Category: Diseases, Syndromes and Conditions

Categories : Diseases, Syndromes and Conditions Gastrointestinal ImmunologyTags :

Taurine Boosts Microbiotic Defences in the Gut

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A new study has discovered that taurine has a role in triggering the gut’s microbiota to identify and destroy invading bacteria, such as Klebsiella pneumoniae, a bacteria commonly found in the gut and responsible for a variety of infections.

It is already known that gut microbiota can protect against infection, but it is not well understood how they accomplish this. A better of understanding of how they confer protection will aid the development of replacements for current antibiotic drugs, which currently harm gut microbiota and whose effectiveness is waning.

Taurine is a complementary (non-essential amino acid, involved in helping break down fats and is present in bile acid. Most taurine is produced by the body but some is also required in the diet. Certain seafoods, seaweed, poultry and beef are good sources of taurine.

The scientists believed that the taurine helped prevent against bacterial colonisation by producing hydrogen sulphide, but during their research they also discovered that a single infection was sufficient to prepare the gut microbiota to resist a second infection. The liver and gallbladder which produce and store bile acids, can develop long-term protection against infection.

While investigating further, the researchers discovered a particular type of bacteria, Deltaproteobacteria, which protected the gut against colonisation by infectious bacteria and which was activated by taurine. Taurine fed to mice in drinking water helped to shield against infection by boosting the function of the protective bacteria, but those fed bismuth subsalicylate (a common over-the-counter diarrhoea treatment), the infection protection diminished, because bismuth suppresses hydrogen sulphide production in the gut.

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions T-cellsTags :

New Study Reveals T-Cell Role in Periodontitis and Bone Loss

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There are mechanisms involved in diseases of bone loss, such as periodontitis that are still not well understood, but an unexpected behaviour of a type of T-cell may shed new light on the matter.

Looking at periodontal disease in mice, scientists found that regulatory T (Treg) cells start behaving unexpectedly. They lose their ability to regulate bone loss and begin to promote inflammation instead.

“That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning,” said lead author Dr Carla Alvarez, a postdoctoral researcher at the Forsyth Institute.

In periodontal disease, bone loss occurs because the immune system responds disproportionately, destroying tissue through inflammation. The Treg cells normally suppress the immune system but lose the ability to do so during periodontal disease.

Understanding this falls into the field of osteoimmunology, which is about understanding the interaction of bone metabolism and the immune system. “This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease,” said Dr Alpdogan Kantarci, at Forsyth and co-author of the paper.

A potential treatment for periodontal disease would involve reactivating the Treg cell’s immunosuppression function, but this is a complex, nonlinear task complicated by the fact that periodontal disease is initiated by oral microbes.

“The relationship between immune response and bone is not so straightforward,” said Alvarez. “There are multiple components. You have to imagine a complex network of signaling and cells that participate.”
The researchers’ next step is to examine the process in humans.

Source:Medical Xpress

Journal information: Alvarez, C., Suliman, S., Almarhoumi, R. et al. Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis. Sci Rep 10, 19018 (2020). doi.org/10.1038/s41598-020-76038-w

Categories : Diseases, Syndromes and ConditionsTags :

A Growing Need to Expand Aneurysm Warnings for Fluoroquinolones

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New research suggests that the fluoroquinolone class of antibiotics may increase the risk of aortic aneurysm (AA).

In 2018 the US Food and Drug Administration added warnings for people at risk of aortic disease, based on data from its reporting system plus four epidemiological studies in other countries. According to a study by a team led by Melina Kibbe, MD at the University of North Carolina at Chapel Hill, cases of AA formation or dissection were 7.5 per 10 000 prescription fills for fluoroquinolones at 90 days compared with 4.6 per 10 000 fills for comparison antibiotics.

Fluoroquinolones include ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin. The FDA had already warned that fluoroquinolones could cause tendon damage and rupture, peripheral nerve damage, mental health disturbance, hypoglycaemic coma and that they are associated with Clostridium difficile infection.

Using a database of health insurance claims for almost 28 million individuals aged 18 to 64,  the researchers searched for associations between fluoroquinolone prescriptions and aneurysms, compared to other antibiotic types.

Fluoroquinolones were associated with excess abdominal AAs (HR 1.31, 95% CI 1.25-1.37) and iliac artery aneurysms (HR 1.60, 95% CI 1.33-1.91), though associations with aortic dissection  or thoracic aortic aneurysm did not reach significance.

“As such, regional differences in the etiology, incidence, and clinical management of aortic disease in the thoracic vs abdominal aorta should be carefully considered,” wrote the researchers.

Adults over 35 also had a greater risk of AA with fluoroquinolones compared to younger cohorts. Limitations of the study included not controlling for the possibility of pre-existing aneurysms, or for the presence of risk factors such as smoking.

However, the researchers believe the results are significant enough to warrant attention. “Almost regardless, this large cohort study of a U.S. population suggests it is time once again to rethink the use of this class of antibiotics for patients with or without aortic disease,” they wrote.

Source: MedPage Today

Journal information: Newton E, Akerman A, Strassle P, Kibbe M. Association of Fluoroquinolone Use With Short-term Risk of Development of Aortic Aneurysm. JAMA Surg. 2021. doi:10.1001/jamasurg.2020.6165

Categories : COVID Diseases, Syndromes and ConditionsTags :

A Four Century Old Manual for Social Distancing Rules

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A feature article from the BBC details how one doctor in the era of the Plague created an eerily familiar set of social distancing guidelines that matches a lot of our non-pharmaceutical COVID controls.

Staying at home and only sending out one person to do the shopping, keeping six feet apart and disinfecting goods – all of these feature in a manual created over four centuries ago to help protect Alghero, a small Italian town against the plague. The methods by a doctor named  Quinto Tiberio Angelerio, published in a 57-page booklet on his methods, titled Ectypa Pestilentis Status Algheriae Sardiniae.

Unlike most plague outbreaks, it failed to spread to neighbouring areas and died out within eight months – though not without claiming about 60% of the town’s initial population of 6000. Angelerio’s rules are thought to be at least partly responsible.

Ravaging Europe as well as Asia and North Africa, the plague left an unimaginable mark on Western society; tunnelling projects in London regularly run into mass graves of plague victims. Italian poet Francesco Petrarca wrote that future generations would likely not be able to grasp the scale of the calamity, and he is probably right in that regard. The plague continued to reappear, and devastated regions when it did – The Great Plague of London saw 24% of its populace dying over 1665 to 1666.

Although the germ theory of disease was then still centuries in the future, and bathing in urine was thought to be effective treatment, physicians in Europe believed in the contagion theory, thinking that diseases were spread through “miasmas” or “bad air”. This enabled them to come up with the idea of quarantines, from the Italian for “forty days” which was the standard isolation period.

Facing huge obstacles from a recalcitrant citizenry, Angelerio nevertheless persevered and soon a lockdown was enacted. This was not unique, as whole cities would be quarantined. Other rules that were enforced included a social distancing of six feet (as measured by a pole to be carried around by anyone outside), advising people to be careful shaking hands during mass, as well as railing preventing customers coming into contact with shopkeepers. He also used superstition to keep people in line, as European people of the time believed the plague to be divine punishment – although rule breakers were common, as they are now with COVID. He also advised cleaning and disinfecting houses, and household goods (or burning if replaceable), in addition to the contemporary practice of disinfecting newly arrived cargo. This was accomplished by fire or exposure to the wind, among others. However, the common practice of killing cats in response to plague was likely counterproductive, as rats hosted plague-carrying fleas.

Nevertheless, Angelero’s work was ahead of its time, and helped lay the foundations of modern disease control.

.Source: BBC Future

Categories : Diseases, Syndromes and Conditions T-cellsTags :

Ginger Promising in Countering Autoimmune Diseases

On By ModernMedia

A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385

Categories : Diseases, Syndromes and ConditionsTags :

Africa has 94% of All Malaria Cases

On By ModernMedia

On November 30, the World Health Organization released this year’s World Malaria Report. Providing an up-to-date overview of the current global malaria disease burden, it also tracks investment, innovation and research against malaria.

Globally, malaria deaths have steadily declined over the years 2000–2019, from 736 000 in 2000 to 409 000 in 2019. The percentage of total malaria deaths that were children under 5 years of age was 84% in 2000 and 67% in 2019.

Six African countries accounted for 51% of global cases, with Nigeria (27%) contributing more than the other five countries combined. Partly this is due to its large relative population size compared to the rest of Africa, having over 200 million citizens.

Elsewhere, great progress is being made, The largest reduction in cases in the WHO South-East Asia Region was seen by India, from about 20 million cases in 2000 down to approximately 5.6 million in 2019.  Sri Lanka has been certified malaria free since 2015.

Source: Outbreak News Today

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

A Common Antibiotic Shows Promise for Zika Protection

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A huge search through known drug compounds showed that a common antibiotic has been shown to be effective against Zika in vitro. Zika, which causes foetal microcephaly, preferentially attacks brain stem cells. 

In order to find a compound that confers Zika protection, the researchers searched for drugs that prevent virus reproduction by blocking the activity of a protein called NS2B-NS3 Zika virus protease. This protease acts to assemble the components of new Zika viruses from protein produced by the virus’ RNA injection into a cell.

“Proteases act like scissors. Blocking protease activity is an effective strategy for counteracting many viruses,” said study leader Rachel Abrams, PhD. “We wanted to look as far and wide as possible for drugs that could prevent the protease from snipping the Zika virus polyprotein into its active pieces.”

To find out which compounds blocked the protease, hundreds of assays were conducted against three different libraries.

An initial screen of 2 000 compounds showed that common tetracycline-based antibiotic drugs, such as methacycline were able to block the protease.

A larger screen of 10 000 compounds found potential candidates in an investigational anti-inflammatory medicine, MK-591, and a failed anti-Alzheimer’s disease drug, JNJ-404.  

Finally, 130 000 compounds were screened virtually, with machine learning being used to investigate what made a good candidate.

The candidate compounds were shown to reduce Zika infections of brain stem cells in vitro.

As methacycline is known to cross the placental barrier, this emerged as a promising candidate to treat pregnant women infected with the virus. However in mouse models, treatment with methacycline only partially protected the brains of newborn mice.

“These results suggest that tetracycline-based antibiotics may at least be effective at preventing the neurological problems associated with Zika virus infections,” said Dr Abrams. “Given that they are widely used, we hope that we can rapidly test their potential in clinical trials.”

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions Gastrointestinal PulmonologyTags :

Gut Microbiome is Linked to Pulmonary Disease

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A link has been shown between the gut microbiome and chronic obstructive pulmonary disease (COPD), a lung disease with an often poor prognosis.

Senior author Prof Phil Hansbro, Director of the Centenary University of Technology Sydney Centre for Inflammation, said, “It’s already known that the lung microbiome is a contributing factor in COPD. We wanted to see if the gut environment was also somehow involved–to determine whether the gut could act as a reliable indicator of COPD or if it was connected in some way to the development of the disease.”

Stool samples of COPD patients showed elevated levels of the bacteria Streptococcus and Lachnospiraceae. Additionally a unique metabolite signature was identified in individuals with COPD, created by the chemical by-products of the metabolic process.

First author Dr Kate Bowerman from the University of Queensland said, “Our research indicates that the gut of COPD patients is notably different from healthy individuals. This suggests that stool sampling and analysis could be used to non-invasively diagnose and monitor for COPD,” she said.
“The ‘gut-lung axis’ describes the common immune system of the lung and gastrointestinal tract. This means that activity in the gut can impact activity in the lung. Our COPD findings suggest that the gut microbiome should now also be considered when looking for new therapeutic targets to help treat lung disease,” Prof Hansbro said.

Source: Medical Xpress

Categories : Diseases, Syndromes and ConditionsTags :

Re-emergence of Scarlet fever

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Scarlet fever has made a re-emergence in recent years due to acquiring a toxin that allows them to better colonise their hosts:

“These supercharged bacterial clones have been causing our modern scarlet fever outbreaks.

“The research team then removed the toxin genes from the clones causing scarlet fever, and these modified ‘knock-out’ clones were found to be less able to colonize in an animal model of infection.”

For the time being, scarlet fever outbreaks have been dampened, largely due to public health policy measures introduced to control COVID-19.

“This year COVID-19 social distancing has kept scarlet fever outbreaks in check for now,” Professor Walker said.

“And the disease’s main target—children—have been at school less and also spending far less time in other large groups.

“But when social distancing eventually is relaxed, scarlet fever is likely to come back.

“We need to continue this research to improve diagnosis and to better manage these epidemics.

“Just like COVID-19, ultimately a vaccine will be critical for eradicating scarlet fever—one of history’s most pervasive and deadly childhood diseases.”

Source: Medical Express

Categories : Diseases, Syndromes and ConditionsTags :

DRC is Ebola-free Once Again After 11th Outbreak Ends

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The 11th outbreak of Ebola in the Democratic Republic of Congo has officially come to an end, and the country has been declared Ebola-free once again.

The outbreak which had spread along the many water bodies of Équateur province, had started just before the end of another deadly outbreak elsewhere in the country which had claimed 2280 lives. This marks the first time in nearly three years that the DRC has been Ebola-free. Logistical challenges in the geographically remote Équateur province hampered efforts to control the latest outbreak.

Experts believe that international involvement was key to bringing the situation under control. The WHO also noted that “women leaders [who] were often at the forefront of the response, empowering other women with information”.

The Secretary-General of DRC’s Red Cross, Jacques Katshishi, said the country needs continued support from the international community. He said, “Bringing Ebola to zero is a huge achievement, but now we are faced with our next challenge: keeping it there. Our teams within the DRC Red Cross are facing Covid-19 within a complex humanitarian and security environment. This is not a moment to be complacent: the world cannot afford a resurgence of Ebola in DR Congo. The time to prepare is now.”

Source: The Guardian