Discussion of Influenza

I don't believe the wild estimates about the numbers of flu cases that are supposedly going to show up this Fall. They're saying all these people are going to wind up in intensive care and that one in four people here is going to get the swine flu. People end up in intensive care from the flu every year, and the flu's pro-thrombogenic effects are thought to cause over 100,000 heart attacks every year in the US. I don't think the swine flu sounds like anything but a slightly more severe variant of the annual flu strain.

I personally always get the intranasal vaccine, because I feel that it causes less thrombogenicity and doesn't cause unnecessary elevations in serum IgE levels or cause as many other aggravating effects. I've never had a major complication from a vaccine or anything, but I think that the absence of the localized, transient granuloma from some of the intramuscular adjuvants (http://scholar.google.com/scholar?q=granuloma+adjuvant+vaccine&hl=en) and the induction of the secretory IgA immune responses [de Haan et al., 2001: (http://journals.pasteur.ac.ir/vaccine2001/1920/19202898.pdf)], in response to the intranasal vaccine, make for a better experience. I guess people over 50 still can't get it, but I think the manufacturer is trying to change that. That's a ridiculous rule. But I definitely can't give medical advice, and the intramuscular vaccine could very well be preferable for some people.

The only thoughts I can discuss superficially, in this area, are that there's a very short window of time during which the antivirals are effective, and the flu comes on very rapidly. I got it one year and found that both a neuraminidase inhibitor and an M2 protein inhibitor, together, were really effective and sort of stopped it in its tracks, even though it took awhile, obviously, to get over the actual virus. But I used them right away, and one ideally has to do it within 12 hours. I don't see how anyone could have a hope of going to the emergency room and really making use of the antivirals (getting the maximal benefit). I do think purine nucleotides would have the potential to reduce complications from influenza, because the disease models in which purines are effective tend to be these wildly inflammatory, animal models of autoimmune diseases. Inosine, which is much less potent than adenosine (i.e. ATP disodium), has been effective in reducing inflammatory and nitrosative damage in all sorts of rodent models of autoimmune diseases. Influenza is basically like a miniature autoimmune disease [one of many: Gurevich et al., 2005: (http://cmbi.bjmu.edu.cn/news/report/2004/imm/8.pdf)]. The viral neuraminidase enzyme is similar to sialidase enzymes, and the viral hemagglutinin causes hemostatic effects from the get-go. They've used isoprinosine, which is inosine dimethylaminoisopropanol para-acetamidobenzoate or something (http://scholar.google.com/scholar?q=isoprinosine+influenza&hl=en), and I doubt that any of those other compounds (those two other compounds) contribute to the supposed antiviral or therapeutic effects of isoprinosine. It's basically a source of small amounts of inosine, in my opinion, and inosine has, in fact, been shown to sometimes have immunostimulatory effects [even though it increased Th2 immune markers, in association with reductions in disease progression in people with multiple sclerosis, according to an article that just came out in 2009 and that I still can't get the full text of] [Markowitz et al., 2009: (http://www.ncbi.nlm.nih.gov/pubmed/19425822)]. Purines can have significant antithrombotic effects, too, but seem to have almost no potential to cause bleeding, in my opinion. The flu causes thrombogenic effects in everyone who gets it, and the combination of immune-mediated thrombogenic effects and thrombocytopenia (which is probably immune-mediated also, to a big extent, at different times during an influenza infection) is not a good combination. Markowitz et al. (2009) mention that some of the people taking inosine developed uric acid kidney stones, and, in my opinion, oral inosine is much more "uricogenic" than oral ATP is. Nonetheless, there would be a need to be cognizant of that potential, even with something like ATP, for hyperuricosuria, etc. Some of the neuraminidase inhibitors are transported (mainly eliminated, exported, apparently) [Shi et al., 2006: (http://scholar.google.com/scholar?hl=en&q=neuraminidase+inhibitor+%22organic+anion%22+transporter)] by the same organic anion transporters that transport uric acid. Uric acid is always being transported in and out of cells, and uric acid derived from ATP (or inosine, to a much greater extent) could potentiate the effects of some neuraminidase inhibitors in an undesirable way. Obviously one would want to discuss these things with one's doctor. I just suggest these things because someone could conceivably choose some dosage, prior to a time at which he or she is really sick, that doesn't elevate the urinary uric acid concentrations much, etc. I don't know. The point is, there would be reason to be careful, because of the renal elimination of some neuraminidase inhibitors. The elimination of some M2 protein inhibitors from the body is also renal, given that some aminoadamantane-based drugs are excreted unchanged (in the kidneys) (http://scholar.google.com/scholar?hl=en&q=aminoadamantane+excretion+unchanged). Combining two classes of anti-influenza drugs would probably not be the wisest or most conservative approach, especially in combination with a source of uric acid, but there is animal research showing that the combination can be advantageous [Govorkova et al., 2004: (http://scholar.google.com/scholar?hl=en&q=M2+protein+inhibitor+neuraminidase+combination+influenza)]. There are two classes of drugs that display relatively specific antiviral activity against influenza, and the older M2 inhibitors can have some usefulness, in combination with neuraminidase inhibitors. I do think purine nucleotides have therapeutic potential in the context of influenza-related complications, though, because of all the wild oxidative and nitrosative stress induced by influenza, etc.