Wednesday, January 7, 2015

Dehydroascorbic acid (DHA)(*) and Vitamin E reduced visibility of Forehead and Nosy Finel iines

By Kyle J. Norton and associates
World wide Copy Right protected. No reproduction of any part of this document is allowed without permission of the writer.
                                                   Dehydroascorbic Acid(*)


                                                                       
                                             
                                                         Vitamin E

                                           

                          Published 2014, August 15 By Kyle J. Norton and associates. All right reserved.
Who does not want to look 5, 10 or 15 year younger than his/her biological age or in comparison of people in the age group.

 The dream of finding such ingredients in maintaining and getting rid of aging fine lines has been ongoing since human civilization. Unfortunately, many ingredients with no commercial values have been discarded due to their effects in dampening the profits of all cosmetic companies.

In our previous studies, we have shown that Dehydroascorbic acid (DHA)(*)  4% concentration improved facial skin, including reduced roughness, black and white heads, lightened aging spots, pigmentation and enhanced elasticity and prevented acne, etc. The combination of Dehydroascorbic acid (DHA)(*)  4% concentration and vitamin E and E effectively reduced visibility of arterial veins on the back the hand, rejuvenated fingers (including knuckles), wrist and forearms from the wrist to elbow. The aim of this study is to test for the effectiveness of Dehydroascorbic acid (DHA)(*)  4% concentration used combination with vitamin E, 3 times daily on 40 healthy subjects.

 Fine line is a result of effect of gravity in aging, and causes of slower process in cell rejuvenation and longer in elastic fibers replacement. Some researchers insisted that adding to the aging skin, free radicals and inflammatory molecules may degrade facial skin even more quickly.

According to the searching on PubMed data base, there are limit information of health effects of Dehydroascorbic acid (DHA)(*) but its un oxidized form.
1. Dehydroascorbic Acid (DHA) (vitamin C supplement oxidized form)
Vitamin C
, also known as L-ascorbic acid, is a water-soluble vitamin found in fresh fruits, berries and green vegetables. It is best known for its free radical scavenging activity and regenerating oxidized vitamin E for immune system support. In skin aging, the vitamin may improve solar radiation protection and epidermal aging (1) through production of collagen due to its antioxidant activity (2)(3).
Epidemiological studies linking vitamin C in prevention of skin damage and aging have produced some certain results (3a)(3b)(3c). Vitamin C oxidized form or dehydroascorbic acid (DHA) processed antiviral and virucidal effects (23), prevented H2O2-induced cell death by increasing the GSH levels mediated by the GPx and GR activities and PPP (17), and regulated neuronal energy metabolism, through facilitating the utilization of glucose via the PPP for antioxidant purposes (18) by increasing antioxidant potential in the central nervous system (19). Dehydroascorbic acid (DHA) may be a potential anti-cancer agent to treat aggressive cancers (20)(21). Dr. Toohey at the Cytoregulation Research said "rapidly-dividing tumour cells make unusually large amounts of homocysteine thiolactone and that administered dehydroascorbic acid enters the cells and converts the thiolactone to mercaptopropionaldehyde which kills the cancer cells" (22).

According to the Minghsin University of Science and Technology, in doses of a dependent manner, the concentration of L-ascorbic acid induced absorption of the collagen solution in exhibition of smoothing wrinkles and clear up spots(8). Ascorbic acid (AA) is essential in stimulating collagen gene expression. In type 1 and type 4 collagen and SVCT2, the vitamin was found to enhance the expression of type 1 and type 4 collagens and SVCT2 mRNA in cultured human skin fibroblasts at 100 μM AA placed every 24h for 5 days to prevent depletion(9). The Chiang Mai University study also supported the effects of ascorbic acid in the anti-aging process through exhibition pro and active MMP-2 inhibitory(10). Combined vitamins, including vitamin C in a single formulation had a slightly lower degradation rate and more stable formulations as compared to different preparations containing only one of the vitamins(11)(12). Application of vitamin C showed a significant reduction of oxidative stress in the skin, an improvement of the epidermal-dermal microstructure and a reduction of fine lines and wrinkles in aged skin within a relatively short period of time of product application(13). The Bruce and Associates study also insisted the effectiveness of vitamin C application over a 12 week period as the vitamin enhanced the overall intensity of pigmentation, fine lines and wrinkles, tactile roughness, and laxity with a 100% satisfaction of overall appearance of the tested subjects’ skin(14).
In fact, many studies have showed that vitamin C, the un oxidized form improved skin roughness and scaliness(26)(27), wrinkles(28)(29), skin elasticity and firming(30)(31)(32)(33)(34)(35), lightened Liver and aging spots(36)(37)(38)(39)(40)(41), Pigmentation(42)(43)(44), reduced Acne and Acne scars(45)(46).

2. Vitamin E
Vitamin E is a fat soluble vitamin consisting of eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrieno with varying levels of biological activity, found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower, safflower oils, etc.) which plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc.

Epidemiological studies linking vitamin E in reduced progression of aging have been inconclusive (47)(48)(49)(50), but some studies showed that vitamin delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins (51) and prevents cellular aging in human diploid fibroblasts (52), protects against oxidative stress-induced cellular ageing by modulating the telomere length possibly via telomerase(54), protects against H(2)O(2)-induced oxidative stress (55). and induced DNA damage and telomere shortening of normal human skin fibroblast cells derived from young and old individual donors(56), UVA(57).  In a study of Indian women with signs of facial aging, the composition of niacinamide, panthenol, and tocopheryl acetate significantly reduced the appearance of hyperpigmentation, improved skin tone evenness, and lightened the appearance of the skin in comparison to the control through 6 weeks(60).

Method
A total of 40 patients were recruited, with ages ranging from 57 - 60 (32 Caucasians, 3 Africans, and 5 Asians; 32 females and 8 males)  to test for the effectiveness of DHA 4% concentration and vitamin E for 3 times daily in 12 weeks against the formation of forehead and nosy fine lines. Patients were instructed to apply DHA 4% concentration first than followed by vitamin E (0.5ml) with duration of 5 minutes in each interval on the affected area.

Total Patients Study
Race
Gender
Ages 57-62
Caucasians
26 females, 6 males
32
Asians
4 females, 1 males
5
Africans
3 females, 0 males
3



Caucasians
Africans
Asians
Total
Ethnicity and Gender
32
3
5
40 (33F, 7M)
Patients are eligible to enter this study if they are in the age group from 55 to 65 (regardless to types of skin) with moderate to severe aging processes causing forehead and nose fine lines. Patients must also agree during the study that they will not to use any other topical products but the testing solution, such as moisturizers, sunscreens, fragrances, make-up, and any facial procedures such as peels, facials, microdermabrasion, and injection of botulinum toxin type A or dermal fillers. The study also examined the patients with any cosmetic surgery and medication use which may interfere with the study, as well as history of facial skin diseases. All patients are also required to sign a informed consent.

Initial examination
Based on a scale from 0-4 (0 - Not applicable, 1 - Minimum, 2 - Mild. 3 - Moderate, 4 - Severe)     
All age groups
Not Applicable
Minimum
Mild
Severe
Forehead fine lines
0
0
7
33
Nosy fine lines
0
0
5
35
 stretch marks between the eyes
0
0
18
22


Treatment solution
1. Equipment contained  Vitamin E an DHA provided and mixed by patients as instructed. DHA  solution was refrigerated and remake every 3 days to protect its effectiveness.

2. DHA 4% was applied 5 minutes then Vitamin E (0.5 ml) 3 times a day, in the morning, afternoon and evening.
3.Application of DHA using a sponge should be taken with glove to void brownness, due to its acidic concentration.
4. Application of vitamin E (0.5 ml)are used by fingers and palm with slightly pressure rubbing against the forearms skin to ensure absorption.
5. Affected areas should be cleansed before applied the first ingredient.
6. After finished application, DHA was returned to refrigerator and Vitamin E to the cabinet.
 
Outcome measure
The result would be measured 3 times:
1. The end of week 4
2. The end of week 8
3. The end of week 12
Patients were measured for the intensity of the applicable area and to check for efficacy of the solution by comparing to the base line.
All patients have completed the study.
 
Results:
Observation report
1. At the end of week 4
Measurement of improvement of the group A using a scale rating from 0 - 100% improvement.
DHA 4% cot 6% concentration  then vitamin E(0.5 ml) with duration of 5 minutes between 2 applications in the morning, afternoon and evening, 3 times daily.

Forehead fine lines       50
Nosy fine lines             30
Stretch marks   20

2. At the end of week 8
Measurement of improvement of the group A using a scale rating from 0 - 100% improvement.
DHA 4% cot 6% concentration  then vitamin E(0.5 ml) with duration of 5 minutes between 2 applications in the morning, afternoon and evening, 3 times daily.
 
Forehead fine lines       65
Nosy fine lines             40
Stretch marks     25
 
3 At the end of week 12
Measurement of improvement of the group A using a scale rating from 0 - 100% improvement.
DHA 4% cot 6% concentration  then vitamin E(0.5 ml) with duration of 5 minutes between 2 applications in the morning, afternoon and evening, 3 times daily.
 
Forehead fine lines       80
Nosy fine lines              50
Stretch marks      30
 
Efficacy and Patient satisfaction:
With a scale ranging from 0 - 4 (0: no effect, 1: minimum, 2: moderate, 3: good, 4 excellent effect)
Forehead fine lines    3.8  
Nosy fine lines 3.2
Stretch marks 2.5
As the data indicates, most patients satisfied with the performance of Solution in reduced visibility of forehead and nosy fine lines but not other fine lines. Reduced visibility of forehead fime line had a high score in patients satisfaction.
 
Tolerability
Through over 12 weeks of application with the designed solution, no adverse effect has been reported.
 
Discussion
For first time, we discovered that the used ingredients are less effective on nosy fine lines (20% in comparison with healthy oral hygiene) on patients with completed denture.
DHA  4% concentration in the previous study, showed the most efficacy in enhanced smoothness, firmness, and elasticity of the skin through stimulation the production of collagen. It also whitened skin and reduced scaliness, photo-pigmentation and aging pigmentation, aging spots, acne, acne scars. It was especially effective in the treatment of black and white heads when compared with other solutions probably through its antioxidant activities and skin absorption. When combined with vitamin E (.5 ml), the application of the combined solution showed effectively in reduced visibility of both forehead and nosy fine lines of aging subject from ages of 57 to 62 as follow after 12 weeks, probably through DHA detoxified, antioxidant and stimulated reproduction of collagen activities via vary unknown mechanisms.

The below are the pictures of 58 years old of the tested subjects
1. Before application

2. After 4 weeks

3. After 8 weeks

4. After 12 weeks
 
Vitamin E used in this studies is Provitamin E sold by Jamieson. Kyle J. Norton and associated DO NOT received funding from Jamieson.  The decision to use such the produced was due to complaints of irritation and stickiness of vitamin E liquids in many testing subjects in previous studies. This decision may also be the cause of withdrawal funding from our 2  long termed sponsors.
Please make sure that you discuss the use of any topical solution in the study with your doctor or related field specialist before applying.

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References
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(8) A stabilized 0.1% retinol facial moisturizer improves the appearance of photodamaged skin in an eight-week, double-blind, vehicle-controlled study by Tucker-Samaras S1, Zedayko T, Cole C, Miller D, Wallo W, Leyden JJ.(PubMed)
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(10) Influence of dietary carotenoids on radical scavenging capacity of the skin and skin lipids by Meinke MC1, Friedrich A, Tscherch K, Haag SF, Darvin ME, Vollert H, Groth N, Lademann J, Rohn S.(PubMed)
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(15) Dermal carotenoid level and kinetics after topical and systemic administration of antioxidants: enrichment strategies in a controlled in vivo study by Darvin ME1, Fluhr JW, Schanzer S, Richter H, Patzelt A, Meinke MC, Zastrow L, Golz K, Doucet O, Sterry W, Lademann J(PubMed)
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(10) Nanoscale gelatinase A (MMP-2) inhibition on human skin fibroblasts of Longkong (Lansium domesticum Correa) leaf extracts for anti-aging by Manosroi A1, Kumguan K, Chankhampan C, Manosroi W, Manosroi J.(PubMed)
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(14) Evaluation of a prescription strength 4% hydroquinone/10% L-ascorbic acid treatment system for normal to oily skin by Bruce S1, Watson J(PubMed)
(15) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)
(16) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)
(17) Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes by Kim EJ1, Park YG, Baik EJ, Jung SJ, Won R, Nahm TS, Lee BH.(PubMed)
(18) The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism by Cisternas P1, Silva-Alvarez C, Martínez F, Fernandez E, Ferrada L, Oyarce K, Salazar K, Bolaños JP, Nualart F.(PubMed)
(19) Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters by Agus DB1, Gambhir SS, Pardridge WM, Spielholz C, Baselga J, Vera JC, Golde DW.(PubMed)
(20) Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy by McCarty MF.(PubMed)
(21) Gelatin crosslinked with dehydroascorbic acid as a novel scaffold for tissue regeneration with simultaneous antitumor activity by Falconi M1, Salvatore V, Teti G, Focaroli S, Durante S, Nicolini B, Mazzotti A, Orienti I.(PubMed)
(22) Dehydroascorbic acid as an anti-cancer agent by Toohey JI.(PubMed)
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Most common diseases of 50 plus - Diseases of Central Nervous system - Free radical causes of dementia (Multiple Sclerosis, MS)

By Kyle J. Norton 
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

               Diseases of Central Nervous system

                                 Dementia



About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.
II. Causes of dementia
B. Free radical causes of dementia
B.3. Multiple Sclerosis
1. Free radicals and Multiple Sclerosis
 Free radical activity is a contributory factors in MS(60) due to proinflammatory cytokines in free radicals production in the peripheral immune system and the central nervous system (CNS)(60).

2. Antioxidants and Multiple sclerosis
Antioxidants protect the neural tissues from damage against inflammation caused by oxidative stress.
a. TNFalpha
 
TNFalpha, an imflammatory cytokine showed to associate with MS inhibited by antioxidants(61)) of green tea(62), and curcumin(63).

b. Melatonin
Melatonin functions as an antioxidant has the ability to protect neurons(65)(66) from free radicals cause of lipid peroxidation(64).

c Selenium
Some studies found that the level of selenium in the blood of people with MS was lower than in that of people without MS(67)(68). In patients with MS,
all abnormalities may be normalized by daily intake of selenium(69),

d. Niacin

Niacin acting as antioxidant is a key to the successful treatment of multiple sclerosis,

. It profoundly prevents the degeneration(70) of demyelinated axons and improves the behavioral deficits(71).

e. Vitamin D

Seurm of 25(OH)D level showed to regulate expression dynamics of a large gene-gene interaction system in immune modulatory processes of MS activity(72). According to the study published by the journal Neurology, group receiving vitamin D supplement demonstrated a remarkable 41 percent reduction in new MS events with no meaningful side effects(73).

f. Etc.
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References
(60) http://www.ncbi.nlm.nih.gov/pubmed/18505779
(61) http://www.ncbi.nlm.nih.gov/pubmed/18322311
(62) http://www.ncbi.nlm.nih.gov/pubmed/25123184
(63) http://www.ncbi.nlm.nih.gov/pubmed/20163327
(64) http://www.ncbi.nlm.nih.gov/pubmed/25427383
(65) http://www.ncbi.nlm.nih.gov/pubmed/23183236
(66) http://www.ncbi.nlm.nih.gov/pubmed/22010042
(67) http://www.ncbi.nlm.nih.gov/pubmed/1702664
(68) http://www.ncbi.nlm.nih.gov/pubmed/10609336
(69) http://www.ncbi.nlm.nih.gov/pubmed/2484516 
(70) http://www.ncbi.nlm.nih.gov/pubmed/25317166
(71) http://www.ncbi.nlm.nih.gov/pubmed/17414505
(72) http://www.ncbi.nlm.nih.gov/pubmed/25285313  
(73) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis,  June 8, 2010 74:1852-1859; published ahead of print April 28, 2010 1526-632X
 

Most common diseases of 50 plus - Diseases of Central Nervous system - Free radical causes of Parkinson's disease

 

 By Kyle J. Norton(Draft Article) 
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.


               Diseases of Central Nervous system

                                 Dementia


About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.
II. Causes of dementia
B. Free radical causes of dementia

B.2. Parkinson's disease
1. Free radicals and Parkinson's disease

 Patients with Parkinson's disease have low levels of polyunsaturated fat in the substania nigra(44)(45) than other part of the brain, but higher levels of lipid peroxidation as indication of higher levels of malonaldehyde(44). Also patients with the disease found to contain waste pigments of lipofusion(46) and other polymers in the neurons(47) where dopamine is most active.


2. Aging and Parkinson's disease
According to  Julius-Maximilians-University, physiological aging and OS-dependent aggregation of proteins, accompanied with environment toxins(49) are found to associated to the progression of the disease(48).

3. Antioxidants and Parkinson's disease
Antioxidants play an vital role for patients with Parkinson's disease.
a. Superoxide dismutase
Researcher found that the progression of the disease may be associated with the decrease levels of superoxide dismutase, a antioxidant enzyme(50). According to University of Thessaloniki, Patients with advanced Parkinson' diseases showed a statistically significant decrease of SOD activity in whole blood and in red blood cells(51).

b. NADH ubiquinone reductase
 Levels of NADH ubiquinone reductase is decreased in the substania nigra(52) in patients with PD, leaded to neurons apoptosis, but this can be treated with antioxidants Acetyl-L-carnitine (53) and alpha lipoic acid(54).

c. Uric acid
 People with a high blood level of the natural antioxidant uric acid have a lower risk of developing Parkinson's disease(55) than do people with lower levels(56), but high levels of uric acid increases the risk of kidney diseases(57) and gout(58).

d. Glutathione
 Glutathoine  showed to deactivate the harmful product HNE of lipid peroxidation(59).


f. Etc.
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References(49) http://www.ncbi.nlm.nih.gov/pubmed/24826210
(50) http://www.ncbi.nlm.nih.gov/pubmed/18243716
(51) http://www.ncbi.nlm.nih.gov/pubmed/9238339
(52) http://www.ncbi.nlm.nih.gov/pubmed/23357119
(53) http://www.ncbi.nlm.nih.gov/pubmed/24023579
(54) http://www.ncbi.nlm.nih.gov/pubmed/21958946
(55) http://www.ncbi.nlm.nih.gov/pubmed/22490478
(56) http://www.ncbi.nlm.nih.gov/pubmed/18618666
(57) http://www.ncbi.nlm.nih.gov/pubmed/23588856
(58) http://www.ncbi.nlm.nih.gov/pubmed/16407889

 

Most common diseases of 50 plus - Diseases of Central Nervous system - Free radical causes of dementia (Alzheimer’s disease)

By Kyle J. Norton (Draft Article)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

               Diseases of Central Nervous system

                                 Dementia



About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.
II. Causes of dementia
B. Free radical causes of dementia
B.1. Alzheimer’s disease
1. Free radical and Alzheimer’s disease
Free radicals causes Alzheimer’s disease is well defined in many researches(25)(26). Oxidative stress-induced injury involved the selective modification of different intracellular proteins may lead to the neurofibrillary degeneration of neurons in the brain(27)(28) (source)

2.  Antioxidants and Alzheimer’s disease
a. Docosahexaenoic acid (DHA)
Change of brain aging in DHA metabolism, was found in patients with Alzheimer's disease(29). DHA, a naturally occurring component found in every cell membrane(29) increases phosphatidylserine(30)(31) is important in decreased production of proinflammatory omega-6 eicosanoids causes of Alzheimer's disease(31) and in improved the memory of animals with Alzheimer's disease by suppressing oxidative damage in the brain(32).

b. Vitamin E

Vitamin E, and drugs(memantine) reduced generalized inflammation, may slow the decline of mental and physical abilities in people with Alzheimer's disease (AD) over the long term(33). Also vitamin E inhibits cells damage and cells death caused by beta-amyloid(34)(35), which is toxic to brain cells(36).

c. Phosphatidylserine

Patients who had Alzheimer’s disease took 100 milligrams per day (mg/day) of phosphatidylserine scored significantly better on standardized memory tests at the end of the 12-week trial period than patients without(37)(38).

d. Antioxidants
Antioxidant are found at much lower levels for patients with Alzheimer’s disease(39)(40)(41) , such as serum of vitamin A, C, E, zinc and transfferin.

e. Muscarinic cholinergic receptors 

 Alzheimer’s disease patients showed to exhibit the significant loss of muscarinic cholinergic receptors neurons(42) causes of reduced volume of neural transmission that can lead to loss of memory(43).

f. Etc.

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Tuesday, January 6, 2015

Most common diseases of 50 plus - Diseases of Central Nervous system - The Deficient Causes of Dementia

By Kyle J. Norton(Draft Article) 
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

               Diseases of Central Nervous system

                                 Dementia


About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.
II. Causes of dementia
A. Deficient cause of dementia due to aging
1. Vitamin D and 1,25-dihydroxyvitamin D(3) deficiency
Vitamin D levels not only plays a important role in the pathogenesis of many age-associated diseases including cancer, heart disease, type 2 diabetes mellitus and stroke, but  also associats with increased risk of prevalent cognitive dysfunction. According to number of studies, raising vitamin D plays a role in decreased cognitive dysfunction and dementia(a).  Evidence from epidemiological also insisted the association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality(b).

2. Folic acid with vitamin B12 deficiency
Folates are vitamins essential to the development of the central nervous system. Deficiency of folate can increase the risk of dementia. According to Cochrane Dementia and Cognitive Improvement Group, folic acid plus vitamin B12 was effective in reducing the serum homocysteine concentrations, with no adverse effects(c).

3. Vitamin B12 deficiency
An association between neuropsychiatric disorders and vitamin B12 deficiency has been recognized since 1849. Deficiency of Vitamin B12 are found in many elder and might contribute to age-associated cognitive impairment, according to the Scientist at Cochrane Dementia and Cognitive Improvement Group(d).

4. Vitamin B6 deficiency
 Vitamin B6 supplementation showed to reduce the risk of developing cognitive impairment by older healthy people, or improving cognitive functioning of people with cognitive decline and dementia, according the study conducted by Cochrane Dementia and Cognitive Improvement Group(e).

5. Deficiency of Insulin-like growth factor (IGF)-1and growth hormones
Deficiency of Insulin-like growth factor (IGF)--1 hormone may contribute to the genesis of cognitive impairment and dementia in the elderly patients. Old age, in the absence of circulating IGF-1, a hormone with a complex role in brain function have linked IGF-1 to an acceleration of neurological diseases(f). Growth hormone and IGF-1 replacement showed to increase neurogenesis, vascular density, and glucose utilization, and alters NMDA receptor subunit composition in brain areas that are implicated in learning and memory, in animal (g)and children(h) studies.

8. Deficiency of cerebrospinal fluid melatonin
 Melatonin plays an essential role to carried in ventricular system via choroid plexus portals. In Alzheimer's disease, inadequate melatonin increases risk of the neuropathological changes due to hydroxyl radicals cause of damage mitochondria and initiated cascade of oxygen radicals(i).

9. Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations
DHEA, a neurosteroid secreted by the adrenal cortex. is also a neurosteroid. The levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrationsare  decline in concentration with age(j).

10. Etc.

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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html

References
(a) http://www.ncbi.nlm.nih.gov/pubmed/21790207
(b) http://www.ncbi.nlm.nih.gov/pubmed/20226390
(c) http://www.ncbi.nlm.nih.gov/pubmed/14584018
(d) http://www.ncbi.nlm.nih.gov/pubmed/12918012
(e) http://www.ncbi.nlm.nih.gov/pubmed/14584010
(f) http://www.ncbi.nlm.nih.gov/pubmed/22503992
(g) http://www.ncbi.nlm.nih.gov/pubmed/16024298
(h) http://www.ncbi.nlm.nih.gov/pubmed/15478038
(i) http://www.ncbi.nlm.nih.gov/pubmed/11461164
(j) http://www.ncbi.nlm.nih.gov/pubmed/19665809

Most common diseases of 50 plus - Diseases of Central Nervous system - Dementia: The Types

By Kyle J. Norton (Draft Article)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

               Diseases of Central Nervous system

                                 Dementia


About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.

I. Types of dementia
1. Alzheimer's disease
 Alzheimer's disease is a brain disorder named for German physician Alois Alzheimer(1). Alzheimer's destroys brain cells, causing problems with memory, thinking and behavior severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal(2). Over 1 million people in US alone are currently afflicted by Alzheimer's disease because of degeneration of hippocampus and cerebral cortex(3) of the brain where memory, language and cognition(4) are located. With this mental disorder, brain cells gradually die and generate fewer and fewer chemical signals day by day resulting in diminished of functions. Overtime memory thinking as well as behavior deteriorates. Today, there is no known cure.

2. Absence of acetylcholine
 If the nerves located in front of the brain perish(5), causing diminished quality of acetylcholine may result of cognitive dysfunction(6) causes of language difficulty, memory loss, concentration problem and reduced moblile skills because of lacking reaction in muscular activity and refection(7) and anxiety- and depression-like behaviors(8).

3. Dementia due to long-term alcohol abuse
 Dementia is common in patients with alcoholism(9). Most classic is the Korsakoff's dementia resulted in extremely poor short term memory(10) and often associated with the memory losses of confabulations due to diminished processing resources and/or an encoding or retrieval deficit(11).

4. Multi-infarct dementia
Also known asvascular dementia , is the second most common form of dementia after Alzheimer's disease in older adults. It is caused by different mechanisms all resulting in vascular lesions(12) in the brain(13).

5. Dementia associated with Parkinson's disease
 Parkinson disease (PD) is a disabling, progressive condition. It is a cognitive deficits due to the interruption of frontal-subcortical loops that facilitate cognition and parallel the motor loop(15)(16) due to loss of substantia nigra pars compacta (SNc) dopamine (DA) neurons(14).

6. Creutzfeldt-Jakob disease (CJD)
People who have eaten contaminated beef(18) for many years may be infected without even knowing it. Creutzfeldt-Jakob disease is a quickly progressing and fatal disease that consists of dementia(19), muscle abnormal functions(17).

7. Subdural hematoma
It is the accumulation of blood beneath the outer covering of the brain that result from the rupture of blood vessel(20)(21). Subdural hemorrhages may increase intracranial pressure(22), causes of compression and damage to delicate brain tissue. Acute subdural hematoma has a high mortality rate(23).

Other types of dementia include metabolic disorders, dementia due to long-term substance abuse, hypothyroidism, and hyperethyroidism.

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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html


References
(1) http://en.wikipedia.org/wiki/Alzheimer%27s_disease
(2) http://www.ncbi.nlm.nih.gov/pubmed/25431401
(3) http://www.ncbi.nlm.nih.gov/pubmed/24548606
(4) http://www.ncbi.nlm.nih.gov/pubmed/25433211
(5) http://www.ncbi.nlm.nih.gov/pubmed/23035090
(6) http://www.ncbi.nlm.nih.gov/pubmed/24938789
(7) http://www.ncbi.nlm.nih.gov/pubmed/8713126
(8) http://www.ncbi.nlm.nih.gov/pubmed/22573727
(9) http://www.ncbi.nlm.nih.gov/pubmed/8949964
(10) http://www.ncbi.nlm.nih.gov/pubmed/4058708
(11) http://www.ncbi.nlm.nih.gov/pubmed/1944875
(12) http://www.ncbi.nlm.nih.gov/pubmed/22705146
(13) http://www.ncbi.nlm.nih.gov/pubmed/23596414
(14) http://www.ncbi.nlm.nih.gov/pubmed/20696315
(15) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181854/
(16)http://books.google.ca/books?id=886cQkUFjMgC&pg=PA28&lpg=PA28&dq=frontal-subcortical+loops+and+Parkinson%27s+disease&source=bl&ots=yikrA4hGSX&sig=xengrjZiGyFRIcC23gjNDLMTimQ&hl=en&sa=X&ei=6W98VNGxCYSWyQS504KgBg&ved=0CEUQ6AEwBQ#v=onepage&q=frontal-subcortical%20loops%20and%20Parkinson%27s%20disease&f=false
(17) http://www.ncbi.nlm.nih.gov/pubmed/25342014
(18) http://www.ncbi.nlm.nih.gov/pubmed/15825799
(19) http://www.ncbi.nlm.nih.gov/pubmed/25315814
(20) http://www.ncbi.nlm.nih.gov/pubmed/24313607
(21) http://www.ncbi.nlm.nih.gov/pubmed/19139303
(22) http://www.ncbi.nlm.nih.gov/pubmed/20220741
(23) http://www.ncbi.nlm.nih.gov/pubmed/24698583

Most common diseases of 50 plus - Upper gastrointestinal (GI) diseases - Gastro-esophageal reflux disease (GERD): Preventions, Managements and Treatments

By Kyle J. Norton  (Draft article)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

              Upper gastrointestinal (GI) diseases

The prevalence of upper gastrointestinal (GI) diseases is increasing in subjects aged 65 years and over. Pathophysiological changes in esophageal functions that occur with aging may, at least in part, be responsible for the high prevalence of
1. Gastro-esophageal reflux disease (GERD) in old age.
2. The incidence of gastric and duodenal ulcers and their bleeding complications is increasing in old-aged populations worldwide.
3.  H. pylori infection in elderly patients with H. pylori-associated peptic ulcer disease and severe chronic gastritis
4.  Almost 40% of GU and 25% of DU in the elderly patients are associated with the use of NSAID(1) and/or aspirin(2).(a)

        Gastro-esophageal reflux disease (GERD)

 Gastroesophageal reflux disease (GERD), also known as gastro-oesophageal reflux disease (GORD), gastric reflux disease, or acid reflux disease, is a chronic condition of liquid stomach acid refluxing back up from the stomach into the esophagus, causing heartburn. According to the study of “Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.” by DeVault KR, Castell DO; American College of Gastroenterology, GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus.

I. The Symptoms 
1. Heartburn
Heart burn is one of common symptom of Gastroesophageal reflux disease (GERD) in adult, as a result of acid reflux cause of burning sensation or pain in the middle of the chest mostly after meal(3)(4)(5).

2. Regurgitation
In gastroesophageal reflux disease (GERD), regurgitation is the expulsion of a small amount of digested foods to the mouth from esophagus. frequent or prolonged regurgitation can lead to acid-induced erosion of the teeth, bad breath or damage to the esophagus(3)(5).

3. Trouble swallowing(dysphagia)
It is caused by damage of the muscles and tissues that must flex for swallowing, as a result of prolonged period of acid reflux that has left untreated(6).

4. Pain when swallow
It may be caused by esophageal motility disorders, due to deglutitive contraction waves that die out in the upper esophagus(6a).

5. Asthma
Approximately, 59% of patients with GERD are experiences symptoms in asthma, according to the Baylor College of Medicine(7).

7. Other symptoms according to Texas A&M University(6) include
a, Stomach pain,
b. Stomach discomfort when eating,
c. Food and drink limits, 
d. Nausea and vomiting,
e. Gas and bloating,
f. Constipation,
g. Blood, and
h. Diarrhea


II. The Causes
1. Slower in emptying of the stomach after eating
Most uncommon causes of Gastroesophageal reflux disease (GERD) is due to the distention of the stomach with food over prolonged period of time that can lead to reflux(7). Approximately 20% of Gastroesophageal reflux disease (GERD) are caused the reason above.

2. Cardia
Cardia is the area between the part of the stomach and the esophagus, a angle where the esophagus enters the stomach acted as a valve to prevent foods and others to reflux back to the esophagus. If the cardia is not functioning well(8), it can cause Gastroesophageal reflux disease (GERD with burning sensation of the esophagus(9).

3. Esophageal contractile defection(11)
If the esophageal contraction fails to performed its function of proper swallowing food, it may not generate enough waves of contractions to push the foods down to the stomach after swallowing and the acid back into the stomach(6a)(10).

4. Hiatal hernia
Hiatal hernia is a condition of a portion of the stomach protrudes upward into the chest, through a tear or weakness in the diaphragm. Hiatal hernia of the esophagus and GERD had been shown to induce hemorrhage(13). GERD patients consuming a late-evening meal had significantly greater supine acid reflux compared to when they consumed an early meal, especially in overweight patients, and in patients with esophagitis or HH(12).

5. Obesity
Obesity increase the risk of Gastroesophageal reflux disease (GERD). Weight loss, through caloric restriction and behavioral modification, may improve reflux inobese patient with GERD(14). Bariatric surgery and Roux-en-Y gastric bypass (RYGB) has been consistently associated with improvement in the symptoms of GERD(14).

6. Esophageal mucosa
 Erosive changes in the esophageal mucosof of  the lower esophagogastric junctionwere strongly associated with GERD(15).

7. Medication
The use of medication such as NSAIDs product can increase the risk of Gastroesophageal reflux disease (GERD)(16).

8. Chronic diseases
Chronic diseases, including cough(17)(18)(19)pulmonary fibrosis(21), earache and asthma(20) are also associated with the higher risk of develop Gastroesophageal reflux disease (GERD).

9. Infection
Infection caused by H. pylori can increase the risk of Gastroesophageal reflux disease (GERD)(22) through the bacteria pylori suppression of gastric acid secretion  (Gastroenterology 1997 Jul;113(1):15-24).

10. Etc.

III. Complications In some severe cases as a result of frequent acid reflux.
1. Ulcers
Damage of the esophagus can lead to result of ulcers as a result of inflammation forming of scar(23).

2. Esophageal strictures
Prolonged period and frequent acid reflux, if keft untreated can lead to inflammation cause of narrowing of the esophagus(24)(25).

3. Barrett’s esophagus
Symptoms of gastroesophageal reflux disease (GERD) are the primary risk factor for Barrett's esophagus (BE)(26). The highest yield for Barrett’s is in older (age 50 or more) Caucasian males with longstanding heartburn(27).

4. Esophageal adenocarcinoma
In GICS 2009: EGF Genetic Variant Increases Risk for GERD-Associated Esophageal Adenocarcinoma ” by Roxanne Nelson posted by Medscape Newa Today, the author wrote that January 16, 2009 (San Francisco, California)

5. Etc.

IV. Diagnosis and tests
If you are experience some of the above symptoms, after recording your family history and physical exam, the following test may be recommended by your doctor.

1. Esophagogastroduodenoscopy (EGD)
Esophagogastroduodenoscopy (EGD) also known as upper gastrointestinal endoscopy is a diagnosis procedure allowed your doctor to check for any abnormality in the lining of the esophagus, stomach, and upper duodenum after a flexible endoscope inserted down the throat.

If any abnormality is found, your doctor order further examinations.
2. Barium swallow
Barium swallow is a medical imaging procedure allowed your doctor to examine the upper GI (gastrointestinal) tract, to exam the lining of the esophagus and the stomach, after you have drunk a suspension of barium sulfate.

3. Chest X-rays
A chest x-ray is an x-ray of the chest that allows your doctor to examine the lining of the esophagus, stomach, and upper duodenum.

4. Biopsy
A biopsy is a test of removal sample of cells or tissues for examination and determination of the grade and type of the tumors examined under a microscope by a pathologist or chemically, if the location of the tumor allows the test to be done without major risk to the patient.

4. Esophageal manometry
Esophageal manometry is a test with the use of a pressure-sensitive tube-like thin instrument passed through your mouth or nose and into your stomach to allow your doctor to examine the motor function of the Upper Esophageal Sphincter (UES), Esophageal body and Lower Esophageal Sphincter (LES).
5. Etc.

V. The GERD Diet
According to the GERD Diet (Gastroesophageal Reflux Disease) in McKinley Health Center of The university of Illinois at Urbana-Champaign
Dietary modifications are recommended to lessen the likelihood of reflux and to avoid irritation of sensitive or inflamed esophageal tissue. Listed below of several recommendations may help to manage GERD:
1. Decrease total fat intake – High fat meals and fried foods tend to decrease LES pressure and delay
2. Avoid large meals – Large meals increase the likelihood of increased gastric (stomach) pressure and reflux.
3. Decrease total caloric intake if weight loss is desired – Since obesity may promote reflux, weight loss
may be suggested by your healthcare provider to control reflux. Reducing both total fat and caloric intake will aid in weight loss.
4. Avoid chocolate – Chocolate contains methylxanthine, which has been shown to reduce LES pressure by causing relaxation of smooth muscle.
5. Avoid coffee depending on individual tolerance – Coffee, with or without caffeine, may promote gastroesophageal reflux. Coffee may be consumed if it is well tolerated.
6. Avoid other known irritants – Alcohol, mint, carbonated beverages, citrus juices, and tomato products all may aggravate GERD. These products may be consumed depending on individual tolerance.
B. Other modifications for treating GERD
7. Maintain upright posture during and after eating.
8. Stop smoking.
9. Avoid clothing that is tight in the abdominal area.
10. Avoid eating within 3 hours before bedtime.
11. Lose weight if you are overweight.
12. Sleep on your left side.
13. Chew non-mint gum which will increase saliva production and decrease acid in the esophagus.
14. Elevate the head of your bed 4-6 inches by placing bricks under the headboard. (Source)

VI. Treatments
A. Conventional medicine
A.1. Medication
1. Proton-pump inhibitors
Proton-pump inhibitors including omeprazole, esomeprazole, pantoprazole, are used to reduce the production of gastric acid in the stomach(28)(29).

2. H2 receptor blocker(30)
H2 receptor blockers include ranitidine, famotidine, cimetidine, etc., Over-the-counter medications are effective in treating symptomatic gastro-oesophageal reflux disease, with 41% with histamine-2 receptor antagonists, 60% with alginate/antacid combinations, and 11% with antacids(31).

3. 5HT4 agonist

Mosapride 40 mg q.d.s. is effective in decreasing acid reflux in the oesophagus in patients with GERD(32).

4. GABA-B Receptor Agonists
 Baclofen, a GABA-B agonist, showed effectively in the treatment of patients with GERD, through inhibition pf 34% to 60% of Transient Lower Esophageal Sphincter Relaxation (TLESR) and improvement of basal lower esophageal sphincter pressure(33).

5. Antacids
Antacids are oral medicine used to relieve symptom of heartburn of gastroesophageal reflux disease (GERB)(34)(35).

4. Pro motility Agents
Promotility Agents are used to improve GERD symptoms for patients with slow gastric emptying by stimulating the muscles of the gastrointestinal tract to reduce acid reflux into the esophagus(36).
5. Etc.

A.2. Surgery: Fundoplication Surgery
The aim of the surgery is to reduce heartburn caused by acid reflux, in severe case of inflammation, such as  hiatal hernia, damage of esophagus, etc.. Fundoplication surgery(37)(38) is the procedure to treat Gastroesophageal Reflux Disease (GERD) by strengthening the valve between the esophagus and stomach as the upper curve of the stomach wrapped and satured around the lower end of the esophagus to prevent acid from backing up into the esophagus with a laparoscopic with a small tunnel made from the stomach muscle to allow foods of the lower part of the esophagus to pass through. The surgery is also by times for the esophagus to heal.
 Laparoscopic fundoplication is effective in controlling symptoms in the majority of patients with Barrett's esophagus(BE) to orevent  the possibility of developing esophageal adenocarcinoma(39)

B. Herbs
1. Deglycyrrhizinated licorice
Deglycyrrhizinated licorice used by people with gastric and peptic ulcers for nearly a hundred years. its three antiulcer agents FM 100, plaunotol, and teprenon showed to increase the content of endogenous prostaglandins in the gastric mucosa,  through its endogenous secretin released and antiulcer effect(40).

2. Aloe Vera
According to the article of “Effect Of Orally Consumed Aloe Vera Juice On Gastrointestinal Function In Normal Humans, excerpts By Jeffrey Bland, Ph.D. (Linus Pauling Institute of Science & Medicine) involved ten healthy subjects – five men (median age: 42; standard deviation: 14 years), and five women (median age: 32; standard deviation: 5 years) – engaged  Aloe vera juice oral supplementation in in a semicontrolled study,  promotes proper gastrointestinal function, such as gastrointestinal motility, increasing stool specific gravity etc. through its regulate gastrointestinal pH effect(41),

3. Mastic gum
 Mastic gum. a resin obtained from the mastic tree (Pistacia lentiscus), showed to consist an ability to support the health of patients with ulcers, GERD and acid reflux, according to the article of Strategies to Protect Against Potential Bone-Destroying Effects”By Chris D. Meletis, ND,

4. Ginger
Ginger has been used for thousands of years to enhance the function of digestive system and treated stomach distress including nausea, vomiting, diarrhea and in digestion, acid reflux, motion sickness, dyspepsia, etc. due to its anti-inflammatory, antimicrobial and analgesic properties.
The methanol extract of ginger rhizome showed to inhibite the growth of all 19 strains of bacteria in vitro with a minimum inhibitory concentration range of 6.25-50 micrograms/ml(42)

5. Peppermint
In vitro, peppermint exhibited significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system etc.,… Caution are necessary for using peppermint oil therapy in patients with GI reflux, hiatal hernia(43).

6. Etc.

C. Traditional Chinese medicine
a. Ban Xia Xie Xin Wan
, also known as "Pinellia Drain Epigastrium Pills" was recorded in classic texts around 210 C.E. used in TCM to treat various gastrointestinal disorders such as gastritis, enteritis, gastric ulcer, gastralgia exhibits its anti-ulcer action (probably based on its ability to protect the gastric mucosa), through improvement of gastric emptying and an anti-emetic action,
according to the study of the effects of hange-shashin-to on gastric function in comparison with sho-saiko-to" by Y Kase, M Yuzurihara, S Iizuka, A Ishige, Y Komatsu,

b. Ingredients
b.1. Ban Xia (Pinellia Tuber)
Main use: Dries Dampness, Transforms Phlegm, Stops vomiting, Resolves masses, Disperses nodules....
b.2. Huang Qin (Skullcap Root)
Main use: Clears Heat, Dries Dampness, Expels toxins, Stops bleeding...
b.3. Dang Shen (Codonopsis Root)
Main use: Tonifies the Middle Burner, Strengthens Qi, Promotes generation of Body Fluids, Nourishes Blood....
b.4. Gan Cao ( Licorice Root)
Main use: Tonifies the Spleen, Benefits the Qi, Moistens the Lungs, Calms cough...
b.5. Huang Lian (Coptis Rhizome)
Main use: Clears Heat, Dries Dampness, Expels toxins...
b.6. Bai Shao
Main use: Nourishes Blood, Preserves the Yin, Nourishes the Liver, Calms pain....
b.7. Chen Pi
Main use: Regulates the Qi, Regulates the Middle, Dries Dampness, Transforms Phlegm...

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References
(a) http://www.ncbi.nlm.nih.gov/pubmed/15588798
(1) http://www.ncbi.nlm.nih.gov/pubmed/16001646
(2) http://www.ncbi.nlm.nih.gov/pubmed/22542157
(3) http://www.ncbi.nlm.nih.gov/pubmed/25232262
(4) http://www.ncbi.nlm.nih.gov/pubmed/25212408
(5) http://www.ncbi.nlm.nih.gov/pubmed/24347282
(6) http://www.ncbi.nlm.nih.gov/pubmed/25148757
(6a) http://www.ncbi.nlm.nih.gov/pubmed/2237280
(7) http://www.ncbi.nlm.nih.gov/pubmed/17682001
(8) http://www.ncbi.nlm.nih.gov/pubmed/16377311
(9) http://www.ncbi.nlm.nih.gov/pubmed/?term=Cardia+and+burning+sensation
(10) http://www.ncbi.nlm.nih.gov/pubmed/24330081
(11) http://www.ncbi.nlm.nih.gov/pubmed/8608873
(12) http://www.ncbi.nlm.nih.gov/pubmed/?term=Administration+of+a+Standardized+Meal.+Does+Timing+Matter
(13) http://www.ncbi.nlm.nih.gov/pubmed/17633874 
(14) http://www.ncbi.nlm.nih.gov/pubmed/?term=weight+loss%2C+through+caloric+restriction+and+behavioral+modification+in+obese+with+GERD
(15) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956342/
(16) http://www.ncbi.nlm.nih.gov/pubmed/23265146
(17) http://www.ncbi.nlm.nih.gov/pubmed/18046990
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(19) http://www.ncbi.nlm.nih.gov/pubmed/25327320
(20) http://www.ncbi.nlm.nih.gov/pubmed/16430100
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(22) http://www.ncbi.nlm.nih.gov/pubmed/10378360
(23) http://www.ncbi.nlm.nih.gov/pubmed/14986731
(24) http://www.ncbi.nlm.nih.gov/pubmed/24564071
(25) http://www.ncbi.nlm.nih.gov/pubmed/24482901
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(27) http://www.ncbi.nlm.nih.gov/pubmed/18341497
(28) http://www.ncbi.nlm.nih.gov/pubmed/21235462
(29) http://www.ncbi.nlm.nih.gov/pubmed/20124466
(30) http://www.ncbi.nlm.nih.gov/pubmed/11552905
(31) http://www.ncbi.nlm.nih.gov/pubmed/17229239
(32) http://www.ncbi.nlm.nih.gov/pubmed/9692698
(33) http://www.medscape.org/viewarticle/434528
(34) http://www.ncbi.nlm.nih.gov/pubmed/10886047
(35) http://www.ncbi.nlm.nih.gov/pubmed/15540548
(36) http://www.ncbi.nlm.nih.gov/pubmed/1349550
(37) http://www.ncbi.nlm.nih.gov/pubmed/25386679
(38) http://www.ncbi.nlm.nih.gov/pubmed/23943388
(39) http://www.ncbi.nlm.nih.gov/pubmed/14759403
(40) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1156688/
(41) http://www.desertharvest.com/physicians/documents/DH127.pdf
(42) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761965/
(43) http://onlinelibrary.wiley.com/doi/10.1002/ptr.1936/abstract