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Saturday, 14 December 2013

The Effects of Hormone Serotonin (3)

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter derived from tryptophan,  primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). In Gut, serotonin regulates intestinal movements, in CNS, it regulates mood, appetite, sleep, memory and learning, etc.
21. Serotonin in the regulation of emotion processing and mood
Monoamines, such as serotonin, dopamine, and norepinephrine, play a crucial role in the regulation of emotion processing and mood. In the study to investigate how polymorphisms of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) influence emotion recognition abilities, researchers at the Department of General Psychiatry, Innsbruck Medical University, found that s-allele carriers performed significantly worse in the recognition of happy faces, but did better in the recognition of fearful faces, compared with homozygous l-carriers of the 5-HTT gene. Neither 5-HTT nor COMT genotypes influenced the ability to discriminate between different intensities of sadness or happiness on the PEAT(21).

22. Hemostasis, platelet function and serotonin in acute and chronic renal failure
In the study to investigate some fibrinolytic parameters and platelet function of 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF), found that since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure(22).

23. Platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin
Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. In  the study to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment in 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week, showed that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy(23).

24. Serotonin and carcinoid
There is a report of a 66-year-old woman was diagnosed with hepatic metastasized carcinoid tumor of the ileocecal junction resulting in elevated plasma chromogranin A levels and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Further examination showed right-sided heart failure with severe tricuspid valve regurgitation. Carcinoid tumors produce serotonin which leads to flushing, secretory diarrhea, bronchospasm and hypotension, known as carcinoid syndrome. Serotonin is metabolized to 5-HIAA, which is inactive, in the liver and the lungs(24).

25. Serotonin and Substance abuse
Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter implicated in regulating substance-use disorder (SUD) acquisition, maintenance, and recovery. According to the VA Connecticut Healthcare/Yale University School of Medicine, During the past several years, an abundance of research has begun discovering and describing specific 5-HT genetic polymorphisms associated with SUDs. Genetic variations in the 5-HT system, such as SLC6A4, HTR1B, HTR2A, HTR2C, HTR3 (HTR3A, HTR3B, HTR3C, HTR3D, and HTR3E), likely play a role contributing to SUD patient heterogeneity(25).

26. Serotonin and the severity of alcohol drinking
Severe drinking can cause serious morbidity and death. In a double-blind controlled trial randomized 283 alcoholics by genotype in the 5'-regulatory region of the 5-HTT gene (LL/LS/SS), with additional genotyping for another functional single-nucleotide polymorphism (T/G), rs1042173, in the 3'-untranslated region, showed that Individuals with the LL genotype who received ondansetron had a lower mean number of drinks per drinking day (-1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo. Among ondansetron recipients, the number of drinks per drinking day was lower (-1.53) and the percentage of days abstinent higher (9.73%) in LL compared with LS/SS individuals. LL individuals in the ondansetron group also had a lower number of drinks per drinking day (-1.45) and a higher percentage of days abstinent (9.65%) than all other genotype and treatment groups combined. For both number of drinks per drinking day and percentage of days abstinent, 5'-HTTLPR and rs1042173 variants interacted significantly. LL/TT individuals in the ondansetron group had a lower number of drinks per drinking day (-2.63) and a higher percentage of days abstinent (16.99%) than all other genotype and treatment groups combined(26).

27. Serotonin and Autism
Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. In the study to test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, by analyzing mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder, found that mice lacking brain serotonin (TPH2-/-) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2-/- mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism(27).

28. Serotonin and  severity of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms.
In the study to examine the association between a common serotonin transporter gene (SLC6A4) polymorphism 5-HTTLPR/rs25531 with severity of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms, researchers at the Department of Psychiatry and Behavioral Sciences, Stony Brook University, showed that the 5-HTTLPR/rs25531 polymorphism or its correlates may modulate severity of ADHD and ASD symptoms in children with ASD, but in different ways. These tentative, hypothesis-generating findings require replication with larger independent samples(28).

29. Serotonin and sexual desire disorders
Hypoactive sexual desire disorder (HSDD) is thought to be the most prevalent form of female sexual dysfunction (FSD), affecting up to 1 in 10 US women. Hypoactive sexual desire disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders, showed that Causes of low desire include chronic medical conditions, medications, surgeries, and psychosocial factors, but not necessarily increased age; both pre- and postmenopausal women can have HSDD, although the frequency appears to vary by age. Sexual function requires the complex interaction of multiple neurotransmitters and hormones, both centrally and peripherally, and sexual desire is considered the result of a complex balance between inhibitory and excitatory pathways in the brain. For example, dopamine, estrogen, progesterone, and testosterone play an excitatory role, whereas serotonin and prolactin are inhibitory. Thus, decreased sexual desire could be due to a reduced level of excitatory activity, an increased level of inhibitory activity, or both. A number of validated self-report and clinician-administered instruments are available for assessing female sexual function; however, most have been used primarily in clinical research trials(29).

30. Monoamine deficiency and relative nutritional deficiency
In the study to to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine) disease is a relative nutritional deficiency induced by postsynaptic neuron damage, showed that humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative nutritional deficiency involving serotonin and dopamine amino acid precursors. Whenever low or inadequate levels of monoamine neurotransmitters exist, a relative nutritional deficiency is present. These precursors must be administered simultaneously under the guidance of monoamine transporter optimization in order to achieve optimal relative nutritional deficiency management. Improper administration of these precursors can exacerbate and/or facilitate new onset of centrally acting monoamine-related relative nutritional deficiencies(30).

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Sources
(21) http://www.ncbi.nlm.nih.gov/pubmed/22013977
(22) http://www.ncbi.nlm.nih.gov/pubmed/8873344
(23) http://www.ncbi.nlm.nih.gov/pubmed/7740505
(24) http://www.ncbi.nlm.nih.gov/pubmed/23139656
(25) http://www.ncbi.nlm.nih.gov/pubmed/22933845
(26) http://www.ncbi.nlm.nih.gov/pubmed/21247998
(27) http://www.ncbi.nlm.nih.gov/pubmed/23139830
(28) http://www.ncbi.nlm.nih.gov/pubmed/23123360
(29) http://www.ncbi.nlm.nih.gov/pubmed/21084789
(30) http://www.ncbi.nlm.nih.gov/pubmed/22615537