, which are made up of neurons and glia that communicate in trillions of connections known as synapses.
These unique neurons are nerve cells that conduct electrical impulses.
Meanwhile, glia cells provide structural protection and nutritional support for the neurons.
The brain is particularly vulnerable to toxic exposure and hypoxic conditions (i.e. low levels of oxygen).
Hence, the brain is shielded from an influx of harmful substances by a layer of tight-packed specialised endothelial cells known as the blood-brain barrier.
This barrier provides a natural protective function to impede the entry of harmful substances from the peripheral blood circulation into the central nervous system (CNS).
It is composed of different cell types, such as astrocytes, pericytes, endothelial cells, neurons and microglial cells.
All these cells play important and interconnecting roles in regulating the function of the brain.
The passage of molecules or ions through the blood-brain barrier is tightly regulated by cellular transporters and carriers.
This allows the delivery of nutrients into the brain, removal of unwanted toxins, and recruitment of leukocytes (white blood cells) or other immune system molecules necessary to maintain normal brain homeostasis.
The integrity of the barrier can be altered by the onset of disease.
Neuroinflammation in an ischaemic stroke (where there’s blockage of a blood vessel supplying the brain), systemic infection and inflammation, inflammatory bowel disease,and hypertensive encephalopathy are some examples of causes linked to a breakdown of the blood-brain barrier.
It is also a natural phenomenon correlated with ageing, initially occurring at the hippocampus situated at the medial temporal lobe, which is essential for episodic and spatial memory.
A link to three conditions
Epilepsy is a chronic CNS disorder characterised by recurrent seizures.
According to a study conducted by local researchers, the frequency of epilepsy was found to be higher in males.
Meanwhile, lifetime frequency, i.e. the frequency of epilepsy at any point of life in the population concerned (in this case, Malaysia) was estimated at 7.8 per 1,000 persons.
One in five patients with epilepsy in Malaysia died from the condition.
This implies the importance of treatments and access to adequate and appropriate treatment and care.
Super small and customisable
The various types of transport methods across the blood-brain barrier. — armin Kübelbeck/wikimedia Commons
There is also a growing body of evidence supporting the theory that seizures can promote amyloid-beta peptide and tau protein deposits, which can then lead to neurodegenerative processes that result in conditions like Alzheimer’s and Parkinson’s.
In two separate studies, it was reported that Alzheimer’s disease occurs six times more often in patients with epilepsy, and that seizures are highly repetitive and also occur in patients with dementia from Alzheimer’s.
A study done in the United Kingdom found that “people with epilepsy are 2.5 times more likely to be diagnosed with Parkinson’s disease than the general population”.
Nanoparticles for transport
An avalanche of research has centred on less or non-invasive methods to avoid some of the side effects associated with intrathecal administration of treatments into the spinal cord.
An intrathecal injection is where the drug is injected into the spinal cord fluid via a lumbar puncture.
Some of the side effects of this procedure include bleeding in the brain (haemorrhage), infection and and swelling of the brain (oedema).
In particular, there has been a growing interest in the use of nanoparticles to traverse through the blood-brain barrier, owing to their very small size, i.e. about 100 times smaller than a strand of human hair in diameter.
Nanoparticles can be designed with different shapes and sizes (within the nanometre range), as well as with desired properties (e.g. biodegradability) to meet the current demands in the production of functional materials.
They have widespread applications; however, the most commonly-known uses are in the cosmetics, food manufacturing and biomedical industries.
In 1995, cancer drug doxorubicin was the firstever nano-based product to be granted approval by the US Food and Drug Administration (FDA).
The number of nanotechnology products entering clinical trials since then have only grown larger.
As one of the approaches widely studied to facilitate the transport of medicinal compounds across the blood-brain barrier, the use of nanoparticles is especially promising as its mechanism does not affect the baseline permeability of the barrier.
Another fascinating approach involves the engineering of the protein corona, red blood cells and extracellular vesicles as nanoparticles bearing naturally-occurring components to cross the blood-brain barrier.
Nanoparticles made with this strategy have “stealth-like” properties as they can evade recognition and sequestration (and removal) by the immune system.
Importantly, this allows the nanoparticles to escape destruction in the event of an inflammatory response.
Crossing the barrier
In the case of epilepsy, Alzheimer’s disease and Parkinson’s disease, encouraging findings have been obtained with a host of nanoparticle strategies, especially with the versatility to accommodate more than one function into the nanoparticle design.
Nanoparticles have been engineered to effectively transport drugs across the blood-brain barrier by targeting receptors involved in endocytosis.
Endocytosis is a process by which a cell brings substances into itself.
The external substance is surrounded by a part of the cell’s membrane, which then breaks off to form a sphere with the substance within it, known as a vacuole.
For this process to occur, the external substance and cell membrane need to be able to “lock” onto one another.
One common way this occurs is when the substance has a ligand that matches with a receptor on the cell membrane, similar to a key and lock.
When the ligand (a molecule or atom) combines with the receptor (a protein molecule), its shape will be changed and this will trigger the endocytic process.
For this approach, the surfaces of the nanoparticles are modified with the appropriate ligands.
A wide range of ligands have been explored by researchers.
Examples include lectin, cardiolipin and heparin surface-decorated nanoparticles for Parkinson’s disease, and lactoferrin, apolipoprotein-e, transferrin and thiolated OX26 for epilepsy, Alzheimer’s disease, as well as Parkinson’s.
Research has also shown that adding in a scaffold of bispecific antibodies, i.e. anti-transferrin receptor and anti-beta secretase, reduces amyloid-beta peptide deposits in the cerebrospinal fluid and brain tissues of cynomolgus monkeys that received the intravenous (IV) injections.
Delivering potential treatments
Nanoparticles might also have the potential to target key mechanisms that fundamentally contribute to the three neurological disorders.
For example, an animal study using rats, described the delivery of an anti-epileptic peptide, galanin, that is capable of inhibiting glutamate release in the hippocampus.
An increase in glutamate, a neurotransmitter, is associated with the onset of seizures. Other studies have targeted the alpha-synuclein protein, which plays a role in Parkinson’s disease. It is thought that there is a misfolding of this protein in people with Parkinson’s, causing the proteins to clump together to form Lewy Bodies.
These clumps are theorised to be toxic and spread the disease throughout the brain as they get passed from one neuron to the other. One animal study using mice, assessed the inhibition of alpha-synuclein fibrillisation and protection from the progressive loss of dopaminergic neurons.
The formation of fibrils by the alpha-synuclein protein contributes to its toxicity, while dopamine, a neurotransmitter, is low in Parkinson’s disease. In another approach, researchers have proven that alpha-synuclein can be prevented from activating in microglial cells via scavenger receptor Cd36-binding nanoparticles.
The CD36 receptor is a glycoprotein found in cells in the bloodbrain barrier, such as astrocytes and microglia.
Another strategy uses glial cell-derived neurotrophic factor (GDNF), which is a key protein in regulating the survival and differentiation of brain cells that produce dopamine.
In a rat model of Parkinson’s disease, lipid nanocarriers loaded with GDNF plasmids were combined with microbubbles for Mriguided focused ultrasound-mediated effects that led to a reduction in nerve cell death and helped alleviate behavioural changes due to the disease.
A plasmid is a small DNA molecule within a cell, which is separate from chromosomal DNA and can replicate by itself. Another method of delivery
using GDNF retrovirus-loaded microbubbles and focused ultrasound also proved successful in delivering the GDNF retrovirus into nerve cells.
Alternatively, the nose-to-brain route of administration (rather than the conventional IV infusion or injection) could be a way to improve the delivery of drug-loaded and/or targeted nanoparticles to specific regions of the brain.
Delivery via this route bypasses the blood-brain barrier and enables direct delivery to the brain along the olfactory and trigeminal nerves.
This strategy, however, requires the nanoparticles to have augmented properties, such as protecting the molecules within them from being destroyed or damaged in the nasal cavity, and getting through the nose’s mucosal barrier.
More to come
A plethora of research on nanoparticles for disease treatment can be expected in the forthcoming years.
This includes clinical trials that can evaluate the potential shortand long-term adverse effects that may be triggered by their administration and uptake in the human body.
Although the journey towards clinical translation (i.e. nanoparticles approved for brain targeting and treatment) may be arduous as it requires substantial time and effort, there remains a light at the end of the tunnel for novel and tailored therapies to be developed in the near future to treat neurological disorders and injuries of the nervous system, in what may be known as the ‘precision medicine’ approach.
By Dr Lee Tze Yan who is a senior lecturer for Molecular Medicine at the Perdana University School of Liberal Arts, Science and Technology. Loo Yan Shan is a PHD student in Nanomedicine at Universiti Putra Malaysia. For more information, email starhealth@thestar.com.my. The information provided is for educational and communication purposes only, and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this article. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.
You are rawr-some: A person in a dinosaur costume checking in on children waiting their turn and receiving the Covid-19 vaccine jab at a vaccination centre in Kota Damansara. — AZHAR
MAHFOF/The Star
Health experts are calling on Malaysia to fine-tune its Covid-19 mitigation strategies to cope with the Omicron surge as the nation braces itself for the wave of cases, which is expected to last some weeks. `
This comes as Malaysia recorded over 10,000 cases over the past 24 hours, something which it had not seen since October. `
Epidemiologist Dr Sanjay Rampal warned that the peak of this new wave of Covid-19 cases would be felt in the coming two or three months. `
He explained that the reason for this could be due to the community transmission of the Omicron strain and decreased health seeking behaviour following the floods at the end of last year. `
“If the recent increase is due to the Omicron strain, I believe that could breach the 20,000 daily cases in four weeks,” he said when contacted yesterday. `
The Health Ministry had also predicted that Malaysia’s Covid-19 cases would continue to show an upwards trend in the coming weeks. `
However, following the precedent in other countries like South Africa, Britain and the United States, where the strain had peaked and ebbed, the surge was likely to last weeks and not months. `
For example, according to Our World in Data, the number of new cases recorded in Britain were over 847,371 on Jan 31 but this had fallen drastically to over 60,114 by Feb 5. `
Similarly, new cases in South Africa peaked at 26,389 on Dec 15 but had fallen to 8,078 cases by Jan 4. On Feb 5, there were 6,135 cases. `
Health authorities, said Rampal, could manage the coming Omicron wave by getting ready the country’s public health services, testing facilities, and primary health care facilities to cope with the possible exponential increase in demand for prevention activities. `
“A failure to plan for surge capacity at the district level will lead to our public health services being overwhelmed and higher levels of Covid-19 community transmission. `
“Although the stress to our hospitals will be relatively lower in this new wave, I expect a very much higher demand for primary health care services,” he added. `
Immunologist Datuk Dr Musa Nordin said the Health Minister would need to take a proactive stance and sound the clarion call to counter the onslaught of Omicron by reactivating the Covid-19 National Task Force (NTF). `
Originally known as the Greater Klang Valley Special Covid-19 Task Force (GKVSTF), the NTF is made up of an inclusive, coordinated multi-agency or sectorial team with varying expertise in pandemic management. `
“The GKVSTF had successfully flattened the Delta curve when earlier efforts, including MCOs and Emergency Ordinances (EO), failed, causing critical case numbers to spike in July last year, resulting in a total collapse of health care services, and a catastrophic number of deaths,” said Dr Musa. `
He also noted that the entire workflow involving district hospitals, quarantine centres, government and private hospitals must be comprehensively addressed, with the implementation of an end-to-end automated outbreak management system. `
“Omicron has also taken a toll on health care workers with many falling sick. It is important that our health care workers are all boosted with mRNA vaccines to ensure that we are not short-staffed when Omicron really hits us. `
“There is no need to reinvent the wheel. We have a working model (GKVTF) and modus operandi that successfully dealt with the Delta wave,” he suggested. `
Universiti Kebangsaan Malaysia health economics, hospital and health management’s Prof Dr Sharifa Ezat Wan Puteh said if proper mitigation plans were not implemented by the relevant authorities, the numbers would continue to go up in the next few weeks. `
“I would strongly urge the authorities to come up with a proper mitigation plan to address this. `
“I am not saying that they should implement a full movement control order because of its adverse impact including to the economy. But they can implement measures, such as enhanced movement control orders, in certain high risk areas, and re-look at prevention plans to limit movement in public areas like offices and schools,” she said. `
“Those who are able to work from home can continue to do so or perhaps employers can consider implementing a hybrid working arrangement,” she said. `
Although Omicron cases were reportedly less severe, Dr Sharifa Ezat urged everyone not to take the situation for granted due to the rapid transmission. `
“It is true that we should not panic but if we don’t do anything, the situation will worsen as fatalities are still being recorded,” she said. `
On whether the numbers would continue to climb, Universiti Putra Malaysia medical epidemiologist Assoc Prof Dr Malina Osman believes this will largely depend on the public’s commitment to adhere to all the standard operating procedures (SOP). `
“I think the community should play a role as well and help our frontliners from being further overburdened by practising all the SOP,” she said. `
In other countries, including Denmark and Britain, governments have announced plans to lift all their domestic Covid-19 restrictions with Omicron not being categorised “as a severe disease for the vaccinated”. `
However, face coverings are still required in healthcare settings, including hospitals, and on public transport. `
Covid passes are also not required for large events and at public venues, and people are no longer being advised to work from home.
2022 Beijing Winter Olympics: Another Takeoff for China & the World!
People In Taiwan Will Choose: A Respected Chinese Or A Dejected Nobody?
The #Beijing2022
Winter Olympics kicks off with around 2,900 athletes from more than 90 countries and regions participating in over 100 events. What to expect at the upcoming winter sports gala? Stay tuned to CGTN Special Coverage on Winter Games. #OlympicLive
In 2015, China won the bid to host the 2022 Winter Olympic Games, following South Korea, which has become a notable power in the rink in recent decades. Recently, Global Times (GT) reporters Shan Jie, Zhao Juecheng and Lin Luwen talked with Kim Jin-gon (Kim), minister-counsellor at the Embassy of ...
Caring for a stranger: Anjala Devi feeding the stroke patient at Hospital Sultanah Aminah.
-1.jpg "blood-brain barrier")
Germany1210527
China94215
