INT15527

Context Info Confidence 0.61 First Reported 1985 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 19 Total Number 27 Disease Relevance 11.15 Pain Relevance 1.08

small molecule metabolic process (FFAR1) plasma membrane (FFAR1) signal transducer activity (FFAR1)

Anatomy Link Frequency plasma 5 muscle 2 skeletal muscle 2 fat 1 brain 1 FFAR1 (Homo sapiens)

Pain Link Frequency Relevance Heat TRP channel 1 98.32 narcan 3 92.32 cINOD 1 90.68 ischemia 16 89.32 anesthesia 9 84.80 Pain 16 82.08 Opioid 1 80.80 Arthritis 1 80.40 opiate 1 79.92 diabetic neuropathy 1 76.00

Disease Link Frequency Relevance Heat Mental Disorders 1026 100.00 Insulin Resistance 138 100.00 Obesity 10 100.00 Cancer 8 99.68 Diabetes Mellitus 147 99.50 Stress 100 97.88 Alzheimer's Dementia 12 96.40 Targeted Disruption 7 94.32 Parasitic Infection 3 91.60 INFLAMMATION 34 90.44

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Free will and mental disorder: Exploring the relationship A link between mental disorder and freedom is clearly present in the introduction of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

Gene_expression (present) of Free will associated with mental disorders

1) Confidence 0.61 Published 2010 Journal Theor Med Bioeth Section Title Doc Link PMC2975916 Disease Relevance 0.88 Pain Relevance 0

Free will may be defined in many ways, but time after time, the central question is, does this specific concept of free will enable us to explain our moral intuitions?

Gene_expression (defined) of Free will

2) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Body Doc Link PMC2975916 Disease Relevance 0.38 Pain Relevance 0.03

As it turns out, philosophers of free will frequently refer to mental disorders as conditions that compromise free will and reduce moral responsibility.

Gene_expression (philosophers) of free will associated with mental disorders

3) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Abstract Doc Link PMC2975916 Disease Relevance 0.95 Pain Relevance 0

In addition, in forensic psychiatry, the rationale for the assessment of criminal responsibility is often explained by referring to the fact that mental disorders can compromise free will.

Gene_expression (compromise) of free will associated with mental disorders

4) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Abstract Doc Link PMC2975916 Disease Relevance 0.96 Pain Relevance 0

Yet, in both domains, it remains unclear in what way free will is compromised by mental disorders.

Gene_expression (compromised) of free will associated with mental disorders

5) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Abstract Doc Link PMC2975916 Disease Relevance 0.95 Pain Relevance 0

And in fact, not only determinism but also indeterminism appears to be problematic for free will, for what room would be left for free will, if everything happened by chance?

Gene_expression (problematic) of free will

6) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Body Doc Link PMC2975916 Disease Relevance 0 Pain Relevance 0

Less attention has been paid to identifying the precise reasons why (certain) mental disorders would diminish free will; a detailed analysis of what it is that mental disorders do that has such an effect on free will is lacking.

Gene_expression (diminish) of free will associated with mental disorders

7) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Body Doc Link PMC2975916 Disease Relevance 0.88 Pain Relevance 0.04

As it turns out, philosophers of free will frequently refer to mental disorders as conditions that compromise free will and reduce moral responsibility.

Gene_expression (compromise) of free will associated with mental disorders

8) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Abstract Doc Link PMC2975916 Disease Relevance 0.95 Pain Relevance 0

I examine two domains in which a connection between mental disorder and free will is present: the philosophy of free will and forensic psychiatry.

Gene_expression (connection) of free will associated with mental disorders

9) Confidence 0.53 Published 2010 Journal Theor Med Bioeth Section Abstract Doc Link PMC2975916 Disease Relevance 0.89 Pain Relevance 0

Diacylglycerol (DG), which is considered to be as a plausible candidate for the source of FFA, was also produced in the ischemic brain, and its acyl chain composition was similar to that of liberated FFAs.

Gene_expression (source) of FFA in brain

10) Confidence 0.47 Published 1986 Journal No To Shinkei Section Abstract Doc Link 3730200 Disease Relevance 0.60 Pain Relevance 0.26

Called VR1, this fatty acid receptor is present only on C fibers, and when activated produces desensitization or degeneration of the sensory afferent.

Gene_expression (present) of fatty acid receptor

11) Confidence 0.42 Published 2000 Journal Clin J Pain Section Abstract Doc Link 10870746 Disease Relevance 0.24 Pain Relevance 0.16

The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels.

Gene_expression (produced) of FFA in plasma associated with obesity

12) Confidence 0.12 Published 1992 Journal Metab. Clin. Exp. Section Abstract Doc Link 1736041 Disease Relevance 0.37 Pain Relevance 0.16

For the c-peptide assay: 4.8% at 472 pmol/l to 3.7% at 2056 pmol/l and for the FFA assay: 10.6% at 112 ?

Gene_expression (assay) of FFA

13) Confidence 0.10 Published 2010 Journal Cardiovasc Diabetol Section Body Doc Link PMC2903514 Disease Relevance 0.31 Pain Relevance 0

The impact of exercise on PDH regulation in skeletal muscle unrelated to the metabolic status of the cell and body may reflect that exercise can overcome potential inhibition of carbohydrate utilization present in resting skeletal muscle when circulating FFA levels are increased (2).

Gene_expression (levels) of FFA in skeletal muscle

14) Confidence 0.07 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0.23 Pain Relevance 0

Thus, although there was no effect of elevated FFA on PDHa activity at rest in the present study, maybe due to the overnight high-fat diet in both trials, elevated FFA levels have been shown to induce insulin resistance (31,32), and individuals with enhanced circulating FFA levels like type 2 diabetic subjects may experience FFA-mediated insulin resistance at rest (33), potentially in part because of FFA-induced downregulation of PDH (1).

Gene_expression (resistance) of FFA-mediated in fat associated with diabetes mellitus and insulin resistance

15) Confidence 0.07 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0.30 Pain Relevance 0

However, in these studies, plasma FFA and muscle glycogen were manipulated simultaneously, making it impossible to discriminate between the role of muscle glycogen and FFA.

Gene_expression (manipulated) of FFA in muscle

16) Confidence 0.07 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0 Pain Relevance 0

In the present study, however, the carbohydrate-rich breakfast meal in one trial ensured lowered plasma FFA levels and normalized plasma insulin, leaving only muscle glycogen different.

Gene_expression (levels) of FFA in muscle

17) Confidence 0.07 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0 Pain Relevance 0

Also based on findings in rat skeletal muscle, plasma FFA is also believed to reduce PDH activity through a peroxisome proliferator–activated receptor (PPAR)-?

Gene_expression (believed) of FFA in plasma

18) Confidence 0.07 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0 Pain Relevance 0

Thus, taken together, the association between changes in muscle glycogen and PDK4 protein as well as between plasma FFA levels and PDK4 protein content supports that PDK4 expression may be regulated by each of these metabolic parameters.

Gene_expression (levels) of FFA in plasma

19) Confidence 0.07 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0 Pain Relevance 0

This breakfast was the only difference between the trials and aimed at obtaining similar insulin levels, whereas FFA levels were different in the two trials.

Gene_expression (levels) of FFA

20) Confidence 0.06 Published 2010 Journal Diabetes Section Body Doc Link PMC2797931 Disease Relevance 0.05 Pain Relevance 0.15

General Comments

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