Diseases, Syndromes and Conditions Archives - Page 23 of 37

New Drugs for Cryptococcal Meningitis Sorely Needed in SA

On April 29, 2022 By ModernMedia

Brain scan image — Image source: Mart Production on Pexels

Despite the greater safety and efficacy of a new short course treatment for HIV-related cryptococcal meningitis (CM), access to the treatment in South Africa will be a challenge, according to a pair of articles by Spotlight.

Following positive results of a trial, the World Health Organization last week announced new recommendations for the treatment of CM, with a single high dose of L-AmB followed by two weeks of flucytosine and fluconazole.

Using L-AmB (AmBisome) and flucytosine for the treatment of CM will be a welcome change for South Africa, which has the world’s highest burden of the condition. This shorter course with fewer side effects than the current treatment involving amphotericin-B could save lives as well as clinical resources in the public sector, but at present the treatment is hamstrung by pricing and availability uncertainty, with a course of L-AmB currently only available at a steep cost.

“Amphotericin B [deoxycholate] is a drug that doctors and nurses used to call ampho-terrible,” Amir Shroufi, Médecins Sans Frontières (MSF) Southern Africa board member told Spotlight.

He explained that “it’s a really nasty drug, doctors and nurses don’t like it because it can cause severe anaemia. It’s toxic to the kidneys, so it can cause kidney damage and even kidney failure… and the infusion line used for the drug can often become infected and it can cause inflammation of the veins where it’s going into the body.”

L-AmB is a “much better drug”, he said, with great benefits of administering it for one day as opposed to a week or two. The seriousness of CM meant hospitalisation will still be required, pointed out Dr Jacqui Miot, division director of the Wits Health Economics and Epidemiology Research office, but means that patients won’t be tethered to a drip and may be able to go home sooner.

Under the treatment regimen, a patient receives a single high dose of L-AmB on the first day of treatment, followed by a 14-day course of flucytosine and fluconazole pills.

For a 60kg patient at the recommended dosage, twelve 50mg vials of L-AmB are needed, which at Gilead’s promised access price would be R2 880. Key Oncologics’ currently charges R34 560 for 12 vials.

Even given the availability of L-AmB, Shrouifi warns that “whatever you’re doing, you have to have flucytosine. That’s your baseline, even if you’re giving liposomal amphotericin B, you have to have the flucytosine”.

Flucytosine is an old, off-patent medicine developed in the 1950s. Despite its age and its demonstrated efficacy in the landmark ACTA trial four years ago, flucytosine was only recently authorised for use in South Africa and is only slowly being rolled out.

Amir Shroufi warned that access to the life-saving medicine remains a major issue. “Doctors are not being given the tools they need to treat [CM],” he said. “The first tool they have to have is flucytosine and they still don’t have flucytosine. So, that’s the thing that needs to happen urgently, you know, tomorrow! Everyone with cryptococcal meningitis must get access to flucytosine.”

Like L-AmB, Mylan’s 250mg and 500mg flucytosine tablets were only registered recently, in December 2021. The Department of Health’s target price for a pack of 100 tablets is R1 500. Fortunately, it appears that the Clinton Health Access Initiative (CHAI) will be able to secure packs of 100 at R1 470 each for use in South Africa’s flucytosine access programme.

The next steps for rollout of flucytosine will be inclusion on the national essential medicines list and in CM treatment guidelines before tenders can be put out.

Source 1: Spotlight

Source 2: Spotlight

Categories : Diseases, Syndromes and ConditionsTags : 28/4/22 atopic dermatitis obesity

Obesity in Mice Causes AD Treatments to Backfire

On April 28, 2022 By ModernMedia

In a new study published in Nature, researchers found that treatments that were effective for atopic dermatitis (AD) in lean mice actually worsened the condition in obese mice.

Tracking the development of AD in obese and lean mice, the researchers found that obese mice developed more inflammation and more severe AD. This increased inflammation was present even after obese mice lost weight. There were similar results in an experimental model of asthma, with obese mice developing more inflammation.

The researchers next looked in detail at immune cells called T cells in lean and obese mice with AD. Lean mice had more T_H2 cells, a class of T cells known to play a role in the development of AD. Obese mice had more of a class of T cells called T_H17. These cells trigger a different type of inflammation.

Similar trends were seen in blood samples taken from people. Markers of T_H17 cell activity increased along with body mass index (BMI) in a database of serum collected from people with AD. Conversely, in samples from patients with severe asthma, T_H2 cell activity decreased as BMI increased.

Drugs that block T_H2 cell activity are used in the treatment of severe AD as well as asthma and other inflammatory conditions. The researchers tested antibodies to block T_H2 cell activity in lean and obese mice with severe AD. While the antibodies reduced skin inflammation in lean mice as expected, they made the condition worse in obese mice. Analysis of immune cells suggested that blocking T_H2 cell activity in the obese mice worsened other forms of inflammation.

Obese mice were also found to have less activity of peroxisome proliferator-activated receptor-γ (PPARɣ) in their T_H2 cells. When lean mice were engineered to lack PPARɣ, their inflammatory response resembled that of obese mice.

Drugs that increase PPARɣ activity increase insulin sensitivity and are approved for the treatment of type 2 diabetes. The researchers found that giving one of these drugs to obese mice changed their inflammatory response to resemble that of lean mice. It also restored their sensitivity to the antibodies that block T_H2 cell activity.

“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” said Dr Ronald Evans from the Salk Institute, who helped lead the work.

Source: National Institutes of Health

Categories : Diseases, Syndromes and ConditionsTags : 28/4/22 autoimmune disease covid gene sequencing lupus

Gene Mutation in Young Girl May Finally Yield Lupus Treatment

On April 28, 2022 By ModernMedia

Facial rash characteristic of lupus. Credit: Statpearls

A study published in Nature has identified mutations in an X chromosome gene that senses viral RNA, as a cause of the autoimmune disease lupus, a finding which may explain why the disease is far more common in females, and which might lead to new treatments.

In the study, whole genome sequencing was performed on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at age 7. Such a severe case with early onset of symptoms is rare and suggests a single genetic cause.

In their genetic analysis, the researchers discovered a single point mutation in the TLR7 gene. Referrals from other institutions, they were able to identify other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team inserted the gene into mice, which went on to develop the disease and showed similar symptoms. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.

Carola Vinuesa, senior author and principal investigator said: “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.

“This is the first time a TLR7 mutation has been shown to cause lupus, providing clear evidence of one way this disease can arise.”

Professor Nan Shen, co-director of CACPI adds: “While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

The mutation identified by the researchers makes TLR7 protein bind more readily guanosine and become more active. This in turn increases the sensitivity of the immune cell, making it more likely to incorrectly target healthy tissue.

Interestingly, other studies have shown mutations that cause TLR7 to become less active are associated with some cases of severe COVID infection, highlighting the delicate balance of a healthy immune system.

The findings could also explain why lupus is 10 times more common in females than in males. Because TLR7 is located on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

Study co-author Dr Carmen de Lucas Collantes, said: “Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery.”

Gabriela, now a teenager, remains in touch with the research team. She said, “I hope this finding will give hope to people with lupus and make them feel they are not alone in fighting this battle. Hopefully the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

The researchers are now investigating the repurposing of existing treatments which target the TLR7 gene. By targeting this gene, they hope to be able to also help patients with related conditions.

Carola added: “There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”

Source: Francis Crick Institute

Categories : Diseases, Syndromes and ConditionsTags : 22/4/22 retinal vein occlusion

Lasting Gains Achieved with Retinal Vein Occlusion Treatment

On April 22, 2022 By ModernMedia

Eye — Source: Daniil Kuzelev on Unsplash

A treatment for retinal vein occlusion yields long-lasting vision gains, with visual acuity remaining significantly above baseline at five years – though many patients still require ongoing treatment, according to a report published in the American Journal of Ophthalmology. The report marked the five-year outcomes of the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2).

Retinal vein occlusion (RVO) is caused by a blockage of the veins carrying blood away from the retina, causing macular oedema where fluid becomes trapped within and under the retina, leading to rapid and severe loss of visual acuity. Central retinal vein occlusion (CRVO) is an occlusion of the main retinal vein posterior to the lamina cribrosa of the optic nerve. CRVO has a better prognosis in younger patients. One-third of older patients improve without treatment, one-third stay the same, and one-third get worse.

The leading treatment for RVO is injections of anti-vascular endothelial growth factor (VEGF) drugs, helping to control blood vessel leakage and swelling.

“While anti-VEGF therapy is associated with significant improvement in both retinal swelling and visual acuity in patients with central or hemi-retinal vein occlusion, our findings show that most of the patients followed still required treatment to control the macular oedema for at least five years,” said the chair of the study, Ingrid U. Scott, MD, MPH, at the Penn State College of Medicine. “This demonstrates the importance of continued monitoring of these patients.”

In 2017, SCORE2 clinical trial investigators reported that two types of anti-VEGF treatment were equally effective at improving visual acuity in people with macular oedema due to CRVO or hemi-retinal vein occlusion (HRVO). CRVO affects the entire retina, while HRVO generally affects about half of the retina. Half of the study participants had received bevacizumab while the other half received aflibercept. Participants received monthly injections over six months. At the six-month mark, the vision of participants in both groups had, on average, improved over three lines on an eye chart.

The researchers followed SCORE2 participants for five years, collecting information about their visual acuity, treatments, and whether their macular oedema had resolved. After the initial 12-month study period, participants were treated at their physician’s discretion, most reducing the frequency of anti-VEGF injections and some switching their patients to the other anti-VEGF drug. At five years, many participants had lost some visual acuity compared to the 12-month mark, but they retained on average three lines of improvement compared to baseline.

“It was surprising to us that despite many participants still needing treatment after five years, their visual acuity outcome remained very good,” said Dr Michael Ip, MD, co-chair of the study from the University of California Los Angeles. “In comparison to this treatment for wet age-related macular degeneration, where initial vision improvements fade over time, these results are quite favourable.”

“This five-year study tells us a lot about what’s happening with retinal vein occlusion patients in the real world,” said Dr Scott. “Prior to this study, retinal vein occlusion was widely considered an acute illness. This study shows that RVO is a chronic disease. It also underscores the importance of disease monitoring and individualised treatment to achieve the best possible vision.”

Source: NIH/National Eye Institute

Categories : COVID Diseases, Syndromes and ConditionsTags : 20/4/22 aerosols covid transmission public health

Vigorous Exercise and Talking Produce Similar Levels of Aerosols

On April 20, 2022 By ModernMedia

Old man jogging — Photo by Barbra Olsen on Pexels

Vigorous exercise produces a similar level of aerosol particles as speaking, but high-intensity exercise produces more, according to new research published in Communications Medicine. This is the first study to measure exhaled aerosols generated during exercise, to help inform the risk of airborne viral transmission of SARS-CoV-2 for gyms and indoor physical training.

Inhalation of infectious aerosol is considered to be the main route of SARS-CoV-2 transmission. In this study, researchers performed a series of experiments to measure the size and concentration of exhaled particles (up to 20µm diameter) which are generated in our respiratory tracts and breathed out, during vigorous and high-intensity exercise.

Using a cardiopulmonary exercise test, 25 healthy participants (13 male, 12 female) with a range of athletic abilities were recruited to undertake four different activities (breathing at rest, speaking at normal conversational volume, vigorous exercise and high-intensity exercise) on a cycle ergometer. Airflow and particles emitted were measured by particle counter. Experiments were carried out in an orthopaedic operating theatre — an environment with ‘zero aerosol background’, letting the researchers to unambiguously identify the aerosols generated by the participants.

The results showed that the size of airborne particles emitted during vigorous exercise was consistent with those emitted while breathing at rest. However, the rate of aerosol mass exhaled during vigorous exercise was found to be similar to speaking at a conversational volume.

Jonathan Reid, scientific lead on the paper, said: “COVID has profoundly impacted sports and exercise, and this study provides a comprehensive analysis of the mass emission rates of aerosol that can potentially carry infectious virus produced from an individual during exercise. Our research has shown that the likely amount of virus that someone can exhale in small aerosol particles when exercising is comparable to when someone speaks at a conversational volume. The most effective way to reduce risk is to ensure spaces are appropriately ventilated to reduce the risk of airborne transmission.”

Source: University of Bristol

Categories : Diseases, Syndromes and ConditionsTags : 19/4/22 carbon dioxide sleep apnoea

An Oral Drug for Sleep Apnoea

On April 19, 2022 By ModernMedia

Sleeping man — Photo by Mert Kahveci on Unsplash

A new study published in the American Journal of Respiratory and Critical Care Medicine has tested a sleep apnoea treatment using a drug that inhibits carbonic anhydrase – an enzyme that balances carbonic acid and carbon dioxide in the body. The treatment reduced breathing pauses by more than 20 per hour for patients given the drug.

Several drugs with carbonic anhydrase (CA) inhibitory properties are already available on the market, and used for treatment of glaucoma, epilepsy and other disorders.

Previous research has not systematically tested whether CA inhibitors also might be used to treat obstructive sleep apnoea. A total of 59 patients with moderate or severe sleep apnoea completed the four-week trial, and were randomised to two groups receiving either 400 or 200 mg of the CA inhibitor, and a control group that received placebo.

The results show that, overall, the treatment reduced the number of breathing pauses and promoted oxygenation during the night. A few patients experienced side effects, such as headache and breathlessness, which were more common in those receiving the highest dose.

The study results together with established safety data of the drug sulthiame provide support for continued research on CA inhibition as a new potential treatment for obstructive sleep apnoea.

“Among the patients who received the higher dosage of the drug, the number of breathing pauses decreased by approximately 20 per hour. For just over a third of patients in the study, only half of their breathing pauses were left, and in one in five the number fell by at least 60 percent,” said first authpr Professor Jan Hedner.

The fact that several approved drugs in the CA inhibitor category are available on the market makes fast-tracking development of an approved drug for sleep apnoea practicable. The drug used in this clinical trial was sulthiame, which is sometimes used to treat epilepsy in children.

Current treatment for a patient with sleep apnoea is either an oral appliance therapy or a CPAP (Continuous Positive Airway Pressure) mask. Both help to maintain airway patency during sleep.

“These therapy options take time to get used to and, since they frequently are perceived as intrusive or bulky. Insufficient user time is therefore common. If we develop an effective drug, it will therefore make life easier for many patients and, in the long run, potentially also save more lives,” said senior author Ludger Grote.

Source: University of Gothenburg

Categories : Diseases, Syndromes and ConditionsTags : 13/4/22 dengue virus Zika virus

Zika Can Mutate to Increase its Infectivity

On April 13, 2022 By ModernMedia

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

Researchers have found that Zika virus has the potential to mutate and increase its infectivity, potentially breaking through pre-existing immunity.

“The world should monitor the emergence of this Zika virus variant,” said LJI Professor Sujan Shresta, PhD, who co-led the La Jolla Institute for Immunology (LJI) study which is published in Cell Reports.

A mosquito-borne virus, symptoms of Zika infection are usually mild in adults. However, in a developing foetus, infection can cause birth defects such as microcephaly.

Zika virus and dengue virus occur together in a number of countries. Both viruses are a mosquito-borne flavivirus, sharing biological similarity: similar enough that prior dengue exposure can offer immune protection against Zika.

“In areas where Zika is prevalent, a vast majority of people have already been exposed to dengue virus and have both T cells and antibodies that cross-react,” said Prof Shresta.

Unfortunately, both viruses share the trait of rapid mutation. “Dengue and Zika are RNA viruses, which means they can change their genome,” she further explained. “When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.”

To study Zika’s fast-paced evolution, the researchers simulated infection cycles that repeatedly switched back and forth between mosquito cells and mice. This painted a picture of how Zika virus naturally evolves as it encounters more hosts.

The LJI team found that an easy change of a single amino acid allows the virus to make more copies of itself — and help infections take hold more easily. This mutation (called NS2B I39V/I39T mutation) boosts viral replication in both mice and mosquitoes – and also in human cells.

“This single mutation is sufficient to enhance Zika virus virulence,” commented study first author Jose Angel Regla-Nava, PhD. “A high replication rate in either a mosquito or human host could increase viral transmission or pathogenicity – and cause a new outbreak.”

Prof Shresta added, “The Zika variant that we identified had evolved to the point where the cross-protective immunity afforded by prior dengue infection was no longer effective in mice. Unfortunately for us, if this variant becomes prevalent, we may have the same issues in real life.”

To help prepare for this variant, Dr Shresta’s laboratory is already looking at ways to tailor Zika vaccines and treatments that counteract this dangerous mutation.

“We want to understand at what point in the viral life cycle this mutation makes a difference,” said Dr Shresta.

Source: La Jolla Institute for Immunology

Categories : Diseases, Syndromes and ConditionsTags : 12/4/22 ageing exercise myotonic dystrophy

Cycling Can Improve Mobility in Myotonic Dystrophy

On April 12, 2022 By ModernMedia

Regular cycling can greatly improve mobility in patients with myotonic dystrophy (MD), an inherited genetic disease that causes muscle degeneration, according to research published in The Journal of Clinical Investigation. Professor Mark Tarnopolsky, senior author of the study, said that cycling for 35 minutes three times a week for 12 weeks led to a 32% increase in overall fitness in people with MD.

The participants also saw a 1.6-kilogram increase in their muscle mass and a two percent reduction of body fat. They were also able to walk an extra 47 metres in six minutes, when tested by researchers at the end of the 12-week trial.

The research team recruited 11 patients with MD to examine how effective cycling was in restoring and maintaining their physical health. Researchers also studied the underlying molecular mechanisms through which exercise strengthens the skeletal muscles, which can be severely weakened by MD.

“Exercise really is medicine – we just need to get the message out,” said Prof Tarnopolsky. “Myotonic dystrophy is a progressive condition that will impair your mobility and can put you in a wheelchair. There is no cure for it and only regular exercise helps you achieve better function.”

Prof Tarnopolsky said that some patients with MD are even advised by their doctors not to exercise, for fear of making their condition worse, but that is now proven false.

Prior studies with mouse models showed a range of similar physiological benefits from regular exercise, the researchers said. MD is the most commonly diagnosed type of muscular dystrophy in adults, and the second most prevalent of all muscular dystrophies, noted Prof Tarnopolsky.

MD’s main symptoms include severe skeletal muscle atrophy, general muscle weakness, reduced lung capacity and impaired heart function. Other symptoms may include cataracts, endocrine disorders including diabetes and gastro-intestinal disorders.

“MD itself is really a form of accelerated ageing,” said Prof Tarnopolsky.

Source: McMaster University

Categories : Diseases, Syndromes and ConditionsTags : 12/4/22 kisspeptin nonalcoholic fatty liver disease

Kisspeptin Might Be a New Treatment for Fatty Liver Disease

On April 12, 2022 By ModernMedia

The Hershey’s Kisses after which the hormone is named. Photo by Aaron Burden on Unsplash

Kisspeptin, a hormone named for the iconic Hershey’s ‘Kisses’ might be developed as a treatment for non-alcoholic fatty liver disease (NAFLD), according to a new study appearing in the Journal of Clinical Investigation. The hormone also serves to regulate puberty and fertility in humans.

Globally, non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease that affects children and adults and is linked to the rise in obesity and Type 2 diabetes. Largely without symptoms in the early stages, NAFLD begins with the accumulation of fat in the liver, leading to ‘fatty liver’. With disease progression, inflammation sets in, resulting in non-alcoholic steatohepatitis (NASH). This is followed by fibrosis and cirrhosis, and a subset of NASH patients with cirrhosis will also develop liver cancer. There are presently no approved therapeutics to treat NASH.

Study lead investigator, Moshmi Bhattacharya, an associate professor at Rutgers University, has spent over 15 years studying kisspeptin in health and disease. Kisspeptin, encoded by the KISS1 gene, was discovered in a city called Hershey, and named for the iconic Hershey chocolate ‘kisses’. As well as playing key roles in pubertal development and maintaining reproductive function, kisspeptin has also been linked to appetite and, coincidentally given its name, sexual attraction.

In the study, mice fed on a high-fat, high-sugar ‘Western’ diet to induce obesity and NAFLD, were protected from the development of fatty liver, NASH and fibrosis when given kisspeptin. Kisspeptin works by binding its receptor, a protein called KISS1R, which, when deleted from liver cells, prevents kisspeptin from functioning, leading mice on Western diets to develop fatty liver. These experiments uncover a powerful relationship between kisspeptin and the reduction of liver fat and fibrosis.
“This work shows the kisspeptin receptor signaling pathway has a potential therapeutic role in NAFLD,” said co-author, Professor Vinod K Rustgi. “It does this by protecting against the development of fat in the liver and reducing inflammation and fibrosis. As such, it has the potential to favorably impact the health and lives of millions of patients around the globe.”

Source: Rutgers University

Categories : Diseases, Syndromes and ConditionsTags : 11/4/22 erectile dysfunction

Category: Diseases, Syndromes and Conditions