Day: July 22, 2021

New Wound Healing Scoring System Proposed

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Researchers have proposed a new scoring system for wound healing in mice based on parameters in each phase of healing.

The researchers described the system in an article in the peer-reviewed journal Stem Cells and Development.

Wound healing processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. In order to evaluate the efficacy of new treatments, there is a need to monitor wound progression accurately and reproducibly over time. 

The parameters include re-epithelisation, epithelial thickness index, keratinisation, granulation tissue thickness, remodeling, and the scar elevation index. These parameters can be assessed using either Hematoxylin & Eosin or Masson’s Trichrome staining. Mari van de Vyver, from Stellenbosch University, and colleagues developed this histology scoring system for cutaneous wounds in mice. They then validated the system in four different types of murine skin wound models.

“This histological scoring system defines and describes the minimum recommended criteria for assessing wound healing dynamics,” state the authors. “The experience and ability of investigators to accurately identify structures in histology slides at different stages of healing is crucial for consistency and repeatability of measures to deliver meaningful results.”

“The development and validation of this scoring system in a randomized blinded investigation by researchers from Stellenbosch University (South Africa), Polish Academy of Sciences in Olsztyn (Poland), University of Texas Southwestern Medical Center (Texas, USA) and Obatala Sciences Inc. (New Orleans, USA) represents a truly international effort to advance the robust and accurate assessment of wound healing,” stated Graham C Parker, PhD, Editor-in-Chief of Stem Cells and Development and The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.

Source: Mary Ann Liebert, Inc.

Journal information: van de Vyver, M., et al. (2021) Histology Scoring System for Murine Cutaneous Wounds. Stem Cells and

Sustained Antipsychotic Benefits of Pimavanesirn Shown in Study

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Evidence of the sustained benefits of an investigational antipsychotic treatment for people with dementia-related psychosis has been published.

Up to half of the 45 million people worldwide who are living with Alzheimer’s disease will experience psychotic episodes, a figure that is even higher in some other forms of dementia. Psychosis is linked to a faster deterioration in dementia, and currently there is no safe and effective treatment for it. Widely-used antipsychotics have significant drawbacks in people with dementia, leading to sedation, falls and increased risk of deaths.

Pimavanserin works by blocking serotonin 5HT2A receptors, with no interaction with dopamine receptors. In the US, it is licensed to treat hallucinations and delusions in people with Parkinson’s disease psychosis.

To test this drug, a clinical trial was conducted in 392 people with psychosis associated with Alzheimer’s disease, Parkinson’s disease, Lewy body, frontotemporal, or vascular dementia. All participants were given pimavanserin for 12 weeks, with those reaching a certain level of symptom improvement were then assigned to pimavanserin or placebo for up to 26 weeks. Due to positive efficacy results however, the trial was concluded early. 

Of the 351 participants, 217 (61.8%) had a sustained initial treatment benefit, of whom 112 were assigned to placebo and 105 to pimavanserin. Relapse occurred in 28/99 (28.3%) of the placebo group, compared to 12/95 (12.6%) of the pimvanserin group, with pimvanserin more than halving the relapse rate and significantly improving the sustained benefit.

Professor Clive Ballard, Executive Dean of the University of Exeter Medical School, said: “Psychosis affects up to half of all people with dementia, and it’s a particularly distressing symptom – yet there’s currently no safe and effective treatment. Currently used antipsychotics are known to cause harms, and best practice guidelines recommend prescribing for no longer than 12 weeks for people with dementia as a result. We urgently need alternatives. It’s exciting that the relapse rate in the pimavanserin group was lower than the placebo group, indicating that the treatment benefits may be sustained over time. We now need longer and larger scale trials to explore this further.”

The trial found headache, urinary tract infection and constipation occurred more frequently in the pimavanserin group, but there was no increase in mortality or the other serious events, such as stroke, which are seen in other antipsychotics.

The full paper is published in the New England Journal of Medicine.

Source: EurekAlert!

Plant-derived Substance Shows Osteoprotective Properties

Researchers have found that a substance derived from Saussurea controversa, a member of the thistle family, may have significant potential in recovering lost bone mass.

Metabolic bone diseases such as osteoporosis are called the silent epidemic of the 21st century. A person may only become aware of their condition by sustaining a hip or spine fracture.

According to statistics, every third woman and every fifth man after 50 have osteoporosis. Thus, it is promising to search for and obtain substances and materials for implants that have osteoinductive properties and are capable of initiating the processes of transformation of stem cells into bone.

Certain trace elements, such as calcium and magnesium, influence the processes of bone regeneration and the maintenance of their normal structure. Organic molecules that can bind to them provide an improvement in the selectivity of their therapeutic action – the resulting complexes play a significant role in bone formation and development. From this point of view, salts of chelidonic acid have great potential, for example, from the Saussurea controversa known since ancient times for its healing properties.

Researchers from the Immanuel Kant Baltic Federal University, Siberian State Medical University, and Tomsk Polytechnic University had previously discovered that calcium chelidonate is a promising drug for bone volume restoration. 

In their latest work, they obtained this substance in a semisynthetic way: extracts from Saussurea controversa were the source of the chelidonic acid, to which an alkali solution and calcium chloride were added.

“The content of this substance differs in the samples of raw material and, most likely, its biosynthesis depends on the amount of calcium in the soil. For pharmaceutical purposes, it is advisable to use calcium chelidonate obtained by a semisynthetic method,” explained Elena Avdeeva, candidate of pharmaceutical sciences, researcher, Siberian State Medical University

An X-ray analysis confirmed that the substance has a structure identical to a natural compound. Researchers tested the effect of the substance in vitro and in vivo: it promoted the conversion of human stem cells derived from adipose tissue (hAMMSC) and mouse mesenchymal stromal cells into osteoblasts respectively. 

Calcium chelidonate is non-toxic and promotes bone regeneration: in vitro studies have shown that a dose of only 10mg/L increases the number of viable stem cells. Titanium implants coated with calcium phosphate and bearing autologous bone marrow were introduced into mice. The researchers found that calcium chelidonate stimulated the growth of new bone on the surface of the implant with daily administration of the drug for 35 days.

“The use of substances with osteoprotective properties, in particular, calcium chelidonate, is promising for the treatment of several diseases associated with bone defects or bone metabolism disorders. We are considering the development of a pharmaceutical form of the substance and its introduction into practical medicine,” concluded Larisa Litvinova, Doctor of Medicine, professor, head of the laboratory of immunology and cellular biotechnology at the IKBFU.

Source: News-Medical.Net

Journal information: Avdeeva, E., et al. (2021) Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo. Pharmaceuticals.

MRI Clear Cell Likelihood Score Matches Renal Carcinoma Growth

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According to a new study, the MRI-derived standardised non-invasive clear cell likelihood score (ccLS) is correlated with the growth rate of small renal masses (cT1a, <4 cm) and could help guide personalised management.

The study was published in the American Roentgen Ray Society’s American Journal of Roentgenology. Extracted from clinical reports, “the ccLS scores the likelihood that the small renal mass represents clear cell renal cell carcinoma, from 1 (very unlikely) to 5 (very likely),” explained corresponding author Ivan Pedrosa from the University of Texas Southwestern Medical Center at Dallas. “Small renal masses with lower ccLS may be considered for active surveillance, whereas small renal masses with higher ccLS may warrant earlier intervention.”

The team’s retrospective study included consecutive small renal masses assigned a ccLS on clinical MRI exams performed from June 2016 to November 2019. Tumour size measurements were obtained from available prior and follow-up cross-sectional imaging examinations, up to June 2020.

Among 389 small renal masses in 339 patients (198 men, 141 women; median age, 65 years) on active surveillance that were assigned a ccLS on clinical MRI examinations, those with ccLS4-5 grew significantly faster (9% diameter, 29% volume yearly) than those with ccLS1-2 (5% diameter, p<.001; 16% volume, p<.001) or ccLS3 (4% diameter, p<.001; 15% volume, p<.001).

With a lack of validated imaging markers to characterise biologic aggressiveness of small renal masses hindering medical decision making, “growth is associated with ccLS in small renal masses,” the authors reiterated, “with higher ccLS correlating with faster growth.”

Source: EurekAlert!

Old Antibiotics as New Weapons against Melanoma

Researchers may have hit upon a new weapon in the fight against melanoma: antibiotics that target a vulnerability in the ‘power plants’ of cancer cells when they try to survive cancer therapy.

“As the cancer evolves, some melanoma cells may escape the treatment and stop proliferating to ‘hide’ from the immune system. These are the cells that have the potential to form a new tumor mass at a later stage,” explains cancer researcher and RNA biologist Eleonora Leucci at KU Leuven, Belgium. “In order to survive the cancer treatment however, those inactive cells need to keep their ‘power plants’—the mitochondria—switched on at all times.” As mitochondria derive from bacteria that, over time, started living inside cells, they are very vulnerable to a specific class of antibiotics. This is what gave us the idea to use these antibiotics as anti-melanoma agents.”

The researchers implanted patient-derived tumors into mice, which were then treated with antibiotics, either as alone or in combined with existing anti-melanoma therapies. Leucci observed: “The antibiotics quickly killed many cancer cells and could thus be used to buy the precious time needed for immunotherapy to kick in. In tumors that were no longer responding to targeted therapies, the antibiotics extended the lifespan of—and in some cases even cured—the mice.”

The researchers made use of nearly antibiotics rendered nearly obsolete because of antibiotic resistance. However, this does not affect the efficacy of the treatment in this study, Leucci explained. “The cancer cells show high sensitivity to these antibiotics, so we can now look to repurpose them to treat cancer instead of bacterial infections.”

However, patients with melanoma should not try to experiment, warned Leucci. “Our findings are based on research in mice, so we don’t know how effective this treatment is in human beings. Our study mentions only one human case where a melanoma patient received antibiotics to treat a bacterial infection, and this re-sensitized a resistant melanoma lesion to standard therapy. This result is cause for optimism, but we need more research and clinical studies to examine the use of antibiotics to treat cancer patients. Together with oncologist Oliver Bechter (KU Leuven/UZ Leuven), who is a co-author of this study, we are currently exploring our options.”

Source: KU Leuven

Journal information: Roberto Vendramin et al, Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma, Journal of Experimental Medicine (2021). DOI: 10.1084/jem.20210571

Second J&J Dose Needed for Delta Variant

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Johnson & Johnson’s COVID vaccine is much less effective against the Delta and Lambda variants than against the original wild-type virus, according to a new study posted on the BioRxiv preprint server on Tuesday.

Though a cause for concern, the results come from in vitro tests, and may not reflect the real world vaccine performance. However, the authors said this adds to evidence that the 13 million people inoculated with the J&J vaccine may need a second dose, preferably an mRNA vaccine, the authors said.
The findings, which are still to be peer reviewed, are however consistent with observations that a single dose of the AstraZeneca vaccine, which is similar to the J&J one, shows only about 33 percent efficacy against developing symptoms with the Delta variant.

“The message that we wanted to give was not that people shouldn’t get the J&J vaccine, but we hope that in the future, it will be boosted with either another dose of  J&J or a boost with Pfizer or Moderna,” said study leader Nathaniel Landau, a virologist at NYU’s Grossman School of Medicine.

Other experts said the results are what they would have expected, because all of the vaccines seem to work better when given in two doses. “I have always thought, and often said, that the  J&J vaccine is a two-dose vaccine,” said John Moore, a virologist at Weill Cornell Medicine in New York.

Dr Moore pointed to several studies in monkeys and people that have shown greater efficacy with two doses of the J&J vaccine, compared with one dose. The new study was particularly credible, he said, because it was published by a team not linked to any vaccine manufacturer.

But the data from the new study “do not speak to the full nature of immune protection,” said Seema Kumar, a spokeswoman for J&J. “Studies sponsored by the company indicate that the vaccine “generated strong, persistent activity against the rapidly spreading Delta variant,” she said.

The Delta variant is the most transmissible of the SARS-CoV-2 variants, and has become dominant in South Africa. 

Several studies have suggested that the mRNA vaccines made by Pfizer-BioNTech and Moderna will maintain their efficacy against the coronavirus, including all variants identified so far. One recent study showed, for example, that the vaccines trigger a persistent immune reaction in the body that may protect against the coronavirus for years. The J&J vaccine is newer, and has had fewer studies.

The J&J vaccine has had reports of rare blood clots and extremely rare neurological disorders, as well as problems with contamination at a US manufacturing plant. This is still not as bad as the disastrous news that the AstraZeneca vaccine was virtually ineffective against the Beta variant which was then the dominant strain in South Africa.

Small studies by J&J affiliated researchers suggested that the vaccine was only slightly less effective against the Delta variant than against the wild-type virus, and that antibodies stimulated by the vaccine grew in strength over eight months.

Dr Dan Barouch, a virologist at Beth Israel Deaconess Medical Center in Boston said it was important to consider the vaccine’s strength over time.

“Fundamentally I don’t see that there’s any discordance,” he said. “The question is that of kinetics, it’s not just magnitude, because immune responses are not static over time.” The new study also did not consider other components of immune defence, he added.

Dr Landau and his colleagues had compared blood samples taken from 17 people who had two doses of an mRNA vaccine and 10 who had one J&J vaccine dose.

The  J&J vaccine started out with a lower efficacy than the mRNA vaccines and showed a bigger drop in efficacy against the Delta and Lambda variants. “The lower baseline means that what’s left to counter Delta is very weak,” Dr Moore said. “That is a substantial concern.”

Very few vaccines are given as a single dose, because the second dose is needed to amp up antibody levels, noted Akiko Iwasaki, an immunologist at Yale University. People who were inoculated with the J&J vaccine “are relying on that primary response to maintain high levels of antibodies, which is difficult, especially against the variants,” she said.

Boosting immunity with a second dose should raise the antibody levels high enough to counter the variants, she said.

Source: New York Times