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Finding a new way to fight late-stage sepsis by boosting cells' antibacterial properties:
Researchers have developed a way to prop up a struggling immune system to enable its fight against sepsis, a deadly condition resulting from the body's extreme reaction to infection.
The scientists used nanotechnology to transform donated healthy immune cells into a drug with enhanced power to kill bacteria.
In experiments treating mice with sepsis, the engineered immune cells eliminated bacteria in blood and major organs, dramatically improving survival rates.
This work focuses on a treatment for late-stage sepsis, when the immune system is compromised and unable to clear invading bacteria. The scientists are collaborating with clinicians specializing in sepsis treatment to accelerate the drug-development process.
"Sepsis remains the leading cause of death in hospitals. There hasn't been an effective treatment for late-stage sepsis for a long time. We're thinking this cell therapy can help patients who get to the late stage of sepsis," said Yizhou Dong, senior author and associate professor of pharmaceutics and pharmacology at The Ohio State University. "For translation in the clinic, we believe this could be used in combination with current intensive-care treatment for sepsis patients."
The study is published today in Nature Nanotechnology.
Sepsis itself is not an infection—it's a life-threatening systemic response to infection that can lead to tissue damage, organ failure and death, according to The Centers for Disease Control and Prevention. The CDC estimates that 1.7 million adults in the United States develop sepsis each year, and one in three patients who die in a hospital have sepsis.
This work combined two primary types of technology: using vitamins as the main component in making lipid nanoparticles, and using those nanoparticles to capitalize on natural cell processes in the creation of a new antibacterial drug. Cells called macrophages are one of the first responders in the immune system, with the job of "eating" invading pathogens. However, in patients with sepsis, the number of macrophages and other immune cells are lower than normal and they don't function as they should.
Journal Reference:
Xucheng Hou, Xinfu Zhang, Weiyu Zhao, Chunxi Zeng, Binbin Deng, David W. McComb, Shi Du, Chengxiang Zhang, Wenqing Li, Yizhou Dong, Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis, Nature Nanotechnology (2020). DOI: 10.1038/s41565-019-0600-1 , https://nature.com/articles/s41565-019-0600-1
(Score: 0) by Anonymous Coward on Wednesday January 08 2020, @06:53PM
Moertel 1985:
This paper calls 10 grams of water soluble vitamin C once a day "high dose". Severely ill people need hundreds of grams split up over the course of the day. This is evidenced by the ability for sick people to absorb more vitamin C than healthy people:
https://i.ibb.co/3MxX81T/jaffe2.png [i.ibb.co]
https://www.ncbi.nlm.nih.gov/pubmed/7321921 [nih.gov]
Vitamin C does selectively kill cancer cells at 1-20 mM concentrations in vitro. Supposedly this via the fenton reaction and lipid/protein oxidation as described earlier, since cancer cells are famously high in iron and glucose transporters (dehydroascorbate competes with glucose for transport). However, there is going to be much less free iron in actual tumor tissue, and much more other stuff for the ascorbate to react with. So likely you need to get even more (40+ mM) to the tumor to get substantial fenton reaction activity.
As mentioned earlier, the primary role of vitamin C is as a reducing agent. So where I would expect to see an effect in cancer patients is when inflammation is a problem. In this paper they gloss over that aspect and even say most patients were asymptomatic (even though 85% died?).
Also, it is strange because they couldn't follow the simple instructions of the paper they were attempting to replicate (give IV vitamin C plus oral supplements all day).
Halperin 1993:
This is a weird one I have never seen. They made a 100 mg/ml (568 mM, assuming ascorbic acid rather than sodium ascorbate) ointment and say that 8% of this penetrated half a mm into the skin. So I guess the skin received a 45 mM dose. For comparison the solubility of ascorbic acid is 330 mg/ml (1,874 mM). Then they had radiotherapy patients apply it and came up with a custom "preference" score based on a 0-4 toxicity scale. They found that (after dropping 45% of the subjects), if anything, the skin/hair was worse off when this ointment was applied.
Well, I have no idea how they came up with that random dose and how it compares to the oxidizing effect of the radiation therapy, but I bet that ointment was acidic and irritating to the skin. There isn't much to make of this study.
Siriwardena2007:
This study gave 2 grams of vitamin C (mixed with other stuff) IV for 2 days and then 1 gram for another 5 days. Then they assessed organ dysfunction. This dose of vitamin C is not going to do anything for cancer patients. Also, they missed a chance to report serum Vitamin C levels in these patients, instead only reporting change from baseline.