Day: December 13, 2021

Categories : Medical Research & TechnologyTags :

Cannabis Use Risks Harmful Drug–Drug Interactions

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Photo by Crystalweed Cannabis on Unsplash

Using cannabis alongside other drugs may come with a significant risk of harmful drug-drug interactions, according to a pair of new studies in the journal Drug Metabolism and Disposition.

The researchers examined cannabinoids and their major metabolites found in the blood of cannabis users and found that they interfere with two families of enzymes that help metabolise a wide range of prescription drugs. Because of this, the drugs’ effectiveness might decrease or their negative effects might increase with too much building up in the body, causing unintended side effects such as toxicity or accidental overdose.

The authors note that despite the early stage of this research, it is important to be careful when using cannabis with other prescription drugs.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said Professor Philip Lazarus, senior author on the papers. “It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact their treatment.”

One study focused on a family of enzymes known as cytochrome P450s (CYPs), whereas the other looked at UDP-glucuronosyltransferases (UGTs), another enzyme family. Together, these two enzyme families help metabolise and eliminate more than 70% of the most commonly used drugs from the body.

While some previous research focused on potential drug interactions caused by cannabinoids, this new research provides the first known comprehensive look at the interaction between three of the most abundant cannabinoids (tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN)) and their metabolites and all of the major CYP enzymes. This is also the first known research that looked for interactions between these cannabinoids and UGT enzymes, specifically.

“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down,” said first author Shamema Nasrin. “The metabolites that result from that process stay in your body for much longer – up to 14 days – and at higher concentrations than cannabinoids and have been overlooked in previous studies, which is why we thought we should focus on those as well.”

Using human kidney cells, they found that cannabinoids and the major THC metabolites strongly inhibited several CYP enzymes. One key discovery was that one of the most abundant THC metabolites, called THC-COO-Gluc seems to play a major role in inhibiting several key enzymes in the liver. Looking at the UGT enzyme family, the researchers found that all three cannabinoids, but especially CBD, inhibited two of the primary UGT enzymes present in the liver. CBD was also found to block three enzymes that account for about 95 percent of kidney UGT metabolism, which helps clear toxins and certain drugs from the body.

“If you have a kidney disease or you are taking one or more drugs that are metabolised primarily through the kidney and you’re also smoking marijuana, you could be inhibiting normal kidney function, and it may have long-term effects for you,” Prof Lazarus said.

Nasrin added that these interactions between CBD and UGT enzymes could be inhibiting kidney function in patients with acute kidney disease or kidney cancer, who may be using CBD to treat pain or to try to reduce the side effects from anti-cancer drugs.

“Taking CBD or marijuana might help your pain but could be making the other drug you’re taking more toxic, and that increase in toxicity may mean that you can’t continue taking that drug,” Nasrin said. “So, there could be serious ramifications for anti-cancer drugs, and that’s only one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions we’re seeing.”

Source: Washington State University

Categories : CancerTags :

Anti-diabetes Drug under Development May Also Treat Breast Cancer

On By ModernMedia
Source: NCI

A new study has shown that a small molecule inhibitor drug, with the unwieldy designation of PF05175157, originally developed to treat diabetes by Pfizer, may help in the treatment of breast cancer by blocking a key enzyme. 

The findings from the Yale Cancer Center-led study were reported at the 2021 San Antonio Breast Cancer Symposium in San Antonio, Texas.

“Our research shows the preclinical, anti-cancer activity using PF05175157 may lead us to bring this drug back into the clinic to help treat patients with breast cancer,” said lead study author Julia Foldi, MD, PhD, a clinical fellow at Yale Cancer Center and Smilow Cancer Hospital. “More studies are needed, but our initial data looks very promising.”

Cancer cells are characterised by altered metabolism. In this study, the Yale team identified new metabolic vulnerabilities in cancer cells that are based on a loss of enzyme diversity. They found that an enzyme called acetyl-CoA-carboxylase-1 (ACC1), is critical for the survival of breast cancer cells. The ACC1 enzyme is the key initial step in fatty acid synthesis. Fatty acids are building blocks of the various types of lipids and fat that are the critical ingredients of cell membranes and play an important role in energy generation in cells. The team’s analysis demonstrated that blocking ACC1 using PF05175157 can inhibit the growth of breast cancer cells grown in mice and also in patient-derived cancer models.

“We are currently testing this drug in combination with other approved breast cancer drugs to see if it could improve their activity, with the hope to bring the most promising combinations to the clinic to help patients with breast cancer,” added Lajos Pusztai, MD, DPhil, Professor of Medicine (Medical Oncology), Director of Breast Cancer Translational Research at Yale Cancer Center, and senior author of the study.

Source: Yale Cancer Center

Categories : Diseases, Syndromes and ConditionsTags :

Apaxiban is an Option in Severe Renal Dysfunction

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

The anticoagulation options for patients with concomitant renal impairment are limited and until recently, warfarin was the only recommended option due to insufficient data supporting alternative drugs in such patients. A new study published in Blood Advances suggests that apixaban is a viable option in patients with severe renal dysfunction.

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. 

A multicentre, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min.


Patients were evaluated for thrombosis and bleeding outcomes six  months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. 

Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio 0.47). There was no statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. 

The results suggest apixaban may be a reasonable option for patients with severe renal dysfunction despite the known increase in apixaban exposure, the researchers concluded. They add that, “These results add to the growing body of evidence of real-world data that apixaban is a reasonable option for patients with severe renal dysfunction.”

The researchers recommend investigating the use of apixaban in patients with a severe renal dysfunction, especially those on haemodialysis, in order to definitively determine the role of apixaban in this patient population.

Source: Blood Advances

Categories : Cancer Respiratory DiseasesTags :

Why People with Asthma Get Fewer Brain Tumours

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Photo by Mart Production on Pexels

A new study reveals why people with asthma seem to be less likely to develop brain tumours than others.

Asthma causes T cell activation, and researchers discovered in a mouse study that asthma causes the T cells to behave in a way that induces lung inflammation but prevents the growth of brain tumours.

The findings, appearing in Nature Communications, suggest that reprogramming T cells in brain tumour patients to act more like T cells in asthma patients could be a new approach to treating brain tumours.

“Of course, we’re not going to start inducing asthma in anyone; asthma can be a lethal disease,” said senior author David H. Gutmann, MD, PhD, at Washington University School of Medicine. “But what if we could trick the T cells into thinking they’re asthma T cells when they enter the brain, so they no longer support brain tumor formation and growth? These findings open the door to new kinds of therapies targeting T cells and their interactions with cells in the brain.”

Based on epidemiologic observations, 15 years ago it was first proposed that people with inflammatory diseases, such as asthma or eczema, are less prone to developing brain tumours. However, there was no explanation for the link between the two very different kinds of diseases, and some scientists questioned whether the association was real.

Gutmann is an expert on neurofibromatosis (NF), a set of complex genetic disorders that cause tumours to grow on nerves in the brain and throughout the body. Children with NF type 1 (NF1) can develop an optic pathway glioma, where tumours grow within the optic nerves. Gutmann, director of the Washington University NF Center, noted an inverse association between asthma and brain tumours among his patients more than five years ago but didn’t know what to make of it. When more recent studies from his lab began to reveal the crucial role that immune cells play in the development of optic pathway gliomas,  he began to wonder whether immune cells could account for the asthma–brain tumour link.

Jit Chatterjee, PhD, a postdoctoral researcher and the paper’s first author, took up the investigation. Working with co-author Professor Michael J. Holtzman, MD, Dr Chatterjee studied mice genetically modified to carry a mutation in their NF1 genes and form optic pathway gliomas by three months of age.

Dr Chatterjee exposed groups of mice to asthma-inducing irritants at age four  weeks to six weeks, and treated a control group with saltwater. Then, he checked for optic pathway gliomas at three months and three months of age. The mice with asthma did not form these brain tumours.

Further experiments revealed that inducing asthma in tumour-prone mice changes the behaviour of their T cells. After the mice developed asthma, their T cells began secreting decorin, a protein that asthma researchers are well acquainted with.

Decorin is a problem in the airways, acting on lining tissues and exacerbating asthma symptoms. But the researchers found that in the brain, decorin is beneficial. There, the protein acts on microglia immune cells, blocking their activation by interfering with the NFkappaB activation pathway. Activated microglia promote brain tumour growth and development.

Treatment with either decorin or caffeic acid phenethyl ester (CAPE), a compound that inhibits the NFkappaB activation pathway, protected mice with NF1 mutations from developing optic pathway gliomas. The findings suggest that blocking microglial activation may be a potentially useful therapeutic approach for brain tumours.

“The most exciting part of this is that it shows that there is a normal communication between T cells in the body and the cells in the brain that support optic pathway glioma formation and growth,” said Prof Gutmann. “The next step for us is to see whether this is also true for other kinds of brain tumours. We’re also investigating the role of eczema and early-childhood infections, because they both involve T cells. As we understand this communication between T cells and the cells that promote brain tumours better, we’ll start finding more opportunities to develop clever therapeutics to intervene in the process.”

Source: Washington University School of Medicine

Categories : Environmental Effects Lab Tests and ImagingTags :

Lab Results are Influenced by Ambient Daily Temperatures

On By ModernMedia
Photo by Louis Reed on Unsplash

Ambient temperature influences many common lab tests, and these distortions likely affect medical decision making, such as whether to prescribe medications, according to new research published in the journal Med. 

To account for this, the researchers suggest that laboratories could statistically adjust for ambient temperature on test days when reporting lab results.

“When a doctor orders a laboratory test, she uses it to shed light on what’s going on inside your body, but we wondered if the results of those tests could also reflect something that’s going on outside of your body” said study co-author Ziad Obermeyer of the University of California, Berkeley. “This is exactly the kind of pattern that doctors might miss. We’re not looking for it, and lab tests are noisy.”

Delving into this problem, Obermeyer and Devin Pope of the University of Chicago analysed a large dataset of test results from different climates. In a sample of more than four million patients, they modelled more than two million test results based on temperature. They measured how day-to-day temperature fluctuations influenced results, over and above the patients’ average values, and seasonal variation.

Temperature was found to affect more than 90% of individual tests and 51 of 75 assays, including measures of kidney function, cellular blood components, and lipids such as cholesterol and triglycerides. “It’s important to note that these changes were small: less than one percent differences in most tests under normal temperature conditions,” Obermeyer said.

These small fluctuations did not likely reflect long-term physiological trends. For example, lipid panels checked on cooler days appeared to suggest a lower cardiovascular risk, resulting in almost 10% fewer prescriptions for cholesterol-lowering drugs called statins to patients tested on the coolest days compared to the warmest days, despite the results likely not reflecting stable changes in cardiovascular risk.

Since the study wasn’t an experiment, the exact mechanisms underlying the fluctuations in lab results could not be pinpointed. However, blood volume, specific assay performance, specimen transport, or changes in lab equipment might explain them. “Whatever their cause, temperature produces undesirable variability in at least some tests, which in turn leads to distortions in important medical decisions,” Pope said.

Laboratories could get around this by statistically adjusting for ambient temperature on the test day when reporting lab results. This could be a way to reduce weather-related variability without expensive temperature control equipment. 

In practice, decisions on adjustment would need to be at the discretion of the laboratory staff and the treating physician, potentially on a case-by-case basis.

According to the authors, the study may also have broader clinical implications. “The textbook way of thinking about medical research is bench to bedside. First, we come up with a hypothesis, based on theory, then we test it with data,” Obermeyer said. “As more and more big data comes online, like the massive dataset of lab tests we used, we can flip that process on its head: discover fascinating new patterns and then use bench science to get to the bottom of it. I think this bedside-to-bench model is just as important as its better-known cousin because it can open up totally new questions in human physiology.”

Source: Science Daily

Categories : CancerTags :

A Novel Therapy for Bone Marrow Cancer

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Source: NCI on Unsplash

Researchers have found that a novel therapy for the bone marrow cancer myelofibrosis to be safe and well-tolerated, and is associated with modest improvements in patients in an early clinical trial. They shared their findings during an oral presentation at the American Society of Hematology annual meeting in December.

The therapy AVID200 showed improvements in patients’ symptom burden, anaemia, and spleen enlargement. The results from the Phase 1b clinical trial showed that the therapy was safe and displayed some evidence of efficacy (although safety and finding optimal dosage was the main goal) and researchers concluded that the therapy would need to be combined with other drugs to optimise effectiveness in patients.

“This is a real testament to cutting-edge translational research at The Tisch Cancer Institute,” said John Mascarenhas, MD, Director of the Institute’s newly launched Center of Excellence for Blood Cancer and Myeloid Disorders. “Our scientists tested this therapy in the lab, physician-scientists conducted a successful phase 1 trial, and now the optimal combination therapy approach is the subject of ongoing laboratory studies at Mount Sinai. The most interesting finding in this trial was that a subset of patients had a lasting improvement in their platelet counts – including three whose counts were normalised – supporting the preclinical studies conducted.”

Myelofibrosis is a bone marrow cancer type that disrupts normal blood cell production, causing an enlarged spleen, extensive scarring in the bone marrow, and low levels of red blood cells and platelets, increasing bleeding risk. Myelofibrosis patients who have failed the available first-line therapy face a well-documented poor prognosis, so additional therapies are urgently needed to help these patients.

Twenty-one patients enrolled in this multicenter trial were given AVID200, and while this trial’s main purpose was to test safety, some patients had an increase in platelets and there was a decrease in the size of their enlarged spleens. However, in spite of the other clinical benefits seen. patients’ bone marrow scarring did not decline, indicating that AVID200 would need to be combined with other rational therapies in the future.   

Source: EurekAlert!

Categories : General InterestTags :

Great Gift Ideas for Healthcare Workers

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Photo by Jess Bailey on Unsplash

If you’re stuck for gift ideas for a certain healthcare worker, or you are one yourself and looking to leave hints for someone stuck for ideas, this list could help. 

1: A Good Pair of Scrubs
This one may seem obvious, but not all scrubs are identical or of high quality, and healthcare providers can never have enough high-quality scrubs. Ones that are soft, flexible, and moisture-resistant are ideal. For the fashion-conscious healthcare worker, go for jogger style.

2: A Massage Gun
The healthcare working environment is a physically demanding one. With long shifts, sometimes up to 24 hours or even longer, much of the time is spent standing. A massage gun can work wonders for sore muscles, aches, and pains.

3: Good Moisturiser or Hand Cream
Healthcare workers wash their hands and use hand sanitiser all day long, which can cause the skin to dry out and lead to painful cracking. A good moisturiser can go a long way. However, avoid those that are heavily scented since some patients may be sensitive to the chemicals. Another great option is hydrating single-use hand masks.

4: Quick Meal Solutions
Gift cards for food delivery services like Uber Eats or Mr D are a great way for healthcare workers to get an easy meal – and can offer healthy alternatives to junk food. Cooking most likely is not at the top of their priority list either on shift or coming off of it, so this can be a practical way to be supportive and make their lives a little easier.

5: Custom Tailored Lab CoatThe long white lab coat is a symbol of office for physicians, a representation of all the long years of hard work they’ve put into their career as well as a reassuring sight for patients. A custom-tailored and embroidered white lab coat would make the perfect gift for any physician.

6: Spa DayTwo years into the pandemic with the constant threat of burnout, there’s nothing quite like having an indulgent spa day for your healthcare worker friend or family member to relax. A good massage to ease stiff muscles and a sauna session is a fantastic way to help unwind, lease the burden and de-stress.

7: Smartwatch
A smartwatch that can track health data and perform other functions can make a great gift for a healthcare worker if they don’t have one already. Smartwatches are of course convenient for checking the time, but they can also monitor activity and exercise levels and overall well-being and sync with mobile phones for calls, alerts, and many apps – some of which can warn if healthcare workers are falling ill.

8: Travel Mug
People who are on the go for their job can always use a travel mug, especially paramedics who spend long nights on shift on the road. This will keep coffee (or tea, hot chocolate, or soup) at just the right temperature for extended periods of time.

9: Compression Socks
Working in a field that requires a great deal of time spent on their feet, most healthcare workers likely know about the benefits of compression socks. They prevent muscle soreness and stiffness in the legs, and just like regular socks (and scrubs), you can never have too many.

10: Blue Light Blocking Glasses
Hours spent sitting at a computer, inputting patient charts can cause some serious eyestrain. This can purportedly be reduced by wearing blue light glasses (which can be either prescription or non-prescription) which filter out blue light, supposedly reducing strain. Evidence for the glasses are mixed, but many swear by them.

Source: MedPage Today

Categories : Respiratory DiseasesTags :

Melatonin May be The Culprit for Nocturnal Asthma

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Source: Pixabay

Why patients with asthma find their condition worsens at night has remained largely unknown, but now researchers have found that the sleep hormone melatonin may be the culprit.

In ‘nocturnal asthma’ , patients with asthma often experience a worsening of asthmatic symptoms at night. More than 50% of asthma deaths occur at night, showing a link between nocturnal asthma symptoms and asthma deaths. Though numerous triggers that explain the pathogenesis of nocturnal asthma have been described, the precise mechanisms regulating this asthma phenotype remain obscured until now. Now, a study published in the American Journal of Physiology Lung Cellular and Molecular Physiology may have explained the relationship via melatonin.

Asthma patients suffer from bronchoconstriction which may be eased with a bronchodilator. However, melatonin, which is often prescribed for insomnia, favours a state of bronchoconstriction and weakens the relaxing effect of a bronchodilator through the activation of the melatonin MT2 receptor.

To elucidate this, the research group identified the expression of the melatonin MT2 receptor in human airway smooth muscle. They observed that the activation of the melatonin MT2 receptor with higher doses of melatonin or melatonin receptor agonist ramelteon greatly potentiated the bronchoconstriction. In addition, melatonin attenuated the relaxing effects of the widely used bronchodilator β-adrenoceptor agonist.

“Although serum concentration of melatonin did not significantly induce the airway constriction, greater doses of melatonin, which is clinically used to treat insomnia, jet lag, or cancer, worsened asthma symptoms and impaired the therapeutic effect of bronchodilators,” said study leader Kentaro Mizuta from Tohoku University Graduate School of Dentistry .

First author Haruka Sasaki added, “The pharmacological therapy that blocks the melatonin MT2 receptor could inhibit the detrimental effects of melatonin on airways.”

Source: Tohoku University