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Please quote Nature Medicine as the source of these items.

The June 2012 issue of Nature Medicine is available online.

June 2012

Rerouting the gut to reduce blood glucose

Nature Medicine Published online 20 May 2012

DOI: 10.1038/nm.2745

The middle intestine, or jejunum, senses glucose and plays a part in a gut-brain-liver axis to regulate glucose production by the liver reports a paper published online this week in Nature Medicine.

A classic hallmark of diabetes is high blood glucose levels. This elevation occurs because insulin cannot signal to the liver to reduce its endogenous glucose production, either owing to insulin resistance, as in type 2 diabetes, or a lack of the necessary hormone, as in type 1 diabetes.

Tony Lam and his colleagues show that the jejunum can sense glucose levels and signal to the brain to order the liver to reduce glucose output through a neuronal relay. A surgical treatment for obesity consisting of duodenal-jejunal bypass surgery showed reduced blood glucose levels in two rat models of type 1 diabetes within two days of the surgery.

Although these results suggest a possible surgical correction of the increased serum glucose observed in type 1 diabetes, the bypass surgery used is still experimental, including in human patients. Also the effects on blood glucose levels were only examined in a narrow time frame, two weeks after surgery. How these effects occur still needs to be determined before any potential translation to human disease.

Rerouting the gut to reduce blood glucose Published online 20 May 2012

Danna M Breen, Brittany A Rasmussen, Andrea Kokorovic, Rennian Wang, Grace W C Cheung, & Tony K T Lam

Published online 20 May 2012 | doi 10.1038/nm.2745

Repurposing an old drug for amebiasis

Nature Medicine Published online 20 May 2012

DOI: 10.1038/nm.2758

Auranofin, an approved drug for the treatment of rheumatoid arthritis, could serve as a potential new therapy for the treatment of Entamoeba histolytica infection, a common parasite worldwide. The finding appears online in Nature Medicine this week and highlights the utility of screening existing drugs for new purposes.

E. histolytica is an intestinal parasite that causes the potentially fatal infection amebiasis, killing around 70,000 people each year. In a screen for new antibiotics to treat this disease, Anjan Debnath and colleagues found that auranofin, a US Food and Drug Administration (FDA)-approved drug for the treatment of rheumatoid arthritis, inhibited E. histolytica growth in vitro and in two animal models of this infection. The authors suggest that auranofin inhibits E. histolytica thioredoxin reductase—an enzyme involved in defense against damage caused by oxygen metabolism—making the parasite more susceptible to oxidative stress.

Based on the potential clinical utility of these findings, the FDA has awarded auranofin status to treat amebiasis in humans.

Repurposing an old drug for amebiasis Published online 20 May 2012

Anjan Debnath, Derek Parsonage, Rosa M Andrade, Chen He, Eduardo R Cobo, Ken Hirata, Steven Chen, Guillermina Garcia-Rivera, Esther Orozco, Máximo B Martínez, Shamila S Gunatilleke, Amy M Barrios, Michelle R Arkin, Leslie B Poole, James H McKerrow & Sharon L Reed

Published online 20 May 2012 | doi 10.1038/nm.2758

Peroxide for viral inactivation in attenuated vaccines

Nature Medicine Published online 27 May 2012

DOI: 10.1038/nm.2763

A new technology platform that uses hydrogen peroxide to inactivate virus strains used for vaccine production is reported in Nature Medicine this week.

Live-attenuated vaccines created from live but weakened viruses are widely used and easy to produce. One of the main problems with this type of vaccines is that current inactivating agents decrease the neutralizing antibody response in the body owing to destruction of key viral proteins that would normally trigger an immune response.

Mark Slifka and colleagues show that hydrogen peroxide treatment circumvents this problem. This approach resulted in protective antibody-mediated immunity in mice vaccinated against two lethal viruses and protective cellular-mediated immunity in mice vaccinated against chronic viral infection.

Whether the cellular immunity induced can be shown in humans, and whether it is equivalent to that from live recombinant vaccines remain to be shown.

Peroxide for viral inactivation in attenuated vaccines Published online 27 May 2012

Ian J Amanna, Hans-Peter Raué & Mark K Slifka

Published online 27 May 2012 | doi 10.1038/nm.2763

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