Sinusitis FAQ

Oxidative stress and diabetic neuropathy

Question:

I take him seriously too!

See my reply to BL; I meant Tom (ironjustice), not Ted. Who did you mean? Cheers Alan, T2, Oz — Everything in Moderation – Except Laughter.

Response:

I take him seriously too! See my reply to BL; I meant Tom (ironjustice), not Ted. Who did you mean?

Ack!  What a mistake!  I thought you meant Ted.  *hanging my head in shame* — Type 2 http://users.bestweb.net/~jbove/

Response:

– Hide quoted text — Show quoted text – Ted, you seem educated. Look up the words "monomania" and "fanatic" in your dictionary. You detract from some of the occasional good links you provide because you are no longer taken seriously. Cheers Alan, T2, Oz He is taken seriously by many here. Myself included. Sleepy Save the whales. Collect the whole set. Fair enough Sleepy. I do read the good links. I know he won’t agree, but it was actually meant as advice, albeit I was a bit strong I suppose.. Cheers Alan, T2, Oz

If you meant crackpot tom aka doe aka iron justice aka jesus was a vegetarian, I take it all back. The white coats just haven’t caught up to him yet! Sleepy Save the whales. Collect the whole set.

Response:

"What are the mechanisms that underlie the development of microvascular complications? (snipped) http://www.jci.org/cgi/content/full/111/4/431

There are a number of graphics that show the various pathways towared diabetic complications in the following article. Page 5 shows a great deal of similarity with the pathways in the above article. The same could be said for the discussion by Dr. John Buse in pages 36-47. He gives current therapies for microvascular complications on page 36. There are a more detailed accounts of these complications and some of the drugs undergoing trials for their treatment to let you know what may be down the pipeline. Earlier discussions mention the commonality amongst the diabetic complications. "There is a common pathologic change no matter whether you look at the retina, the kidney, or the nerve. The changes that one sees are related to base membrane, endothelium, and pericytes. This (graphic) shows the retina, the glomerulus, and the nerve. The changes are those of thickening of base membrane, endothelial cell changes, and pericyte cell death. These are common to all the so-called microvascular complications of diabetes." Furthermore, the complications can begin even at the stage of impair glucose tolerance. Changes are occuring in the eye before there are obvious signs of retinopathy. This is true in the kidneys and nerves. These changes may not be transparent to the patient. Hyperglycemia is still the main culprit but not the only one. Pathways Leading to Diabetic Microvascular Complications and the Latest Clinical Therapies http://www.medscape.com/viewprogram/2636 Frank

Response:

OK people.  I think Alan meant Tom, not Ted, due to the thread.  Ted hasn’t posted to this thread.  Furthermore Ted rarely provides "links."  Tom does.   Tom– you know, he’s our iron man, and we can’t figure out his connection to diabetes, but he quotes MEDL:INE studies all the time about iron, vegetarianism, etc..  Once in a while it will be about something else but usually it is an iron chelator. Ted–everyone knows him, but we haven’t seen much of him lately.   Alan wasn’t your post about Tom?   Alan, IMHO Tom is incapable of following your advice.   Nice try.

Yep. Thanks for pointing that out. My apologies Ted; we argue at times, but I did mean Tom in this case. Once again finger trouble, I think I’d better get a proof-reader. Mea culpa. Cheers Alan, T2, Oz — Everything in Moderation – Except Laughter.

Response:

Ted, you seem educated. Look up the words "monomania" and "fanatic" in your dictionary. You detract from some of the occasional good links you provide because you are no longer taken seriously. Cheers Alan, T2, Oz He is taken seriously by many here. Myself included.

I take him seriously too! — Type 2 http://users.bestweb.net/~jbove/

Response:

- Hide quoted text — Show quoted text – Frank, thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc? This article speaks to the finding of lowering of iron stores down to the levels found commonly in vegetarians. Iron reduction therapy has been coined to be the FUTURE in effective antioxidant therapy due to its effectiveness and price.

Doe is an anti-iron nut. He keeps stretching various pro-vegatarian tests and studies to claim that all diabetes is caused by iron, much as Betty Martini claims that all brain tumors and cellulite are actually lumps of Sweet&Low embedded in your body. Ignore him and get on with your life….

Response:

OK people.  I think Alan meant Tom, not Ted, due to the thread.  Ted hasn’t posted to this thread.  Furthermore Ted rarely provides "links."  Tom does.   Tom– you know, he’s our iron man, and we can’t figure out his connection to diabetes, but he quotes MEDL:INE studies all the time about iron, vegetarianism, etc..  Once in a while it will be about something else but usually it is an iron chelator. Ted–everyone knows him, but we haven’t seen much of him lately.   Alan wasn’t your post about Tom?   Alan, IMHO Tom is incapable of following your advice.   Nice try. – Hide quoted text — Show quoted text -He is taken seriously by many here. Myself included. Sleepy Save the whales. Collect the whole set. Fair enough Sleepy. I do read the good links. I know he won’t agree, but it was actually meant as advice, albeit I was a bit strong I suppose.. Cheers Alan, T2, Oz — Everything in Moderation – Except Laughter.

BL "As the waves pass the rock, their shape is changed.  There is a hologram of the rock within the wave that comes forward and crashes on the beach, then there’s a reflected wave back."   Ralph Abraham   "I’d like to learn to windsurf."  BL

Response:

Ted, you seem educated. Look up the words "monomania" and "fanatic" in your dictionary. You detract from some of the occasional good links you provide because you are no longer taken seriously. Cheers Alan, T2, Oz

He is taken seriously by many here. Myself included. Sleepy Save the whales. Collect the whole set.

Response:

- Hide quoted text — Show quoted text – Ted, you seem educated. Look up the words "monomania" and "fanatic" in your dictionary. You detract from some of the occasional good links you provide because you are no longer taken seriously. Cheers Alan, T2, Oz He is taken seriously by many here. Myself included. Sleepy Save the whales. Collect the whole set.

Fair enough Sleepy. I do read the good links. I know he won’t agree, but it was actually meant as advice, albeit I was a bit strong I suppose.. Cheers Alan, T2, Oz — Everything in Moderation – Except Laughter.

Response:

Ted, you seem educated. Look up the words "monomania" and "fanatic" in your dictionary. You detract from some of the occasional good links you provide because you are no longer taken seriously. Cheers Alan, T2, Oz — Everything in Moderation – Except Laughter.

Response:

- Hide quoted text — Show quoted text – Frank, thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc? This article speaks to the finding of lowering of iron stores down to the levels found commonly in vegetarians. Iron reduction therapy has been coined to be the FUTURE in effective antioxidant therapy due to its effectiveness and price. Doe is an anti-iron nut. He keeps stretching various pro-vegatarian tests and studies to claim that all diabetes is caused by iron, much as Betty Martini claims that all brain tumors and cellulite are actually lumps of Sweet&Low embedded in your body. Ignore him and get on with your life….

Nico .. is stupid .. Listen to him and you will be stupid .. too .. Oh yeah .. AND will continue to have diabetes .. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking

Response:

Thanks Frank – think I keep eating my blueberries. – Hide quoted text — Show quoted text – Brad: thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc? 2) nonenzymatic glycation of proteins yielding advanced glycation end-products (AGEs); (Note: metformin falls under this category as an inhibitor of AGE. Not all drugs are bad.) I saw this article on another ng and reposted it here. Diabetes Metab. 2003 Sep;29(4 Pt 2):88-94.   Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Leverve X, Guigas B, Detaille D, Batandier C, Koceir E, Chauvin C, Fontaine E, Wiernsperger N. INSERM E-0221 Bioenergetique Fondamentale et Appliquee, Universite Joseph-Fourier, Grenoble, France. Several links relate mitochondrial metabolism and type 2 diabetes or chronic hyperglycaemia. Among them, ATP synthesis by oxidative phosphorylation and cellular energy metabolism (ATP/ADP ratio), redox status and reactive oxygen species (ROS) production, membrane potential and substrate transport across the mitochondrial membrane are involved at various steps of the very complex network of glucose metabolism. Recently, the following findings (1) mitochondrial ROS production is central in the signalling pathway of harmful effects of hyperglycaemia, (2) AMPK activation is a major regulator of both glucose and lipid metabolism connected with cellular energy status, (3) hyperglycaemia by inhibiting glucose-6-phosphate dehydrogenase (G6PDH) by a cAMP mechanism plays a crucial role in NADPH/NADP ratio and thus in the pro-oxidant/anti-oxidant cellular status, have deeply changed our view of diabetes and related complications. It has been reported that metformin has many different cellular effects according to the experimental models and/or conditions. However, recent important findings may explain its unique efficacy in the treatment of hyperglycaemia- or insulin-resistance related complications. Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism(s), which is (are) not completely elucidated as yet. Although it is clear that metformin has non-mitochondrial effects, since it affects erythrocyte metabolism, the mitochondrial effects of metformin are probably crucial in explaining the various properties of this drug. PMID: 14502105 [PubMed - in process] Frank

Response:

 Brad: thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc? 2) nonenzymatic glycation of proteins yielding advanced glycation end-products (AGEs); (Note: metformin falls under this category as an inhibitor of AGE. Not all drugs are bad.)

I saw this article on another ng and reposted it here. Diabetes Metab. 2003 Sep;29(4 Pt 2):88-94.   Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Leverve X, Guigas B, Detaille D, Batandier C, Koceir E, Chauvin C, Fontaine E, Wiernsperger N. INSERM E-0221 Bioenergetique Fondamentale et Appliquee, Universite Joseph-Fourier, Grenoble, France. Several links relate mitochondrial metabolism and type 2 diabetes or chronic hyperglycaemia. Among them, ATP synthesis by oxidative phosphorylation and cellular energy metabolism (ATP/ADP ratio), redox status and reactive oxygen species (ROS) production, membrane potential and substrate transport across the mitochondrial membrane are involved at various steps of the very complex network of glucose metabolism. Recently, the following findings (1) mitochondrial ROS production is central in the signalling pathway of harmful effects of hyperglycaemia, (2) AMPK activation is a major regulator of both glucose and lipid metabolism connected with cellular energy status, (3) hyperglycaemia by inhibiting glucose-6-phosphate dehydrogenase (G6PDH) by a cAMP mechanism plays a crucial role in NADPH/NADP ratio and thus in the pro-oxidant/anti-oxidant cellular status, have deeply changed our view of diabetes and related complications. It has been reported that metformin has many different cellular effects according to the experimental models and/or conditions. However, recent important findings may explain its unique efficacy in the treatment of hyperglycaemia- or insulin-resistance related complications. Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism(s), which is (are) not completely elucidated as yet. Although it is clear that metformin has non-mitochondrial effects, since it affects erythrocyte metabolism, the mitochondrial effects of metformin are probably crucial in explaining the various properties of this drug. PMID: 14502105 [PubMed - in process] Frank

Response:

Brad: thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc?

You are on the right track for some of the oxidative stress mechanisms when you discuss diet/foods. There have been post to this ng on most of these mechanism to some degree or another. You can do Google searches on your own or search the Google groups archives at http://www.google.com/grphp. Address each of the four mechanisms individually. Search links for some journals where you might find something on these mechanisms:   1) http://diabetes.diabetesjournals.org/search.dtl 2) http://www.jbc.org/search.dtl 3) http://intl-jcem.endojournals.org/search.dtl 4) http://edrv.endojournals.org/search.dtl Quentin has written quite a few post that relate to the anti-oxidant aspects of foods, i.e, polyphenols. The following link includes more than his. http://groups.google.com/groups?q=polyphenols&ie=ISO-8859-1&hl=en&btn… I posted the following link: http://groups.google.com/groups?q=polyphenols&start=20&hl=en&lr=&ie=U… "What are the mechanisms that underlie the development of microvascular complications?  …  microvascular complications share a common pathophysiology. … four major pathways of glucose metabolism in the development of microvascular complications. … direct or indirect consequence of hyperglycemia-mediated superoxide overproduction by the mitochondrial electron transport chain. Either inhibition of superoxide accumulation or euglycemia restores the metabolic and vascular imbalance and blocks both the initiation and progression of complications."   Source: Oxidative stress and diabetic neuropathy: a new understanding of an old problem – http://www.jci.org/cgi/content/full/111/4/431 These include: 1) increased polyol pathway activity leading to sorbitol and fructose accumulation, NAD(P)H-redox imbalances, and changes in signal transduction; http://groups.google.com/groups?q=polyol+pathway&hl=en&lr=&ie=UTF-8&s… 2) nonenzymatic glycation of proteins yielding advanced glycation end-products (AGEs); (Note: metformin falls under this category as an inhibitor of AGE. Not all drugs are bad.) http://groups.google.com/groups?hl=en&lr=&ie=ISO-8859-1&q=nonenzymati… 3) activation of PKC thereby initiating a cascade of stress responses, http://groups.google.com/groups?hl=en&lr=&ie=ISO-8859-1&q=activation+… and 4) increased hexosamine pathway flux. http://groups.google.com/groups?hl=en&lr=&ie=ISO-8859-1&q=hexosamine+… This kind of research can take a lot of time and energy. Enjoy! Frank

Response:

Frank, thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc?

This article speaks to the finding of lowering of iron stores down to the levels found commonly in vegetarians. Iron reduction therapy has been coined to be the FUTURE in effective antioxidant therapy due to its effectiveness and price. <<snip no matter how induced, Fe (iron) depletion consistently enhanced glucose disposal <<snip  Br J Nutr 2001 Oct;86(4):515-9 Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians.     Hua NW, Stoohs RA, Facchini FS    Department of Medicine, Division of Nephrology, San Francisco General    Hospital, San Francisco, CA, USA.    [Medline record in process]    The efficacy of insulin in stimulating whole-body glucose disposal    (insulin sensitivity) was quantified using direct methodology in    thirty lacto-ovo vegetarians and in thirty meat-eaters. All subjects    were adult, lean (BMI <23 kg/m2), healthy and glucose tolerant.    Lacto-ovo vegetarians were more insulin sensitive than meat-eaters,    with a steady-state plasma glucose (mmol/l) of 4.1 (95 % CI 3.5, 5.0)    v. 6.9 (95 % CI 5.2, 7.5; respectively. In addition, lacto-ovo    vegetarians had lower body Fe stores, as indicated by a serum ferritin    concentration (mg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI    45, 100) for meat-eaters To test whether or not Fe status might    modulate insulin sensitivity, body Fe was lowered by phlebotomy in six    male meat-eaters to levels similar to that seen in vegetarians, with a    resultant approximately 40 % enhancement of insulin-mediated glucose    disposal Our results demonstrate that lacto-ovo vegetarians are more    insulin sensitive and have lower Fe stores than meat-eaters. In    addition, it seems that reduced insulin sensitivity in meat-eaters is    amenable to improvement by reducing body Fe. The latter finding is in    agreement with results from animal studies where, no matter how    induced, Fe depletion consistently enhanced glucose disposal.    PMID: 11591239, UI: 21475355 Free Web space and hosting – 7h.com HOME Biochem Pharmacol 1999 Jun 15;57(12):1345-9 Therapy by taking away: the case of iron. Polla BS Laboratoire de Physiologie Respiratoire, UFR Cochin Port-Royal, Paris, The recent finding of the beneficial effects of iron deprivation in the outcome of muscle necrosis in an animal model of genetic myopathy served as the basis of this commentary. Here, "taking away" iron by controlled dietary deprivation is proposed as a reasonable, feasible, cheap, and efficient clinical approach to many diverse diseases, all of which have a free radical component. Indeed, iron potentiates the generation of the highly reactive and toxic hydroxyl radical, and, thus, of oxidative damage. Iron deprivation may represent the first really efficient antioxidant, preventing oxidative stress in all subcellular compartments, tissues, and organs. Iron/iron deprivation also modulates programmed cell death (apoptosis), which should be the subject of further studies to better define the mechanisms mediating these complex effects. Finally, related to its antioxidant effects, iron deprivation may find applications in the anti-aging field, whether programmed or premature aging, and whether in cosmetics or in gerontology. Publication Types: * Review * Review, tutorial PMID: 10353254, UI: 99279694 CONCLUSION In conclusion, therapy by taking away (iron) has a great potential for many different diseases, all of which share ROS-mediated mechanisms. The development of new, non-toxic , easily administrable iron chelators such as IRCO11 may shortly become the most efficient and fashionable antioxidant, anti-aging, anti-infectious, and anti-inflammatroy therapy. In the meantime, although taking away by controlled dietary deprivation is less attractive , it should be considered in all of the above, as well as in the currently incurable, devastating genetic or acquired myopathies such as DMD. Who loves ya. Tom – Hide quoted text — Show quoted text – "What are the mechanisms that underlie the development of microvascular complications? …  microvascular complications share a common pathophysiology. … four major pathways of glucose metabolism in the development of microvascular complications. These include: 1) increased polyol pathway activity leading to sorbitol and fructose accumulation, NAD(P)H-redox imbalances, and changes in signal transduction; 2) nonenzymatic glycation of proteins yielding advanced glycation end-products (AGEs); 3) activation of PKC thereby initiating a cascade of stress responses, and 4) increased hexosamine pathway flux. While specific inhibitors of each pathway block one or more diabetic microvascular complications, only recently has a link been established that provides a unified mechanism of tissue damage. Each pathway becomes perturbed as a direct or indirect consequence of hyperglycemia-mediated superoxide overproduction by the mitochondrial electron transport chain. Either inhibition of superoxide accumulation or euglycemia restores the metabolic and vascular imbalance and blocks both the initiation and progression of complications." Source: Oxidative stress and diabetic neuropathy: a new understanding of an old problem http://www.jci.org/cgi/content/full/111/4/431 A graphic flow chart of the above mentioned mechanisms: Mechanisms leading to neuronal degeneration in hyperglycemia involve reactive oxygen species (ROS) formation. http://www.jci.org/content/vol111/issue4/images/large/JCI0317863.f1.jpeg Frank

Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking

Response:

Frank, thanks – so what do we do about it?  Likely control BG to prevent oxidative stress – what about anti-oxidant foods like green tea, dark choc, blueberries, etc? – Hide quoted text — Show quoted text – "What are the mechanisms that underlie the development of microvascular complications? …  microvascular complications share a common pathophysiology. … four major pathways of glucose metabolism in the development of microvascular complications. These include: 1) increased polyol pathway activity leading to sorbitol and fructose accumulation, NAD(P)H-redox imbalances, and changes in signal transduction; 2) nonenzymatic glycation of proteins yielding advanced glycation end-products (AGEs); 3) activation of PKC thereby initiating a cascade of stress responses, and 4) increased hexosamine pathway flux. While specific inhibitors of each pathway block one or more diabetic microvascular complications, only recently has a link been established that provides a unified mechanism of tissue damage. Each pathway becomes perturbed as a direct or indirect consequence of hyperglycemia-mediated superoxide overproduction by the mitochondrial electron transport chain. Either inhibition of superoxide accumulation or euglycemia restores the metabolic and vascular imbalance and blocks both the initiation and progression of complications." Source: Oxidative stress and diabetic neuropathy: a new understanding of an old problem http://www.jci.org/cgi/content/full/111/4/431 A graphic flow chart of the above mentioned mechanisms: Mechanisms leading to neuronal degeneration in hyperglycemia involve reactive oxygen species (ROS) formation. http://www.jci.org/content/vol111/issue4/images/large/JCI0317863.f1.jpeg Frank

Response:

"What are the mechanisms that underlie the development of microvascular complications? …  microvascular complications share a common pathophysiology. … four major pathways of glucose metabolism in the development of microvascular complications. These include: 1) increased polyol pathway activity leading to sorbitol and fructose accumulation, NAD(P)H-redox imbalances, and changes in signal transduction; 2) nonenzymatic glycation of proteins yielding advanced glycation end-products (AGEs); 3) activation of PKC thereby initiating a cascade of stress responses, and 4) increased hexosamine pathway flux. While specific inhibitors of each pathway block one or more diabetic microvascular complications, only recently has a link been established that provides a unified mechanism of tissue damage. Each pathway becomes perturbed as a direct or indirect consequence of hyperglycemia-mediated superoxide overproduction by the mitochondrial electron transport chain. Either inhibition of superoxide accumulation or euglycemia restores the metabolic and vascular imbalance and blocks both the initiation and progression of complications." Source: Oxidative stress and diabetic neuropathy: a new understanding of an old problem http://www.jci.org/cgi/content/full/111/4/431 A graphic flow chart of the above mentioned mechanisms: Mechanisms leading to neuronal degeneration in hyperglycemia involve reactive oxygen species (ROS) formation. http://www.jci.org/content/vol111/issue4/images/large/JCI0317863.f1.jpeg Frank

Response:

Filed under: Pathophysiology

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