Yeast and Cancer

The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression.

Diaz-Ruiz R, Rigoulet M, Devin A.

Source

Oxygen Sensing and Cancer Laboratory, Ludwig Institute for Cancer Research Ltd., Karolinska Institute, Nobels väg 3, SE-171 77 Stockholm, Sweden.

" From a metabolic point of view, the fermenting yeast Saccharomyces cerevisiae and tumor cells share several features. "

Yeast therapy for the treatment of breast cancer: a nude mice model study.

Ghoneum M, Wang L, Agrawal S, Gollapudi S.

Source

Drew University of Medicine and Science, Department of Otolaryngology, Los Angeles, CA, USA. mghoneum@ucla.edu

"S. cerevisiae is a promising anti-cancer agent that induces significant levels of apoptosis in malignant cells in vivo. However, yeast therapy for the treatment of breast cancer has yet to pass controlled clinical trials."

Yeasts encoding tumour antigens in cancer immunotherapy

Franzusoff A, Duke RC, King TH, Lu Y, Rodell TC

GlobeImmune, Inc., 12635 E. Montview Blvd, Aurora, CO 80010, USA.

"Recombinant yeast cells are capable of stimulating the immune system to produce highly specific and potent cellular responses against target protein antigens with little toxicity. Data from animal models suggest that Tarmogens (yeast-based immunotherapeutics) can elicit protective immunity against xenografted and chemically induced tumours."

A Brief Explanation of my Serotonin-Autoimmunity Research

On the off chance that anyone out there besides me is reading these studies I am posting, and wondering where it's all leading, I wanted to write up a little explanation.

I started this blog not long after I learned that I suffer from esophageal motility dysfunction. I also have mild Raynaud's Phenomenon, Hashimoto's Thyroiditis and an elevated ANA. For the past 18 months (just about) I have been pursuing treatment in the effort to prevent further progression of autoimmune disease... toward Lupus, RA or Scleroderma.

I follow the antibiotic protocol developed by Dr. Thomas McPherson Brown who believed that mycoplasma infection underlay arthritis and rheumatic disease.

My feeling has been that even if they have not yet proved the infectious theory, it doesn't matter - I just want to get well. I haven't really cared about the mechanism for *why* the antibiotic at low doses work... I am just so grateful that they have helped me to get so much of my life and strength back.

Recently I stumbled across a study that proved serotonin as the link between vascular disease and fibrosis. This was a real eye opener to me.

Scleroderma patients suffer from the following problems:

Reduced motility of the esophagus (reduced or no peristalsis in the lower 2/3 of the esophagus)
Raynaud's Phenomenon
Telangiectasias
Calcinosis
Sclerodactyly
Pulmonary Fibrosis
Cardiac Problems
Kidney Fibrosis

Could serotonin be the common link that connects the vascular disease (Raynaud's) that proceeds onset of scleroderma to the process of fibrosis?

Even more importantly, the study I read stated that it was possible to REVERSE and even prevent fibrosis:

"Dermal fibrosis was reduced in 5-HT2B mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT2B also effectively prevented the onset of experimental fibrosis and ameliorated established fibrosis. Moreover, inhibition of platelet activation prevented fibrosis in different models of skin fibrosis."

This is pretty incredible stuff.

If fibrosis can be reversed by the inactivation of the 5-HT2B serotonin neurotransmitter, it might save the lives of people I now know and care about... people who live courageously with scleroderma every day.

Heck, it might save me too!

And that would be more wonderful than I can say. I have three small children and I don't want to miss a minute with any of them.

That's the thing about autoimmunity - it seems to mainly strike women in our reproductive years. I have a lot of friends now, all somewhere near my age, with kids... who suffer from Lupus, RA, Sjogrens and scleroderma.

This is a very personal research story then... I want to figure this thing out and save us all.

Unfortunately, I am not a scientist!

I was an English major in college and then an elementary and middle school teacher for 10 years. I scurried away from math and science just as quickly as my feet could carry me back in the day before my health went south.

So grappling with the language in these studies is really tough for me. I feel like I need a science dictionary just to wade through the different terms.

My husband, bless his heart, was a biology major and he understands much of this stuff a lot better than I do. I've been turning to him then, frequently, to ask what the scientific jargon means.

What I'm trying to do here in this blog is aggregate all of the articles I can find that show the relationship between the serotonin receptor function and development of autoimmune disease.

I'm hoping that if I can read enough articles, maybe I'll finally understand the "big idea" - the relationship between genetics, pathogens, tryptophan, serotonin and the development of autoimmune problems that I and countless others face.

Here's the catch:

I can't tell yet whether I have too much or too little serotonin in my system!

I can't tell yet what the feedback loops are between serotonin in the brain and serotonin in the rest of the body.

I haven't been able to figure out whether I need MORE serotonin (possible to achieve through supplementation, exercise and diet) or LESS serotonin, possible to achieve with medications and reduction in the amount of tryptophan I consume.

The whole thing is still a mystery to me.

What I do know is that taking doxycycline has helped me vastly with inflammation. I also learned in the last few days that doxycycline actually increases the thickness of serotonin receptors... which could explain how it helps to modulate the amount of serotonin released. This may explain why doxycycline and minocycline have shown themselves to be very helpful in the management of collagen vascular diseases.

In time when I have collected enough research I want very badly to share it with medical researchers who can understand it all... who might be able to have that "Aha!" moment where they put 2 and 2 together and come up with an actual cure or treatment for these devastating chronic diseases.

I don't need to be a hero and nobody even needs to know my name. I just want to motivate scientists and physicians to look harder at the connection between serotonin and autoimmunity... and to encourage everyone from pharmaceutical companies to Chinese medicine doctors to naturopaths to pursue targeting the 5-HT2B receptor so that millions of us will be freed from our disease conditions and able to pursue worthy, fulfilling, productive lives.

If you are out there reading this and you understand the science that I do not, please continue reading and examine these 57 studies (and counting!) I have put together. I really believe there is something important here.

From the bottom of my heart, I ask you to take a good look and see if there isn't an answer here to a perplexing mystery that has brought strong men to their knees, torn families apart, taken away the freedom and mobility that many of us so cherish... and ended lives too soon.

Thank you!

Serotonin and Liver Function

Serum Serotonin Levels are Associated with Antiviral Therapy Outcomes in Patients with Chronic Hepatitis C. (2010)
Loftis JM, Morasco BJ, Menasco D, Fuchs D, Strater M, Hauser P.
Source

Department of Psychiatry, Oregon Health & Science University; Research & Development Service, 3710 SW US Veterans Hospital Road, Portland Veterans Affairs Medical Center, Portland, Oregon, USA.

"Significant differences in serotonin levels were found between patients who achieved sustained viral responses (SVRs) and those who did not. Regression analysis revealed that serotonin was the only variable with a statistically significant relationship with antiviral therapy outcomes, even after controlling for other variables known to be associated with outcomes. "

The function of serotonin within the liver
Ruddell RG, Mann DA, Ramm GA.
Hepatic Fibrosis Group, The Queensland Institute of Medical Research, PO Royal Brisbane and Women's Hospital, Brisbane, Qld 4029, Australia. Richard.Ruddell@qimr.edu.au

"Serotonin or 5-hydroxytryptamine (5-HT) is known to regulate several key aspects of liver biology and these functions include hepatic blood flow, innervation and wound healing."

Liver Function and Alzheimer's Disease

Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: implications for Alzheimer's disease.
Sutcliffe JG, Hedlund PB, Thomas EA, Bloom FE, Hilbush BS. (2011)

"We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease."


Peripheral Amyloid-β Levels Regulate Amyloid-β Clearance from the Central Nervous System
Marcos A. Marques,abc1 J. Jacob Kulstad,abd1 Christopher E. Savard,be Pattie S. Green,be Sum P. Lee,be Suzanne Craft,abc G. Stennis Watson,abc and David G. Cookabef (2009)

"These data also support and extend previous findings by illustrating the substantial contribution of the liver to peripheral Aβ clearance. To the extent the peripheral circulatory system can act as an Aβ sink, these data demonstrate that the liver is the primary drain."

Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D.
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. (2010)

"Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease...The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain."

Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model.
Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T.
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. (2010)

"In vivo studies had indicated a significant reduction in brain Aβ deposition and improvement in behavioral abnormalities in amyloid precursor protein (APP) transgenic mice that had been preventively treated with a powdered diet containing 0.1% silymarin for 6 months. The silymarin-treated APP mice also showed less anxiety than the vehicle-treated APP mice."


Fatty liver disease can mimic symptoms of Alzheimer's Disease
By Roz Zurko on 2011-06-18

"The doctors explained that Wilson's memory lapses and erratic behavior was due to liver disease. "When you think about this kind of thing, you think about dementia or Alzheimer's," Patricia says. "You don't think about the liver," which is most likely what any average person would be thinking under the circumstances.

The diagnosis was cirrhosis of the liver, just like alcoholics get, but Wilson's disease was not from alcohol, it was caused by fat that was deposited in his liver over the years. He is overweight and too much fat in his liver eventually caused it to malfunction. This is not an isolated incident by any means."


Heme Oxygenase: A Font of Multiple Messengers
Solomon H Snyder MD and David E Baranano
The Johns Hopkins University, School of Medicine, Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, Baltimore, MD USA

"We have recently obtained direct evidence for a neuroprotective role of HO2 linked to Alzheimer's disease (Takahashi et al. 2000). Yeast 2-hybrid and other protein-binding studies reveal HO2 and HO1 binding to the amyloid precursor protein (APP). This interaction has no effect on APP processing but does result in inhibition of HO activity. The APP derivatives that occur in familial forms of Alzheimer's disease are much more potent than normal APP in inhibiting HO activity. To examine in vivo consequences of this finding, we utilized mice with the "Swedish" mutant APP. HO2 activity in cerebral cortical cultures from these mice is markedly reduced as is evident by profoundly diminished staining for bilirubin. Moreover, neurotoxicity elicited by hemin or hydrogen peroxide is markedly increased in cultures from Swedish mutant brain. While the HO inhibitor tin protoporphyrin IX worsens neurotoxicity in control cultures, it is ineffective in Swedish cultures in which NO activity is already diminished. We presume that the loss of physiologic protection by bilirubin in brains of patients with familial Alzheimer's disease increases sensitivity to the neurotoxic effects of the high levels of amyloid beta peptide generated in these patients."

Decreased plasma antioxidants in patients with Alzheimer's disease.
Kim TS, Pae CU, Yoon SJ, Jang WY, Lee NJ, Kim JJ, Lee SJ, Lee C, Paik IH, Lee CU.
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea. (2006)

"A significant reduction in the albumin, bilirubin, and uric acid levels in the AD group was found compared to those of the control group... This study showed that oxidative injuries could be involved in the pathogenesis of AD."


Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease.
Neurology. 2001 Oct 23;57(8):1515-7.
Adair JC, Knoefel JE, Morgan N.
Neurology Service, Albuquerque Veterans Affairs Medical Center, New Mexico, USA.

"Comparison of interval change favored NAC treatment on nearly every outcome measure, although significant differences were obtained only for a subset of cognitive tasks."

Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.
Hager K, Kenklies M, McAfoose J, Engel J, Münch G.
Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany. (2007)

"The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog)... our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD."

Research on Serotonin Levels in Autoimmunity

Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE
HH Hofstetter,* R Mössner,† KP Lesch,† RA Linker,*‡ KV Toyka,* and R Gold*‡ (2005)

"These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses."


Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature

"In the present case, we see that treatment of co-morbid depression with an SSRI led to complete remission of arthritis in a 60-year-old individual. Postulated mechanisms through which antidepressants mediate this effect include their agonistic action on 5-HT2A receptors or inhibition of the signaling of Toll-like receptors that are responsible for mediating innate immunity. The relation between mediators of inflammation and biologic substrates of mood seem to be bidirectional."


Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis.
Sigvard Kopp and Per Alstergren
Department of Clinical Oral Physiology, Institute of Odontology, Karolinska Institutet, Box 4064, 141 04 Huddinge, Sweden.

"RESULTS: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5-HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5-HT than the seronegative patients (14 nmol/l, p < 0.001)." Effect of Clonazepam on Raynaud's Phenomenon and Fingertip Ulcers in Scleroderma
Murat Colakoğlu, MD
Associate Professor in Nephrology, Departmen of Nephrology, School of Medicine, Pamukkale University, Denizli, Turkey
Veli Cobankara, MD
Associate Professor in Rheumatology, Department of Rheumatology, School of Medicine, Pamukkale University
Tekin Akpolat, MD

"Clonazepam, unlike many other benzodiazepines, appears to have serotonergic effects, which may contribute to its psychotropic and antimyoclonic properties. While the therapeutic action remains unclear, clonazepam's serotonergic effects may be responsible for the beneficial effect on Raynaud's phenomenon and fingertip ulcers.

Raynaud's phenomenon and erythromelalgia are both vascular acrosyndromes. Serotonin has been involved in the pathogenesis of both Raynaud's phenomenon and erythromelalgia."


Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
A Kling1, M Seddighzadeh2, L Ärlestig3, L Alfredsson4,5, S Rantapää-Dahlqvist3, L Padyukov2
Accepted 1 November 2007

"In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease."



Association between the use of serotonin receptor 2A–blocking antidepressants and joint disorders
Anders Kling1,*, Marit Danell-Boman1, Hans Stenlund2, Rune Dahlqvist1
Article first published online: 29 SEP 2009

"In the Swedish material, the 5-HT2A antagonists were 45 times more often reported to give joint ADRs when related to sales figures and compared with the selective serotonin reuptake inhibitors (SSRIs; P < 0.001). Joint disorders constituted 6.6% of the total number of reports of possible ADRs for the three 5-HT2A–blocking substances mianserin, mirtazapine, and nefazodone compared with 0.5% for the SSRIs (P < 0.001). In the WHO material, the joint disorders constituted 1.3% of all ADRs for the 5-HT2A–blocking antidepressants and 0.6% for the SSRIs (P < 0.001)." Ann Rheum Dis 2006;65:816-819 doi:10.1136/ard.2005.042473 Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis
A Kling1, S Rantapää-Dahlqvist2, H Stenlund3, T Mjörndal1

"The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease"

5-Hydroxytryptamine and tryptamine pathways in scleroderma
A. STACHOW, S. JABLONSKA, A. SKIENDZIELEWSKA (2006)

"These results suggest impaired transformation of serotonin into 5-hydroxyindoleacetic acid. A disproportionately high ratio of total indoles to indoleacetic acid suggests the presence of excess of tryptamine. The results of the study may indicate that in scleroderma metabolism of biogenic amines derived from tryptophan is abnormal, probably as a result of impaired activity of monoamine oxidase."


Intraplatelet and urinary serotonin concentrations in systemic lupus erythematosus with reference to its clinical manifestations
Kanai H, Tsuchida A, Yano S, Naruse T.
Third Department of Internal Medicine, Gunma University School of Medicine, Japan

"Active SLE showed a significantly higher urinary 5-HT concentration, 0.37 +/- 0.15 nmol/ml/mg Cr, than normal controls, 0.21 +/- 0.08 nmol/ml/mg Cr (p less than 0.01). Serial measurements of intraplatelet and urinary 5-HT levels in five patients with SLE revealed a significant correlation between clinical activity and intraplatelet and urinary 5-HT levels. "


Serum Factors Releasing Serotonin from Normal Platelets: Relation to the Manifestations of Systemic Lupus Erythematosus
MARK H. GINSBERG, M.D.; and MICHAEL O'MALLEY, B.S.

"In three patients with episodes of thrombocytopenia, increases in serotonin releasing activity temporally coincided with drops in platelet count. These data show that levels of circulating platelet serotonin releasing factor(s) vary in the course of systemic lupus erythematosus and these variations may be inversely related to the platelet count in particular patients."


Headache, Raynaud’s syndrome and serotonin receptor agonists in systemic lupus erythematosus


Analysis of 5HT3Ra gene expression by real time PCR in Systemic Lupus
Erythematosus (SLE) patients
Mohammad Sabery Anvar, Ghasem Ahangari, Mohiedin Jafari, Shahin Dokht Samangouei, Raheleh Torabi
,Mohammad Taghi Sadeghi Kohpaieh

"We found over expression of 5HT3Ra in patients in comparison with healthy individuals group. Interestingly, some nucleotide changes have been found in 5HT3Ra gene in patients but not found sequential nucleotide changes in healthy individuals group. This study supposed that over expression of 5HT3Ra gene in SLE patients lead to over activation of immune cells that derived from over stimulation of them from serotonin blood serum that finally lead to autoimmune reactions that terminated in SLE."

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome.
Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA.
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.

Alteration of serotonin transporter density and activity in fibromyalgia
by Laura Bazzichi, Gino Giannaccini, Laura Betti, Giovanni Mascia, Laura Fabbrini,

The Expanded Biology of Serotonin
Annual Review of Medicine
Vol. 60: 355-366 (Volume publication date February 2009)
DOI: 10.1146/annurev.med.60.042307.110802

"Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new “expanded serotonin biology” and discuss how drugs targeting specific serotonin receptors are beginning to help treat a wide range of diseases.'
Miles Berger,1 John A. Gray,1,2 and Bryan L. Roth


Ablation of Serotonin 5-HT2B Receptors in Mice Leads to Abnormal Cardiac Structure and Function
Circulation. 2001;103:2973-2979
doi: 10.1161/01.CIR.103.24.2973

"Conclusions—Mutation of 5-HT2B receptor leads to a cardiomyopathy without hypertrophy and a disruption of intercalated disks. 5-HT2B receptor is required for cytoskeleton assembly to membrane structures by its regulation of N-cadherin expression. These results constitute, for the first time, strong genetic evidence that serotonin, via the 5-HT2B receptor, regulates cardiac structure and function."
(Circulation. 2001;103:2973.)




Recent advances in understanding serotonin regulation of cardiovascular function
Francine Côté1, Cécile Fligny1, Yves Fromes2, Jacques Mallet1, , Guilan Vodjdani1

"Recent studies have provided evidence that, in the absence of peripheral serotonin synthesis, blood serotonin (which is almost exclusively stored in platelets) is markedly reduced, and that this drop leads to heart failure. This implies that the level of circulating serotonin is a key factor in maintaining normal cardiovascular activity. These findings offer new prospects for the use of serotonin in therapies for cardiovascular diseases."


Int J Cardiol. 1988 Jun;19(3):335-9.
Plasma free and intraplatelet serotonin in patients with Raynaud's phenomenon.

"Serotonin was significantly higher in plasma (P less than 0.005) and in platelets (P less than 0.005) from Raynaud's patients than from normal controls. Moreover, plasma circulating serotonin could differentiate primary from secondary Raynaud's phenomenon, with significantly higher levels (P less than 0.05) for patients with an underlying connective tissue disease. Our data indicate a role for serotonin in Raynaud's phenomenon."
Biondi ML, Marasini B, Bianchi E, Agostoni A.
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Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome
SM Connolly, SR Quimby, WL Griffing, RK Winkelmann

"These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading."

Relationship between Infection (Viral, Bacterial) and Serotonin

Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting
Marie Hagbom1#, Claudia Istrate1,2#¤a, David Engblom3, Thommie Karlsson4, Jesus Rodriguez-Diaz5¤b, Javier Buesa5, John A. Taylor6, Vesa-Matti Loitto4, Karl-Eric Magnusson4, Håkan Ahlman7, Ove Lundgren8, Lennart Svensson1*
1 Division of Molecular Virology, Medical Faculty, University of Linköping, Linköping, Sweden, 2 Unidade de Biologia Molecular, Centro de Malaria e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal, 3 Division of Cell Biology, Medical Faculty, University of Linköping, Linköping, Sweden, 4 Division of Medical Microbiology, Medical Faculty, University of Linköping, Linköping, Sweden, 5 Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain, 6 School of Biological Sciences, University of Auckland, Auckland, New Zealand, 7 Department of Surgery, University of Gothenburg, Gothenburg, Sweden, 8 Department of Physiology, University of Gothenburg, Gothenburg, Sweden

More research on Serotonin, Depression and Scleroderma

Commonly Used Antidepressants May Also Affect Human Immune System 2006

Depression may involve autoimmune attack on serotonin (5-HT) Dec 2011

"The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%)."

Biogenic amines derived from tryptophan in systemic and cutaneous scleroderma.
(PMID:84460)

"An increased T/IAA ratio seems to be of prognostic significance in scleroderma, suggesting an adverse course of the disease."

NeuroScience - Offers Urine Test for 5HT levels

How to lower serotonin levels naturally... (Livestrong)

Effect of antibiotics on D-serotonin-reactive structures

Balancing gut flora and the "second brain" without prescription medication

Cardiac fibrosis and Serotonin

Tryptophan Depletion and Mood Disorders


Tryptophan, serotonin, and aging This man is a genius (Ray Peat)

Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: Reduction by a selective serotonin reuptake inhibitor

Neurogenesis and Serotonin

Too much not too little serotonin may trigger depression

The Other Brain Also Deals With Many Woes
By HARRIET BROWN
Published: October 11, 2011

Serotonin Findings Cause Depression Rethink

Serotonin Syndrome

Think Twice: How the Gut's "Second Brain" Influences Mood and Well-Being

Serotonin and Gut/Esophageal Peristalsis (Important to Scleroderma Patients)
The effect of erythromycin on human esophageal motility is mediated by serotonin receptors.


Acute autoimmune encephalomyelitis in mice. II. Susceptibility is controlled by the combination of H-2 and histamine sensitization genes.

Compounds that induce autoimmunity in the Brown Norway rat sensitize mast cells for mediator release and interleukin-4 expression
David B. G. Oliveira1,*, Kathleen Gillespie1, Karen Wolfreys1, Peter W. Mathieson1, Faieza Qasim1, John W. Coleman2


Elevated Serotonin Levels in Autism: Association with the Major Histocompatibility Complex
Article first published online: 23 NOV 2005

Inhibition of Hypoglycemia-Induced Cortisol Secretion by the Serotonin Antagonist Cyproheptadine

Effect of the Serotonin Precursor, Tryptophan, on Pituitary Hormone Secretion
These effects are presumably mediated by conversion of tryptophan to serotonin within the central nervous system and suggest that serotonin is a potent inhibitor of hypothalamic CRF elaboration in man.

Effects of Selective Serotonin Reuptake Inhibitors on Thyroid Function in Depressed Patients with Primary Hypothyroidism or Normal Thyroid Function
Gisah Amaral de Carvalho, Saint-Clair Bahls, Anke Boeving, and Hans Graf. Thyroid. July 2009, 19(7): 691-697. doi:10.1089/thy.2008.0261.

Serotonin and its precursors as modulators of the immunological responsiveness in mice.

Association of erythromelalgia and Raynaud's disease responding to a serotonin reuptake inhibitor
1999, Vol. 10, No. 2 , Pages 141-144

Scleroderma treatment differs between experts and general rheumatologists
Janet E. Pope, Janine M. Ouimet, Adriana Krizova
"Erectile dysfunction (25–30) and depression (31–35) seem to be frequent problems in scleroderma, each with a substantial impact on patients, and this has been reported in the literature." = excess serotonin!!!

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.
Psychosom Med. 2010 Nov;72(9):925-32. Epub 2010 Oct 14.