The stuff related to this (http://hardcorephysiologyfun.blogspot.com/2009/12/multiple-revisions-of-old-paper-of-mine.html) just got really complicated, but that's that. I got the intranasal H1N1 flu vaccine on Wednesday, and the people did do a good job conducting the clinic. It's like the mild symptoms from it are slightly worse than with the seasonal intranasal one but aren't much worse. I was going to mention some approaches to dealing with post-influenza issues or low-level, ongoing effects of influenza, I should say. I've discussed some of the pharmacological issues with antivirals' potential interactions with exogenous purines or sources of inorganic phosphate (via the organic anion transporters and multidrug resistance proteins, as in efflux transporters in hepatocytes and proximal tubule epithelial cells, etc.) (http://eahblog2.blogspot.com/2009/08/discussion-of-influenza.html). I think the use of even relatively low doses of oral purines could be useful in dealing with the kind of ongoing, low-level thrombogenicity that one would expect to see, following an influenza infection, from elevated anti-ganglioside autoantibody titers (or from elevated antiphospholipid autoantibody titers in general) and anti-hemagglutinin antibodies that one would expect to exert thrombogenic/hemostatic effects. There tends to be a perception that something like Guillain-Barre syndrome from influenza is an all-or-nothing event, and it is. But one would expect to see elevated anti-ganglioside autoantibody titers and immunity following influenza infections, and influenza vaccination has produced prolonged but asymptomatic elevations in antiphospholipid autoantibody titers in normal people (for 3-6 months or so). Here's a search that shows some articles discussing the issue in various contexts (http://scholar.google.com/scholar?q=antiphospholipid+influenza+vaccine+OR+vaccination&hl=en&as_sdt=2001&as_sdtp=on). This search (http://scholar.google.com/scholar?hl=en&q=ganglioside+autoantibodies+lipopolysaccharide+OR+antiphospholipid&as_sdt=2000&as_ylo=&as_vis=0) shows that anti-ganglioside antibodies can exhibit cross-reactive binding to lipopolysaccharide(s), which are bacterial endotoxins, and that fits in with this article showing that the injection of viral neuraminidase proteins from influenza viruses causes a rapidly-induced thrombocytopenic response in rodents [see (http://eahblog2.blogspot.com/2009/08/influenza-is-it-big-man-on-campus-is.html); Choi et al., 1972: (http://www.ncbi.nlm.nih.gov/pubmed/5060079)(http://www3.interscience.wiley.com/cgi-bin/fulltext/120727425/PDFSTART)]. That could be explained by some sort of rapid release of IgE from mast cells or something, but mast cells can participate in all sorts of different immune responses and can actually serve as antigen-presenting cells, etc., and all-around "loose-cannons" of the immune system. But it could be that the viral neuraminidase elicits an existing, established, anti-lipopolysaccharide antibody response or multifaceted response that causes cross-reactive, antibody-mediated clearance of platelets. Choi et al. (1972) found evidence that the platelets' membranes were damaged over that short time course. They were being degraded and damaged, and the platelets were being destroyed, if I remember correctly. It sounded like an anti-platelet glycoprotein or antiphospholipid autoreactivity or contact hypersensitivity type of response. Elevations in antiphospholipid autoantibodies generally cause thrombogenic symptoms, with or without bleeding, etc. Here's another search (http://scholar.google.com/scholar?hl=en&q=influenza+ganglioside+autoantibodies&as_sdt=2000&as_ylo=&as_vis=0), but the point is that influenza neuraminidase enzymes cleave sialyl (or disialyl, I think) residues on cell-surface proteins of human cells and allow influenza to enter cells (http://scholar.google.com/scholar?hl=en&q=influenza+neuraminidase+sialic+OR+acetylneuraminic+OR+ganglioside&as_sdt=2000&as_ylo=&as_vis=0). The viral neuraminidase is a sialidase enzyme, and humans have sialidase enzymes, of course. One would expect antibodies to the (anti-influenza) antibodies to the active site or associated residues of a viral neuraminidase enzyme to potentially bind to gangliosides or other phospholipids (and to potentially lead to anti-ganglioside or more generalized antiphospholipid autoreactivity). The viral hemagglutinin proteins agglutinate red blood cells, meaning the red blood cells clump together and produce hemostatic effects or microthrombi that constantly are reforming and being degraded in a dynamic manner. Then that can lead to a big mess of chaotic immune responses, etc.
The general idea, in my opinion, is that hemostatic conditions will inevitably lead to some problems with energy metabolism and that the elevated levels of pro-inflammatory cytokines in many different tissues, following the influenza-induced increases in mast-cell density just about everywhere, for example, will also disturb mitochondrial functioning. TNF-alpha and other cytokines rapidly and reliably impair mitochondrial functioning and induce oxidative stress. Antiphospholipid and anti-ganglioside autoantibodies would be expected to produce thrombogenic effects and, basically, low-level neuropathic effects, in my opinion. One approach would be to consider the potential effects of exogenous uridine or triacetyluridine, for their supposed, generalized anti-inflammatory effects and for their potential effects on glucose uptake and energy metabolism (pyrimidines' effects, I mean, on those processes, as discussed in past postings), and to potentially consider the utility of L-glutamine supplementation as a way of addressing the supposed, low-level neuropathy and adverse effects on energy metabolism. Anti-ganglioside autoantibodies would clearly compromise energy metabolism, and, in people without overt Guillain-Barre syndrome, glutamine might help to address a supposed, low-level conduction blockade from elevated anti-ganglioside antibody titers, etc. Glutamine can produce anti-inflammatory effects, and so can uridine, in a lot of different models of inflammation, and glutamine [see Amara, 2008, cited here, for a review of three trials on the use of glutamine in the prevention of chemotherapy-drug-induced neuropathy, implying that it acts as an energy substrate or has some other generic effects (it's likely to basically be acting as an energy substrate/precursor of TCA cycle intermediates, in my view): (http://hardcorephysiologyfun.blogspot.com/2009/08/some-more-old-papers-of-mine.html)] and uridine (PN401 = RG2133 = triacetyluridine: cited as ref 32 in Ashour et al., 1996(?); the research exists somewhere, maybe here, as shown: (http://scholar.google.com/scholar?hl=en&q=neuropathy+acetyluridine+OR+RG2133+OR+PN401&as_sdt=2000&as_ylo=&as_vis=0)] have both been used in the treatment of peripheral neuropathy, implying some generic usefulness in addressing neuropathy of inflammatory origins (). There might well be research specifically on glutamine in influenza infections [(http://scholar.google.com/scholar?hl=en&q=%22L-glutamine%22+influenza+supplement+OR+exogenous&as_sdt=2000&as_ylo=&as_vis=0)], but this article [Neu et al., 2002: (http://www.victusinc.com/VictusTecnical_files/Glutamine%20in%20Radioterphy/Docs/09.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/11790953)] cites some of the research showing anti-inflammatory effects of glutamine (elevations in interleukin-10 expression or release, etc.). I'm pretty sure there's research showing that glutamine protects against the adverse effects of lipopolysaccharide on energy metabolism or the cellular redox state. Yeah, there is (http://scholar.google.com/scholar?as_q=&num=100&btnG=Search+Scholar&as_epq=glutamine&as_oq=lipopolysaccharide+endotoxin&as_eq=&as_occt=title&as_sauthors=&as_publication=&as_ylo=&as_yhi=&as_sdt=1.&as_sdtp=on&as_sdts=5&hl=en). This article shows that lipopolysaccharide induces DNA damage and deficits in energy metabolism in macrophages [Zingarelli et al., 1996: (http://www.ncbi.nlm.nih.gov/pubmed/8598485?dopt=Abstract)]. Anyway, there are lots of articles on the anti-inflammatory effects of uridine and on its capacity to protect against neuronal loss or other effects of inhibitors of mitochondrial respiration, such as sodium azide, [see here for a lot of the articles showing protection against the effects of respiratory-chain enzyme inhibitors by triacetyluridine-derived uridine and other pyrimidines: (http://hardcorephysiologyfun.blogspot.com/2009/08/some-more-old-papers-of-mine.html)]. Some other time, soon, I'll put the links to some of the articles that show anti-inflammatory effects of uridine, but these are some [Uppugunduri et al., 2004: (http://www.ncbi.nlm.nih.gov/pubmed/15251120); Tian et al., 2009 (protection against damage due to cerebral ischemia, meaning it would potentially be useful for the ischemia one would expect from compromised energy metabolism and thrombogenicity per se and all the other mess of influenza): (http://linkinghub.elsevier.com/retrieve/pii/S030439400901180X); Evaldsson et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17570319)]. The article by Evaldsson et al. (2007) showed anti-inflammatory effects of uridine in a model or models of lung inflammation. I haven't looked at the article in awhile and forget the details. Then there's the massive elevations in peroxynitrite formation from activated macrophages, during influenza, and purines (all purines, by more or less similar reactions, interestingly) are peroxynitrite scavengers. But then there's the issue of uric acid competing for efflux with active metabolites of neuraminidase inhibitors or even with M1 protein inhibitors that are excreted unchanged, as in adamantane derivatives. Magnesium would probably be useful, assuming a person can tolerate it, and I'm not finding any easy searches that would explain my reasoning. Magnesium is just depleted strongly by any physiological stress, even exercise, and it produces antithrombotic effects that are less likely to be accompanied by bleeding (just as purines' antithrombotic or anti-cell-adhesion effects are not too likely to be hemorrhagic, in my view), in my opinion, than other antithrombotic strategies. It's hard to convince people of the effects of magnesium. It's like the research is scattered and is so vast that it's hard to convey. Magnesium is really important, in my opinion, as discussed in...past postings. It has crucial effects on energy metabolism (partly as a result of its mild calcium-channel antagonistic effect, as is the case with its antithrombotic effects) and can reduce lipid peroxidation by blunting calcium influx, etc. Here's a hastily-done search that shows some articles on the anti-inflammatory effects associated with magnesium repletion (http://scholar.google.com/scholar?hl=en&q=allintitle%3A+magnesium+inflammatory+OR+inflammation&as_sdt=2000&as_ylo=&as_vis=0). There's a bonus article showing glutamine (or ammonia) can limit the replication of influenza virus replication [Eaton and Scala, 1961: (http://www.ncbi.nlm.nih.gov/pubmed/13725527)]. That's actually a sort of "Saturday-roadkill" type of article, and the effect of ammonia could just be a generalized toxic effect. But it could be that ammonia can serve as a pyrimidine precursor. Who knows.
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