October 2, 2013

Hepatitis C Treatment in Ukraine: A Victory For Patients

Andriy Klepikov Executive Director, International HIV/AIDS Alliance in Ukraine

Posted: 10/02/2013 5:52 pm

Price is a game changer. Just look at the effects caused by the advent of low-cost airlines. Flying has never been cheaper and people who could not afford boarding a plane can now travel to places they had only dreamed of. In other words, it has brought changes to the industry and to people's lifestyle. The same applies to health. Cheaper health products change people's lives. Ukraine has the highest prevalence in Europe of hepatitis C, a chronic liver disease that can be especially deadly when it strikes HIV patients. The number of people infected is estimated at 1.2 million for a population of 44 million. Yet the high cost of medication has been a serious impediment to treatment. A near monopoly in the pharmaceutical market by Merck (MSD) and Roche, the two companies that manufacture Pegylated Interferon, has kept prices stubbornly high. But thanks to the support of the Global Fund, Alliance Ukraine recently negotiated a steep discount with a pharmaceutical manufacturer for medication, enabling treatment to be significantly expanded for highly vulnerable patients co-infected with HIV and hepatitis C. This news is of little relief for the 300,000 people who died of hepatitis C since the beginning of the year, but could save the lives of 150 million people infected with the virus.

Hepatitis C is often called "the hidden or the silent epidemic," as very little is known about the risks and spread of hepatitis C. But this is not an excuse for international and national decision-makers to remain silent. The hepatitis C epidemic knows no borders and has no war-chest to combat it. No global targets have been set by global health stakeholders to improve access to hepatitis C treatment, as has been the case in the treatment of HIV/AIDS, tuberculosis and malaria. Despite efforts by patients, civil society, doctors' associations and many governments across the world, treatment worldwide for hepatitis C continues to be beyond reach for most patients. In my country, however, we recently scored an important victory. Since the beginning of 2011, only 80 courses for treating adults infected with hepatitis C were procured, in addition to some for children. The situation resembled that of HIV antiretroviral therapy (ART) 10 years ago, when the treatment per person cost $10,000, compared to $150 now. Before the Global Fund began providing funds to International HIV/AIDS Alliance in Ukraine, there were only 250 patients receiving ART in the entire country. Today, there are nearly 50,000 people, and 83% out of them are getting treated with drugs procured from Ukraine's national budget.

The hepatitis C treatment initiative allows Alliance Ukraine to acquire drugs at a cost of US$5,000 for a single 48-week course of treatment, a reduction from the previous price of US$13,200. It is the first time the treatment, combining Pegylated Interferon and Ribavarin, will be available in a Global Fund-supported program in Ukraine. The initiative has stimulated action by the government and has become a catalyst for change. On 17 September, a decision by the cabinet of ministers to set up a national program for hepatitis with US$4.2 million came into effect. The Health Ministry has acknowledged that the US$5,000 price would now be considered by the Ministry as a benchmark for governmental procurement of the medication. With Global Fund support, Alliance Ukraine has procured 100 courses totaling US$500,000. Using this price benchmark, the government has committed itself to procuring at least 13,000 courses totaling US$ 65 million by the end of 2015.

This is a victory for patients and for public health in Ukraine, and one that will have an enormous market impact. Hopefully, the Ukrainian example will change the minds of donors, politicians and pharmaceutical manufacturers, making treatment of hepatitis C treatment not only affordable in Ukraine, but worldwide.

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By Mark James on October 2, 2013

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What Now? Remind Me is, despite its name, an extraordinarily lucid, moving portrait of illness, artistry, and, rarest of all, time. Portuguese filmmaker Joachim Pinto lenses himself as he goes through experimental drug trials for HIV and Hepatitis-C, partially as a note-taking exercise and obliquely as a last will and testament. The drugs he takes make him forgetful and scattered, and he’s afraid they might not work, or they might poison him along the way. But before long, the elegiac quality of the film lifts to allow amused, contemplative shadings to drape themselves over Pinto’s memory, letting tenderness and humor nose their way in.

The running time is over two and a half hours, though putting yourself through the entire course of treatment is more than good for you: it shows you the importance of saving your own life.

The notebook of a year of rest, this movie attains the religious insights of a true Sabbath. Non-practicing Pinto gives himself over to the arms of his Christ-like husband Nuno, and illness draws out the beatitude latent in fatigue. Weakened but essentially unhurt, Pinto delivers a serene rejoinder to the unseen doctors and viruses arrayed in tandem against his life. He is alive; who is more alive than someone for whom slipping in and out of beams of light counts as a triumph? Everyone else, with their frenetic energies, their evasions and their aggrandizements, inflates their bodies with death. Pared down, Pinto is the stubborn core of vivacity. He may be skinny, but his skin bears no superfluity, except possibly under his eyes.

Though Pinto has worked primarily as a sound designer, it’s clear he has scopophilic tendencies. The film is teeming with close-ups of flies, bees, frogs, slugs, protists, plants, and trees. A trip to a museum with wax casts of syphilis victims’ genitals is an opportunity to linger on each one, the cream-colored paraffin lit so as to offset its tinted and enflamed pustules and penises. He visits a lab in order to film the virus he’s hosting, but he has to make do with filming the technicians at work. The leaning Gate of Europa tower in Madrid, once for him a reference to an Almodóvar film but repossessed in memory by the economic crisis, appears in the background of an extended shot of an elegant butterfly, out of focus and less compelling than the ancient creature’s alien and filigreed wings. A dying wasp writhes on its back, straining its antennae as much as its legs, grasping equally at salvation and sensation.

This is the heart of the film and the message which it is worth sitting through to receive. Touching, handsomely shot, and historically significant, Pinto’s film achieves a spiritual grace which is rare enough in the world, but that he does it by attention to the specific qualities of sickness and cinema makes What Now? Remind Me all the more of a treasure. Do watch this movie if you have a stake in being alive.

Early on, Pinto mentions he’d tried to use a calendar to keep track of his good days and bad days. There were only bad days, so he gave up. Winston Churchill referred to his depression as “a black dog” that followed him, but Pinto is trailed by four lighter-coated companions. They are true beasts: They look like unmaned lions, or small bears. They suffer their own medical complications and keep Pinto and his husband Nuno on regular work hours while they plant trees on their land. The dogs are the embodiment of good nature, with unmistakable smiles and instinctual care for the sick. Although in his diaristic voiceovers Pinto floats theories about the origin of viruses in the domestication of animals and agriculture, he counter-poses this with scenes of pastoral bliss with his dogs panting in the tall grass and buttercups, nuzzling with handsome Nuno. Evil or suffering may have an entry point into the world, but Pinto can have no regrets.

“Lights and sounds hurt me,” he says. It must be a difficult admission for a filmmaker, but it also reminds us of the real pain inextricable from what we are watching. Pinto is tender in both senses—to the touch, and to those around him. Recalling the Vietnamese classmates he met at university in East Germany, a year after the war ended, he says, “As if extreme experiences lead to extreme sensitivities.” It’s an extreme year for everybody: his friend Jó is starting the same drug trial, the rain has stopped falling, the banking crisis is a constant, raw pain. But extremity isn’t exceptional anymore. This is the way things will be now. From now on, his body will hurt until it dies. Water lilies on the pond bear ashes from frequent fires. He develops resistances to the treatments.

How did I get here? he asks. He means the island as well as the present. He casts a wide net for answers. He considers the Neanderthals, the origin of language, natural life, evolution, extinction. In 1957, the year he was born, Sputnik launches into space to look back at Earth. In 1957, proteins are discovered in viruses; they are called interferons, the name of the medicine he is on. In Germany, he recalls meeting a young activist named Angela Merkel. Now, she ministers to the disease in the Eurozone economy, a comorbid infection with his HIV. She puts it on an experimental treatment with known drastic side effects, including health cuts. She doesn’t know if it will work.

Pinto doesn’t activate memory to search for a distant source of blame. He’s too tired to care about that. His memories comfort him and allow him to relive moments of joy and communion, though they are, unhappily, punctuated by the deaths of friends and icons: Passolini dies, then it’s Foucault, then it’s Guy Hocquenghem. Pinto and Nuno are in Morocco to film Carmen Maura, then it’s the beginning of antiretrovirals. In Paris, it’s the support and presence from Claudio, then the death of Phillip Brooks. Then it’s last time “we” were all together, the last concert of Nuno’s metal band held, spreading a friend’s ashes in the ocean, encountering Rufus, their first dog. Then he’s in his house on the island, and we are with him.

Half an hour before it’s all over, Joachim stops the treatment, too. He couldn’t go on; it was too painful. In Madrid to receive his final test results, he reads an illustrated manuscript of the history of the world, written in the 1600s. Over an image of Eros, he thinks he sees the words “Nuno” and “love.” It’s actually a Virgil quote, “NUNC SCIO QUID SIT AMOR,” “now I know what love is.” It’s the same thing. Nuno is nunc, now, the present without length, the site of all duration and what all experience must pass through. We are living in sad times, he says, but now I know what love is.

And the film continues: In the car, after treatment has ended and life goes on, the rains come again. The virus will go too; maybe not for Joachim, but for humans. Though they’ll still die some other way, they’ll have been alive. What Now? Remind Me makes it seem like enough.

The Upside: Epic in scale at over two and a half hours it rewards patient viewers with a very intimate portrait and affirmation of living.

The Downside: None.

On The Side: Winner of the 2013 Locarno Jury Prize and the FIPRESCI award at the Swiss festival. It’s currently playing the New York Film Festival, but no US release is yet scheduled.

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Mural to raise awareness for Hep C

Provided by Forbes Advocate

By Sophie Harris Oct. 3, 2013, 5 a.m.

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Isiaha Ramsay with the mural that he helped create with fellow classmates at Forbes High School. 0913mural(17)

A number of year nine and 10 Aboriginal students at Forbes High have been busy creating a street art mural as part of a program to raise awareness for hepatitis C.

The project, Your Mob, My Mob, Our Mob, is run by the Aboriginal Health and Medical Research Centre (AHMRC) and aims to raise awareness and increase knowledge of hepatitis C through peer education.

The project is aimed at Aboriginal adolescents aged between 12 and 19, who are taught key messages about hepatitis C in a three day workshop.

Hepatitis C Project Officer at AHMRC, Lisa Panton is in charge of running the project at Forbes High with the help of Kerry Walker, the Aboriginal Project Officer for Hepatitis at the NSW Aboriginal and Community Controlled Health Services (ACCHS).

They say the idea of the project is that on the completion of the workshop, the students will become peer educators and help to communicate information about hepatitis C to their peers.

The creation of the street art mural is part of the program and is used to continue the conversation about hepatitis.

The 11 students who participated in the program helped design and create the mural with the help of a professional graffiti artist.

Ms Walker says that involving the students in painting the mural establishes a sense of community.

“When you’ve got something like a mural that they’ve created themselves, it creates a sense of pride and having a mural that’s forever on display will continue the buzz around hepatitis,” she said.

Ms Panton says the mural is a great way to reinforce the information the students have learnt and will continue to raise awareness as a constant physical reminder.

“Everyone at the school was watching the mural go up and after we leave, they’ll still be talking about it, which is the idea,” she said.

“It keeps the conversation going,” Ms Walker adds.

The women say it’s important to talk about hepatitis to help break down the stigma and shame associated with being ill-informed about the virus.

“So we want to open up the communication channel,” Ms Walker said.

The girl who features in the mural is Nadika Vidler-McKeown, one of the Aboriginal students who participated in the workshop.

She is very happy with being chosen as the face of the mural.

“It feels awesome, I’m really proud,” she said.

“I like being able to represent my culture with things like that.”

Nadika says the students all got a lot out of the workshops and learnt some valuable information that will stick with them.

“They were really good, I learnt so much…it makes you think twice about some of the things you do,” she said.

One of the most important things the students learnt was to avoid sharing items such as toothbrushes, razors and syringes and to steer clear of getting backyard tattoos or piercings, as these can easily spread the hepatitis C virus.

This is represented in the wall mural which will be a permanent reminder to students.

At an assembly to officially present the mural to the school, principal of Forbes High, David Harris thanked the women for coming to Forbes High as part of their initiative and thanked everyone involved in the creation of the mural.

“This is fantastic and lifts up this area quite a bit,” he said.

“It’s quite worthwhile and a very big credit to you.”

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Despite FDA shutdown, Gilead, Amarin still on for high-profile panels

Provided by FierceBiotech

October 1, 2013 | By Damian Garde

As of today, the FDA has been virtually halved, and while the mandatory furloughs spelled out by a government shutdown may imperil some of the agency's duties, it appears that drug approvals and reviews will go unmarred.

Yesterday, an FDA spokesperson told FierceBiotech that, because agency advisory panels are funded by industry-paid user fees and not tax appropriations, "generally speaking, these meetings would continue in some way" after a shutdown. That's not exactly a clear-cut guarantee, and, unsurprisingly, there's no one around to clarify this morning. That said, the drugmakers with products on the line are optimistic their timelines will stay intact.

Gilead ($GILD) has an Oct. 25 date to with the Antiviral Drugs Advisory Committee to discuss sofosbuvir, a hep C treatment it hopes to get approved this year, and that meeting hasn't been canceled, the company told us. Johnson & Johnson ($JNJ) is due before the same panel the day before to discuss simeprevir, its late-stage hepatitis C treatment under the FDA's priority review, but the company couldn't confirm whether the review was on schedule.

Amarin Pharmaceuticals ($AMRN) is gearing up for a weighty Oct. 16 panel vote on whether to approve Vascepa paired with statins to reduce cholesterol, and the company said it hasn't been informed of any delays. On the device side, Medtronic ($MDT) has an Oct. 8 date with the Circulatory System Devices Panel, asking for an expanded indication for its fleet of pacemakers and implanted defibrillators, and the company said that meeting is still on.

The FDA is down 6,620 employees this morning, losing about 45% of its staff to furloughs, and the agency has suspended the "majority" of its internal lab research, according to a Department of Health and Human Services briefing. Also on hold is the FDA's usual stream of guidances and new regulations, as government agencies have been instructed to publish only documents that support activities related to "imminent threats to the safety of human life or protection of property."

It remains anyone's guess how long the shutdown will last. The House and Senate have thus far traded party-line votes on sure-to-be-rejected budget bills, with Republicans pushing to include provisions that would delay aspects of the Affordable Care Act while Democrats insist on a stripped-down resolution to reopen the government.

Related Articles:
What happens to the FDA in a government shutdown?
Government shutdown would likely roil FDA's drug-approval process
Device tax at center of government funding battle

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Clin Ther. 2013 Sep;35(9):1458-73. doi: 10.1016/j.clinthera.2013.07.421. Epub 2013 Aug 22.

Prakash RK, Kanna S, Mullen KD.

MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio. Electronic address: ravi.prakash@case.edu.

Abstract

BACKGROUND: Hepatic encephalopathy (HE), which may be categorized as minimal or overt, is a serious and progressive neuropsychiatric condition that occurs in patients with liver disease or portosystemic shunting. Overt HE (OHE) presents as a wide spectrum of clinical signs and symptoms, ranging in severity from mild confusion to life-threatening coma. Minimal HE (MHE) is a more subtle form of the condition; it is characterized by deficits in cognitive function in patients with a normal clinical examination.

OBJECTIVE: The purpose was to review the effect of MHE on patients and caregivers, as well as its currently available diagnostic and treatment options.

METHODS: A MEDLINE search of published diagnostic assessments, clinical trials, and guidelines from 1985 to 2012 were reviewed and analyzed to assess the potential effect of MHE in the clinical practice setting.

RESULTS: Accumulating evidence suggests that MHE has a substantial negative effect on patient quality of life, particularly in activities that require attention, motor skills, and visuospatial ability. Because MHE lacks obvious clinical signs, specialized testing is required for diagnosis, although there is no consensus on the most appropriate assessment tools or treatment algorithms. Compounds derived from bacterial activities in the gut can cause neurochemical changes in the brain. These gut-derived toxins (eg, ammonia, benzodiazepine-like substances) are implicated in the pathophysiology of OHE. In patients with liver disease or portosystemic shunting, these toxins are inefficiently detoxified, accumulate in the blood, cross the blood-brain barrier, and result in abnormalities such as altered neurotransmission, astrocyte swelling, and impaired energy metabolism. Therefore, treatments have focused on toxin removal and the management of gut flora levels. Several studies have indicated that probiotics, nonabsorbable disaccharides, and nonsystemic antibiotics can all be effective in improving the symptoms of MHE. Furthermore, prophylaxis for MHE in patients with cirrhosis could serve to improve patient quality of life while preventing its transition to OHE.

CONCLUSIONS: Although MHE detection and treatment is not currently the standard of care, several therapies have been reported to improve cognitive function and quality of life. Interest is increasing in the proactive diagnosis and management of MHE in the clinical practice setting. However, research is required to determine the conditions under which the putative benefits of prophylactic MHE therapy outweigh the costs.

© 2013 Published by Elsevier HS Journals, Inc.

KEYWORDS: cirrhosis, hepatic encephalopathy, lactulose, minimal, overt, probiotics, rifaximin

PMID: 23972578 [PubMed - in process]

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Antimicrob Agents Chemother. 2013 Oct;57(10):5037-44. doi: 10.1128/AAC.00910-13. Epub 2013 Jul 29.

Wilfret DA, Walker J, Adkison KK, Jones LA, Lou Y, Gan J, Castellino S, Moseley CL, Horton J, de Serres M, Culp A, Goljer I, Spreen W.

GlaxoSmithKline, Research Triangle Park, North Carolina, USA.

Abstract

GSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We performed a three-part, randomized, double-blind, placebo-controlled study in 46 healthy subjects and 23 HCV-infected subjects. After an overnight fast, healthy subjects received GSK2336805 as 10 mg, 30 mg, 30 mg plus food, and 60 mg in a single dose and 10 mg (7 days), 30 mg (7 days), and 75 mg (14 days) in a once-daily multiple dose. Subjects with HCV received GSK2336805 as a 1- to 120-mg single dose. In subjects with HCV, reductions in HCV RNA were observed within 4 h and a single dose of GSK2336805 of ≥10 mg resulted in a statistically significant ≥2-log reduction in HCV RNA compared with placebo at 24 h postdose. GSK2336805 was readily absorbed in all subjects, and the half-life (t1/2) was suitable for once-daily dosing. Administration of GSK2336805 with food had no effect on plasma GSK2336805 exposure; however, absorption was delayed, with a median tmax (time to maximum concentration of drug in serum) of 4.5 versus 2.0 h. Twenty subjects who received GSK2336805 experienced mild to moderate adverse events; none were serious. GSK2336805 was well tolerated and exhibited rapid, significant antiviral activity after a single dose in HCV-infected subjects. These results support the conduct of further studies evaluating GSK2336805 administered once daily for longer durations in combination with peginterferon, ribavirin, and other direct-acting antivirals. (This study has been registered at ClinicalTrials.gov under registration no. NCT01277692.).

PMID: 23896477 [PubMed - in process]

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Also See: A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 When Given as Monotherapy and in Combination With Peginterferon alfa-2a and Ribavirin in Hepatitis C Virus Genotype 1-infected Treatment-naive Subjects

Liver International

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

Stephen Gardner1,*, Amy Cutrell1, Cindy Elko-Simms2, Kimberly Adkison1, Robert Hamatake1, Jill Walker1, Maribel Rodriguez-Torres3, Zhi Hong1

DOI: 10.1111/liv.12334

This article is protected by copyright. All rights reserved.

Publication History

Accepted manuscript online: 25 SEP 2013 06:46AM EST
Manuscript Accepted: 6 SEP 2013
Manuscript Revised: 22 AUG 2013
Manuscript Received: 10 JUN 2013

Keywords: GSK2336805; Peginterferon alfa-2a; Ribavirin; Hepatitis C; direct acting antiviral

Abstract

Background

GSK2336805 is a HCV NS5A inhibitor for chronic hepatitis C (CHC). In a prior Phase I study, GSK2336805 was well tolerated and had an antiviral and pharmacokinetic profile suitable for once daily administration.

Aims

The current 28-day, double-blind, randomized, placebo-controlled study evaluated once daily GSK2336805 60mg alone or in combination with peginterferon alfa-2a (180 μg per week) and ribavirin (1000-1200 mg daily) (PEG/RIBA) in treatment-naive genotype 1 CHC subjects.

Methods

5 centers enrolled 16 subjects in the USA and Puerto Rico who received GSK2336805 + PEG/RIBA or placebo + PEG/RIBA.

Results

Following a single monotherapy dose of GSK2336805 on Day 1, median reduction from Baseline in HCV RNA was -2.96 log10 (N=11) versus -0.13 log10 (N=4) for placebo. With the addition of PEG/RIBA on Day 2, subjects receiving GSK2336805 exhibited greater decreases in viral load over the 28-day treatment period as compared with placebo. At Day 28, median reduction from Baseline was -4.86 log10 (N=9) in the GSK2336805 + PEG/RIBA group as compared with -1.98 log10 (N=4) in the placebo + PEG/RIBA group. At Day 28, rapid virologic response (RVR) occurred in 8/11 (73%) of the GSK2336805 + PEG/RIBA subjects as compared with 1/4 (25%) of the placebo + PEG/RIBA subjects. Adverse events were consistent with those reported in clinical trials of peginterferon and ribavirin, and no unique adverse events appeared to be associated with GSK2336805.

Conclusions

GSK2336805 is a potent NS5A inhibitor that showed a substantial antiviral effect as a monotherapy and in combination with peginterferon and ribavirin.

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Discovered in foods toxins that can cause cervical and liver cancer

Provided by MedicalXpress

October 1, 2013

Mexican scientists identified and quantified the amount of aflatoxins (carcinogenic) in food such as corn tortilla, rice, chili pepper, processed sauces, chicken breast and eggs, and revealed its relationship with cervical and liver cancer in humans.

The research won the National Award in Food Science and Technology in the Science Professional in Foods category organized jointly by CONACYT (National Council of Science and Technology) and the Mexican Coca-Cola Industry. It explains that both types of cancer can be originated by the ingestion of food contaminated with aflatoxins produced by the fungi Aspergilus flavus and A. parasiticus.

Magda Carvajal Moreno from the Biology Institute at UNAM (National Autonomous University of Mexico) and head of the research explained that this is the first time both conditions are related with the presence of aflatoxins, "the most frequent carcinogenic we ate daily" she said.

UNAM researcher analyzed 800 kilos of tortilla in Mexico City, ten different kinds of chili pepper, rice and corn among others. She also studied how much of this substance stays in animal tissues after ingesting this kind of food, and found that aflatoxins are present in chicken breast, gizzard, liver and eggs –white and yolk.

Carvajal Moreno explained that such molecule was recovered from tissue samples of liver and cervical cancer in humans, therefore aflatoxins are a very important factor in triggering this diseases.

"This research is the first in the world to report that cervical cancer can also be caused by ingesting aflatoxin contaminated food. This carcinogenic has also been detected as a trigger of colorectal, pancreatic, breast and lung cancer."

The specialist clarified that Human Papillomavirus is more carcinogenic and prone to trigger cervical cancer than aflatoxins.

The toxins –the researcher said- are in the water, soil and airborne, the fungi that produce them are an olive green mold that can be found in refrigerators, besides they are very resistant to high temperatures.

Every day, Carvajal Moreno said, each person consumes traces of millionths or milligrams of aflatoxin that accumulate over the years in DNA, decreased resistance in people and generate disease.

To avoid these substances, the UNAM researcher suggests properly storing food, which would control the production of the toxin. Also, vary the foods one ingests and preferably consume wheat tortilla and fish, as well as antioxidants.

The research that Carvajal Moreno did in collaboration with Jaime Berumen Campos from the Genomic Medicine Unit from General Hospital of Mexico now will be focused in studying stomach, esophagus and prostate cancer to determine if there is an association with aflatoxins.

Explore further: Is a common food fungus worsening the AIDS epidemic?

Provided by Investigación y Desarrollo

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