Designing a combination therapy for acute ischaemia

If one were to design a combination therapy for neuroprotection and neurosupport following a major ischemic stroke, they might decide to do something like this in continuous IV delivery form:

To limit reperfusion injury, and limit apoptosis cascades, and provide immediate support

L-Glutathione, Vitamin C, N-Acetyl Cysteine, and Sodium Butyrate to help limit reperfusion injury, and limit the infarction injury areas to only the immediately affected neurovascular system, including reducing glutamate-related toxicity.

Many of these substances have more than one purpose in this mix. The L-Glutathione and N-Acetyl Cysteine operate as ROS-antioxidants and prevent other forms of cellular damage. The Vitamin C takes some of the load off the vitamin C scavenger pathways which exhaust L-Glutathione stocks to recycle Vitamin C after use, ensuring that L-Glutathione can focus on its other role.

A DHA/triglyceride emulsion should be included in this mix delivered for the first few hours, then later should be replaced by DHA/EPA (see below).

Neurosupport, neurogenesis, repair and remodelling

To the above neurovascular protectants, we add: L-Serine, phosphatidylserine, and citicoline to provide the necessary building blocks for neurogenesis, repair and remodeling.

(Phosphatidylserine might be left out of this mix - testing is required to determine if it’s more helpful than L-Serine alone, or if it interferes with healing. If in doubt stick to just L-Serine. Depending on the kind of injury, phosphatidylserine might help more in some cases than others, as it’s expressed at the damaged ends of nerves to target them for repair).

Thromboyltic agents (anti-clotting agents)

rPTA therapy is currently the gold standard for breaking down clots, and should probably be administered once the above listed substances are in the blood stream in sufficient concentration (or co-administered). rPTA can tail off without stopping delivery of the other listed substances.

Matrix metalloprotease inhibitors (e.g. doxycycline, tetracycline, minocycline)

These should be used to prevent large scale remodeling of the area during repair (and potentially also protect the area from certain classes of bacteria - and possibly also further clots/bleeds by inhibiting porphyrin/gingipain-producing bacteria).

Capillary/Endothelial relaxation

Nicotinic acid (vitamin B3) to trigger flushing reaction and relax the endothelium, particularly in small capillaries.

Nutritional support

DHA/EPA as raw building blocks (in addition to normal TPN nutrition for proteins). This is after the first day or so of DHA + triglycerides.

B-vitamins, and other protein sources are pretty obvious. But omega 3’s are essential for some of the necessary repair work. They should be fresh, and have been kept chilled to avoid rancidity, ideally only being warmed to body temperature during infusion, and possibly kept in an anoxic environment, with a short wavelength-light blocking bag.

Delivery phases

  • This would be delivered in phases - first the anti-ROS group, neurogenesis group. MMPI antibiotics + rPTA after a few minutes (rPTA therapy ramping off over time according to the existing protocols for use). DHA/trigly. replaced with DHA/EPA after about a day or two. Not sure when to start introducing the B-vitamins, particularly B3.

Contraindications

Extreme care would be needed before attempting this on a patient with an intracranial haemmorhage or bleed, rather than a clot. For patients already on blood thinners who have a seemingly paradoxical clot, consider increasing the dose of matrix-metalloprotein inhibitor antibiotics and reducing the blood thinners dosage gently as DHA/EPA, NAC and other treatments in this list all have a blood-thinning/anti-clotting effect.

Notes

The difficulty with such a therapy is not only getting anyone outside of researchers in Barcelona to try this, but the fact that it works best within the first three hours. I expect something like the above mix to become standard medical practice in about 30 years, assuming we don’t come up with better mechanisms involving nanotech or RNA therapy.

(more...)
#stroke, #combination therapy, #reperfusion injury
This entry was posted under Medicine. Bookmark the permalink.

A possible connection between Propionic Acid (Calcium Propionate) and Autism

This news flew around the web a bit about a month or two ago, but just in case you didn’t see it, I wanted to rebroadcast it here.

Propionic acid is a relatively common preservative (also known as E208, or Calcium Propionate). It’s an anti-mold/fungal agent that is added to some baked goods and cheeses to increase their shelf life, and also created in the body by some kinds of gut bacteria under specific circumstances. It’s also created naturally in some cheeses, for example Swiss.

This study came out recently, and was published in Nature: Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder

It appears to be a potential cause of Autism-like symptoms, and some subset of Autism cases. It triggers the same kind of bad speciation/incorrect migration of neurons seen in the brain in people with Autism, as well as similar inflammatory markers seen in those people.

(more...)
#autism, #propionic acid, #calcium propionate
This entry was posted under Medicine. Bookmark the permalink.

A New Life Awaits You in the Off-World Colonies

I’ve just spent the last ten years of my life working inside of the Xbox Advanced Technology Group, a merry team of techninjarocketsurgeons known for being air-dropped into games companies to help them optimize their games for the Xbox console, and in doing so I’ve worked on thousands of games, from AAA to Indie titles, and helped everyone I could wherever I could. Including helping Xbox get together with Sony and others in the industry to set up an open-standards body around HDR gaming.1

We also did a bunch of things like helping developers write Windows games, write Kinect-based games for Xbox 360, a little research and development here and there on technology which may or may not have ever shipped, and who knows what else. We also did a bit of tech support, documentation, education (I also ran our games technology conferences - usually owning the entirety of the content production, strategy and planning side of the house, and doing everything from writing and structuring keynotes to giving a ton of highly-rated talks myself).

Xbox ATG has been around for 19 years at this point2, and I’m proud to have been a part of it for half of its lifetime. Not a bad innings.

Either way though, ten years is a long time. It’s time for a change.

  1. I’d claim that I had a hand in enabling Sony and Microsoft’s recent partnership to provide backend services for PSN Network, but to be honest, I have no idea if I did or not. That said, I’m relatively certain that if the stuff I’d worked on with them hadn’t work out well, and had soured the relationship between the companies (which was at risk), it would have been much more difficult for that deal to happen. So maybe that went a little easier because of me. I can’t really say. 

  2. I came up with the Latin motto3 for Xbox ATG for its 16th (or 0x10th, or %1000’th if you prefer) anniversary. It reads: “INDISCRETA MAGICAE • SCIENTIAS ET ARTES • IGNIS, LVX ET SONVM” which means “Indistinguishable from Magic - Science and Art - Fire, Light and Sound”… because any sufficiently Advanced Technology Group is indistinguishable from magic… 

  3. You can do this by round-tripping between English and any other language you want in an auto-translator such as Google Translate. Just keep slightly changing your sentence until you come up with something that you can translate with it to the other language and back again intact. If it does this, then you’ve probably got something which is a stable translation (if not always a good one), as it’s not shifting when it’s translated in either direction. 

(more...)
#new job smell, #Google, #Googler, #Noogler
This entry was posted under Me. Bookmark the permalink.

Flat People, Resumes and Coded Language

People often speak in coded language - some more than others. The problem with coded language is that it requires a secret decoder ring to figure out what they mean.

I'm not talking about jargon and vocabulary which are used in exclusionary ways. That particularly insidious form of manipulation - taking commonly used and understood terminology and morphing it to have a different, specific, and subtly different meaning - is often used as a two-pronged way in unfair, point-scoring debate:

(more...)

Altruism in an Uncaring Universe, and The Good Place

The last episode of Season 2 of The Good Place had a fantastic message buried inside of it.

Nobody is truly altruistic in the dictionary definition of the word. (But that's okay - we're only human, so we make human decisions).

Altruism does not exist in a vacuum. A good person doing kind acts will only perform those acts for so long before they stop doing them, if you kick them in the face every time they do them. Because they're good, not stupid.

(more...)

subscribe via RSS