tag:blogger.com,1999:blog-8550919611653842066.post3770818149990364128..comments2023-10-24T19:10:17.771-07:00Comments on The High-fat Hep C Diet: Does reductive stress drive an adaptive inflammatory response, in depression linked to diet and lifestyle?Unknownnoreply@blogger.comBlogger9125tag:blogger.com,1999:blog-8550919611653842066.post-50900490041826540742014-01-29T17:12:02.369-08:002014-01-29T17:12:02.369-08:00The cost of IDO activation, and how viruses exploi...The cost of IDO activation, and how viruses exploit it:<br /><br />MDSC produce high levels<br />of indoleamine-2,3-dioxygenase (IDO), which catalyzes the<br />degradation of tryptophan into kynurenine and results in cell starvation<br />and apoptosis [75]. When T cells are exposed to IDO, they<br />undergo apoptosis and significant dysfunction [76]. Interestingly,<br />when SIV-infected rhesus macaques receiving antiretroviral<br />therapy were treated with the IDO inhibitor 1-methyl-D-tryptophan<br />(d-1mT) for 13 days, they showed increased plasma level of<br />tryptophan and lower virus load [77]. Treatment with this IDO<br />inhibitor in cancer setting also reduced the suppressive effects of<br />MDSC and enhanced the anti-tumor effects [78,79].Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-87124028141882062262014-01-29T16:33:43.082-08:002014-01-29T16:33:43.082-08:00Coronary calcium scoring: the thinner the calcium ...Coronary calcium scoring: the thinner the calcium is, the more dangerous it appears to be:<br /><br />http://jama.jamanetwork.com/article.aspx?articleid=1780017<br /><br />This is consistent with Linus Pauling's idea that atherosclerosis was a protective response.<br />When the job's half-done, or was carried out by incompetent or improperly informed tradesmen, using the wrong tools, it's more dangerous.<br /><br />- link from Richard Lehman's very excellent blog http://blogs.bmj.com/bmj/category/richard-lehmans-weekly-review-of-medical-journals/Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-5282497947773370222014-01-29T16:23:48.302-08:002014-01-29T16:23:48.302-08:00Great stuff Jack.
In this paper, evidence that oxi...Great stuff Jack.<br />In this paper, evidence that oxidised LDL can be anti-atherogenic<br />http://www.jlr.org/content/40/12/2143.full<br /><br />Earlier I posted a paper about endotoxin being an important endogenous hormone<br />http://cid.oxfordjournals.org/content/41/Supplement_7/S470.full<br /><br />This makes sense if you realise we are not designed to live forever, necessary repairs will never be as perfect as the original material, everything has a cost, and everything thrown up by evolution can be re-used by evolution to create a survival advantage.<br />Thus damage generates damaged molecules that are adapted into signals that trigger repair. These signals look bad, because they're associated with damage, and you can produce them in test-tubes by doing bad things to the orginal cells or macromolecules but by God we need them to get damaged.<br />We just need enough nutrition so our tool chest is stocked for the repairs we'll be doing, and so that we have the energy to carry them out.<br />Supplementary antioxidants are VERY helpful when you're acutely ill with hepatitis because their local protective effect outweighs any damping of the overall signalling, but are probably not how we should live our whole lives.<br />Nietzsche was a physiologist; what doesn't kill us does make us stronger in many ways.<br /><br />Probably better to retain the immunosuppressive response to chronic infection unless you're sure of being able to clear it, or unless it's causing obvious problems. A chronic virus isn't TRYING to kill you, its natural selection would prefer you to live on a bit longer.Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-11146148644724919832014-01-29T14:22:38.484-08:002014-01-29T14:22:38.484-08:00Confusion occurs when you only focus on input, thr...Confusion occurs when you only focus on input, thru put or output. What happens inside them and upstream of them is far more important. Understanding aging is the best way to prevent illness. This metabolic shift is further mediated by insulin resistance since a sedentary life does not require the metabolic demands that need to be regulated by insulin. Collectively, this epigenetic oxidative redox shift in aging results in a downward spiral of inability to respond to energy demands or environmental stressors which leads to stress-induced catastrophic initiation of cellular death pathways and organ failure. Complex.......but understandable when you get what mitochondria are really designed to do with charges subatomic particles from our environment.Anonymoushttps://www.blogger.com/profile/06619419812590914435noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-58216796370160606402014-01-29T14:22:20.382-08:002014-01-29T14:22:20.382-08:00The free radical theory of aging that Harman propo...The free radical theory of aging that Harman proposed long ago that oxidized macromolecules accumulate with age to decrease cell function and shorten life-span has little support these days (Harman, 1968). Unfortunately today this is biologic dogma because no one else has any better ideas how mitochondria are really designed to work in nature. Recent experimental work has shown it is dead wrong. When your experiments do not match your theory, your theory is wrong. Moreover, recent nutritional and genetic interventions to boost antioxidants have generally failed to increase life-span. The overall result of 19 clinical trials finds supplementation with the lipid-soluble antioxidant vitamin E failed to reduce mortality (Miller et al., 2005). The water soluble antioxidant vitamin C is also generally ineffective in reducing all-cause mortality (Bjelakovic et al., 2007). An even more important test of the free radical theory of aging involves genetic overexpression of antioxidant enzymes. To date, increases in SOD, or catalase or a combination, while lowering oxidized macromolecules, fail to increase lifespan in mice (Perez et al., 2009). Only overexpression of the peroxide and redox active thioredoxin 1 (Mitsui et al., 2002) and mitochondrial targeted catalase (Schriner et al., 2005) have been shown to increase mouse lifespan. In addition, the free radical theory fails to explain why higher levels of oxy-radical damage occurs constantly with exercise (Powers et al., 2008), which generally promotes healthy human aging (Nakamura et al., 1996) and extends lifespan in some rodents (Navarro et al., 2004) (Holloszy et al., 1985). The answer is not increasing the ORAC levels of food. It is found in metabolic epigenetic redox switches that happen upstream to mitochondria to alter where and how subatomic particles are fed into the ETC when nutrients are delivered to this organelle for processing. . The metabolically initiated redox shift happens "upstream" of the commonly observed increase in reactive oxidative damage to lipid membranes, receptors, and macromolecules in tissues. This shift has been constantly observed experimentally in normal aging; It occurs in the oxidized direction of the relative levels of important reductants and oxidants in cells. It manifests itself as an extracellular decrease in the ratio of cysteine/cystine in tissues with a simultaneous intracellular decrease in the ratio of GSH/GSSG and NAD(P)H/NAD(P). The oxidized redox shift is initiated by low demand for bursts of energy produced by mitochondria. The loss of energy efficiency is the key signal This low demand for energy also is manifest by observed low levels of physical and mental activity in people with this issue. This initiates a vicious cycle of oxidized membrane receptors, signaling molecules, transcription factors and epigenetic transcriptional regulators on a chronic basis. This increase ubiquination and the process steepens with respect to time. Organ failure and aging increase with respect to chronologic age. Epigenetic factors modulated by aging include the histone deacetylase family which includes the sirtuins as well as histone acetylases and DNA methyltransferases. Together and collectively, the epigenetic mediators impose the metabolic shift away from use of mitochondrial energy toward reliance on glycolysis. All of these complex epigenetic coupled factors are tied to inflammation generation via the NRF2 and KEAP1 transcription factors. This is why inflammation appears to be tied to all these things we talk about in the blogosphere. The key is understanding what happens proximal to the mitochondria and then how the mitochondria respond. Anonymoushttps://www.blogger.com/profile/06619419812590914435noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-20870441113385049342014-01-29T04:58:43.586-08:002014-01-29T04:58:43.586-08:00"If there was no inflammation the disease wou..."If there was no inflammation the disease would probably progress faster" - that is what drives me crazy! We need to reconcile these empirical observations with other types of evidence suggesting an overall decrease in inflammation might actually be helpful for the pathology in question.<br /><br />Thanks for addressing the contradictory points and not shying away from them - this is a practice that is all too rare in most of the paleo/health/blogosphere (especially with i.e., RS, Kitavans, Inuits, apoB, cholesterol etc....)raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-90688209021055340562014-01-29T02:27:02.612-08:002014-01-29T02:27:02.612-08:00I tend to think inflammation is seen as the bad gu...I tend to think inflammation is seen as the bad guy too often.<br />Like firemen being blamed for the fire.<br />Even with chronic inflammation like hep B and C.<br />They are good examples actually because the root cause is obviously still there as replicating virus.<br />If there was no inflammation the disease would probably progress faster.<br />People who are immunosuppressed have faster progression of hep C and B. George Ghttps://www.blogger.com/profile/01827157443037269420noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-70451330635622010982014-01-28T12:48:49.949-08:002014-01-28T12:48:49.949-08:001. Inflammation, of this sort, if I'm right, i...1. Inflammation, of this sort, if I'm right, is how we round up extra NAD when we're deficient, this being adaptive and protective. But if we have low NAD+/NADH ratio when overfed, this isn't likely in evolution, and getting extra NAD+ from tryptophan may be less protective.<br />Inflammatory responses are meant to serve a short-term purpose, this is protective, or at least "patches us up" to survive.<br /><br />2. Chronic inflammatory processes, what happens to the liver in chronic Hep B or C might be a guide to what goes wrong. Unfinished business becomes dangerous, like repeated DIY repairs that eventually compromise structure and function.<br /><br />Good inflammation/bad inflammation, understanding the difference, seems to be very complicated. I'll need a kaleidoscope, not a microscope, for this. Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-8550919611653842066.post-50920438731225568442014-01-28T07:38:48.168-08:002014-01-28T07:38:48.168-08:00Hi George,
2 things:
1. I'm trying to unders...Hi George,<br /><br />2 things:<br /><br />1. I'm trying to understand whether diseases like pellagra are on the same spectrum as other conditions strongly linked to inflammatory states...or if such diseases eventually appear when specific, yes or no, binary type conditions are met at some point. Threshold? Spectrum? Both? What beast are we dealing with as regards the subject of your post?<br /><br />2. I'm trying to wrap my head around the ubiquity of inflammatory processes found at the scene of the crime of so many diseases. How can we start understanding when inflammation is a 'cause' and when it's a 'protective response'? Do we have specific models where this has been settled for certain conditions?<br /><br />I have ideas floating around my head which are hard for me to pin down as clear questions - please excuse my vagueness/lack of clarity!raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.com