http://www.jbc.org/content/270/51/30290.full – NITRIC OXIDE MORPHINE
http://www.jbc.org/content/270/51/30290.full – NITRIC OXIDE MORPHINE
Oh baby…On its way via AMAZON.
Taurosodeoxycholic acid (TUDCA) is a bile salt and liver supplement naturally produced by our gallbladders that has many health benefits. 
TUDCA works either by its interactions with other bile salts or by preventing cells from apoptosis. 
Taking bile salts is a long-established way for people to prevent gallstones.  TUDCA also helps to dissolve gallstones that may already be forming. 
TUDCA may help with diabetes by making the liver and the muscles more sensitive to insulin, allowing them to use glucose more effectively and cause fewer blood sugar drops and spikes. 
TUDCA can be used as a therapy for fatty liver disease, primary biliary cirrhosis, chronic hepatitis disease, and liver problems caused by cystic fibrosis. [10, 11, 12]
TUDCA also protects the liver from damage caused by sleep apnea. The lack of oxygen can damage organs by causing oxidative damage and increasing stress on cell structures – TUDCA prevents this liver damage and alleviates this stress. 
TUDCA reduces some of the stress on the endoplasmic reticulum protecting the kidney against injury from toxins, diseases, and normal wear and tear. 
TUDCA renders IBS symptoms less intense and improves the diversity of the bacteria in the bowels and digestive system. 
While strokes will always cause some damage, people on TUDCA experience less – nearly half as much in some studies – damage from strokes and better healing over time. 
TUDCA’s protective property is mostly for the same reasons that it protects against stroke damage – much of the nerve damage is from apoptosis, which TUDCA prevents from happening. [1, 20, 23]
TUDCA has been shown to slow the progression of neurodegenerative diseases and to reduce their symptoms. 
TUDCA is water soluble, not fat soluble like other bile salts. This means that it does not have a detergent-like effect, making it less damaging. 
The advantage of TUDCA is that it is better absorbed and stored by the body, meaning that a dose of TUDCA would have a larger benefit than the same dose of UDCA.  Therefore, TUDCA is better to take. 
To protect the liver, about 10-13mg are used daily.
In insulin sensitivity or fatty liver, this dose can be as high as 1750mg daily.
Higher doses reduce cholesterol but have few other additional benefits or side effects. 
The most common, and possibly the only, side effect on record is diarrhea, which is usually not severe enough to be life-threatening. 
TUDCA has no reported interactions with statins or other drugs,
TUDCA vs Milk Thistle
Milk thistle can be taken with TUDCA (with caution) or on its own. However, milk thistle has a high risk of allergic reactions, higher risk of side effects, and lower effectiveness, making TUDCA a better option to take on its own. [30, 31]
Actinobacteria are a group of Gram-positive bacteria with high guanine and cytosine content in their DNA, which can be terrestrial or aquatic. Though they are unicellular like bacteria, they do not have distinct cell wall, but they produce a mycelium that is nonseptate and more slender.
Proteobacteria is a major phylum of Gram-negative bacteria. They include a wide variety of pathogens, such as Escherichia, Salmonella, Vibrio, Helicobacter, Yersinia, Legionellales and many other notable genera. Others are free-living (non-parasitic) and include many of the bacteria responsible for nitrogen fixation.
Cyanobacteria also known as Cyanophyta, are a phylum of bacteria that obtain their energy through photosynthesis and are the only photosynthetic prokaryotes able to produce oxygen. The name cyanobacteria comes from the color of the bacteria.
Bacteroidetes are gram-negative bacteria that ferment polysaccharides and otherwise indigestible carbohydrates and produce short-chain fatty acids (SCFAs) that have many beneficial effects in the gut.
The parasitic worm Ascaris suum contains the opiate alkaloid morphine as determined by HPLC coupled to electrochemical detection and by gas chromatography/mass spectrometry. The level of this material is 1168 ± 278 ng/g worm wet weight. Furthermore, Ascaris maintained for 5 days contained a significant amount of morphine, as did their medium, demonstrating their ability to synthesize the opiate alkaloid. To determine whether the morphine was active, we exposed human monocytes to the material, and they immediately released nitric oxide in a naloxone-reversible manner. The anatomic distribution of morphine immunoreactivity reveals that the material is in the subcuticle layers and in the animals’ nerve chords. Furthermore, as determined by RT-PCR, Ascaris does not express the transcript of the neuronal μ receptor. Failure to demonstrate the expression of this opioid receptor, as well as the morphine-like tissue localization in Ascaris, suggests that the endogenous morphine is intended for secretion into the microenvironment.
Successful parasitism, in which the host survives for extended periods, can be characterized as an equilibrium between the parasite and the host, more specifically between the host’s immune system and the parasite’s ability to create a permissive microenvironment in situ. One mechanism that a parasite may use to modify the host immune response is to down-regulate the host’s response (1, 2, 3). Capron and colleagues (4, 5, 6, 7) suggested that parasites may communicate with their hosts via common signaling molecules that diminish host immune surveillance. In this regard, morphine is generally acknowledged as an immune down-regulating agent (8). This finding is enhanced by the fact that morphine is present in several mammalian tissues, including brain and adrenal gland (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20), supporting its role as a neural or inflammatory mediator.
Recently, we have demonstrated that free-living and parasitic invertebrates produce several major opioid peptide precursors, i.e., prodynorphin, proopiomelanocortin, and proenkephalin (21). These mammalian-like opioid peptides exhibit high sequence identity to their mammalian counterparts. For example, Mytilus adrenocorticotropin has greater than 90% sequence identity with its mammalian counterpart (21). We have also identified a tentative morphine-like molecule in Schistosoma mansoni by way of radioimmunoassay (22).
Given this and the fact that the pig intestinal parasite Ascaris suum can live in its host for extended periods of time, we surmised that it might be using morphine to escape detection by the host’s immune system. In this study, we report for the first time that A. suum synthesizes morphine, thereby strengthening the common-signal molecule hypothesis, i.e., using either similar or identical host signaling to escape host immunosurveillance.
Almost 2 years into this different life.
What if…It’s not us sticking our dirty fingers in our mouth that [possibility]make us sick, but our fingers become dirty, under the nails and cracks etc., from sticking them in our ears, nose and mouth?
I ask this because I have been rather shocked to see that my digital health has improved DRASTICALLY since I quit, with GREAT intentionality, sticking my fingers in my ears, nose and mouth.
The reason I started this practice was to eliminate any possibility of auto-infection of any sort happening.
In hyper-infection syndrome, complete disruption of the GI mucosa, ulcerations, paralytic ileus with exudative enteropathy as well as massive GI bleeding may also occur due to the direct invasion of the larvae. Profound diarrhea, malabsorption with consequent hypo-albuminemia and electrolyte disturbances were all consistent with hyper-infection related enteropathy in our patient. On the other hand, effective anthelminthic treatment in hyper-infected patients can lead to mass-destruction of intraluminal and intramural larvae and to release of huge amounts of different toxic inflammatory and vaso-active compounds[7,8].
What is added by this report?
Donor-derived Strongyloides infection might be more common than previously believed. In these investigations, a single donor was the source of infection for three of four organ recipients. Testing of pretransplant serum contributed to the determination that infection was donor derived.
Strongyloides stercoralis is an intestinal nematode endemic in the tropics and subtropics. Immunocompetent hosts typically are asymptomatic, despite chronic Strongyloides infection. In contrast, immunocompromised patients are at risk for hyperinfection syndrome and disseminated disease, with a fatality rate >50% (1–3). The infection source for immunocompromised patients, such as solid organ transplant recipients, is not always apparent and might result from reactivation of chronic infection after initiation of immunosuppressive therapy or transmission from the donor. In October 2012, the United Network for Organ Sharing (UNOS) notified CDC of a left kidney and pancreas recipient in Pennsylvania diagnosed with strongyloidiasis. This report summarizes the results of the investigation of the source of Strongyloides infection in three of four organ recipients. Testing of pretransplant donor and recipient sera confirmed that infection in the recipients was donor derived. This investigation underscores the importance of prompt communication between organ procurement organizations, transplant centers, and public health authorities to prevent adverse events in recipients when transmission is suspected. Additionally, it emphasizes the utility of stored pretransplant samples for investigation of suspected transplant-transmitted infections and the need to consider the risk for Strongyloides infection in organ donors.
On October 4, 2012, UNOS notified CDC of a left kidney and pancreas transplant recipient diagnosed with strongyloidiasis. UNOS also identified three additional organ recipients: the right kidney recipient, who received his transplant at the same institution as the index case; the liver recipient, who died within a few days after the transplantation; and the heart recipient, who was diagnosed with suspected reactivation of chronic strongyloidiasis 2 weeks earlier. CDC requested stored pretransplant serum from all organ recipients, along with stored donor serum for testing, to determine if infection with Strongyloides in the recipients was donor derived or reactivation of chronic infection. Evaluation of these specimens revealed that no recipient had detectable Strongyloidesantibody before transplantation, but the donor had evidence of chronic infection based on positive serologic results.
Organ donor. In July 2012, a Puerto Rico-born Hispanic man, aged 24 years, was admitted to a local emergency department with multiple gunshot wounds. After a 9-day hospitalization, he died, and his heart, kidneys, pancreas, and liver were transplanted into four recipients the next day. History obtained from his mother indicated that the donor was a healthy young male who often visited Puerto Rico. Strongyloides infection risk was not considered; therefore, testing was not performed before organ recovery.
Kidney and pancreas recipient. This recipient is a U.S.-born white man, aged 64 years, with end-stage renal disease secondary to long-standing diabetes mellitus who had never traveled outside the United States. Nine weeks posttransplant, he developed severe nausea, anorexia, and abdominal distention and was admitted to the hospital. Stool studies and biopsies performed during an esophagogastroduodenoscopy revealed S. stercoralis adult worms; larvae were found in urine studies. The patient was treated with ivermectin and albendazole, and after a hospitalization complicated by Enterobacter cloacae bacteremia, periduodenal abscess, and loss of pancreatic transplant function, he was discharged in stable condition on ivermectin. Repeat stool analyses were negative 3 days after starting therapy.
Kidney recipient. This recipient is a U.S.-born adolescent, aged 14 years, with end-stage renal disease as a result of a single dysplastic kidney; he had never traveled outside the United States. He was contacted for evaluation 10 weeks posttransplant, after the left kidney and pancreas recipient received a diagnosis of strongyloidiasis. He was discovered to be ill with fever, rash, malaise, anorexia, nausea, vomiting, and diarrhea. He was diagnosed with strongyloidiasis via esophagogastroduodenoscopy-obtained biopsy and stool testing. He was treated with ivermectin for 4 weeks and albendazole for 2 weeks. Repeat stool specimens were negative 3 days after starting therapy and remained negative as of November 2012.
Liver recipient. This recipient was a Hispanic man, aged 66 years, with a history of hepatic failure secondary to chronic hepatitis C infection. He tolerated surgery and was clinically stable until postoperative day 4, when his heart stopped and he was unresponsive to attempts at resuscitation. At autopsy, no evidence of Strongyloides infection was found; cause of death was undetermined.
Heart recipient. This recipient was a U.S.-born Hispanic man, aged 59 years, with ischemic cardiomyopathy; he lived in Puerto Rico for 6 months as a teenager. He remained clinically stable posttransplant and was discharged 11 days after surgery. He experienced multiple episodes of organ rejection and was treated with high doses of steroids. Seven weeks posttransplant, he was readmitted to the hospital with fever and a respiratory illness and required intubation in response to rapid decompensation. He was diagnosed with a viral respiratory illness and given oseltamivir and antibiotic and antifungal medications. A bronchoscopy performed on hospital day 3 showed S. stercoralis larvae. He was started on ivermectin and albendazole for treatment of suspected reactivated chronic strongyloidiasis. He developed gram-negative and enterococcal bacteremia and vancomycin-resistant enterococcal meningitis and became neurologically compromised. Life support was withdrawn, and he died 11 weeks posttransplant.
Anjum Hasan, MD, Marie Le, MD, Jessica Pasko, MD, Karen A. Ravin, MD, Geisinger Medical Center; Heather Clauss, MD, Temple Univ Hospital; Richard Hasz, MFS, Gift of Life Donor Program; Elizabeth A. Hunt, MPH, Pennsylvania Dept of Health. Elizabeth Bosserman, MPH, Isabel McAuliffe, MS, Susan P. Montgomery, DVM, Div of Parasitic Diseases and Malaria, Center for Global Health; Matthew J. Kuehnert, MD, Susan N. Hocevar, MD, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases; Francisca Abanyie, MD, EIS Officer, CDC. Corresponding contributor: Francisca Abanyie, email@example.com, 404-718-4775.
Most Strongyloides infections in organ transplant recipients are thought to be caused by reactivation of chronic infection after initiation of immunosuppressive therapy. Donor-derived infection has been reported, but the incidence of transmission is unknown (4,5). During 2009–2012, CDC assisted in seven investigations of organ donors and associated recipients with strongyloidiasis determined to be donor derived. Donor-derived infection is difficult to prove, especially if the infected recipient is from a region in which Strongyloides is endemic. Archived pretransplant serum samples were available for recipient testing in this investigation. Results of that testing contributed to the determination that infection was donor derived and not reactivated chronic infection in the recipients.
This investigation revealed several gaps in current understanding and assessment of the risk for transplant-transmitted strongyloidiasis. Specific recommendations are lacking for Strongyloides testing of organ donors from areas in which it is endemic. The parasitic infections sections of the American Society for Transplantation’s guidelines for screening prior to solid organ transplantation recommend testing donors and recipients for Toxoplasma and Trypanosoma cruzi (the cause of Chagas disease), but only recommend screening for Strongyloides in recipients from areas in which the nematodes are endemic, with no mention of donor screening (6,7). These guidelines are not policy, thus screening of donors and recipients for parasitic infections is voluntary, resulting in varied practices among organ procurement organizations and transplant centers based on the perceived risk in their respective patient populations. The growing evidence of transplant transmission of Strongyloides, reported here and in the recent literature, might support development of recommendations for specific testing of donors and recipients from endemic regions to prevent severe strongyloidiasis in recipients (1,4,5). A minimum of three serial stool examinations for larvae, using specialized concentration techniques, is the gold standard for diagnosis of Strongyloides infection, but this might not be feasible in patients who have poor gastrointestinal function or are brain dead. Tests to detect parasite-specific antibody, such as an enzyme-linked immunoassay, also are available and are valuable in identifying Strongyloides infection (8). If infection is confirmed in the donor, prophylaxis could be given to recipients to avert adverse outcomes.
Rapid communication among transplant centers with patients who received organs from a single donor also is essential. The Organ Procurement and Transplant Network encourages organ procurement organizations and transplant programs to communicate promptly through its Patient Safety System, especially when there is concern for potential transmission of disease or medical conditions to the organ recipient from the donor. Such communication ideally should occur within 24 hours after knowledge of or concern for transmission, because multiple recipients might be adversely affected (9).
This investigation illuminates two gaps that need to be filled to improve transplant safety in solid organ recipients at risk for Strongyloides infection: 1) developing recommendations for screening of donors from Strongyloides-endemic areas, and 2) improving communication among transplant centers and organ procurement organizations. Advances in these areas might be life-saving for immunocompromised hosts.
Christine McGarry, Gift of Life Donor Program; Justine Gaspari, Milton S. Hershey Medical Center, Pennsylvania. Patricia Wilkins, PhD, Div of Parasitic Diseases and Malaria, Center for Global Health, CDC.
Strongyloides stercoralis, a worldwide-distributed soil-transmitted helminth, causes chronic infection which may be life threatening.
Limitations of diagnostic tests and nonspecificity of symptoms have hampered the estimation of the global morbidity due to strongyloidiasis. This work aimed at assessing S. stercoralis-associated morbidity through a systematic review and meta-analysis of the available literature. MEDLINE, Embase, CENTRAL, LILACS, and trial registries (WHO portal) were searched. The study quality was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) of the association between symptoms and infection status and frequency of infection-associated symptoms were calculated. Six articles from five countries, including 6,014 individuals, were included in the meta-analysis-three were of low quality, one of high quality, and two of very high quality. Abdominal pain (OR 1.74 [CI 1.07-2.94]), diarrhea (OR 1.66 [CI 1.09-2.55]), and urticaria (OR 1.73 [CI 1.22-2.44]) were associated with infection. In 17 eligible studies, these symptoms were reported by a large proportion of the individuals with strongyloidiasis-abdominal pain by 53.1% individuals, diarrhea by 41.6%, and urticaria by 27.8%. After removing the low-quality studies, urticaria remained the only symptom significantly associated with S. stercoralis infection (OR 1.42 [CI 1.24-1.61]). Limitations of evidence included the low number and quality of studies. Our findings especially highlight the appalling knowledge gap about clinical manifestations of this common yet neglected soil-transmitted helminthiasis. Further studies focusing on morbidity and risk factors for dissemination and mortality due to strongyloidiasis are absolutely needed to quantify the burden of S. stercoralis infection and inform public health policies.
~Because…Too many tabs…8-)
WORMBOOK <—Awesome Sause
A 12-yr-old girl with systemic lupus erythematosus requiring steroid therapy was found to have a circulating microfilaria during an exacerbation of her illness. Morphologically, the microfilaria does not correspond precisely with any previously described species, though similarities exist between the patient’s microfilaria and those of Dipetalonema reconditum of the dog and D. interstitium of the grey squirrel. The organism reported here is probably an undescribed species from a wild mammal. Although the association may be merely coincidental, this case suggests that compromised immunity might have led to this unusual infection with a non-human filaria.
Copyright © 1978 by The American Society of Tropical Medicine and Hygiene