Tag: 16/2/22

Categories : CancerTags :

‘A-Maize-ing’ Nanoparticles Target Cancer Cells Directly

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Computer=generated depiction of nanoparticles

Researchers have recently developed novel nanoparticles derived from maize that can target cancer cells directly, via an immune mechanism. The results of this study, published in Scientific Reports, are encouraging, and the technique has demonstrated efficacy in treating tumour-bearing laboratory mice with no adverse effects.

Nanoparticles, or particles whose size varies between 1 and 100nm, have shown tremendous potential in many areas of science and technology, including therapeutics. However, conventional, synthetic nanoparticles are complicated and expensive to produce and alternatives such as extracellular vesicles (EVs) have mass production challenges.
Another recently emerging option is that of plant-derived nanoparticles (NPs), which can be easily produced in high levels at relatively lower costs. Like EVs, these nanoparticle-based systems also contain bioactive molecules, including polyphenols (which are known antioxidants) and microRNA, and they can serve as vehicles for targeted drug delivery.

Recently, researchers from the Tokyo University of Science (TUS) developed anti-cancer bionanoparticles, using corn (maize) as the raw material.
Lead researcher Professor Makiya Nishikawa explained: “By controlling the physicochemical properties of nanoparticles, we can control their pharmacokinetics in the body; so, we wanted to explore the nanoparticulation of edible plants. Maize, or corn, is produced in large quantities worldwide in its native form as well as in its genetically modified forms. That is why we selected it for our study.” 

The team centrifuged a super-sweet corn juice and then filtered it through a syringe filter with a 0.45μm pore size, then ultracentrifuged to obtain NPs derived from corn. The corn-derived NPs (cNPs) were approximately 80nm in diameter with a tiny net negative charge of -17mV.

The research team then set up experiments to see whether these cNPs were being taken up by various types of cells. In a series of promising results, the cNPs were taken up by multiple types of cells, including the clinically relevant colon26 tumor cells (cancer cells derived from mice), RAW264.7 macrophage-like cells, and normal NIH3T3 cells. RAW264.7 cells are commonly used as in vitro screens for immunomodulators.

The results were astounding: of the three types of cells, cNPs only significantly inhibited the growth of colon26 cells, indicating their selectivity for carcinogenic cell lines. Moreover, cNPs were able to successfully induce the release of tumour necrosis factor-α (TNF-α) from RAW264.7 cells. TNFα is primarily secreted by macrophages, natural killer cells, and lymphocytes, which help mount an anticancer response. “The strong TNFα response was encouraging and indicated the role of cNPs in treating various types of cancer,” explains Dr. Daisuke Sasaki, first author of the study and an instructor and researcher at TUS.

A luciferase-based assay revealed that the potent combination of cNPs and RAW264.7 cells significantly suppressed the proliferation of colon26 cells. Finally, the research team studied the effect of cNPs on laboratory mice bearing subcutaneous tumours. Once again, the results were astonishing: daily injections of cNPs into colon26 tumours significantly suppressed tumour growth, without causing serious side effects, or weight loss.

“By optimising nanoparticle properties and by combining them with anticancer drugs, we hope to devise safe and efficacious drugs for various cancers,” observed an optimistic Prof Nishikawa.

Source: Tokyo University of Science

Categories : Neurology Obstetrics & GynaecologyTags :

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

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Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh

Categories : COVID PaediatricsTags :

High COVID Mortality Rate Found in African Children and Adolescents

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Photo by Roman Nguyen on Unsplash

African children and adolescents hospitalised with COVID experience much higher mortality rates than Europeans or North Americans of the same age, according to a recent six-country study which included South Africa.

The study, published in JAMA Pediatrics. was conducted by researchers from the Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) and the Institute of Human Virology Nigeria (IHVN). Both organisations are members of the Global Virus Network (GVN).

“This study provides important information about COVID among African children, which was not previously available at this scale. We now have evidence from multiple countries to show that African children also experience severe COVID; they experience multisystem inflammatory syndrome; some require intensive care; some also die, and at much higher rates than outside Africa,” said co-first author Nadia Sam-Agudu, MD, Associate Professor of Pediatrics at the UMSOM’s Institute of Human Virology.

The AFREhealth study collected data from 25 health facilities across Nigeria, Ghana, Democratic Republic of the Congo, Kenya, South Africa, and Uganda. The study included 469 African children and adolescents aged three months to 19 years hospitalised with COVID between March and December 2020. The team reported a high overall mortality rate of 8.3%, compared with 1% or less totaled from Europe and North America. Furthermore, African children less than a year old and with pre-existing, non-communicable diseases were more likely to have poorer outcomes.

Eighteen participants had suspected or confirmed multisystem inflammatory syndrome (also known as MIS-C), and four of these children died.

Dr Sam-Agudu, who led the West Africa team for the study, urged health authorities and policymakers in Nigeria and other African countries to act upon the study findings “to protect children by expanding vaccine approvals and procurements for children specifically, as the variants emerging since our study’s completion have either caused more severe disease and/or more cases overall. We cannot leave children behind in the pandemic response.”

Source: University of Maryland

Categories : Mental Health Substance UseTags :

Illicit Use of Amphetamines Magnifies Psychosis Risk

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Source: Andrew Neel on Unsplash

The illicit use of amphetamines (aka ‘speed’) is linked to a 5-fold heightened risk of psychosis, according to the results of a decade-long study published in the journal Evidence-Based Mental Health.

This increased risk was seen across all age groups, but was especially noticeable among women and those who had been arrested several times for possession of the drug, the findings show.

The estimated global prevalence of amphetamine use is less than 1%, but around 1 in 10 users become addicted.

The drug affects neurotransmitter signalling in the brain and often causes psychosis, the symptoms of which mimic those of schizophrenia, with paranoia, voices, and hallucinations. Though these psychotic episodes usually subside after a few days, in up to 15% of users they may last for years.

While the link between amphetamine misuse and psychosis has been known for many decades, it’s not clear exactly what the magnitude is of this risk or how effective rehab is at successfully weaning users off the drug.

To try and find out, the researchers drew on information supplied to the Taiwan Illicit Drug Issue Database (TIDID) and the National Health Insurance Research Database (NHIRD) between 2007 and 2016.

The TDID contains anonymised data on date of birth, sex, arrest records and deferred prosecution for rehabilitation treatment for illicit drug users, while the NHIRD contains anonymised data on mental and physical health issues for the population of Taiwan.

The researchers identified 74 601 illicit amphetamine users and 298 404 age- and sex-matched comparisons. Their average age was 33 and most (84%) were men.

Compared with those who weren’t using, illicit amphetamine users had poorer health: depression (2% vs 0.4%); anxiety (0.9% vs 0.3%); ischaemic heart disease (1.3% vs 0.8%); cardiovascular disease (0.8% vs 0.45%); and stroke (1.3% vs 0.7%).

By the end of the 10 year monitoring period, amphetamine users were more than 5 times as likely to experience psychosis than those who weren’t using after accounting for age, sex, and coexisting health issues. The annual cumulative incidence rates for psychosis among the comparison group and amphetamine users were 77 and 468 per 100 000 people, respectively.

The number of new cases of psychosis was similar across all age brackets, but was more common in the amphetamine users among those aged 45 and above.

While psychosis risk increased with comorbidities, overall, it was higher among illicit amphetamine users without coexisting conditions, suggesting a direct impact of amphetamine on inducing psychotic symptoms, the researchers said. Psychosis risk rose in tandem with the number of arrests, and fell when patients received psychotherapy for their addiction (rehab).

Those who had been arrested 5 or more times were more than 6 times as likely to experience psychosis, while users who went to rehab during deferred prosecution were 26% less likely to experience psychosis than those who didn’t. This suggests that rehab may help to stave off the risk of subsequent psychosis, say the researchers.

In common with previous research, illicit amphetamine use was linked to greater levels of anxiety and depressive symptoms as well as cardiovascular complications.

“Because persistent psychotic symptoms could represent a risk for cognitive decline in amphetamine users, identifying [those] with psychosis and providing treatment early might prevent subsequent damage of cognitive functions,” write the researchers. But rehab is voluntary, and only offered to around 1 in 10 users, they point out.

By way of an explanation for the gender discrepancy observed, the researchers suggest that the detrimental impact of amphetamines on behaviour might be enhanced by the presence of oestrogen.

“Another possibility is that women arrested for illicit amphetamine use were particularly disadvantaged in comparison with men, with higher levels of trauma, lack of psychosocial support and stigma,” they noted.

As an observational study, it cannot establish cause, and addiction could not be quantified. Illicit amphetamine use could also precipitate and aggravate schizophrenic symptoms, so it’s possible that amphetamine induces rather than causes the psychotic symptoms seen in amphetamine users.

The researchers concluded: “The relation of an induced paranoid psychosis with amphetamine abuse has been known for many decades. None the less, our findings are from a detailed and comparative analysis using a comprehensive and large population dataset.

“Furthermore, it would be worthwhile to investigate the health benefits and cost effectiveness of deferred prosecution for drug crime offenders by providing appropriate therapy for drug addiction.”

Source: The BMJ

Categories : Ageing COVIDTags :

Higher Oestrogen Levels Protect Older Women Against Severe COVID

On By ModernMedia
Photo by Ravi Patel on Unsplash

An older woman’s oestrogen levels may be linked to her chances of dying from COVID, with higher levels of the hormone seemingly protective against severe infection, according to a study published in BMJ Open.

Supplemental hormone treatment to curb the severity of COVID infection in post-menopausal women could be investigated, the researchers suggested.

Even after accounting for other factors, women seem to have a lower risk of severe COVID infection than men. This holds true for other serious recent viral infections, such as MERS (Middle East Respiratory Syndrome).

Oestrogen may have a role in this gender discrepancy, so to invesitgate the researchers compared the potential effects of boosting and reducing oestrogen levels on COVID infection severity.

They drew on Swedish national data, and the study sample included 14 685 women in total: 227 (2%) had been previously diagnosed with breast cancer and were on oestrogen blocker drugs (adjuvant therapy) to curb the risk of cancer recurrence; and 2535 (17%) were taking hormone replacement therapy (HRT) to boost their oestrogen levels in a bid to relieve menopausal symptoms.

Some 11,923 (81%) women acted as the comparison group as they weren’t on any type of treatment, either to enhance or reduce their systemic oestrogen levels.

Analysis of all the data showed that compared with no oestrogen treatment, the crude odds of dying from COVID were twice as high among women on oestrogen blockers but 54% lower among women on HRT.

After accounting for potentially influential factors, COVID mortality risk remained significantly lower (53%) for women on HRT.

Unsurprisingly, age was significantly associated with COVID mortality risk, with each extra year associated with 15% greater odds, while every additional coexisting condition increased the odds of death by 13%.

And those with the lowest household incomes were nearly 3 times as likely to die as those with the highest.

As an observational study, it cannot establish cause. There were no data on the precise doses of HRT or oestrogen blocker drugs, or their duration, nor on weight or smoking, while the number of women on adjuvant therapy was relatively small.

These factors may have been influential. But the researchers conclude: “This study shows an association between oestrogen levels and COVID death. Consequently, drugs increasing oestrogen levels may have a role in therapeutic efforts to alleviate COVID severity in postmenopausal women and could be studied in randomised control trials.”

Source: EurekAlert!