Tag: 2/2/21

Simvastatin Treatment Hope for Subtype of Ovarian Cancer

Researchers have found that simvastatin has anti-proliferative potential against ovarian clear cell carcinoma, a highly lethal gynaecological cancer.

Dr Ingrid Hedenfalk from The Lund University explained: “Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) accounting for 5–10% of cases diagnosed in Europe and America, while the incidence in Asia is reported to be higher (10–20%).”

GTPases are a range of enzymes that hydrolyse guanosine triphosphate (GTP) to guanosine diphosphate (GDP). They are also involved in cells as switches and timers. Rho GTPases have been studied for their role in cancers. However, it is difficult to target Rho GTPases directly, so research has involved indirect strategies.

The researchers tested three cell lines of OCCC and one line of high-grade serous ovarian carcinoma (HGSOC) with simvastatin, which is a Rho GTPase interfering drug, and another GTPase interfering drug, CID-1067700, as a control. CID-1067700 is a pan-GTPase, which makes it useful as a comparator.

The research was motivated by a study which found deregulated expression of both Rho GTPases and cytoskeletal pathways in primary human OCCC tumours. The OCCC cell lines treated with simvastatin showed reduced c-Myc protein expression and signs of cell death, as well as curbing proliferation and migration.

Simvastatin could act through Rho GTPase interference as simvastatin affects the cytoskeletal integrity of OCCC cells at clinically relevant levels. However, the mechanism involved is different from Rho GTPase inhibition by CID-1067700.

However, caution is warranted with simvastatin as combination with chemotherapy may yield an antagonistic response. Further research is warranted to develop simvastatin as a potential drug candidate for the treatment of OCCC. 

Source: Oncotarget

Journal information: Arildsen N, Hedenfalk I. Simvastatin is a potential candidate drug in ovarian clear cell carcinomas. Oncotarget. 2020;11(40):3660-3674. doi:10.18632/oncotarget.27747

Eating Saturated Fats can Cut Symptoms of Pancreatitis


A study has found that symptoms of pancreatitis are less severe when foods with saturated fats are eaten.

The study, by researchers from Mayo Clinic, the Saint Louis University School of Medicine and the Washington University School of Medicine, examines the obesity paradox in which obese patients had better results when being treated for certain conditions, compared to non-obese patients.

Pancreatitis is the leading cause of hospitalisation from gastrointestinal disorders in the United States. It can have a variety of causes, such as gallstones, having abdominal surgery or overconsumption of alcohol.
Saturated fats are found in meat and dairy, while unsaturated fats are found in plants and fish, and in general consumption of unsaturated fats over saturated fats is encouraged as it is associated with reduced risk of heart disease and other conditions. However, exceptions such as the obesity paradox exist.

To delve into this question, the researchers examined 20 clinical reports from 11 countries, where fat intake in obese patients was monitored. They found that among obese patients who developed pancreatitis, those who ate a diet heavy in saturated fats had less severe symptoms than those who did not. 

To determine the cause of this protective effect, the researchers fed mice a diet rich in either saturated or unsaturated fats, and then induced pancreatitis in them. Those fed saturated fats developed less severe symptoms. On closer examination, they found that saturated fat did not interact well with pancreatic triglyceride lipase, reducing production of long-chain non-esterified fatty acids, which reduced the symptoms of pancreatitis.  

Source: Medical Xpress

Journal information: Biswajit Khatua et al. Adipose saturation reduces lipotoxic systemic inflammation and explains the obesity paradox, Science Advances (2021). DOI: 10.1126/sciadv.abd6449

Young Athletes’ Recovery Helped by New Concussion Guidelines

A study has found that the adoption of new concussion guidelines, which emphasises a more active form of rest, reduced the duration of symptoms among athletes aged 11 to 18.

Concussions are the most common form of traumatic brain injury, often occurring either as a direct result of a blow to the head, or from forces experienced by the body that impart an acceleration to the head. Symptoms include mood changes, cognitive changes, sensory phenomena such as headaches or dizziness, and changes in sleep pattern.

The researchers compared medical records from 2016-18, which used the newer guidelines, to a set from 2011-13, which used the older guidelines.

Lead researcher John Neidecker, DO, and Sports Concussion Specialist, explained: “The most significant change in care involved a shift from strict rest or cocoon therapy to a return to low-intensity physical or cognitive activity after 24 to 48 hours. Our results show active rest dramatically improved recovery times among young athletes with first-time concussions.”

Active rest involves light activity that steadily increases under supervision, with minimal head movement.

“If diagnosis of a pre-existing condition has never been given, patients cannot be expected to report one during our concussion assessment,” said Dr. Neidecker. “This is especially true in the adolescent age group, as some may have a condition that they are not aware of yet. This makes screening for preexisting conditions more complex, yet even more essential for this age group.”

For example, intolerance to 3D movies could indicate an unrelated pre-existing condition. Information from parents about preinjury personality and behaviour could uncover anxiety.

“This more individualised, osteopathic approach in screening the athletes’ past medical history helped us identify health issues that may have been overlooked in the past,” said Dr Neidecker. This allows treatment to be more effectively tailored, he explained.

Knowledge about concussions has improved; in the 2011-13 dataset, the counselling given was more cautious and ominous, Dr Neidecker noted. Adequate communication and a positive outlook may have helped reduce reported symptoms, and may be essential for patients with anxiety. 

Source: News-Medical.Net


Journal information:
 Neidecker, J. M., et al. (2021) First-time sports-related concussion recovery revisited: management changes and impact on recovery. Journal of Osteopathic Medicine. doi.org/10.1515/jom-2020-0106.

Smoking Risks for Allergic and Asthmatic Cannabis Users

A survey in the US has shown that cannabis users are often asthmatic, and some have allergies from cannabis smoking or its second-hand smoke.

Cannabis allergies can potentially cause respiratory symptoms, contact urticaria, angioedema, and uncommonly anaphylaxis. Inhalation of cannabis may also manifest in allergic rhinitis, conjunctivitis, wheezing, and throat oedema. Given the widespread legal use of cannabis, more information is needed on the effects of cannabis use, particularly smoking, on individuals with asthma and allergies.

The anonymous survey, conducted in concert with the Allergy & Asthma Network, consisted of 489 participants, 18% of whom reported cannabis use. A surprising 60% were asthmatic, and 40% had uncontrolled asthma. 

Inhalation routes were the most popular way of taking cannabis. About half of users smoked cannabis, while a third vaped it. Only 40% reported being asked by their physician about cannabis use, and about the same proportion of participants were willing to talk to a physician about their cannabis use, said study co-author and cannabis allergy expert, William Silvers, MD.

“In order to more completely manage their allergy/asthma patients, allergists should increase their knowledge about cannabis and inquire about cannabis use including types of cannabinoid, route of use, reasons for use, and adverse effects,” said Dr Silvers. “As with cigarette smoking, efforts should be made to reduce smoking of cannabis, and recommend other potentially safer routes such as edibles and sublingual tinctures.”

Reported positive effects of cannabis use (eg, reduced pain, calm, improved sleep) were more frequent than adverse effects (eg, cough, increased appetite, anxiety). Approximately 20% of survey respondents reported coughing from cannabis, which was associated with smoking cannabis; this was cause for concern as it may indicate smoking risks for cannabis users.

“It surprised me that over half of the cannabis users in this study who have asthma were smoking it,” said principal investigator Joanna Zeiger, PhD. “And further, of those with uncontrolled asthma, half reported smoking cannabis. We also found that people with asthma are not routinely being asked or advised by their physician about cannabis and how they are consuming it.”

The researchers commented that further research into the relationship of cannabis and allergies is warranted.
“We look forward to future studies of larger, more diverse cohorts to better explore more deeply the effect of cannabis use on asthma and other allergic disorders,” said Dr Zeiger.

Source: News-Medical.Net

Journal information: Zeiger, J. S., et al. (2021) Cannabis attitudes and patterns of use among followers of the Allergy & Asthma Network. Annals of Allergy, Asthma & Immunology.doi.org/10.1016/j.anai.2021.01.014.

Anti-HIV Drugs may Combat Macular Degeneration

New research has shown that anti-HIV drugs may fight macular degeneration – overturning a preconception about DNA in the process.

Macular degeneration is the leading cause of blindness in developed countries. Even though HIV does not cause dry macular degeneration, the drugs prevented the loss of vision.

“We are extremely excited that the reduced risk was reproduced in all the databases, each with millions of patients,” said Jayakrishna Ambati, MD, a leading macular degeneration researcher at the University of Virginia School of Medicine. “This finding provides real hope in developing the first treatment for this blinding disease.”

A Big Data Archeology review of four health insurance databases showed that Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a commonly used HIV treatment, reduced the incidence of dry macular degeneration by 40%. The records spanned two decades and covered over 100 million patients. The drugs had also previously been shown to possibly prevent diabetes.

The finding also comes with the discovery that DNA can be produced inside the cytoplasm. Alu DNA (found exclusively in primates), which makes up 10% of the human genome, is transposable and can insert itself into other places on the genome. It was long considered “junk” DNA, but are now believed to have important functions, such as allowing for multiple expressions of proteins from a single Alu element. Since it cannot replicate itself, Alu DNA requires a transposon called L1 to accomplish this, which was now reported to allow the production of Alu DNA outside the chromosome. The buildup of Alu DNA in cells contributes to macular degeneration, by killing off cells that support the retina.
The researchers are urging further investigation into NRTIs or safer derivatives known as Kamuvudines, both of which block a key inflammatory pathway, can be useful in preventing vision loss from dry macular degeneration.

“A clinical trial of these inflammasome-inhibiting drugs is now warranted,” said Ambati. “It’s also fascinating how uncovering the intricate biology of genetics and combining it with big data archeology can propel insights into new medicines.”

Source: Medical Xpress

Journal Information: Shinichi Fukuda el al., “Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.202275111