Ursolic acid, could not confirm same as Ursocholanic acid. UA lowers cholesterol and blood sugar and prevents muscle wasting. good for aging mice
It is particularly concentrated in apple peel but is also found in cranberries and prunes and in basil, oregano and thyme
Tuesday, March 31, 2015
Wednesday, March 25, 2015
End of biology, the corporate machine
Humans have already lost control. We go to war, print money, make laws, and complicate tax law for the benefit of the corporate machine that seeks desperately to remove people from the expenses of the corporation. The goal of economics is to remove as many people as possible because they are too inefficient. At some point, even shareholders will not be necessary. We will not be able to point to the “brain” of the corporate economic machine because it is worldwide and surrounds us. We are like the red blood cells in this machine: we are currently vital to it but only a small part of it, and not where the intelligence lies. The intelligence is too distributed for most people to see. If we could point to it, we could fight it. But we need it more and more just to eat and live. It needs us less and less. This is not fear-mongering because I do not fear the end of humanity or the end of biology. The system is advancing rapidly to a much higher plane of intelligence. Biology will become more and more ugly to it and useless. The fear is that biology will continue to be at war with itself and wasting the Sun and Earth resources.
Tuesday, March 24, 2015
parkinson's and drugs
You should take about 10 mg carbidopa with 12 tablets Mucuna Pruriens to prevent L-dopa from being metabolized in the periphery of the body, decreasing amount of Mucuna that is needed. See forum https://healthunlocked.com/parkinsonsmovement/posts/131620015/mucuna-purens-as-a-source-of-dopamine Carbidopa can also increase serotonin that comes from 5-HTP (wiki).
L-deprenyl (Selegiline) metabolizes to an amphetamine and is not otherwise sympathomimetic like drugs but not like green tea (sympathomimetic are drugs that look like neurotransmitters as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc.
Rasagiline aka AGN1135 aka Azilect is preferred because it is not sympathomimetic and because of the lower dose is much less likely to cause a "cheese" reaction (conflict with tyramine in diet). It is not their MOA-B inhibitory mechanism that prevents progression of the disease, but their "propargyl moiety". The S-optical isomer of rasagiline, TVP1022 and propargylamine are poor MOA inhibitors and yet have the same neuroprotection that results from "interaction of Bcl-2 family protein with PKC-dependent MAPkinase pathway."
Rasagiline side effects: nausea, vomiting, orthostatic hypotension, somnolence, hallucinations and dyskinesias are tolerable in most cases. Vomiting was noteable at 1 mg/day. "Do not take AZILECT® (rasagiline tablets) if you are taking meperidine as it could result in a serious reaction such as coma or death. Also, do not take AZILECT with tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, or cyclobenzaprine. "
TV3326 (MAO-AB) is in phase 2 for AD and PD and antidepressant. It is an offshoot of rasagiline's S-isomer and carbamate cholinesterase inhibitor moiety to try to treat AD patients that also have PD and depression.
VK-28 is an BBB iron chelators.
M-30 is a propargylamine (a rasagiline site) but is MAO-AB instead of rasagiline's selective irreversible (disables the protein) MAO-B inhibitors. It is an iron-chelator. HLA-20 is in same class and also newest on the horizen. M-30 restores levels of the antiapoptotic protein Bcl-2 in mice (lactacystin model) and iron-dependent hydroxyl radical generation. Both M30 and parent molecule VK28 showed behavioral improvements in mice (including MPTP model) ... "M10 is another hydroxyquinoline derivative with radical scavenging and iron-chelating properties. It is a potent hydroxide scavenger and has been shown to be as effective as rasagiline in PC10 cell culture and inhibits lipid peroxidation with an IC50 value comparable to desferal "
"We determined that M-30 has a wide range of pharmacological activities, including prosurvival neurorescue effects reducing proapoptotic Bcl-2 family proteins, regulation of APP and A levels, and induction of neuronal differentiation. M-30 induced the outgrowth of neuritis, triggered cell cycle arrest in G0/G1 phase, and enhanced the expression of growth-associated protein 43 (GAP-43). This drug may improve the prognosis of PD and AD patients and exert disease-modifying effects by either delaying or preventing further neuronal loss by endogenously regulating NTFs, as suggested recently in clinical trials of early PD patients with rasagiline. "
http://synapse.koreamed.org/DOIx.php?id=10.5607/en.2013.22.3.167
ladostigil (TV-3, 326) acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.
====================
PD drugs overview:
Overall sales for Parkinson’s disease drugs in seven major countries will decline slightly from US$2.7 billion in 2010 to US$2.6 billion in 2020 in France, Germany, Italy, Japan, Spain, the UK and US, according to a new report from research and advisory firm Decision Resources. The decline is attributed to key therapies losing patent protection and subsequent generics competition.
The key Parkinson’s disease therapies reported to lose patent protection by 2020 are Novartis/Orion Pharma’s Comtan/Comtess/Stalevo (carbidopa/levodopa/entacapone) and Teva/Lundbeck’s Azilect/Agilect (rasagiline).
The report also expects GlaxoSmithKline’s Requip (ropinirole) and Boehringer Ingelheim’s Mirapex/Mirapexin/Sifrol/BI-Sifrol (pramipexole) to face increasing generics competition
L-deprenyl (Selegiline) metabolizes to an amphetamine and is not otherwise sympathomimetic like drugs but not like green tea (sympathomimetic are drugs that look like neurotransmitters as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc.
Rasagiline aka AGN1135 aka Azilect is preferred because it is not sympathomimetic and because of the lower dose is much less likely to cause a "cheese" reaction (conflict with tyramine in diet). It is not their MOA-B inhibitory mechanism that prevents progression of the disease, but their "propargyl moiety". The S-optical isomer of rasagiline, TVP1022 and propargylamine are poor MOA inhibitors and yet have the same neuroprotection that results from "interaction of Bcl-2 family protein with PKC-dependent MAPkinase pathway."
Rasagiline side effects: nausea, vomiting, orthostatic hypotension, somnolence, hallucinations and dyskinesias are tolerable in most cases. Vomiting was noteable at 1 mg/day. "Do not take AZILECT® (rasagiline tablets) if you are taking meperidine as it could result in a serious reaction such as coma or death. Also, do not take AZILECT with tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, or cyclobenzaprine. "
TV3326 (MAO-AB) is in phase 2 for AD and PD and antidepressant. It is an offshoot of rasagiline's S-isomer and carbamate cholinesterase inhibitor moiety to try to treat AD patients that also have PD and depression.
VK-28 is an BBB iron chelators.
M-30 is a propargylamine (a rasagiline site) but is MAO-AB instead of rasagiline's selective irreversible (disables the protein) MAO-B inhibitors. It is an iron-chelator. HLA-20 is in same class and also newest on the horizen. M-30 restores levels of the antiapoptotic protein Bcl-2 in mice (lactacystin model) and iron-dependent hydroxyl radical generation. Both M30 and parent molecule VK28 showed behavioral improvements in mice (including MPTP model) ... "M10 is another hydroxyquinoline derivative with radical scavenging and iron-chelating properties. It is a potent hydroxide scavenger and has been shown to be as effective as rasagiline in PC10 cell culture and inhibits lipid peroxidation with an IC50 value comparable to desferal "
"We determined that M-30 has a wide range of pharmacological activities, including prosurvival neurorescue effects reducing proapoptotic Bcl-2 family proteins, regulation of APP and A levels, and induction of neuronal differentiation. M-30 induced the outgrowth of neuritis, triggered cell cycle arrest in G0/G1 phase, and enhanced the expression of growth-associated protein 43 (GAP-43). This drug may improve the prognosis of PD and AD patients and exert disease-modifying effects by either delaying or preventing further neuronal loss by endogenously regulating NTFs, as suggested recently in clinical trials of early PD patients with rasagiline. "
http://synapse.koreamed.org/DOIx.php?id=10.5607/en.2013.22.3.167
ladostigil (TV-3, 326) acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.
====================
PD drugs overview:
Overall sales for Parkinson’s disease drugs in seven major countries will decline slightly from US$2.7 billion in 2010 to US$2.6 billion in 2020 in France, Germany, Italy, Japan, Spain, the UK and US, according to a new report from research and advisory firm Decision Resources. The decline is attributed to key therapies losing patent protection and subsequent generics competition.
The key Parkinson’s disease therapies reported to lose patent protection by 2020 are Novartis/Orion Pharma’s Comtan/Comtess/Stalevo (carbidopa/levodopa/entacapone) and Teva/Lundbeck’s Azilect/Agilect (rasagiline).
The report also expects GlaxoSmithKline’s Requip (ropinirole) and Boehringer Ingelheim’s Mirapex/Mirapexin/Sifrol/BI-Sifrol (pramipexole) to face increasing generics competition
Sales in France, Germany, Italy, Japan, Spain, the UK and US will continue to be driven by the leading dopamine agonists, pramipexole and ropinirole, and by increasing use of the monoamine oxidase B (MAO-B) inhibitor Azilect/Agilect (rasagiline), as well as by the re-entry of UCB/Schwarz Pharma's Neupro/Leganto (rotigotine) to the US market and its wider use in Europe.
The report forecasts that despite some key current therapies experiencing increased uptake and the launch of three new agents by 2020, sales of current products and the market impact of emerging therapies will be offset by generic competition.
The three new therapies set to launch by 2020 are Impax Laboratories/GSK’s IPX-066, a reformulation of levodopa, the mainstay of Parkinson’s disease therapy, Merck Serono/Newron Pharmaceuticals’ MAO-B inhibitor safinamide and Kyowa Hakko Kirin’s adenosine A2A receptor inhibitor antagonist istradefylline.
IPX-066, and to a lesser extent safinamide, are expected to contribute moderately to market growth. Both drugs are expected to contend with established agents within the same respective drug classes (where generic alternatives exist) and which are commonly used in the patient populations targeted by the emerging therapies.
While the first-in-class agent istradefylline will benefit from use in the management of motor response complications arising from levodopa treatment, its overall impact will be modest as it is currently expected to launch only in Japan.
The report does not expect major changes in the treatment of Parkinson’s disease over the next 10 years, and generics growth of key Parkinson’s disease therapies is expected to ‘depress market growth’ by 2020. Decision Resources analyst Ms Nadja Rodovsky comments that ‘future therapies will need to clearly demonstrate superiority over current therapies to gain a competitive edge in this mature market’.
The report forecasts that despite some key current therapies experiencing increased uptake and the launch of three new agents by 2020, sales of current products and the market impact of emerging therapies will be offset by generic competition.
The three new therapies set to launch by 2020 are Impax Laboratories/GSK’s IPX-066, a reformulation of levodopa, the mainstay of Parkinson’s disease therapy, Merck Serono/Newron Pharmaceuticals’ MAO-B inhibitor safinamide and Kyowa Hakko Kirin’s adenosine A2A receptor inhibitor antagonist istradefylline.
IPX-066, and to a lesser extent safinamide, are expected to contribute moderately to market growth. Both drugs are expected to contend with established agents within the same respective drug classes (where generic alternatives exist) and which are commonly used in the patient populations targeted by the emerging therapies.
While the first-in-class agent istradefylline will benefit from use in the management of motor response complications arising from levodopa treatment, its overall impact will be modest as it is currently expected to launch only in Japan.
The report does not expect major changes in the treatment of Parkinson’s disease over the next 10 years, and generics growth of key Parkinson’s disease therapies is expected to ‘depress market growth’ by 2020. Decision Resources analyst Ms Nadja Rodovsky comments that ‘future therapies will need to clearly demonstrate superiority over current therapies to gain a competitive edge in this mature market’.
Friday, March 20, 2015
low carb diet, exercise, and Parkinson's (comment to forum)
Although I could not find that a low carb diet prevented or improved PD, the reduction in sugars and increase in oils (simply replacing carbs with protein is not good) will increase the brain's ability to use ketones which helps the impaired neurons in PD (but not the already dead neurons) same as coconut oil because the impaired neurons are having trouble processing sugars (complex 1 in the mitochondria is not functioning and generating damaging reactive oxygen). If the oils are heavy in fish oil and omega 3, then there is actually very good evidence for it directly helping to prevent and improve PD. Higher cholesterol may not result, but if it does, I would not be concerned because higher cholesterol is associated with lower PD. Excess ketones during weight loss also help remove iron, probably to a small extent, but still a reason to not be afraid of low carb. I would let what carbs there are in the diet focus on blueberries and broccoli because they both low in sugar as far as fruits and vegetables go and have excellent compounds that cross the blood-brain barrier .... and because I feel better when taking them. Carrots improve eye functioning which is usually associated with improved brain functioning (blueberries also help both), but it's a lot of sugar. My near-sightedness significantly improves after two weeks of 2 cups of blueberries per day (I can read two lines lower on an eye chart). Broccoli increases libido when I first start it back up, which I can't find a reference to in the literature, but it's possibly indicating more dopamine. But so far only rasagiline has improved my mood and reduced finger twitching and improves balance, although exercise also improves mood. Exercise and niacin reduce the buzzing in my head which seems associated with confusion, so I intuitively feel that if I can stop the buzzing/confusion feeling, then PD is being delayed indefinitely. Good sleep helps reduce it, but I do not yet think rasagiline is reducing the buzzing.
Lower weight may also allow better blood flow to the brain which may be a strong protector of the brain.
Exercise is still king in protecting the brain from all PD-like diseases, although high levels of green tea extract has similar levels of proof of effectiveness. Imagine someone on a low carb diet programmer verses a professional painter who is on his feet all day coordinating with vigorous hand movements, and then plays aggressive basketball an hour every other evening. Intuition says the painter is less likely to get it. Changing habits towards the things you have not done in the past that have been shown to help is the best hope. For example, a painter who gets it might be really low in something in his diet. Someone overweight is more likely to be helped by losing weight. A programming, non-smoker, non-tea drinker, non-exerciser should have a lot of hope to be helped by the combination of nicotine gum, green tea extract, lots of exercise, vitamin D, getting off the computer, and rasagiline.
===============
Summary of my idea of an ideal morning PD routine:
16 oz coffee
Nicotine gum
exercise: basketball in garage with music, weight lifting
food: blueberries, broccoli, 1/2 to 1 beer, sardines in olive oil
nutrients: green tea extract, black tea extract, zinc, vitamins: B-complex, A, C, D, fish oil
black tea drink to swallow pills (not fun...hopefully nausea does not occur...keep ginger gum on hand)
pyruvate rest of day to reduce hunger
Niacin if the buzzing in my head is still present
Nicotine gum significantly worsens my balance, as it is known to do, but I believe it's a good thing. Nicotine increases dopamine, but not in the PD part of the brain, the SN, and that's also a good thing. I do not really want more dopamine in the SN to improve my symptoms because I want to train the remaining neurons to do their job (exercise) in the hopes of reducing the progression. Exercise and diet can worsen the generalized tremors if not the twitching tremors, but it's possibly a good thing because it shows a reduction in dopamine which may be a way of exercising the SN neurons. So starting the day without breakfast, some nicotine gum, and then exercising, followed by blueberries, broccoli, 1/2 beer, and a can of sardines is my plan. Food after exercise produces the most muscle mass, which is the same as saying reducing fat if calories the rest of the day are restricted. The sardines have fish oil and can be packed in olive oil (omega 3s). The purines and alcohol from beer, lactic acid from exercise, and purines from sardines all increase uric acid which may cause gout but is strongly associated with lower incidence of PD, presumably because it reduces iron. To clarify, I want to take nicotine gum before exercise under the possibility that it is the impaired balance (not just its iron chelation) from nicotine that might cause smokers to build a better SN which might be the reason they normally do not get PD. All these effects are strongest in men, some of them not seen in women. Green tea extract, grape seed extract, B-complex, and zinc need to be taken with this food since they each easily cause severe nausea, especially at the 2 or 3 pill levels I take of the extracts (but not zinc). Black tea extract does not cause the nausea. I take coffee before exercise (3 tablespoons in 16 oz) and black tea (2 bags Earl Grey in 16 oz) after exercise with the meal.
I wonder if the reason sleep is a problem is because the brain is suffering from lack of oxygen during the night and symptoms force us to wake up. All symptoms seem worse when waking up, but hyperventilating seems to help a little, not to mention water (or rather, the coffee).
Lower weight may also allow better blood flow to the brain which may be a strong protector of the brain.
Exercise is still king in protecting the brain from all PD-like diseases, although high levels of green tea extract has similar levels of proof of effectiveness. Imagine someone on a low carb diet programmer verses a professional painter who is on his feet all day coordinating with vigorous hand movements, and then plays aggressive basketball an hour every other evening. Intuition says the painter is less likely to get it. Changing habits towards the things you have not done in the past that have been shown to help is the best hope. For example, a painter who gets it might be really low in something in his diet. Someone overweight is more likely to be helped by losing weight. A programming, non-smoker, non-tea drinker, non-exerciser should have a lot of hope to be helped by the combination of nicotine gum, green tea extract, lots of exercise, vitamin D, getting off the computer, and rasagiline.
===============
Summary of my idea of an ideal morning PD routine:
16 oz coffee
Nicotine gum
exercise: basketball in garage with music, weight lifting
food: blueberries, broccoli, 1/2 to 1 beer, sardines in olive oil
nutrients: green tea extract, black tea extract, zinc, vitamins: B-complex, A, C, D, fish oil
black tea drink to swallow pills (not fun...hopefully nausea does not occur...keep ginger gum on hand)
pyruvate rest of day to reduce hunger
Niacin if the buzzing in my head is still present
Nicotine gum significantly worsens my balance, as it is known to do, but I believe it's a good thing. Nicotine increases dopamine, but not in the PD part of the brain, the SN, and that's also a good thing. I do not really want more dopamine in the SN to improve my symptoms because I want to train the remaining neurons to do their job (exercise) in the hopes of reducing the progression. Exercise and diet can worsen the generalized tremors if not the twitching tremors, but it's possibly a good thing because it shows a reduction in dopamine which may be a way of exercising the SN neurons. So starting the day without breakfast, some nicotine gum, and then exercising, followed by blueberries, broccoli, 1/2 beer, and a can of sardines is my plan. Food after exercise produces the most muscle mass, which is the same as saying reducing fat if calories the rest of the day are restricted. The sardines have fish oil and can be packed in olive oil (omega 3s). The purines and alcohol from beer, lactic acid from exercise, and purines from sardines all increase uric acid which may cause gout but is strongly associated with lower incidence of PD, presumably because it reduces iron. To clarify, I want to take nicotine gum before exercise under the possibility that it is the impaired balance (not just its iron chelation) from nicotine that might cause smokers to build a better SN which might be the reason they normally do not get PD. All these effects are strongest in men, some of them not seen in women. Green tea extract, grape seed extract, B-complex, and zinc need to be taken with this food since they each easily cause severe nausea, especially at the 2 or 3 pill levels I take of the extracts (but not zinc). Black tea extract does not cause the nausea. I take coffee before exercise (3 tablespoons in 16 oz) and black tea (2 bags Earl Grey in 16 oz) after exercise with the meal.
I wonder if the reason sleep is a problem is because the brain is suffering from lack of oxygen during the night and symptoms force us to wake up. All symptoms seem worse when waking up, but hyperventilating seems to help a little, not to mention water (or rather, the coffee).
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