• Psychedelic Medicine

INFECTION | +50 articles

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Ibogaine in the treatment of Hepatitis C

by Bruce Blaus | Creative Commons

The hepatitis C virus (HCV), which is common among drug users, was first described as non-hepatitis A and non-hepatitis B virus in 1973, until finally identified in 1989 by genetic engineering of the hereditary material. In Central Europe, most people are now vaccinated against the hepatitis A virus and the hepatitis B virus, but there is currently no available immunisation against HCV.

Symptoms of hepatitis C include an inflammed liver, pain in the liver and increased production of liver enzymes. There are different treatment options for HCV. The standard treatment option combines interferon with ribavirin. However, this treatment option has no guaranteed success. In addition, the long treatment period of 24 to 72 weeks is unpleasant due to the numerous side effects.

In 1990, the antiviral effect of Ibogaine was reported for the first time, and since then there have been reports of cures and documented reductions in HCV concentration after Ibogaine treatment. In 2005, Howard Lotsof filed a patent application for the use of Ibogaine and other Iboga alkaloids to treat hepatitis C and related symptoms.

The results of Ibogaine-assisted HCV therapy are promising. Repeated administration of small doses of Ibogaine HCL lowers the viral load slightly but continuously. A single staggered treatment of a high dose of Ibogaine HCl, significantly reduces the viral load of the hepatitis C genotype 3 and is favourably comparable with the interferon-ribavirin therapy.

 
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Anti-HIV-1 activity of the iboga alkaloid congener 18-MC*

Silva, Cirne-Santos, Frugulhetti, Galvo-Castro, Saraiva, Kuehnem, Bou-Habib

Infection by the HIV-1 virus is a global health problem affecting more than 42 million people worldwide. HIV-1 persistently replicates in the lymphoid tissues, leading to a progressive deterioration of the immune system. An effective vaccine against HIV-1 infection has not been developed yet.

Two decades after the discovery of the first cases of AIDS, the clinical use of the abundant anti-retroviral repertoire has decreased the morbidity and mortality of HIV-1 infection. However, this treatment does not completely eradicate HIV-1 from the infected tissues, and its long-term use is restricted by metabolic disorders and toxicities, emergence of drug-resistant viruses and complex administration. Thus, the search for other anti-retroviral compounds is critical, and numerous new anti-HIV-1 agents that target different phases of viral replication cycle are under development or in clinical trials.

The Iboga-type indole alkaloid coronaridine is found in many species of the plant kingdom and has been studied for its potential anti-addictive properties. Because of the side effects such as tremor, cerebellar neurotoxicity and bradycardia associated with COR, chemical structure modifications were made to reduce its side effects, which was attained with a meth-oxylation at carbon-18, resulting in the Iboga analogue 18-methoxycoronaridine (18-MC).

Since many alkaloids have been described as capable of inhibiting HIV-1 infection in vitro, we investigated whether 18-MC is also endowed with anti-retroviral properties. We found that 18-MC inhibits HIV-1 replication in human peripheral blood mononuclear cells and in monocyte-derived macrophages, and that this activity is at least partially mediated by reducing the activity of the HIV-1 enzyme reverse transcriptase.

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Coronaridine

Results and discussion

In this paper, we report that the indole alkaloid congener 18-MC inhibits HIV-1 infection. The infection assays were performed with primary cells to avoid the genotypic and phenotypic changes that might occur during viral passages in tumor cell lines. We also used primary isolates, which are closer to the viral population present in HIV-1-infected patients.

In preliminary experiments, we found that naturally occurring COR decreased the infection in a dose dependent manner. Since 18-MC is an improved molecule of the natural compound coronaridine, presenting little to none of the adverse effects associated with the original molecule, we continued our anti-retroviral studies using the new alkaloid congener 18-MC.

Our present results warrant further investigation on the mechanisms by which 18-MC decreases HIV-1 replication in vitro. Considering that 18-MC demonstrates a vigorous leishmanicidal activity in vitro, its potential therapeutic properties may be uniquely useful for the treatment of HIV-1-infected individuals as well as patients co-infected with Leishmania and HIV-1.

*From the article here :
 
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Emory University School of Medicine

In animal models, a 'shocking' step toward a potential HIV cure

by Emory University | Medical Xpress | 22 Jan 2020

It's a leading research strategy for eliminating HIV from the body: "shock and kill." The idea is to activate the dormant virus from within the immune cells where it hides, then eliminate it. One obstacle has been finding a safe way to wake up the virus.

In two complementary Nature papers, researchers now report that they have come closer to that goal. The papers are from researchers at the Yerkes National Primate Research Center of Emory University and the University of North Carolina at Chapel Hill, funded by the National Institutes of Health.

The papers rely on studies involving two animal models of HIV infection. Each study took a different approach. But both yielded promising results, disrupting viral latency at levels not seen before.

That means that the virus came out of its hiding places, even in the presence of antiretroviral drugs that had stopped it from replicating for months.

The findings do not represent a cure and follow-up studies in animals, as well as clinical studies in humans, are needed and planned. But the results represent an advance because they could potentially be combined with other approaches directed against the virus, the scientists say.

"If our goal is to cure HIV/AIDS, then we have to disrupt viral latency," says Guido Silvestri, MD, co-senior author of one of the Nature papers. "What we're doing now is a new combination approach that provides unprecedented levels of virus reactivation."

Silvestri is interim chair of pathology and laboratory medicine at Emory University School of Medicine, chief of microbiology and immunology at Yerkes National Primate Research Center, and a Georgia Eminent Research Scholar.

Past results of latency reversal experiments were not as sustained and extensive, says co-senior author J. Victor Garcia, Ph.D., director of the International Center for the Advancement of Translational Science and professor at the University of North Carolina School of Medicine.

"Previously, no one had successfully demonstrated systemic HIV induction in humans or an animal model with human cells, and then replicated this success in a completely different species infected with a different virus," Garcia says.

Ann Chahroudi, MD, Ph.D., co-senior author on both papers, says the studies described in the two papers take different approaches. She is associate professor of pediatrics and director of the Center for Childhood Infections & Vaccines at Emory and Children's Healthcare of Atlanta.

Both approaches were tested at Yerkes in monkeys infected with SIV, a close relative of HIV, and treated with antiretroviral drugs. At UNC, tests were also conducted in mice transplanted with human immune cells.

One paper describes a drug called AZD5582, which activates an intracellular pathway that leads to HIV and SIV reactivation. AZD5582 appears to be safe and relatively non-toxic in non-human primates. In 12 monkeys treated with the drug, just one experienced a temporary fever and loss of appetite. With the aim of beginning clinical trials, researchers at UNC and Qura Therapeutics—a partnership between UNC and ViiV Healthcare—are investigating compounds related to AZD5582.

"AZD5582 was remarkable in its ability to reactivate latent SIV from resting CD4+ T cells, and to induce continued virus production in the blood when monkeys were still receiving daily antiretroviral therapy," says Chahroudi.

In the study described in the second paper, researchers stimulated the cells that are the main viral hosts (CD4+ T cells) while also depleting another kind of immune cell (CD8+ T cells), which normally keeps the virus in check.

The combination of immune interventions was especially potent; both the stimulation and depletion components were necessary to see SIV re-emerge,” Silvestri says. His lab had previously observed a similar but smaller effect with CD8 depletion alone. “That means that CD8 T cells must have a role in keeping the virus inactive, which needs to be understood better,” he says.

"The old paradigm is that you need CD8 cells to clear other infected cells," Silvestri says. "We're showing that CD8 cells are also involved in repressing latency reversal."

The main obstacle to a cure for HIV infection is the reservoir: immune cells that harbor the inactive virus when someone is being treated with antiretroviral drugs. Neither intervention—drug or immune stimulation/depletions—reduced the size of the reservoir, because once the animals were taken off antiretroviral drugs, viral levels did rebound. The scientists think the initial viral reactivation needs to be combined with other modes of treatment, such as antibodies directed against the virus itself.

"The exciting thing about these papers being published together are the concordance of the results in two animal models with both approaches, and the opening up of new avenues for research towards the goal of an HIV cure," said Chahroudi.

 
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Infections account for 13% of all cancer cases*

by Roxanne Nelson, RN, BSN | Medscape | Jan 21 2020

An estimated 13% of all cancer cases in 2018 may be attributable to infections, concludes a new global survey. This equates to about 2.2 million cancer cases diagnosed worldwide.

The primary causes were Helicobacter pylori, human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV).

Of note, a third of global cancer cases attributable to infection are in China, which accounted for 42% of cancers caused by H pylori and for 69% of those caused by HBV.

"The present work estimates for the first time incidence rates of infection-attributable cancer in 2018 at an individual country level," write the authors, led by Catherine de Martel, MD, of the Infections and Cancer Epidemiology Group at the International Agency for Research on Cancer, France.

"Our study can help to raise awareness and inform recommendations for action against cancer, which tends to be viewed as a non-communicable disease," they add.

A causal association between certain infections and human malignancies is already well established, the authors comment. Previous research by de Martel and her group found that H pylori, HBV, HCV, and HPV were responsible for 2 million of 12.7 million cancer cases. Most of these were gastric, hepatic, and cervix uteri cancers.

For the current analysis, the authors used the GLOBOCAN 2018 database of cancer incidence and mortality rates. They estimated the attributable percentages and global incidence for specific cancers that have already been associated with infectious pathogens. The absolute numbers and ASIR were calculated at the country level and were stratified by sex, age group, and country.

Their results showed that H pylori was responsible for 810,000 new cancer cases in 2018, primarily underlying noncardia gastric adenocarcinoma. This was followed by HPV, responsible for 690,000 new cases, primarily causing cervix uteri carcinoma.

HBV contributed to 360,000 new cases, and HCV was responsible for 160,000 new cases, both primarily causing hepatocellular carcinoma.

Other infectious agents - Epstein-Barr virus, human T-cell lymphotropic virus, human herpesvirus, and parasitic infections - contributed to the remaining 210,000 new cases.

Variation by sex and income

Overall, men and women were equally affected by cancers caused by infections, but the types of pathogens and cancers varied by sex.

There was also considerable variation by geographic region. Eastern Asia had the highest rates of infection, followed closely by sub-Saharan Africa. Conversely, the lowest number of cases was in northern Europe and western Asia.

China accounted for 35% of the new infection-attributable cases in 2018. Of those, 340,000 were linked to H pylori, and 250,000 to HBV. South Korea also had a very high incidence of cancer caused by H pylori infection, as did Japan. There was also a high incidence of cancer cases related to HBV in South Korea.

Cervix uteri carcinoma accounts for approximately 80% of cancers that could be attributed to HPV. Women were the most affected by HPV, accounting for 90% of the 690,000 attributed cases globally. These proportions were highest in the lowest-income countries.

In contrast, the proportions of the other types of HPV-related anogenital cancers, along with head and neck cancers, were higher in high-income countries, with a greater proportion seen in men.

"It should be emphasized that the data we present here are a snapshot of the burden of cancer attributable to infections worldwide in 2018, and comparisons with previous results are not possible because of changes in data sources, notably for cancer incidence estimates, as well as other methodological modifications," the authors wrote.

*From the article here :
 
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Evelyn Ayo, a vaccinator at the Reproductive Health Uganda clinic in Gulu, administers an HPV vaccine.

Women can be protected from cervical cancer – so why aren't we doing it?

by Nelly Mugo | The Guardian | 24 Feb 2020

Amid a global shortage of HPV vaccine, more must be done to steer supplies towards those most at risk: girls in poor countries.

For too many women, cervical cancer is a death sentence. But it doesn’t have to be. A life-saving preventative vaccine can dramatically cut cases and put the world on track to eliminate this deadly disease.

The UK first began offering a vaccine against HPV – the primary cause of cervical cancer – in 2008. According to a 2018 study by Public Health England, infections of certain cancer-causing types of HPV have since fallen by 86 percent among 16- to 21-year-old women. A study conducted in Scotland last year found that the vaccine reduced pre-cancerous cervical lesions by up to 90 percent.

But such impact has been largely confined to wealthy countries, where the vaccine is widely available. Today, 90 percent of all cervical cancer deaths around the world occur in developing countries, many of which have yet to introduce inoculation. Just 21 low-income countries have the vaccine.

While demand for the vaccine is high, efforts to roll it out in developing countries have been threatened by a global supply shortage. With limited doses available, millions of women and girls are left without protection against a largely preventable disease, simply because of where they live.

Last summer, the UK announced the expansion of their HPV vaccination programme to include boys. Other countries, including the US, Germany and Australia, have implemented similar policies. The US also recommends the vaccine for certain women up to 45.

Encouraging more people to get vaccinated is unquestionably a positive thing. But, in the context of a global shortage, expanding the population that receives inoculation could mean girls and women in poorer countries are left behind.

It should be noted that vaccinating girls against HPV protects boys too, through herd immunity: when enough girls in a community are protected, the virus can’t spread from person to person and everyone is safeguarded.

The effects of the vaccine shortage are compounded by lack of access to timely screening and treatment options in low- and middle-income countries. Reliable preventive care services to spot cancer early, like pap smears and visual inspection with acetic acid, are often unavailable. This can mean that cancer diagnoses are often made too late, if at all.

Even when cervical cancer is diagnosed, many areas do not have healthcare facilities with cancer specialists, or the equipment for treatments like radiation and chemotherapy. These services are also expensive, putting them out of reach for many. Without access to the HPV vaccine, girls and women in the regions of highest need are left without any tools to protect themselves.

In November, the World Health Organization’s strategic advisory group of immunisation experts recommended that all countries temporarily postpone the implementation of HPV vaccination strategies for boys and older age groups. The expert group also suggested that countries consider adopting a vaccination schedule where the second dose is administered three to five years after the first, as appropriate to the national context. Deferring the second dose for younger girls does not affect the vaccine’s effectiveness and will make more doses available now, when they are urgently needed.

Implementing these recommendations and steering vaccine supply toward countries at high risk could save hundreds of thousands of lives.

The HPV vaccine shortage has an end in sight – new manufacturers are entering the market and more doses will be available eventually, though probably not until 2024 at the earliest. But millions of girls should not have to wait years to receive the life-saving benefits of HPV vaccination.

To create a future where girls and women don’t have to bear the burden of cervical cancer, leaders need to take steps to ensure that the limited doses we have go to the regions where they can save the most lives. Countries must also invest in life-saving services like cervical cancer screening and treatment programmes that can protect women who haven’t received the vaccine.

If we take these actions, we’ll be sending a clear message that the lives of girls and women in poorer countries really are equal to those in rich ones.

From the article here: https://www.theguardian.com/global-...from-cervical-cancer-so-why-arent-we-doing-it


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Drop in HPV seen after just one shot of HPV vaccine

by Will Boggs MD | Medscape | 30 Dec 2019

Even a single dose of human papillomavirus (HPV) vaccine is associated with a reduced prevalence of HPV infection among U.S. women, according to findings from the National Health and Nutritional Examination Survey.

"Getting adolescents to initiate their first dose should be a priority, with the goal that they will complete the recommended series," Dr. Ashish A. Deshmukh from UTHealth School of Public Health, in Houston, Texas, told Reuters Health by email. "Our findings are promising; however, they are not suggestive that only one dose is adequate until we get further definite answers from currently ongoing trials."

While about two-thirds of adolescents in the U.S. have received at least one dose of the HPV vaccine, only about half have completed the three-dose series.

Dr. Deshmukh's team used NHANES 2009 to 2016 data to investigate HPV-infection prevalence among U.S. women by the number of vaccine doses received.

Among the 1,620 women included in the study, 1,004 were unvaccinated, while 106 had received one dose, 126 had received two and 384 had received three.

The prevalence of infection with HPV 18 was significantly lower among women who received the vaccine than among unvaccinated women, the researchers reported.

The predicted probability of infection with these HPV types remained significantly higher in unvaccinated women (8 percent) than in women who received the vaccine.

The predicted probability of infection with these HPV types was significantly greater among black women (11 percent) than among white women (7 percent) and among women with more than five lifetime male sexual partners (12 percent) than among women with fewer lifetime male partners (3 percent).

"If a single dose of HPV vaccine could provide protection for a long-enough duration similar to currently recommended 2 or 3 doses, then receiving the vaccine will be a more achievable metric of population coverage," Dr. Deshmukh said. "The implication of our findings will be greater in low-resource countries where cervical cancer still remains one of the leading causes of cancer mortality."

"Yet, the HPV-vaccination coverage is extremely poor, as getting adolescents to receive their first dose itself is a big hurdle, and in many countries, as generally, there is not adequate infrastructure to provide the recommended vaccine series,"
he said.

Dr. Deshmukh added, "Continued and effective physician recommendation has a great potential to overcome the existing hurdles, mainly parental indecision about both vaccine initiation and completion."

Dr. Margaret Stanley of the University of Cambridge, in the UK, who has researched various aspects of HPV infection, told Reuters Health by email, "These observations should be placed in context with other studies, but my view is that the available evidence is that immunization with even 1 dose of HPV vaccine at high coverage over 80 percent of sexually naïve adolescents is protective against vaccine-type persistent HPV infection for at least 10 years. However, for policy changes and implementation of a 1-dose schedule, evidence from randomized controlled trials will be necessary."

"The name of the game is to get HPV vaccine into as many 9- to 15-year-old boys and girls as possible, even if it's only one dose,"
she said.

From the article here: https://www.medscape.com/viewarticl...CPEDIT_TEMP2&uac=341393BJ&impID=2278909&faf=1
 
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Paraíba strain of Zika virus responsible for microcephaly in Brazilian newborns*

by Tamara Bhandari | Washington University School of Medicine | 19 Feb 2020

Due to the Zika virus, more than 1,600 babies were born in Brazil with microcephaly, or abnormally small heads, from September 2015 through April 2016. The epidemic took health professionals by surprise because the virus had been known since 1947 and was not linked to birth defects.

As scientists scrambled to figure out what was going on, one fact stood out: 83% of microcephaly cases came from northeastern Brazil, even though Zika infections were recorded nationwide.

Researchers from Washington University School of Medicine in St. Louis have since learned that the strain of virus circulating in the northeastern Brazilian state of Paraíba in 2015 was particularly damaging to the developing brain. Kevin Noguchi, Ph.D., an assistant professor of psychiatry and the study's senior author, spoke about the findings, which are available online in The Journal of Neuroscience.

How did you determine that the Paraíba strain was unusually harmful?

We studied two strains of Zika virus—one from an outbreak in French Polynesia in 2013 that was associated with a low risk of microcephaly, and another from Paraíba in 2015. We infected one group of newborn mouse pups with one strain and a second group with the other strain. The brains of newborn mice are at a similar stage of development to a second-trimester human fetus, when Zika virus causes considerable damage. Each strain led to about the same number of deaths, but the brain damage in the surviving mice was dramatically different. The mice infected with the French Polynesian strain seemed to successfully fight off the infection within about two weeks, and we did not see any additional signs of damage after that. In contrast, we saw neurodegeneration in the mice infected with the Paraíba strain up to 30 days later, and they had smaller brains.

Is that why babies born in Paraíba were at high risk of microcephaly?

Maybe. It tells us that the strain from Paraíba was more capable of causing severe brain damage than the one from French Polynesia. It doesn't rule out other possibilities.

For instance, other environmental factors in Paraíba—such as dengue or other viruses that were circulating at the same time—could have affected Zika's ability to overwhelm the body's defenses and cause severe brain damage.

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What is it about the Paraíba strain that made it so dangerous?

That's our next step. We have started a collaboration with Dr. Luis Martínez-Sobrido, Ph.D., and his colleagues at the University of Rochester. They found a mutation in the Paraíba strain that may affect its virulence, or the ability to cause disease.

If the Paraíba strain is so harmful, why didn't it cause an epidemic of microcephaly the next year?

Everyone was bracing for another massive increase in microcephaly the next year, but it didn't happen. We also saw more limited increases of microcephaly in other parts of Latin America and the Caribbean, even as the virus spread into those areas. Nobody really knows why. It could be that pregnant women started wearing more insect repellant and putting screens on their windows. In Brazil, it could be that so many people got infected the first year that many pregnant women were immune the next year. It's also possible that the virus was just too virulent for its own good. If you kill your host, you also kill the opportunity to get passed on to the next person. So it could be that Zika reached peak virulence in 2015 and then evolved to be less virulent over time. That's another thing we'd like to find out.

*From the article here :
 
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HCV screening recommended for all US adults aged 18-79

by Marcia Frellick | Medscape | 2 Mar 2020

The US Preventive Services Task Force has expanded its recommendation for one-time hepatitis C virus (HCV) screening to include all asymptomatic US adults ages 18-79 years, including pregnant women, who do not have known liver disease.

It is a B-level recommendation, indicating that screening for HCV will have a substantial net benefit. The B level is also important because the Affordable Care Act requires that private insurers and Medicaid cover preventive services recommended at an A or B level by the USPSTF with no deductibles or copayments.

"HCV is associated with more deaths than the top 60 other reportable infectious diseases combined, including HIV," the group, led by Douglas K. Owens, MD, Stanford University, California, stated.

Among reasons for the change, authors cite the almost 3.8-fold increase in cases in the last decade, largely because of more injection drug use and better monitoring.

Owens and colleagues noted that research indicates the most important risk factor for HCV is injection drug use.

"In the United States, recent increases in HCV incidence have predominantly been among young persons who inject drugs (PWID). Approximately one third of PWID aged 18 to 30 years are infected with HCV, and 70% to 90% of older PWID are infected," they said.

Patients need to know the test is voluntary

The authors point out it is important for clinicians to let patients know that screening is voluntary and to communicate what HCV is, how it is acquired, what a positive or negative test means, and potential harms and benefits of treatment.

The USPSTF also suggested that clinicians consider screening patients considered high risk (past or current injection drug users even if they fall outside the recommended age range).

The recommendations come in light of several developments over the past decade.

One is the convincing evidence that the newer direct-acting antiviral (DAA) regimens result in cure rates above 95% for adults ages 18-79 years, and the "adequate evidence of sustained virologic response in adolescents."

In addition, the duration of treatment has declined. Whereas older, interferon-based regimens required as long as 48 weeks of treatment, DAA-based regimens require just 8 to 12 weeks of therapy.

Additionally, screening and treatment rates have varied widely. Screening rates have been high in healthcare systems serving insured people, some academic medical centers, and Veterans Health Administration centers.

However, the authors said, "national HCV screening rates in community health centers and from the National Health Interview Study were 8.3% and 17.3%, respectively; one study of four safety-net primary care practices serving low-income and uninsured or underserved populations found that only 0.8% of persons born in 1945 through 1965 were screened over a 1-year period."

The USPSTF did not find evidence of harm in screening in any new studies.

Test can give results quickly

Kalyan R. Bhamidimarri, MD, MPH, chief of the division of hepatology at the University of Miami in Florida, told Medscape Medical News that although much of the testing will fall on primary care physicians, rapid testing with a swab or finger stick can mean results are quickly available.

At their facility, they give patients a fingerstick test in the waiting room so results are ready to discuss during appointments, he said.

"Even if rapid testing is not available and the blood sample needs to be sent out," he said, "testing is able to capture more than 98% of HCV infection, and false-positives are very, very low."

He pointed out that primary care offices are already on alert to watch for signs of fatty liver disease, which has become an epidemic.

Bhamidimarri said the USPSTF move was important because while hepatitis C infections have decreased in the baby boomer group covered by the previous recommendations, they have increased in other groups as opioid use has increased, particularly in young people.

"The biggest challenge with hepatitis C is underscreening and undiagnosis," said Bhamidimarri, an associate professor of clinical medicine at the university.

He said acute infections have risen sharply in recent years and warns that without screening and treatment they will become chronic.

"So we are going to see another peak where individuals will have cirrhosis and will need a liver transplant sometime in the future," he said. "If this goes untreated we will see a major public health burden later on. In all these years they are untreated, they are going to horizontally spread the infection to others."

The broad screening that the USPSTF recommends is also important because it gets around possible stigma. Just asking people if they have risk factors won't work because people may come to appointments with a significant other and don't want to admit behaviors or talk about them with physicians, Bhamidimarri said.

Consistent with other recommendations

The USPSTF recommendation is very similar to the draft update of guidelines by the Centers for Disease Control and Prevention (CDC), which recommends screening for HCV at least once in a lifetime for all adults 18 years old and over.

The CDC's draft guidelines continue, "All persons with risk factors (eg, persons with HIV, prior recipients of blood transfusions, persons who have ever injected drugs and shared needles, and persons who are born to an HCV-infected mother) should be tested for HCV, with periodic testing while risk factors persist."

The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommends one-time, opt-out HCV screening for everyone at least 18 years old and one-time testing for all people younger than 18 years at increased risk of exposure. They also recommend periodic screening for people with increased risk of exposure as well as yearly HCV tests for all people who inject drugs and HIV-infected men who have unprotected sex with men.

 
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Scientists uncover how Zika virus spreads through sexual contact

by Experimental Biology | Medical Xpress | 27 April 2020

Zika virus is capable of replicating and spreading infectious particles within the outermost cells lining the vaginal tract, according to new research. The findings provide the first molecular-level insights into how the virus can move from person to person through sexual contact.

While Zika is primarily spread by mosquitoes, researchers have been aware of its potential for sexual transmission based on cases in which people became infected after having sex with a partner who had visited a Zika-affected area. Previous studies have also found Zika particles present in semen and vaginal fluid from infected individuals.

Having a more detailed understanding of how Zika infiltrates the body through sexual contact could help scientists identify new ways to prevent or treat Zika infections. The new study examined how Zika particles behaved in cultures of human vaginal epithelial cells and identified the virus's likely entry point as a protein on the surface of the cells called tyrosine-protein kinase receptor UFO, which is encoded by the AXL gene.

"The outcome of this research highlights how local replication of Zika in the vaginal epithelium plays an important role in mediating sexual transmission and subsequent systemic infection in the human host," said lead study author James Mungin Jr., a doctoral candidate at Meharry Medical College. "Additionally, our research findings confirming that the receptor UFO (AXL) promotes viral entry can be very instrumental in developing drugs and antibody-based therapies that target and block this receptor, therefore eliminating the pathology caused by this virus."

Mungin was scheduled to present the research at the American Society for Investigative Pathology annual meeting in San Diego this month. Though the meeting, to be held in conjunction with the 2020 Experimental Biology conference, was canceled in response to the COVID-19 outbreak, the research team's abstract was published in this month's issue of The FASEB Journal.

Zika spread rapidly around the world during a major 2015-2016 outbreak, causing about 42,000 infections in the United States and its territories. While the number of cases has since dropped precipitously, the virus is still considered a health threat in many places around the world. Babies born to mothers infected with Zika have a high risk of birth defects.

Mungin and colleagues found that Zika virus particles were able to successfully enter vaginal epithelial cells through the UFO receptor, replicate their RNA genome and steadily release infectious viral particles inside the cells. The research team plans to further study the factors that contribute to Zika replication for insights on how those factors might be interrupted.

Like Zika, many other viruses in the flavivirus family are spread by insects. However, research on those other viruses, such as dengue and yellow fever, does not always translate well to Zika because they are not sexually transmitted.

"Interestingly, sexual transmission among flaviviruses is in fact unique in nature," said Mungin. "As of now, Hepatitis C and Zika virus have been identified as the only two flaviviruses known to establish infection via sexual contact with an infected partner."

According to the U.S. Centers for Disease Control and Prevention, using condoms can prevent sexual transmission of Zika.

 
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Injectable drug more effective at blocking HIV than daily pills

by Lenny Bernstein | Washington Post | 7 Jul 2020

The pill Truvada is used to prevent HIV infection. Research shows that a new long-acting form of the drug injected every two months is even more effective at preventing HIV.

A long-acting drug injected every two months is more effective at preventing HIV than the pills most commonly used by people at risk of acquiring the infection, according to research released Tuesday at an international AIDS conference.

The drug cabotegravir was tested on more than 4,500 cisgender men who have sex with men and transgender women who have sex with men in 43 countries. While Truvada, the pill used most often to block the virus, is also highly effective, the injectable drug proved to be even better, the research shows.

Perhaps more importantly, an injection every two months may allow more people to remain on medication, known as "pre-exposure prophylaxis" or PrEP, that blocks the virus. People whose medical care is inconsistent, including homeless people, intravenous drug users and others in unstable situations, have trouble remaining on the daily pills. Others are reluctant to obtain them because of the stigma still associated with HIV.

"Giving individuals an option of an injection every eight weeks instead of taking a daily pill to prevent HIV provides choices and flexibility," Monica Gandhi, San Francisco co-chair of the AIDS 2020 conference, said in an email. The worldwide conference is taking place online this week.

Truvada and Descovy, both manufactured by Gilead Sciences, are the only PrEP drugs approved by the Food and Drug Administration on the market. A generic form of Truvada is expected soon, but Gilead has been the target of activist groups for setting high prices for its drugs.

The injectable drug tested in the new study is made by ViiV Healthcare.

Kimberly Smith, head of research and development for the company, said removing the problem of adhering to a daily drug regimen accounts for the injectable's superior performance. Adherence to pills starts off strong in many men, she said, but wanes over time.

Overall, 52 people in the study contracted HIV in a little less than three years - 39 who were on daily pills and 13 who received the experimental injections. Test subjects were enrolled at 43 sites in the United States, Africa, Asia and Latin America.

"I believe the result is primarily driven by the fact that you don't need to adhere to a regimen every day," Smith said.

About 1.7 million people throughout the world became infected with HIV last year - a figure experts say could be greatly reduced if more people had access to PrEP and stayed on it. Taken daily, the drug is more than 90% effective at preventing sexual transmission of the virus and more than 70% effective at blocking it among people who inject street drugs and share needles.

But in the United States, only about 10 to 20% of the 1.1 million people considered at risk of contracting HIV are on PrEP. A disproportionate number of those not on medication are black and Latino men who have sex with other men. The United States has launched a program that, in part, focuses on them in a bid to end transmission of HIV by 2030.

Smith said the company made a point of enrolling African American men who have sex with men in the hope that good results would persuade that group to adopt the medication. Half the U.S. subjects in the study, 844 men, were in that category, she said.

"Black men who have sex with men did extremely well" in the trial, Smith said. "This is a message we can carry to that population."

 
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New drug could stop deadly superbug, save tens of thousands of lives

by Chris Adam | Purdue University | Medical Xpress | 10 Sep 2020

Vancomycin-resistant enterococcus (VRE) is among the leading causes of hospital-acquired infections in the United States. An estimated 20,000 people in the U.S. become infected with it each year, and nearly 10% of people who get it die from it.

These superbugs typically develop from infections in the intestinal tract, where the bacteria become resistant to the antibiotic vancomycin. People who stay in a hospital have the highest odds of getting VRE.

A pair of Purdue University researchers from the College of Pharmacy and the College of Veterinary Medicine developed small molecules to combat deadly, drug-resistant enterococcus.

They created their molecules by repurposing a drug that has been used for more than 80 years to treat glaucoma, congestive heart failure and some other health issues. Their work is published in the Journal of Medicinal Chemistry.

"The potency of these molecules and the ability to tune the molecules' properties to target VRE in different compartments of the body make this an exciting project," said Daniel Flaherty, an assistant professor of medicinal chemistry and molecular pharmacology. "I believe our discovery may help to change the way people treat VRE in the future."

"We can have molecules that can be used to treat deadly systemic VRE infections, or through manipulation of the properties of the molecule, design a compound that will reside solely in the gastrointestinal tract to reduce VRE colonization. By working across disciplines at Purdue, we have been able to improve the effectiveness of this drug 600 times better than where we started in treating VRE."


Mohamed Seleem, a professor of microbiology, who co-created the molecules with Flaherty, said the problem with antibiotics on the market is that they are used for a wide variety of illnesses.

"These antibiotics can really rip apart the guts and destroy good bacteria," Seleem said. "Then someone can develop Clostridium difficile, also known as C. diff, which kills about 30,000 people each year in the United States. Scientists across the globe are working on better solutions, but I think we are far away from seeing narrow-spectrum antibiotics proliferate the market."

The Purdue team's small molecules have been shown to target VRE and have the properties necessary to treat VRE in both systemic circulation or in the GI tract, where all VRE infections originate.

 
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CBD is a powerful antibiotic

University of Queensland | Neuroscience News | 28 Jun 2019

New research has found that CBD is active against Gram-positive bacteria, including those responsible for many serious infections such as Staph aureus and Streptococcus pneumoniae, with a potency similar to that of established antibiotics such as Vancomycin.

CBD, the main non-psychoactive chemical compound extracted from cannabis and hemp plants, has been approved by FDA for the treatment of a form of epilepsy and is being investigated for a number of other medical conditions, including, anxiety, pain and inflammation. While there is limited data to suggest CBD can kill bacteria, the drug has not been thoroughly investigated for its potential as an antibiotic.

Work led by Dr Mark Blaskovich at The University of Queensland’s Institute for Molecular Bioscience’s Centre for Superbug Solutions, in collaboration with Botanix Pharmaceuticals Ltd, an early stage drug discovery company investigating topical uses of synthetic CBD for a range of skin conditions, found that CBD was remarkably effective at killing a wide range of Gram-positive bacteria, including bacteria that have become resistant to other antibiotics, and did not lose effectiveness after extended treatment.

“Given CBD’s documented anti-inflammatory effects, existing safety data in humans, and potential for varied delivery routes, it is a promising new antibiotic worth further investigation,” said Dr. Blaskovich.

Importantly, the drug retained its activity against bacteria that have become highly resistant to other common antibiotics. Under extended exposure conditions that lead to resistance against vancomycin or daptomycin, CBD did not lose effectiveness. CBD was also effective at disrupting biofilms, a physical form of bacteria growth that leads to difficult-to-treat infections.

 
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Pilot study of psilocybin-assisted group therapy in older AIDS survivors

by Michael Haichin, PharmD | Psychedelic Science Review | 19 Nov 2020

Feasibility, safety, and potential efficacy of psilocybin-assisted group therapy was demonstrated in treating demoralization in this marginalized population.

Evidence for psilocybin-assisted psychotherapy (PcbAP) continues to accumulate for treating a number of psychiatric conditions. However, the majority of modern trials studying this treatment have been time-, staff-, and resource-intensive. A significant amount of two therapists’ time is required as part of pre-drug preparatory sessions, supervision during, and post-drug integration sessions. As a result, concerns about high costs and limited access have loomed over the potential translation to real-world clinical practice settings if it is approved. PcbAP administered in a group setting is regarded as a potential solution, though until recently, no modern trials examined whether it is feasible, safe, or effective.

Why psychedelic group therapy?

Traditionally, plant-based psychedelics like psilocybin, ayahuasca, and peyote were used in group settings by various Indigenous groups for healing and religious purposes. This group framework was replicated in earlier clinical studies of psychedelics in the 1960s-70s, which found promising evidence in treating alcohol use disorder and neuroses, predominantly with LSD. However, those studies were not up to present-day clinical trial standards, thus limiting what conclusions could be drawn about the safety and efficacy of psychedelic group therapy.

In an open-label trial of individual PcbAP for treatment-resistant depression, social connectedness was identified as a possible underlying mechanism of therapeutic change.4 Other contemporary trials’ participants have requested to meet other trial subjects, as well as corroborating the importance of connecting with those who have undergone the challenging-to-describe psychedelic experience. These results suggested that psychedelic group therapy may improve therapeutic outcomes and participant satisfaction.

The historical use, previous research, and more recent findings, combined with the cost-saving potential, pointed to the need to explore the psychedelic group therapy model more rigorously. A research team led by Brian Anderson, MD from the University of California San Francisco, therefore, conducted a pilot study to explore the feasibility, safety, and potential efficacy of psilocybin-assisted group therapy.

Older, long-term AIDS survivors and demoralization

This trial examined a marginalized population unique to psychedelic therapy: older, long-term AIDS survivors (OTLAS) suffering from demoralization. Demoralization, a prevalent response to serious medical illness, is a form of existential distress characterized by poor coping and feeling hopeless, helpless, and without meaning or purpose.5 These individuals were diagnosed with HIV/AIDS when it was considered a terminal diagnosis and lived through the overwhelming loss of loved ones, resulting in demoralization. The average age of participants included in the study was 59 years. This population also has complex past medical and psychiatric histories, reflected in 50% of the trial participants meeting criteria for a comorbid mental health condition (e.g., anxiety disorder, panic disorder, and borderline personality disorder).

Study design

In this single-arm, open-label trial, 18 self-identified gay men suffering from moderate to severe demoralization were enrolled into three cohorts of six. Participants met as a group on four occasions led by two therapists, before receiving a single, individual psilocybin (0.3-0.36 mg/kg) session. Four to six more group therapy sessions occurred after the psilocybin administration to integrate their experiences.

The feasibility was determined by rates of recruitment and retention of enrolled participants. Safety was evaluated with multiple measures and categorized by the severity and rate of any adverse events. The primary clinical outcome was the change in demoralization, assessed by the self-reported Demoralization Scale-II (DS-II), from baseline to end-of-treatment and at a 3-month follow-up. Various secondary clinical outcomes were measured due to the complex psychiatric needs of OLTAS, most notably related to trauma and unresolved grief.

Study findings

Rates of recruitment were high, and attendance to group therapy was 95%, attesting to the feasibility. It is important to note the participants were highly motivated, either on disability or retired, and had flexible schedules to attend group meetings. If the 18 participants received their therapy in the standard 1:2 subject to therapist ratio used in other psilocybin studies, a total of 954 therapist hours would be required. Because of the group therapy format, that time was reduced almost in half, down to 472 hours.

Despite a study population with greater psychiatric comorbidity than any other modern psilocybin trial, the treatment was found to be relatively safe. No psilocybin-related serious adverse events occurred, and two unexpected adverse reactions were detected during post-medication visits (post-traumatic stress flashback and methamphetamine relapse). Fourteen of 18 participants experienced moderate-to-severe expected psilocybin-related adverse reactions that resolved by the end of the administration session. While this is a relatively high adverse event rate, the researchers suspect it is partly related to the clinical complexity of the study population. The most common of those were high blood pressure (67 percent), anxiety (44 percent), and nausea (33 percent).

Demoralization scores were reduced from baseline at both end-of-treatment and at the 3-month follow-up, by an average of 6.67 (SD=6.51) and 5.78 points (SD=6.01), respectively. To put those results in context, the demoralization scale totals 32 points and a 2-point improvement is considered clinically meaningful. A >50% reduction in demoralization compared to baseline was found in 50% of participants at end-of-treatment and 33.3% at 3-month follow-up. Secondary measures related to trauma and grief also showed significant reductions over that time period.


Future research directions

While this pilot study demonstrated the feasibility, safety, and potential efficacy of psilocybin-assisted group therapy in treating demoralization among OTLAS, the results cannot be considered conclusive due to its small sample size and single arm, unblinded design. Larger, randomized, placebo-controlled trials are needed to confirm these promising results. An accompanying qualitative paper with the patients’ perspectives on the group therapy process is expected and can potentially corroborate the value of a group framework.

The results open the door to future studies assessing psilocybin-assisted group therapy in other populations where demoralization is present, such as those with substance use disorders, chronic pain, obesity, and the elderly. The social isolation, shame, and stigma associated with a variety of mental health conditions can be uniquely addressed with group therapy. The trailblazing pilot trial by Brian Anderson and colleagues lays the groundwork for combining that unique capability and the social connectedness brought on by psilocybin and may prove useful to improve access and lower costs should it become an approved treatment.

 
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Research establishes antibiotic potential of CBD*

University of Queensland | Science News | 19 Jan 2021

Synthetic cannabidiol, better known as CBD, has been shown to kill the bacteria responsible for gonorrhoea, meningitis and legionnaires disease, which could lead to the first new class of antibiotics for treatment-resistant bacteria in 60 years.

The research collaboration between The University of Queensland and Botanix Pharmaceuticals Limited could lead to the first new class of antibiotics for resistant bacteria in 60 years.

The UQ Institute for Molecular Bioscience's Associate Professor Mark Blaskovich said CBD -- the main nonpsychoactive component of cannabis -- can penetrate and kill a wide range of bacteria including Neisseria gonorrhoeae, which causes gonorrhoea.

"This is the first time CBD has been shown to kill some types of Gram-negative bacteria. These bacteria have an extra outer membrane, an additional line of defence that makes it harder for antibiotics to penetrate," Dr Blaskovich said.

In Australia, gonorrhoea is the second most common sexually-transmitted infection and there is no longer a single reliable antibiotic to treat it because the bacteria is particularly good at developing resistance.

The study also showed that CBD was widely effective against a much larger number of Gram-positive bacteria than previously known, including antibiotic-resistant pathogens such as MRSA (methicillin-resistant Staphylococcus aureus) or 'golden staph'.

Dr Blaskovich said cannabidiol was particularly good at breaking down biofilms -- the slimy build-up of bacteria, such as dental plaque on the surface of teeth -- which help bacteria such as MRSA survive antibiotic treatments.

Dr Blaskovich's team at the Centre for Superbug Solutions mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD's killing power.

"Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during 'treatment'."

"We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don't know yet exactly how it does that, and need to do further research.


The research team also discovered that chemical analogs -- created by slightly changing CBD's molecular structure -- were also active against the bacteria.

"This is particularly exciting because there have been no new molecular classes of antibiotics for Gram-negative infections discovered and approved since the 1960s, and we can now consider designing new analogs of CBD within improved properties."

Vince Ippolito, the President and Executive Chairman of Botanix, said the research showed vast potential for the development of effective treatments to fight the growing global threat of antibiotic resistance.

"Congratulations to Dr Blaskovich and his team for producing this significant body of research -- the published data clearly establishes the potential of synthetic cannabinoids as antimicrobials," Mr Ippolito said.

"Our Company is now primed to commercialise viable antimicrobial treatments which we hope will reach more patients in the near future. This is a major breakthrough that the world needs now."

Dr Blaskovich said collaborating with Botanix has sped up the research, with Botanix contributing formulation expertise that has led to the discovery that how cannabidiol is delivered makes a huge difference in its effectiveness at killing bacteria.

The collaboration has enabled Botanix to progress a topical CBD formulation into clinical trials for decolonisation of MRSA before surgery.

"Those Phase 2a clinical results are expected early this year and we hope that this will pave the way forward for treatments for gonorrhoea, meningitis and legionnaires disease.

"Now we have established that cannabidiol is effective against these Gram-negative bacteria, we are looking at its mode of action, improving its activity and finding other similar molecules to open up the way for a new class of antibiotics."


*From the article here :
 
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University of Queensland

CBD shown to kill treatment resistant bacteria*

University of Queensland | Science Daily | 19 Jan 2021

CBD, has been shown for the first time to kill the bacteria responsible for gonorrhoea, meningitis and legionnaires disease.

The research collaboration between The University of Queensland and Botanix Pharmaceuticals Limited could lead to the first new class of antibiotics for resistant bacteria in 60 years.

The UQ Institute for Molecular Bioscience's Associate Professor Mark Blaskovich said CBD -- the main nonpsychoactive component of cannabis -- can penetrate and kill a wide range of bacteria including Neisseria gonorrhoeae, which causes gonorrhoea.

"This is the first time CBD has been shown to kill some types of Gram-negative bacteria. These bacteria have an extra outer membrane, an additional line of defence that makes it harder for antibiotics to penetrate," Dr Blaskovich said.

In Australia, gonorrhoea is the second most common sexually-transmitted infection and there is no longer a single reliable antibiotic to treat it because the bacteria is particularly good at developing resistance.

The study also showed that CBD was widely effective against a much larger number of Gram-positive bacteria than previously known, including antibiotic-resistant pathogens such as MRSA (methicillin-resistant Staphylococcus aureus) or 'golden staph'.

Dr Blaskovich said cannabidiol was particularly good at breaking down biofilms -- the slimy build-up of bacteria, such as dental plaque on the surface of teeth -- which help bacteria such as MRSA survive antibiotic treatments.

Dr Blaskovich's team at the Centre for Superbug Solutions mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD's killing power.

"Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during 'treatment'."

"We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don't know yet exactly how it does that, and need to do further research. The research team also discovered that chemical analogs -- created by slightly changing CBD's molecular structure -- were also active against the bacteria."

"This is particularly exciting because there have been no new molecular classes of antibiotics for Gram-negative infections discovered and approved since the 1960s, and we can now consider designing new analogs of CBD within improved properties."


Vince Ippolito, the President and Executive Chairman of Botanix, said the research showed vast potential for the development of effective treatments to fight the growing global threat of antibiotic resistance.

"Congratulations to Dr Blaskovich and his team for producing this significant body of research -- the published data clearly establishes the potential of synthetic cannabinoids as antimicrobials," Mr Ippolito said.

"Our Company is now primed to commercialise viable antimicrobial treatments which we hope will reach more patients in the near future. This is a major breakthrough that the world needs now."

Dr Blaskovich said collaborating with Botanix has sped up the research, with Botanix contributing formulation expertise that has led to the discovery that how cannabidiol is delivered makes a huge difference in its effectiveness at killing bacteria.

The collaboration has enabled Botanix to progress a topical CBD formulation into clinical trials for decolonisation of MRSA before surgery.

"Those Phase 2a clinical results are expected early this year and we hope that this will pave the way forward for treatments for gonorrhoea, meningitis and legionnaires disease."

"Now we have established that cannabidiol is effective against these Gram-negative bacteria, we are looking at its mode of action, improving its activity and finding other similar molecules to open up the way for a new class of antibiotics."

*From the article here :
 
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Cannabis may slow or even prevent HIV's damaging effects on the brain*

by Randy Robinson | 24 Jan 2020

One of HIV’s lesser-known symptoms is neurodegeneration, a slow but progressive failure of the nervous system. But new data suggests cannabis may slow or, even prevent, HIV's damaging effects on the brain.

HIV and aging share one thing in common: They can both irreparably damage the nervous system. But cannabis may, potentially, halt both aging and HIV in their tracks when it comes to a deteriorating human brain.

A new study recently published in the Journal of Acquired Immunity Deficiency Syndrome found that HIV patients who consumed cannabis showed significantly less cognitive impairment compared to HIV patients who didn’t.

Here’s how the study went down. The researchers collected data from 679 people living with HIV and 273 people who didn’t have HIV. Participants’ ages ranged from 18- to 79-years-old. The researchers then assessed each participant to see how well their brain worked, their general state of health, and what kinds of drugs they were currently taking — FDA-approved or otherwise.

By the end of it, the researchers found that regular cannabis consumers living with HIV were at a 53 percent lower risk of developing cognitive impairments compared to people living with HIV who didn’t partake.

How could our favorite flower profoundly impact a disease that modern medicine still hasn’t found a (feasible) cure for? The researchers in the latest study concluded, “A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for people living with HIV." They noted that “further investigations are needed to better understand how cannabis could work as a neuroprotective HIV medication."

HIV can cause neural degeneration, even though the virus solely targets human immune cells, not our nerves or brain cells. But HIV’s presence in the brain triggers inflammation due to toxins released by both the virus and the immune cells it destroys. Our neurons are incredibly fragile, and constant inflammation in the brain will cause those neurons to degenerate and eventually die. HIV-associated neurocognitive disorders, or HANDs, can permanently impair memory, motor coordination, natural reflexes, speech, and emotional regulation.

If a HAND progresses even further, it can develop into AIDS dementia complex (ADC), a condition that’s kind of like a cross between Parkinson’s and Alzheimer’s, both of which usually only affect aging populations. At the end stages of ADC, the individual essentially slides into a vegetative state, paralyzed and likely unable to communicate with others.

However, in industrialized countries such as the US, readily available anti-retroviral drugs can stop HIV from developing into AIDS — assuming the individual can afford the medications, that is. But seeing as cannabis is known to control several other HIV/AIDS symptoms, receiving additional neuroprotective benefits in one small, joint-sized package should qualify weed as an essential part of the standard HIV/AIDS pharmaceutical regimen.

*From the article here :
 
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Injection prevents women from contracting HIV, study finds

Results so far suggest that the injectable drug cabotegravir was 89 percent more effective than pills at preventing HIV infection.

Al Jazeera | 9 Nov 2020

Researchers are stopping a study early after finding that a shot of an experimental medicine every two months worked better than daily pills to help prevent women from contracting HIV from an infected sexual partner.

The news is a boon for AIDS prevention efforts – especially in Africa, where the study took place and where women have few discreet ways of protecting themselves from infection.

Results so far suggest that the drug, cabotegravir, was 89 percent more effective at preventing HIV infection than Truvada pills, although both reduce that risk.

The results mirror those announced earlier this year from a similar study testing the shots versus the daily pills in gay men.

Cabotegravir is being developed by ViiV Healthcare, which is mostly owned by GlaxoSmithKline, with Pfizer Inc and Shionogi Limited. The study was sponsored by the United States National Institutes of Health (NIH), the Bill and Melinda Gates Foundation and ViiV. The drugs were provided by ViiV and Truvada’s maker, Gilead Sciences.

“This is a major, major advance,” said Dr Anthony Fauci, the top infectious disease doctor at the NIH. “I don’t think we can overemphasise the importance of this study.”

"The drug promises HIV prevention help to young women – those who need it the most,”
Fauci said.

Young women may be twice as likely as men to get HIV in some areas of the world, according to one study leader, Sinead Delany-Moretlwe of the University of the Witwatersrand in Johannesburg, South Africa.

“They need discreet options … without having to negotiate with their partners to use measures such as condoms," said Deborah Waterhouse of ViiV.

The study involved more than 3,200 participants in seven African countries who were randomly assigned to get either the shots every two months or daily Truvada pills. Independent monitors advised stopping the study after seeing that only 0.2 percent of women receiving the shots caught the AIDS virus versus 2 percent of women on the pills.

There were more side effects, mostly nausea, with the daily pills.

Cabotegravir’s makers are seeking approval from regulators to sell it for this purpose, and Truvada already is widely used.

“The urgent work now” is to make all prevention medicines affordable and more widely available," said Mitchell Warren, who heads AVAC, formerly known as the AIDS Vaccine Advocacy Coalition, a non-profit focused on prevention efforts that had no role in the study.

Condoms remain widely recommended because they help prevent a host of sexually spread diseases, not just HIV.

“People need choices for HIV prevention,” and this gives a new option," Warren said in a statement.

 
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Medicinal plants: What to know about herbal antibiotics

by Mary Villareal | Matural News | 2 Aug 2021

Bacteria tend to develop resistance to industrial antibiotics sooner or later, but this isn’t the case with herbal antibiotics. Herbal antibiotics work in a way where bacteria resistance becomes unlikely, even futile.

Medicinal plants, including herbal antibiotics, have been used in the management of infectious diseases since ancient times. In modern times, the effectiveness of many of these remedies has been proven in scientific methodologies. While these mechanisms focused on plant-derived remedies are not fully understood, the fact remains that herbal medicine is effective in curing infectious diseases, and many plants are beneficial against illnesses.

Plants such as garlic and aloe vera are used as natural antibiotics for relief in burns, and respiratory tract infections. They are also known to enhance the immune system and even lower blood pressure. When the immune system is weak, unwanted microbes can infect and thrive in or outside our bodies, and the microbial activities of microorganisms can cause infections.

While not all bacteria are harmful, various strains of the same bacteria can cause symptoms like diarrhea and vomiting. Natural antibiotics such as herbs and spices have the desired properties that minimize the spread of harmful microbes in the body.

Natural antibiotics found in herbal medicine have fewer side effects. That said, while herbal medicinal or herbal products are considered for low risk for adverse effects compared to synthetic drugs, you should still take care when using them as taking too much may still lead to some adverse effects. To stay safe, be sure to consult with your healthcare professional before trying any new medicine, herbal or otherwise.

How plants work differently from pills

Unlike pills, plant chemistry is complex. They have dozens of distinct chemical compounds that make it impossible for bacteria to develop any kind of resistance to them. These compounds may defeat the bacteria, but they can also promote healing, provide pain relief and reduce inflammation to make recovery faster. When these plants and herbs are combined, chances are that improvements will be faster.

Fortunately, plants are easy to grow for medicinal purposes. While it does not take going to medical school to learn about them, it is still important to be aware of their interactions. Plants are safer than conventional alternatives, with fewer side effects. Adverse drug reactions are among the leading cause of death in the United States, and plants can help minimize such adverse effects. (Related: WHO warns world running out of synthetic antibiotics, but refuses to acknowledge power of natural herbal antibiotics.)

Powerful antibiotics in your kitchen

Prevent antibiotic overkill by using these plant alternatives instead:​
  1. Manuka Honey – one of nature’s best antimicrobial sources, it received even more attention because of its antibacterial properties as well. Clinical studies showed that Manuka honey can inhibit multiple drug-resistant pathogens and has a broad spectrum of antibacterial capabilities. Studies also showed that it can disperse and kill bacterial in biofilms or enclosed communities of cells; thus, it can be used to prevent bacteria in wounds and implanted devices.​
  2. Garlic – the chemical compounds in garlic have been proven to display antimicrobial activities that help kill pathogens responsible for common and rare infections. Garlic has been used for centuries to combat infectious diseases.​
  3. Oregano oil – one of the most powerful antibacterial essential oils, oregano contains antibacterial and antifungal compounds that make it effective against many strains of bacteria, including Escherichia coli (E. coli).​
Bonus: Probiotics can also reduce harmful and resistant bacteria while increasing good bacteria in your gut. Research showed that taking probiotics not only helps boost your immune system, it is also important to take them after antibiotics to replenish the good bacteria in your body.

Read more about alternative medicine in food at Medicine.news.

Sources include:

PrepSchoolDaily.BlogSpot.com

InTechOpen.com

Observer.com

 
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University of Queensland

CBD shown to kill treatment-resistant bacteria*

University of Queensland | Science Daily | 19 Jan 2021

CBD, has been shown for the first time to kill the bacteria responsible for gonorrhoea, meningitis and legionnaires disease.

The research collaboration between The University of Queensland and Botanix Pharmaceuticals Limited could lead to the first new class of antibiotics for resistant bacteria in 60 years.

The UQ Institute for Molecular Bioscience's Associate Professor Mark Blaskovich said CBD -- the main nonpsychoactive component of cannabis -- can penetrate and kill a wide range of bacteria including Neisseria gonorrhoeae, which causes gonorrhoea.

"This is the first time CBD has been shown to kill some types of Gram-negative bacteria. These bacteria have an extra outer membrane, an additional line of defence that makes it harder for antibiotics to penetrate," Dr Blaskovich said.

In Australia, gonorrhoea is the second most common sexually-transmitted infection and there is no longer a single reliable antibiotic to treat it because the bacteria is particularly good at developing resistance.

The study also showed that CBD was widely effective against a much larger number of Gram-positive bacteria than previously known, including antibiotic-resistant pathogens such as MRSA (methicillin-resistant Staphylococcus aureus) or 'golden staph'.

Dr Blaskovich said cannabidiol was particularly good at breaking down biofilms -- the slimy build-up of bacteria, such as dental plaque on the surface of teeth -- which help bacteria such as MRSA survive antibiotic treatments.

Dr Blaskovich's team at the Centre for Superbug Solutions mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD's killing power.

"Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during 'treatment'."

"We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don't know yet exactly how it does that, and need to do further research. The research team also discovered that chemical analogs -- created by slightly changing CBD's molecular structure -- were also active against the bacteria."

"This is particularly exciting because there have been no new molecular classes of antibiotics for Gram-negative infections discovered and approved since the 1960s, and we can now consider designing new analogs of CBD within improved properties."


Vince Ippolito, the President and Executive Chairman of Botanix, said the research showed vast potential for the development of effective treatments to fight the growing global threat of antibiotic resistance.

"Congratulations to Dr Blaskovich and his team for producing this significant body of research -- the published data clearly establishes the potential of synthetic cannabinoids as antimicrobials," Mr Ippolito said.

"Our Company is now primed to commercialise viable antimicrobial treatments which we hope will reach more patients in the near future. This is a major breakthrough that the world needs now."

Dr Blaskovich said collaborating with Botanix has sped up the research, with Botanix contributing formulation expertise that has led to the discovery that how cannabidiol is delivered makes a huge difference in its effectiveness at killing bacteria.

The collaboration has enabled Botanix to progress a topical CBD formulation into clinical trials for decolonisation of MRSA before surgery.

"Those Phase 2a clinical results are expected early this year and we hope that this will pave the way forward for treatments for gonorrhoea, meningitis and legionnaires disease."

"Now we have established that cannabidiol is effective against these Gram-negative bacteria, we are looking at its mode of action, improving its activity and finding other similar molecules to open up the way for a new class of antibiotics."


*From the article here :
 
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Albert Hofmann

Anti-viral effects of Ibogaine

Dr. Vic Hernandez

Ibogaine in its administered forms has typically been applied to persons seeking a chemical dependence addiction treatment. The target population not only has had to contend with chemical dependence issues but issues concerning other infections, most notably HIV and/or HCV or co-infection. As antidotal and preliminary scientific information is noted concerning Ibogaine treatments, trends suggest potential applications to these pathogens. Medical science has not rigorously pursued investigation into the potential applications of Iboga alkaloids in in vitro work, animal and human studies.

My work concerns oxidative stress and HIV, and its contribution to the understanding of pathogenesis and pathophysiology. I am involved in developing guidelines for physicians treating HIV, trial design and methodology. I have worked on developing practitioner education forums to support understanding and treatment for isolated populations infected with HIV, notably active users. My unique relationship to communities affected by HIV, activism and passion for my work has brought me to unique understandings and relationships that I have brought to other public health work. I received a congressional citation for this work. Working with Lynn Mofenson at the NIH we moved to look at micro-nutrient intervention in HIV non-progressors to affect HIV progression and delay ARV intervention without compromising patient health by allowing HIV to run unabated. The fruits of this work have been born out in the African studies noted in US papers recently. Working with Lynn, Fauzi at Harvard and others, we established a treatment approach that was frowned upon when we started back in 1993 into accepted and respected reality.

Noted work included the resurrection of Alfa Lipoic Acid as a micronutrient effecting Liver toxicity. It would later be applied to HCV cases. In recent years, needing and wanting a break from HIV, I've worked in the realm of cancer, looking at the role of genetics in identifying trends in non-progressors utilizing non-conventional therapies or no therapeutic interventions. This work has allowed me to look at orthomolecular medicine (effect of micro-nutrients on the biochemistry of the body, pathogen infection, self cells run amuck and wellness and quality of life). Working with colleagues and mentors as Lynn Margulis at U Mass Amherst and Walter Willet at Harvard, I began to understand as Lynn puts it: the symbiosis of medicine, and as Walter puts it, as the effect of the basic building blocks of body systems and their abilities to stay healthy. Why mention this blather? You need to know where I am going with this information, so we can understand where we headed, now and in the future.

HIV. Where we are, and what it means

HIV research and treatment approaches have been checkered and somewhat baffling in approach and far too complex to delve into at this meeting or in this short of time. From a conventional medicine perspective, there are three steps required for HIV to enter cells: Attachment, Binding to a co-receptor, and Fusion of HIV into CD-4 cell. The currently available classes of drugs work to prevent the process of HIV reproducing itself and infecting new cells after HIV enters the CD-4 cell: They are Nucleoside Analogues, Non-nucleoside Analogues and Protease Inhibitors. These drugs have been administered in combination, at varied intervals, and in varying doses to tease out efficacy for the particular viral strain(s) expressed by the patient. Toxicities to body systems and healthy cells require strict and watchful management.

There is a new class of drugs called Entry Inhibitors which block HIV from entering CD-4 cells. They work by blocking the HIVs ability to enter and infect a cell. Essentially there are two steps to entry of HIV into the CD-4 cell. HIV attaches to the CD-4 cell and then fuses with it. After fusing with the cell, HIV can dump its genetic material into the CD-4 cell, the material it needs to reproduce itself in the CD-4 cell. There are two steps to attachment: attaching to the CD-4 receptor and then to a co-receptor, either CCR5 or CXCR4.

Basically, how Entry Inhibitors work is first by:

- Attachment
- Co-receptor binding
- Fusion

Currently available HIV drugs other than Fuzeon, prevent HIV from reproducing once HIV in the cell.

HIV Super-infection and HIV Drug Resistance. Let's start with HIV super-infection. Studies over the past two years suggest this is a real problem. Super-infection is when a person who has HIV gets infected with a second viral strain of HIV. Super-infection, based on study, occurs 5 to 13 months after estimated date of initial infection. The super-infection strain can be associated with ARV susceptibility and adherence. In some cases, a person can be infected with a drug resistant strain and then become infected with a super-infection wild-type or visa-versa. Initial co-infection cannot be ruled be ruled out. Molecular investigation determines evidence of super-infection coupled with progression and ARV response. The rate of the super-infection based on study hovers somewhere around 6.5% annually. Harm reduction counseling is recommended by the researchers.

There are some in the medical science community that are trying to link the super-infection to a patient zero that originated from New York. Nonsense! This was tried at the beginning of the HIV/AIDS pandemic by saying that HIV started in North America with a Canadian airline steward. It is impossible to narrow down such a claim. By the way, in that case, it was refuted by the testing of IDU blood samples from the early seventies that had been banked at Beth Israel. HIV was found in those cohorts, long before the Canadian air-steward stuff. At a recent conference, Paul Volberding MD from UCSF noted that the super-infection business hinged on one reliable case and that the bally-who was uncalled for. This should not minimize sound and reliable public health interventions such as safer sex practices.

Unfortunately, we are learning about HIV pathophysiology and pathogenesis as we go along instead of developing the understanding first. This may deal a blow to 18-MC, if applied to HIV or not.

As for HIV drug resistance, it was not until ICAAC in October of 2004 did the rates found seem alarmingly worrisome. Soon after, the media has grabbed a hold on this information. Studies are finding an escalation of HIV drug resistance during primary infection period (shortly after infection). And the resistances vary among drug classes. Drug resistant HIV acquired at time of infection can establish itself as the dominant virus population and become archived in the latent cellular reservoir. This may result in sub-optimal response to ARV interventions and promote the accumulation of mutations and jeopardize already limited treatment options. In further study, HIV drug resistance has been found in 1 of 7 treated in the US of a cohort of 317 in 40 US cities. The prominent resistance was found in the non-nukes class of drugs. Ethnic differences were noted. Latinos and Asian patients had a lower prevalence of reduced susceptibility (6 percent, with Caucasians at 27 percent, and Blacks at 23 percent. There were no gender differentiations or comparisons done. These were among male cohorts.

HCV and co-infection

HCV therapeutic interventions are limited in pharmaceutical application (interferon and pegalated interferon [riboviron and interferon]) are limited. There are surfacing reports indicating significant efficacy with TCM. In the co-infected individual, treatment options reduce due to the environment of the liver.

When Howard approached me with this paper, I read it and got excited. I like new ideas and approaches especially if the science is tight and is respectful of change. No one has the ace card and false hope, especially for patients, is highly unethical. Ask David Ho MD at Rockefeller's Aaron Diamond Center regarding the premature delivery of HIV cure based on invitro data. After reading the paper Howard shared, the questions flooded through my head and as we talked, he suggested I say a few words. Reluctantly, I accepted. I have been trying to avoid public gigs (especially those that risk pissing contests). The paper (above) by Silva et al from Brazil entitled: Anti-HIV-1 Activity of Iboga Alkaloid Congener 18-MC is a significant piece of work. It was an in vitro (in lab) study using human cells. The Iboga alkaloid 18-MC was introduced to human Peripheral Blood Mononuclear cells (PBMCs) and monocyte-derived macrophages. The result was the significant inhibition of isolates of HIV-1 in a dose dependent manner.

The approach of this anti HIV-1 inhibitory activity study went something like this: An in vitro study of donor PBMCs cells from healthy donors was executed with monocyte-derived human macrophages isolated from the PBMCs. This was not a formal clinical trial with subjects. Materials and methods seemed valid and reliable. Then HIV-1 primary isolates (3) were used. AZT, a nucleoside analogue was used as a control probably because the mechanism of action of 18-MC is as reverse transcriptase inhibitor and AZT is a nucleoside analogue used to affect reverse transcriptase. PBMCs were exposed to viral suspensions of HIV-1 P-24 antigen. Viral replication was assessed by measuring P-24 antigen. Dose ranges from 12.5 to 50 micromolers significantly effected HIV proliferation. Time durations varied from 3, 10, 14 and 21 days. A variety of doses, durations were done to observe safety, and effect. Compared to the control (AZT) which was rigorous as expected, 18-MC faired very well. It should be noted that the infection assays were performed with primary cells (acutely infected PBMCs and macrophages) to avoid the genotypic and phenotypic changes that might occur during viral changes that might occur during viral passages in tumor cell lines. They also used primary isolates, which are phenotypically closer to the viral population present in HIV-1 infected patients. Additionally, they looked at the naturally occurring COR and its anti HIV-1 effect and found significant results, but the data was not reported. They did report the indole alkaloid congener 18-MC molecule of the natural COR, presenting little to none of the adverse effects associated with the original molecule in this antiviral study reported. These study design considerations contributed to a tight study with valid and reliable outcomes.

Basically, 18-MC inhibits HIV-1 replication in human PBMCs and in monocyte-derived macrophages. This antiviral effect of the alkaloids may be due to their action on different steps of viral replication, such as inhibition of syncytium formation and reducing the activity of HIV-1 enzyme reverse transcriptase. So how this applies to the HIV treatment intervention picture is up for grabs. Certainly, further study needs to be done on the mechanisms by which 18-MC decreases HIV replication in vitro, in addition to inhibition of HIV reverse transcriptase. It is worth doing for a number of potential reasons:

1. 18-MC has a lower toxicity profile compared to the drugs in the study control class (nucleoside analogues). And I would venture to say in the other three classes that prevent the process of HIV from reproducing itself and perhaps infecting new cells after HIV enters the CD-4 cell.

2. 18-MC provides a potentially safe ARV therapeutic intervention in less virulent strains of HIV and minimizing toxicities.

3. Co-therapeutic intervention can be matched with micro-nutrient regimens which have been shown in study to delay ARV therapeutic intervention for up to 5 years, notably in women and infected infants.

4. 18-MC, based on its mechanism of action against HIV in comparable drug classes, could be applied to HIV infected pregnant women to affect mother to fetus transmission rates. The studies among these populations used AZT, the control for the 18-MC. I believe 18-MC has a less toxic profile than AZT even thought AZT showed significant interruption of mother to fetus HIV transmission.

5. Given the pharmacodynamics of Iboga alkaloids in the brain, the potential for crossing the blood brain barrier is significant.

6. As mentioned earlier in Dr. Onaivis presentation, the potential of Ibogaine to regulate inflammation (genetically) is significant for persons living with HIV/AIDS where inflammatory states are hallmark.

7. I believe it would be cost effective in poorer nations struggling with HIV infection.

There are issues here, too.

1. Since this 18-MC affects HIV-1 at reverse transcriptase, such as other classes of drugs, perhaps there is a chance for drug resistance as found in other drugs in that class or a shorter duration to it?

2. Perhaps it can be used in initial therapy in super-infections or drug-resistant strains until it succumbs to those viral expressions.

3. In combination with other drug classes such as nukes, non-nukes and protease, there is a strong potential for side effects. But given their toxicity to body systems and healthy cell lines that the nukes, non-nukes and protease inhibitors have, pairing them up with this group may not be wise. This is dependent on dose levels and state of the patient.

4. Perhaps it can be paired up with the new Entry Inhibitors to provide a well-rounded combination to thwart HIV. This I see as the most promising combination.

5. In the case of co-infection, particularly for those with HIV/HCV infection and dicey livers, this may prove to be questionable. I believe the verdict is not in, and further research is needed.

6. Regarding potential psychedelic effects, it should be noted that Sustiva reports similar side effects (like hypnogocic hallucinations) and has been controlled through a variety of provider and patient interventions.

What medical science needs to do

Simple, more study, but the politics of what gets studied and how it gets funded are sad realities. But history has shown us that vigilant activism can effect epistemology, study approach even study design and recruitment. For example, a medical treatment support group comprised of non-active injection drugs users (IDUs) based in the Bronx found the Hypericin study at Bellevue Medical Center in NYC to be of interest. But they found the route of administration (subcutaneous) a bit unwelcoming since it brought up potential triggers to use again. They met with the principal investigator (PI) Fred Valentine MD and persuaded him to add an arm that was orally administered. He agreed and they (the patients) help recruit for the study.

Since the study was done in Brazil and not in the US, the chances for further investigation are probably more promising. Based on this limited work, an Investigational New Drug (IND) designation can be developed, funding lined up, bring it up with Community Review Boards (CRBs), cultivate interested researchers are among the many avenues medical science must go with this. Working with the Institutional Review Boards (IRBs), who wheel a lot of political power to support pursuit of an Iboga-alkaloid as an anti-viral. This is most effective if you have a PI lined up with a clear focus, good science under his/her belt coupled with sufficient funding source(s).

What can patients and advocates do?

I believe there are many things that can be done here, to name a few:

1. Brainstorm with constituencies of patients in effected populations. Dr. Ken Alper and others have mentioned the comradery of the group having been treated with Ibogaine. These people serve as a constituency who can affect the fast tracking of treatments.

2. Develop proactive treatment support groups that can be involved in trial design, methodology, trial recruitment, trial implementation, and adherence. For example, I have started HIV/AIDS treatment support groups called AMEN (Attitude, Medications, Exercise, Nutrition). These groups encourage patients to be their own primary healthcare advocate. They are involved in all aspects of patient treatment intervention(s), advocacy, and often times drug development.

3. Treatment support group can not only promote such objects as patients being their own primary healthcare advocate but also informal researchers. For example, setting up simple databases that encourage the observation of trends of persons taking Ibogaine and the effect on say HCV or HIV. Blood work-up can be a point measure to observe trends.

4. Cultivate active and fruitful relationships between the treatment support group members and their healthcare providers, especially when it comes to understanding the population of active and non-active users, their medical conditions and predispositions, and above all the dynamic of behavior notably addiction.

Remember, some of the most profound discoveries and epistemology in medical science have come from non-medical and/or science trained patients and their advocates.

https://ibogainedossier.com/v_hernandez.html
 
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Harmaline | C13H14N2O

Harmaline and its derivatives against the infectious Multi-Drug Resistant Escherichia coli

Hina Siddiqui, Sehar Tasneem, Saba Farooq, Amtul Sami, Atta-Ur Rahman, Muhammad I Choudhary
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan

Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. The harmala alkaloids are psychoactive in humans.

Multidrug resistance (MDR) is a major challenge in the treatment of infectious diseases. The MDR in urinary tract infection causing bacteria, such as Escherichia coli, has made treatment of UTI very difficult. The aims of the current study were to synthesize a library of harmaline derivatives, and to evaluate their activity against various strains of multi-drug resistance (MDR) E. coli. Harmaline derivatives were synthesized by the reaction of harmaline with various acid halides and anhydrides. These compounds were subjected to susceptibility determination by in vitro MTT assay. The changes in morphology of the bacterial cells after the treatment with harmaline and its derivatives were studied through scanning electron, atomic force and fluorescence microscopy. The current study demonstrated that harmaline, and its derivatives were identified as anti-MDR agents against MDR strains of E. coli.

Harmaline and its derivatives were identified as anti-MDR agents against various highly resistant MDR clinical isolates of E. coli. These compounds may serve as the leads for further studies towards the development of treatment against the infections caused by MDR E. coli.​

DOI: 10.2174/1573406413666170125113832

https://www.ncbi.nlm.nih.gov/pubmed/28124613
 
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