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  Coluracetam

Submitter: Nexus
Category: Guides / Tutorials - Health / Medical
exhibition Date: 2015-01-23 05:11:44
Views: 698
Score: (not yet rated)
 
Coluracetam decision, research and reviews.

     
  Gordon Dentistry

Submitter: Limitless
Category: Guides / Tutorials - Health / Medical
exhibition Date: 2017-03-20 08:31:22
Last Update: 2017-03-20 08:33:54
Views: 296
Score: (not yet rated)
 
o
5 stars Dennis P Customer since 2013

Very professional doctor and staff. Pleasant, warm and carrying professionals! My family are warmly received and cared for.

10 days ago
5 stars Roger G Customer since 2010

Great experience. Very thorough and considerate.

13 days ago
5 stars Linda J Verified customer

Painless, kind, wonderful care!

18 days ago
5 stars Anonymous Verified customer

Dr. Gordon & staff are always professional and polite. Dr. Gordon truly cares for her patients.

19 days ago
5 stars Sarah B Customer since 2016

I have never felt more cared for in any dentistry setting than I have with Dr. Gordon and her team, Her knowledge and compassion for the patient blended with her dental skills took away any fears of dental work.

25 days ago
5 stars Anonymous Verified customer

Great service and teamwork!

a month ago
5 stars Beverly O Verified customer

First visit. Nice people. Clean, nicely decorated office. Dr. Gordon was professional. Good experience.

a month ago
5 stars Robert L Customer since 2012

Very nice

a month ago

     
  Marijuana Risks vs Benefits for Seizure Treatment

Submitter: Limitless
Category: Guides / Tutorials - Health / Medical
exhibition Date: 2018-02-11 03:22:56
Last Update: 2018-03-10 02:07:22
Views: 171
Score: 5.00 / 5.00 (Based on 3 votes.)
 
Cannabinoids are inherently neuroprotective substances—in fact, our brain produces its own cannabinoids when injured to reduce damage and promote healing. Cannabinoids have a superior safety profile compared to most anti-epileptic drugs, many of which have been shown to impair brain function and development.

     
  NORML Action Center

Submitter: [anonymous]
Category: Guides / Tutorials - Health / Medical
exhibition Date: 2018-05-06 07:26:59
Last Update: 2018-05-06 07:27:29
Views: 132
Score: 5.00 / 5.00 (Based on 1 votes.)
 
NORML's Action Center

Register to Vote
Federal Priorities:
AG Jeff Sessions: Tell Congress to Reject Jeff Session's Reversal of the Cole Memo
MJ Justice: The Marijuana Justice Act of 2017 Introduced
Caucus: Tell Your Congressional Representative: Join the Cannabis Caucus
Protect Our Progress: Bipartisan Leaders Reintroduce the Respect State Marijuana Laws Act
Deschedule Marijuana: The Ending Marijuana Prohibition Act of 2017
Tell Your State Lawmakers To Put Marijuana On Their 2018 Agenda
2018 Legislation Pending Gubernatorial Action
Georgia: Legislation to Expand Medical CBD Access
Hawaii: Medical Marijuana Reciprocity Effort
Kansas: Legislation to Legalize the Retail Sale of CBD
Maine: Legislation to Expand Medical Marijuana Access
Maryland: Industrial Hemp Expansion Legislation
Missouri: Legislation to Allow Industrial Hemp Research
New Hampshire: Legislation to Expand Patient Access
2018 State Legislation: Legalization
Timely! New Jersey: Deschedule Marijuana
Connecticut: Marijuana Legalization Effort
Delaware: Marijuana Legalization Effort
Illinois: Legislation to Put Legalization to a Public Vote
Illinois: Marijuana Legalization Effort
Minnesota: Marijuana Legalization Effort
New Jersey: Marijuana Depenalization Effort
New Jersey: Marijuana Legalization Effort
New York: Marijuana Legalization Effort
Vermont: Legislation to Tax and Regulate Marijuana
2018 State Legislation: Decriminalization
Alabama: Marijuana Decriminalization Effort
Pennsylvania: Marijuana Decriminalization Effort
2018 State Legislation: Medical
Timely! New Jersey: Tell Regulators to Put Patients First
California: Protect Medical Marijuana Patients from Employment Discrimination
Colorado: Legislation to Protect Medical Marijuana Patients from Employment Discrimination
Delaware: Legislation to Expand Medical Marijuana Program
Florida: Medical Marijuana Reciprocity Effort
Illinois: Permit Doctors to Recommend Cannabis in Place of Opioids
Louisiana: Legislation to Expand Medical Cannabis Program
New Jersey: Legislation to Expand Patient Access
New Jersey: Let Doctors Decide When to Recommend Medical Marijuana
New Jersey: Protect Medical Marijuana Patients from Employment Discrimination
New York: Legislation to Expand Veteran Access to Medical Marijuana
New York: Let Doctors Decide When to Recommend Medical Marijuana
New York: Permit Physicians to Recommend Cannabis in Place of Opioids
Rhode Island: Protect Medical Marijuana Patients from Employment Discrimination
South Carolina: Medical Marijuana Legislation
Tennessee: Legislation to Establish Medical Marijuana Access
Tennessee: Legislation to Regulate Medical Marijuana Extracts
Tennessee: Medical Marijuana Exemption Bill
District of Columbia: Legislation to Expand Medical Cannabis Access
2018 State Legislation: Other
Alaska: Legislation to Seal Past Marijuana Convictions
Alaska: Legislation to Expand Banking Options to Cannabis Businesses
Alaska: Seeking Sanctuary State Status for Marijuana Operators
California: Legislation to Automatically Expunge Past Marijuana Convictions
California: Legislation to Expand Banking Options for Marijuana Businesses
California: Legislation to make California a Marijuana Industry Sanctuary State
California: Legislation to Temporarily Lower Cannabis Taxes
California: Protect Cannabis Delivery Services
Delaware: Legislation to Expunge Past Cannabis Possession Convictions
Illinois: Legislation to Expunge Past Cannabis Law Violations
Iowa: Legislation to Expand Medical CBD Program
Massachusetts: Bill Seeking Sanctuary State Status for Marijuana Operators
New Hampshire: Legislation to Allow Expungement of Certain Marijuana Convictions
New Jersey: Legislation to Allow Expungement of Marijuana Convictions
New Jersey: Legislation to Protect Cannabis Consumers from Employment Discrimination
Oklahoma: Establish the Oklahoma Cannabis Commission
Pennsylvania: Resolution Urging Congress to Deschedule Marijuana
Vermont: Legislation to Expunge Past Marijuana Convictions
Washington: Legislation to Expand Banking Options for Marijuana Businesses
2018 State Legislation: Hemp
Illinois: Industrial Hemp Expansion Legislation
Iowa: Industrial Hemp Research Legislation
2018 State Legislation NORML Opposes
Missouri: Oppose Unscientific Zero Tolerance DUI Drug Legislation
New Hampshire: Oppose Additional Possession Penalties
Oklahoma: Legislative Effort to Preemptively Amend Pending Medical Marijuana Legislation
Additional Federal Efforts:
Medical: Legislation to Protect Lawful Medical Marijuana Use From Housing Discrimination
Veterans: Legislation to Explicitly Authorize the Veterans Administration to Facilitate Medical Marijuana Research
Medical: Acknowledge the Role of Cannabis in Combating the Prescription Drug Overdose Epidemic
Judicial: Protect Legal Marijuana from Federal Interference
Legalization: The Marijuana Revenue and Regulation Act Introduced (Senate and House Bill)
Veterans: House Bill Introduced to Expand Veterans’ Access to Medical Marijuana
Medical: Legislation To Protect Medical Marijuana Patients Pending In Senate (CARERS Act)
Medical: Bill Seeks to Reschedule Marijuana Under the CSA
Medical: Remove Federal Restrictions on CBD
Judicial: Demand That The New US Attorney’s Respect State Marijuana Laws
Judicial: End Arbitrary License Suspensions For Minor Marijuana Possession (The Better Drive Act)
Economic: Legislation Pending To Halt Federal Forfeiture Actions Against Marijuana Facilities
Economic: Legislation Pending To Cease Penalizing State-Compliant Marijuana Businesses Under the Federal Tax Code
Economic: Support The Secure and Fair Enforcement Banking Act (SAFE Banking Act)
Economic: Support the State Marijuana And Regulatory Tolerance (SMART) Enforcement Act
Economic: Support the Sensible Enforcement Of Cannabis Act
Economic: House and Senate Measures Seek to Protect Marijuana Businesses and Consumers
Economic: The Stop Civil Asset Forfeiture Funding for Marijuana Suppression Act
Hemp: Exclude Hemp From the Controlled Substances Act
Research: Legislation Introduced to Facilitate Federally-Approved Cannabis Research
Science: Legislation To Facilitate Medical Marijuana Research
Advocacy: Tell AAA To Stop Lying About Legalization
Advocacy: Tell President Trump to Abolish the Office of the Drug Czar
Advocacy: Tell the ONDCP Opioid Commission: Medical Marijuana as an Alternative
2018 State Enacted Legislation
Alaska: Industrial Hemp Pilot Program Legislation
Indiana: Legislation to Expand CBD Access
Kansas: Industrial Hemp Pilot Program Legislation
Maine: Legislation Implements Retail Adult Use Sales, Amends Home Grow Limits
Massachusetts: Marijuana Expungement Bill Provision Signed Into Law
Oklahoma: Industrial Hemp Pilot Program Legislation
Utah: Legislation to Allow Medical Marijuana Research
Vermont: Marijuana Depenalization Effort
Virginia: Expand State's Medical CBD Law

     
  PPARδ agonist GW501516 for enhancing running

Submitter: [anonymous]
Category: Guides / Tutorials - Health / Medical
exhibition Date: 2017-01-24 01:00:29
Views: 405
Score: 5.00 / 5.00 (Based on 1 votes.)
 
A metabolomic study of the PPARδ agonist GW501516 for enhancing running endurance in Kunming mice
Wei Chen, Rong Gao[…]Lili Wang
Scientific Reports 5, Article number: 9884 (2015)
doi:10.1038/srep09884

Published online:
06 May 2015

Discussion

This study demonstrated that GW501516 increases exhaustive running performance and the proportion of SDH-positive muscle fibres in both trained and untrained mice. Slow-twitch myofibres are rich in mitochondria and have a high oxidative capacity. Formation of slow-twitch muscle fibres revolves around PGC-1α and its transcripts17,18. Like exercise, GW501516 alone is sufficient to improve running endurance of untrained mice, even after only 1 week of administration (Supplementary Fig. S1 online). Enhanced running endurance is the results of increased fatty acid utilization after PPARδ activation that upregulates PDK4 and other key components of fatty acid oxidation pathways. Accordingly, blood glucose levels of GW501516-treated mice were significantly higher after exercise while blood lactate was lower compared to untrained controls. Although GW501516 or exercise each enhanced fatty acid oxidation in skeletal muscle, GW501516 predominately induces fatty acid metabolism, while training also induced protein metabolism as an energy source.

Studies have demonstrated that GW501516 significantly increased the running performance of trained C57Bl/6J mice5, but not in untrained mice that were treated with 5 mg/kg over periods lasting 4 weeks to 5 months, or 3–30 mg/kg/day gavaged for 2 months5. Our study found that GW501516 increased running performance in KM mice regardless of training and the magnitude of improvement was unexpectedly greater for untrained mice. This finding could be due to different GW501516 administration protocols, exhaustive running protocols, or strain differences. In this study, running performance was determined by wheel running rather than treadmill running because it is more natural for mice, which are specialized climbers, and better measures their natural running abilities. Additionally, studies have shown significant differences in aerobic capacity, treadmill performance, and exercise training responses between different inbred and hybrid rodent strains19,20. The running distance of untreated trained mice (TN) was relatively higher than that of GW501516-treated untrained mice (NG). The effects of wheel training and the skills acquired during the training period cannot be ignored, but are difficult to control for.

PPARδ is the principle isoform involved in regulating muscle fuel utilization. Previous studies demonstrated that changes in expression of genes regulated by PPARδ occurred after 3 days of GW501516 treatment5. We also found that expression of PGC1α, PDK4, and selective biomarkers for fatty acid β oxidation in skeletal muscle were significantly increased by GW501516 treatment. Both palmitic acid and the earlier intermediate in the fatty acid oxidation pathway, 3-hydroxy-hexadecanoic acid, were elevated compared to untrained control mice. However, why the downstream products of fatty acid oxidation were not found to be increased in the GW501516-treated group warrants further investigation. Additionally, GW17046 (another PPARδ agonist) treatment in ob/ob mice markedly reduced levels of saturated long chain fatty acids (15–24 carbon atoms) in untrained GW501516-treated (NG) mice compared to untreated untrained (NN) mice21. This result suggests that unlike exercise, GW501516 is limited to promoting hydrolysis of triglycerides and that the increased serum palmitic acid observed in GW501516-treated (NG) mice may be due to the catabolism of saturated fatty acids. In contrast, the decrease in serum saturated fatty acids was completely reversed when GW501516 treatment was combined with training. Presumably, this is because of enhanced fat metabolism. GW501516 also increased blood glucose and lowered blood lactate compared to control mice, particularly after running tests and in trained mice. This suggests that glycolysis in muscle tissue is reduced after treatment with GW501516, and becomes more apparent immediately after the exhaustive running (Fig. 1 and Supplementary Fig. S1 online). Consistent with this reduced glucose metabolism, increased serum galactose was also only observed after GW501516 treatment. Although glycolytic metabolism of galactose yields no net adenosine triphosphate (ATP), previous research demonstrated that galactose induces a metabolic shift towards a more oxidative phenotype and enhances aerobic mitochondrial metabolism in myotubes22.

PPARδ is intricately involved in enhanced running endurance. It mediates oxidative adaption following exercise training and increased expression in skeletal muscle was reported after both acute exercise and endurance training12,23,24. Similar to chemical activation of PPARδ, endurance training increases fatty acid metabolism in skeletal muscle and reduced lactate production during exercise25. Accordingly, the running distance of untreated trained (TN) mice is over 100% greater of that of untreated untrained (NN), blood glucose levels in the TN group are significantly higher and blood lactate levels are significantly lower than those measured in the NN group. Enhanced fatty acid oxidation in skeletal muscle was also observed by measuring elevated components of the fatty acid oxidation pathway including palmitic acid and octanoic acid. Caproic acid and butyric acid were not significantly different between groups in our assay, but the sensitivity to detect these metabolites may be insufficient. The underlying mechanism for PPARδ and PPARα activation to increase fatty acid oxidation in skeletal muscle is by upregulating components of the electron transport chain (CYT-C and UCP3) and CPT1b in the mitochondria. Serum inositol is also increased by training and may help increase endurance in trained mice. Inositol can help transport fat from the liver and improve the distribution of fat throughout the body, allowing it to be used more efficiently as an energy source. Our results further corroborate that exercise training promotes fat mobilization and fatty acid oxidation as energy substrates during running. Furthermore, this is likely mediated through exercised-induced PPARδ expression in a way that is similar to what was reported previously in human skeletal muscle following exercise training12.

One of the most striking differences between drug treatment and exercise was the increase of serum PUFA and hydroxybutyrate. Compared to training, GW501516 increased levels of UFA, especially PUFA, and they were further increased by the combination of GW501516 and training. This is in agreement with previous studies that showed increases of enzymes that produce UFA after treatment with a PPARδ agonist5,21. Our study demonstrated GW501516 increased levels of 3 PUFA (α-linolenic acid, arachidonic acid, and its precursor 8,  11,  14-Eicosatrienoic acid) regardless of exercise training. Previous studies have demonstrated that all long-chain fatty acids and their derivatives are putative PPAR ligands2,26,27. Endogenous fatty acids that have been shown to activate PPAR include PUFAs such as some ω-3 PUFA (e.g. α-linolenic acid and docosahexaenoic acid), some ω-6 PUFA (e.g. linoleic acid and arachidonic acid), and some saturated fatty acids (e.g. stearic acid)2,3,26,27. UFA and PUFA in particular, could act as activators of PPARδ after being increased by GW501516. Additionally they are sensed by the liver which then mobilizes fatty acids and stimulates hepatic fatty acid oxidation28. We observed hydroxybutyrate, the major constituent of ketone bodies, was significantly increased by GW501516, but not exercise. Leucine, a ketogenic amino acid, was also increased by GW501516 only. However, exercise did increase other BCAA. Increased hepatic synthesis of ketone bodies would be expected during increased release of fatty acids from fat stores and further suggests that GW501516 promotes hepatic fatty acid oxidation that can provide muscle with an alternative energy source during exercise. Ketone bodies are an important energy substrate under stress and hydroxybutyrate can freely enter muscle mitochondria and be metabolized to acetyl CoA.

The impacts of training or GW501516 treatment on essential amino acids were slightly different. The glycogenic amino acids that can be metabolized to form pyruvate (alanine, serine and threonine) were only significantly increased after training alone. This suggests more energy is utilized from pyruvate after training. Elevations in these amino acids were reversed by GW501516 treatment suggesting that GW501516 inhibits gluconeogenesis or the conversion of glycogenic amino acids into pyruvate that was induced by training. This indirectly suggests that GW501516-treated mice specifically rely on fatty acids as energy. Three BCAA (valine, leucine, and isoleucine) were increased by both GW501516 and training. Long-distance running involves mobilization of BCAA29 and many studies demonstrate that BCAA concentrations immediately after exercise are reduced in the serum, but not in muscle30. We found that training or GW501516 treatment, preserved serum BCAA levels after exhaustive running. As essential amino acids, BCAA are primarily metabolized in muscle and are important for protein synthesis, neurotransmitter synthesis, and repair of exercise-induced skeletal muscle damage31,32. Increased BCAA may both act as an energy source (Supplementary Fig. S3 online) and protect mitochondria from exercise-induced damage to preserve mitochondrial function. In addition, increased serum BCAA may reduce tryptophan uptake in the brain and delay fatigue by competitively inhibiting 5-hydroxytryptamine (5-HT) synthesis31,32.

Metabolomic analyses are relatively new technology. It is limited by the complexity of techniques, high inter- and intra- subject variability, incomplete metabolite databases, and incomplete understanding of metabolic pathways. Although there are a total of 122 peaks measured in serum samples, only 43 peaks could be matched to known metabolites.

In conclusion,this study demonstrated that 3-week treatment with GW501516 increased running performance of both trained and untrained mice. Like training, GW501516 promoted mitochondrial fatty acid oxidation and increased fat metabolism in muscle tissue (Summarized in Supplementary Fig. S4 online). However, exercise increased energy supply by promoting catabolism of protein, glycolysis and glucogenesis from amino acids, while GW501516 increased fatty acid oxidation through BCAA and ketone body pathways.