Category: Diseases, Syndromes and Conditions

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More Evidence Linking Erectile Dysfunction Drugs to Eye Conditions

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Photo by Mike Dorner on Unsplash

The risk of developing one of three serious eye conditions increases by 85 percent for regular users of common erectile dysfunction (ED) medications such as the phosphodiesterase 5 (PDE5) inhibitors, sildenafil, tadalafil, vardenafil and avanafil, according to new research.

Previously, two of the three conditions had been linked to ED medications only by anecdotal case studies. Now, these links have been confirmed for the first time by a large, epidemiological study, which appears in JAMA Ophthalmology.

“These are rare conditions, and the risk of developing one remains very low for any individual user. However, the sheer number of prescriptions dispensed each month in the US – about 20 million – means that a significant number of people could be impacted,” said first author Dr Mahyar Etminan. “Regular users of these drugs who find any changes in their vision should take it seriously and seek medical attention.”

The researchers analysed health insurance claim records of 213 000 men in the US without a history of these eye problems in the year before they became regular users of ED medications.

They followed the records to see how many men developed one or more of the three conditions, and how that rate compared to men who didn’t use the medications. After accounting for conditions associated with eye problems, such as hypertension, diabetes and coronary artery disease, they found the increased risk for each to be as follows:

A key limitation was that the study could only show correlation between eye conditions and use of these drugs, and could not prove causation. However, possible explanations can be found in the way ED medications function.

“These medications address erectile dysfunction by improving blood flow, but we know that they can also hinder blood flow in other parts of the body,” explained Dr Etminan. “So although our study doesn’t prove cause-and-effect, there is a mechanism by which these medications could conceivably lead to these problems. The totality of the evidence points toward a strong link.”

The potential risk of SRD and RVO is not covered in the information currently provided to patients along with their ED medications, unlike the ION risk which has been demonstrated by previous research.

Dr Etminan hopes his team’s work will change that. Patients who are unaware of all potential side effects might not seek help in time to avoid serious visual consequences.

Source: University of British Columbia

Categories : Diseases, Syndromes and Conditions HospitalsTags :

Community-acquired Antimicrobial Resistant UTIs can be More Deadly

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Pseudomonas
Scanning Electron Micrograph of Pseudomonas aeruginosa. Credit: CDC/Janice Carr.

A study from Australia’s scientific organisation CSIRO has revealed that antimicrobial resistant (AMR) bacteria in urinary tract infections are more lethal, especially Enterobacteriaceae. The findings are published online in Open Forum Infectious Diseases.

Antimicrobial resistance (AMR) bacteria can be passed between humans: through hospital transmission and community transmission. While hospital acquired resistance is well researched, there are few studies focusing on the burden of community transmission.

To address this, the study analysed data from 21 268 patients across 134 Queensland hospitals who acquired their infections in the community. The researchers found that patients were almost two and a half (2.43) times more likely to die from community acquired drug-resistant UTIs caused by Pseudomonas aeruginosa and more than three (3.28) times more likely to die from community acquired drug-resistant blood stream infections caused by Enterobacteriaceae than those with drug-sensitive infections. The high prevalence of UTIs make them a major contributor to antibiotic use, said CSIRO research scientist, Dr Teresa Wozniak.

“Our study found patients who contracted drug-resistant UTIs in the community were more than twice as likely to die from the infection in hospital than those without resistant bacteria,” Dr Wozniak said. “Without effective antibiotics, many standard medical procedures and life-saving surgeries will becoming increasingly life-threatening. “Tracking the burden of drug-resistant infections in the community is critical to understanding how far antimicrobial resistance is spreading and how best to mitigate it.”

The study’s findings will provide further guidance for managing AMR in the community, such as developing AMR stewardship programs that draw on data from the population being treated.

CEO of CSIRO’s Australian e-Health Research Centre, Dr David Hansen, said the magnitude of the AMR problem needs to be understood to mitigate it. “Tracking community resistance is difficult because it involves not just one pathogen or disease but multiple strains of bacteria,” Dr Hansen said. “Until now we haven’t been using the best data to support decision making in our fight against AMR. Data on community acquired resistance is an important contribution to solving the puzzle. “Digital health has an important role in using big data sets to describe patterns of disease and drive important population health outcomes.”

Source: CSIRO

Categories : Diseases, Syndromes and ConditionsTags :

Caffeine May Help with Cognitive Symptoms of ADHD

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Coffee cup and beans
Photo by Mike Kenneally on Unsplash

Researchers in Spain have found that caffeine may be beneficial in alleviating cognitive symptoms of ADHD, such as improving attention span and retention capacity. Their findings, published in Nutrients, may provide a less controversial addition to the therapeutic arsenal for this disorder.

Attention deficit hyperactivity disorder (ADHD) diagnoses have increased exponentially over the last 20 years. It is currently estimated that this disorder affects between 2% and 5% of children in Spain, an average of one or two children per classroom, and up to 4% of the adult population.

Despite these high incidence rates, controversy surrounds the treatment of this pathology and the therapeutic approach to it. This varies widely depending on each patient, the symptoms they present and their intensity. For this reason, experts are continuing to investigate different components and substances that may be capable of providing new treatment opportunities for patients diagnosed with ADHD.

A team of experts at the Universitat Oberta de Catalunya (UOC) has investigated caffeine to alleviate some of the symptoms of ADHD, given the controversy surrounding the use of some medicines derived from methylphenidate, among others. Their systematic review of animal studies concludes that a prescribed consumption of caffeine can increase attention and retention capacity in adolescents and adults with ADHD.

“The therapeutic arsenal for alleviating ADHD is limited, and there is a certain degree of controversy around the use of some types of medications and stimulants, especially during childhood and adolescence. That’s why it’s useful to study the efficacy of other substances, such as caffeine,” explained Javier Vázquez, one of the paper’s main authors.

This is the first systematic review with results linking caffeine consumption in different animal models of ADHD with an increased attention span, improved concentration, learning benefits, and improvements in some types of memory.

“This substance improves these types of cognitive procedures, and increases capacity and flexibility in both spatial attention and selective attention, as well as in working memory and short-term memory,” emphasised Vazquez, who added that controlled treatment with this substance “doesn’t alter blood pressure, and doesn’t lead to an increase or reduction in body weight.”

The researchers point out that while possibly effective for cognitive symptoms, the results are unclear for other characteristic symptoms of ADHD, such as hyperactivity and impulsivity. “The results are very positive, but we must be much more careful when prescribing a caffeine-based medical treatment for these symptoms. In diagnoses in which the problem is purely attentional, caffeine may be an appropriate therapy, but if there’s a symptomatological presence of hyperactivity or impulsivity, we must be more cautious,” said Vasquez.

However, the results show that caffeine has a clear benefit in ADHD’s cognitive symptoms. “Our results reinforce the hypothesis that the cognitive effects of caffeine found in animal models can be translated and applied in the treatment of ADHD in people, especially at young ages such as adolescence,” the authors concluded.

“We want to emphasise that we aren’t against medication for ADHD, but we’re open to investigating all possible alternatives for improving this type of disorder, and for being able to use caffeine from a therapeutic point of view with all the appropriate medical supervision, a prescribed treatment and follow-up,” said Vázquez.

Source: Universitat Oberta de Catalunya (UOC)

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New Hope for Alopecia Treatment with JAK Inhibitor Baricitinib

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Before and after images for participants who received 36 weeks of treatment for alopecia areata with baricitinib. Credit: Yale University

Results from a new study in three patients with alopecia areata treated with a Janus kinase (JAK) inhibitor, baricitinib, were able to regrow hair. The study is based on Phase III clinical trials using baricitinib – a drug commonly used for arthritis – to treat alopecia areata, a skin disease characterised by loss of hair from the scalp and sometimes eyebrows and eyelashes.

“This is so exciting, because the data clearly show how effective baricitinib is,” said Dr. Brett King, an associate professor of dermatology at the Yale School of Medicine and lead author of the new study, published in the New England Journal of Medicine. “These large, controlled trials tell us that we can alleviate some of the suffering from this awful disease.”

Alopecia areata is an autoimmune disorder in which the body’s immune system attacks hair follicles, and which typically occurs in people under the age of 40. At present there is no FDA-approved treatment for the disease.

To test the drug, the researchers conducted two large, randomised trials involving a total of 1 200 people. The participants were adults with severe alopecia areata, who had lost at least half of their scalp hair.

For 36 weeks, participants were randomised to either a daily dose of either 4mg of baricitinib, 2mg of baricitinib, or a placebo. One-third of the patients who received the larger dose grew hair back.

According to the researchers, baricitinib works by disrupting the communication of immune cells involved in harming hair follicles. Baricitinib and other JAK inhibitors are routinely used to treat autoimmune forms of joint disease.

“Alopecia areata is a crazy journey, marked by chaos, confusion, and profound sadness for many who suffer from it,” King said. “It will be incredible to have a medicine to help people emerge on the other side, normalcy restored, recognizable again to themselves and those around them.”

Over the past decade, A/Prof King has developed methods for using JAK inhibitors to treat a variety of skin diseases — including eczema, vitiligo, granuloma annulare, sarcoidosis, and erosive lichen planus.

A/Prof King noted that the clinical trials involving baricitinib are ongoing, allowing researchers to assess the long-term effectiveness and safety of the treatment.

Source: Yale University

Categories : Diseases, Syndromes and ConditionsTags :

Why Some Infections Can Be so Persistent

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C. difficile bacteria. Source: CDC

University of Utah researchers have discovered a novel mechanism that infectious bacteria use to rapidly adapt to environmental stress, which could help explain why certain types of common infections such as sepsis can be so persistent.

The mechanism, described in the journal Nucleic Acids Research, alters the precision with which the bacteria make the proteins that carry out most of the work in cells. These changes may improve the bacteria’s chance for survival.

“Understanding how pathogens survive stressful situations can reveal new targets for development of anti-microbial drugs and vaccines,” said the study’s senior author, Professor Matthew Mulvey.

Adapt or die
Bacteria infecting a host are exposed to stresses such as acidity or antibiotics. If even one of the bacteria’s key pathways for survival is crippled, the entire population could die off.

However, bacteria can adapt, an ability that relies on a slight twist to basic principles of biology.

Traditionally, each gene is thought to carry instructions for making a single kind of protein. A molecule called transfer RNA (tRNA) then uses these instructions to oversee protein production in the cell. In times of stress, though, random changes to the tNRA-mediated process can be an especially quick way to alter a cell’s array of proteins. This can generate useful new proteins that help the organism to thrive.

“There is a growing appreciation that a little bit of noise in the system can be good,” Prof Mulvey said.

Shifting expectations
A graduate student in the lab happened to stumbled onto a bacterial enzyme, MiaA, which turned out to be both sensitive to environmental stress and key to regulating protein expression. In one experiment, he created a version of an especially pathogenic bacteria that lacked the gene that encodes MiaA.

“Every kind of stress we exposed the MiaA-deficient strain to seemed to cause problems,” said the study’s co-first author Matthew Blango, PhD, who is now a junior research group leader at the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany. “So, we really thought that this protein might be playing an important role in gene regulation.”

Bacteria lacking MiaA did not thrive and did not cause urinary tract infections or sepsis in mice. This same effect also occurred with bacteria manipulated into expressing too much MiaA. “There appears to be a Goldilocks zone, where just the right amount of MiaA allows the optimal stress response,” Dr Blango said.

Seeing how badly things went when MiaA levels were out of balance, Brittany Fleming, PhD, the study’s co-first author, investigated further. She discovered that knocking out MiaA caused random ‘frameshifting’ – an error where tRNA delivers three-letter genetic codes to be translated into proteins that are off by one letter. For example, a genetic code of “CAT CAT GTA” might read as “ATC ATG TA…” when frameshifted. In the bacteria, the result of such a shift was impaired production of important proteins and production of unexpected proteins.

Another co-first author, graduate student Alexis Rousek, showed that changing levels of MiaA could alter the availability of key metabolites that feed into other important stress response pathways within the bacteria. These findings implicate MiaA as a key player within a web of pathways that can impact pathogen stress resistance

Prof Mulvey says his lab’s next step is learning how environmental stress alters MiaA levels within bacteria.

The implications for this research may extend beyond infection control. Humans express a version of MiaA that is linked to certain cancers and metabolic diseases. “What we learned about how MiaA works is likely to be relevant to research on cancer and other non-infectious human diseases,” Mulvey said.

Source: University of Utah

Categories : Diseases, Syndromes and Conditions GenderTags :

Sex Differences in Nonalcoholic Fatty Liver Disease Explained

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Toilet sign male and female
Photo by Tim Mossholder on Unsplash

Investigators may have discovered the reason why fewer women than men develop nonalcoholic fatty liver disease (NAFLD). They published their findings in Nature Communications.

One of the most common disorders globally, NAFLD is a leading cause of death worldwide. Its progressive form, ‘nonalcoholic steatohepatitis’ (NASH), affects about 30% of all NAFLD patients, and can lead to cirrhosis and liver cancer. Despite intensive research, the underlying mechanisms of NAFLD/NASH are still poorly understood and effective treatment is lacking as a result.

However, it is known that NAFLD/NASH is more common among men than women, especially premenopausal women. The reasons for this are still unclear, but evidence so far suggests that oestrogen plays a protective role. On the other hand, the protein formyl peptide receptor 2 (FPR2) is known to play an important role in mediating inflammatory responses in multiple organs. However, no study so far has determined its role in the liver. Could FPR2 be involved in the sex-related differences regarding NAFLD prevalence and severity?

Addressing this question, a research team led by Professor Youngmi Jung of Pusan National University, Korea, recently conducted a study using mice model, shedding light on the role of FPR2 in NAFLD/NASH and its relationship to the observed sex-based differences. This work is among the very few studies on NAFLD that relies on sex-balanced animal experiments rather than the more common male-only designs.

The researchers first found that Fpr2 was highly expressed in healthy livers of female mice. Furthermore, it was expressed differently in the livers of male and female mice that were fed a special NAFLD-inducing diet. Silencing the Fpr2 gene made the male and female mice equally vulnerable to NAFLD, suggesting that FPR2 has a protective effect on the liver.

Interestingly, the researchers also found that FPR2 production in the liver is mediated by oestrogen. Males supplemented with external oestrogen produced more Fpr2 and were more resistant to NAFLD, whereas females that had their ovaries removed exhibited reduced liver Fpr2 levels. “Taken together, our findings suggest that FPR2 is a potential therapeutic target for developing pharmacological agents to treat NAFLD/NASH,” says Prof Jung. “In addition, our results could help in the development of gender-based therapies for NASH.”

This unprecedented discovery of the female-specific production of FPR2 in the liver and its role in providing resistance against NAFLD/NASH will hopefully pave the way not only for novel treatments but also a more comprehensive and sex-aware approach when doing science. Prof Jung remarked on this: “Our research highlights the pressing need for designing and developing better sex-balanced animal experiments, considering that the sex-specific expression of FPR2 in the liver had been completely overlooked in previous studies.”

Source: Pusan National University

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An Unexpected Ally: Pathogen Enhances Antifungal Drug

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Scanning Electron Micrograph of Pseudomonas aeruginosa.
Credit: CDC/Janice Carr

While pathogens usually work against drug treatments, sometimes, they can actually strengthen them, according to a new University of Maine study published in the journal Infection and Immunity.

Polymicrobial infections, which are a combination of bacteria, viruses, fungi and parasites, are challenging to treat because it is not well understood how pathogens interact during infection and how these interactions affect the drugs treating them.

In a study published in Infection and Immunity, University of Maine researchers examined two common pathogens that often occur at similar sites, particularly in cystic fibrosis and mechanically ventilated patients: Candida albicans and Pseudomonas aeruginosa.

Candida is the fourth most common hospital-acquired pathogen, and many antifungal agents only slow it rather than kill it outright. Meanwhile, P. aeruginosa infects 90% of all adult cystic fibrosis patients. Combined, C. albicans and P. aeruginosa cause more serious disease in cystic fibrosis and ventilated patients.

The researchers investigated the effectiveness of the antifungal drug fluconazole in vitro and then during infection of the zebrafish with both pathogens. Fluconazole slows fungal growth, but Candida can become tolerant to the drug and not only survive, but also evolve tolerance that leads to therapy failure and, potentially, death.

The results showed that P. aeruginosa in fact works with fluconazole to eliminate drug tolerance and clear the C. albicans infection in the culture and the zebrafish.

“Polymicrobial infections are challenging to treat not only because of the lack of understanding of how invading microorganisms interact but also because we don’t know how these interactions affect treatment efficacy. Our work demonstrates that polymicrobial interactions can indeed affect treatment efficacy and, most importantly, it highlights the importance of nutrient availability in the environment -; such as iron in our study -; and how it modulates treatment efficacy,” explained Siham Hattab, lead author of the study.

What’s more, the bacteria also enhance the drug’s ability against a second pathogenic Candida species that tends to be more resistant to the drug.

The increased effectiveness of the drug suggests to the researchers that there is still much more to learn about how current drugs work when targeting these dangerous and complex polymicrobial infections.

Senior study author, Robert Wheeler, associate professor of microbiology said: “We are really excited to have revealed that sometimes drugs against fungal infection can work even better in a more ‘real-world’ situation than in the test tube. There is still a lot to learn about how pathogens interact during infection, and it will be interesting to see how the bacteria manage to work with the drugs to target Candida.”

Source: University of Maine

Categories : Diseases, Syndromes and Conditions VaccinesTags :

Boosting the BCG Vaccine by Blocking IL-10

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Vaccine injection
Image source: NCI on Unsplash

Briefly blocking interleukin-10 (IL-10) when administering the BCG vaccine for tuberculosis vastly improves long-term protection in mice, researchers reported in the Journal of Immunology. The finding, if it continues to hold true in nonhuman primates and clinical trials, has the potential to save millions of lives.

“We are very excited that we can reverse BCG’s waning effectiveness by combining it with a host-directed therapy into one dose, which makes it very practical for the clinic,” said senior author Joanne Turner, PhD.

The study builds on research showing the effect of IL-10 on TB, which normally helps dampen excessive inflammation during infection, but Dr Turner’s previous work showed that IL-10 overall actually drives infection.

The researchers combined the BCG vaccine with an antibody that blocks IL-10 activity for about one week. Since the antibody targets the host, not the pathogen, that makes it a “host-directed therapy.” They gave the mixture to mice in one shot, waited six weeks to ensure the IL-10 blocker was no longer present and the BCG protection had been generated, and then exposed the mice to TB. Those mice controlled TB infection for nearly a year, which is significant for mice with normal lifespans of about two years. In contrast, mice given only the BCG vaccine lost control of TB infection within two months and had significant inflammation and damage in the lungs. Notably, the mice given the vaccine/IL-10 blocker had higher levels of various long-term memory immune cells, which are critical for ongoing TB control.

“This shows that the early development of an immune response is key for controlling TB infection in the long run, and that IL-10 inhibits the development of that long-term immunity,” Dr Turner said. “But by briefly blocking IL-10 at the same time as giving the vaccine, it allows the vaccine and immune system to do their jobs, creating those long-lasting memory immune cells.”

The researchers plan to move to nonhuman primates and then human clinical trials if those are successful. The team is optimistic, especially since the BCG vaccine is already in widespread use and the IL-10 blocker is being tested against other diseases.

Source: Texas Biomedical Research Institute

Categories : Diseases, Syndromes and ConditionsTags :

Malaria’s Growing Resistance Requires New Insight

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Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

To deal with malaria’s growing resistance to existing drugs, researchers are exploring new areas of the deadly parasite’s life cycle. Research published in PLOS Pathogens has identified key processes the malaria parasite uses to remodel blood cells it hides inside.

Senior author Paul Gilson, an associate professor at Burney University, said the growing resistance to antimalarial medicines needs to be addressed soon to avoid serious treatment failures in the future.

“It’s only a matter of time before resistance becomes so bad that current measures perhaps become worthless,” he said.

“Current drugs tend to target very similar things. By discovering new targets and developing drugs to these, we can hopefully overcome resistance.

“Our research identifies processes in the parasites that are essential for its survival. And the more we understand about those processes, the better position we’re in to develop new treatments to block those processes.”

The research, A/Prof Gilson explains, looked into the nature of malaria parasites, particularly their need to renovate their host blood cells to grow rapidly and to escape the immune system.

The dynamic is analogous to an international arrivals terminal in need of better security.

“The renovations are carried out by special exported proteins made by the parasite that are only allowed to travel into the blood cell if they have the right passport,” he said.

“We used to think that gateways around the parasite called PTEX acted like immigration officers at the airport only allowing exported proteins with the right passports to pass through.

“What this study now shows is that the immigration officers appear to leave the airport and travel inside the parasites to check the exported protein passports not long after they are first made.

“The officers then pair up with their exported proteins and take them to the airport to let them go straight through into the blood cells.”

A/Prof Gilson said that hopefully, a greater understanding of the ways parasite proteins enter and modify blood cells could result in new drugs that block exported proteins from carrying out essential renovations to their blood cells.

The COVID pandemic has disrupted and set back malaria elimination programs in several countries, making the need for new drug developments to combat the disease all the more vital.

“Many countries only have very limited resources, and it’s estimated that there’s been quite a big increase in the number of malaria cases around the world because so much effort has been diverted to combat COVID,” he said.

Even though COVID has taken the global spotlight, A/Prof Gilson said that malaria is still a major issue. In 2020 there were an estimated 241 million cases of malaria worldwide, with an estimated 627 000 deaths, according to World Health Organization figures.

A/Prof Gilson said that over recent years significant inroads have been made in eliminating malaria, pointing out that annual death rates were in the millions at the start of the 21st century.

“We can’t let COVID undermine all the great work that’s been achieved over the years, as we aim to one day totally eliminate malaria.”

“Research into new drugs to combat malaria parasites, which are becoming resistant to existing drugs, is a crucial part of these efforts.”

Source: Burnet Institute

Categories : Diseases, Syndromes and ConditionsTags :

Accuracy of Flu Self-tests Comparable to Clinical Tests

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Runny nose and sneezing symptoms
Photo by Britanny Colette on Unsplash

Home-based, self-administered tests for influenza are comparable in accuracy to rapid diagnostic tests in clinical settings, according to a study reported in JMIR Public Health and Surveillance.

“Home tests are a valuable tool to support the management of influenza and other respiratory infections,” explained senior author Matthew J. Thompson, professor at the University of Washington School of Medicine in Seattle.

“The tests facilitate earlier diagnoses and reduce the time from the onset of symptoms to patients seeking appropriate care,” he said.

More than 600 residents in the Seattle area participated in the 2020 study conducted between February and the end of May. Participants received influenza testing kits in the mail. After swabbing their noses, they either recorded the results through an app, or returned the kits to the lab of Lea Starita, assistant professor of genome sciences at the UW School of Medicine and a study co-author.

The researchers found that self-test’s sensitivity and specificity test were comparable with those of influenza rapid diagnostic tests used in clinical settings. They noted that false-negative results were more common when the self-test was administered after 72 hours of the appearance of symptoms, but were not related to inadequate swab collection or severity of illness.

“This study underscores the imperative of expanding access to testing and lowering the costs,” said Barry Lutz, associate professor of bioengineering and another co-author of the paper.

Source: UW Medicine