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ARTICLES: M. Pierantozzi, A. Pietroiusti, L. Brusa, S. Galati, A. Stefani, G. Lunardi, E. Fedele, G. Sancesario, G. Bernardi, A. Bergamaschi, A. Magrini, P. Stanzione, and A. Galante Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations Neurology 2006; 66: 1824-1829 [Abstract] [Full text] [PDF]

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Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations

Richard G. Fiddian-Green   (4 December 2006)

Reply from the Authors

Antonio Pietroiusti, Mariangela Pierantozzi, Antonio Pietroiusti, Livia Brusa, Salvatore Galati, Alessandro Stefani, Gianluigi Lunardi, Ernesto Fedele, Giuseppe Sancesario, Antonio Bergamaschi, Andrea Magrini, Paolo Stanzione, and Alberto Galante   (4 December 2006)

Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations 4 December 2006
Richard G. Fiddian-Green, None Sanders, 12 Temple Gardens, Moor Park, Rickmansworth, UK. Send Correspondence to journal: Re: Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations richardfg{at}hotmail.com Richard G. Fiddian-Green	Pierantozzi et al [1] did not consider that the H pylori infections might have been the result of a systemic metabolic abnormality that was the primary cause of the PD and gut dysfunction as in peptic ulceration. [2] H pylori requires a microaerophilic environment and optimally a much pCO2 higher than that found in the lumen of the gut of healthy subjects in which to thrive in vitro. A common cause of an abnormally elevated gastric intraluminal pCO2 in ambulatory patients is chronic mesenteric ischemia but may only be present during metabolic stress because of metabolic compensation. [3] A chronically reduced intramucosal pH, often associated with an elevated pCO2, might be the product not only of mesenteric artery disease but also of mitochondrial toxins including translocating gut endotoxin and the cytokines it releases. An abnormally low intramucosal pH appears to be an indication of a decline in Daniel Atkinson energy charge [4]; this is thought to be the final common pathway in the evolution of chronic gastrointestinal dysfunction, acute mucosal injury, translocation and indeed all organ dysfunctions. Gut dysfunction may be necessary for H pylori infection and for any dysfunction or injury that might be induced by the by H pylori. While the gut mucosa is considered the canary of the body in the face of acute reductive stress in the critically ill, the brain would seem to be the canary of the body of acute and acute on chronic reductive stress in ambulatory patients. Synaptic vesicles in the brain that concentrate and store catecholamines, including dopamine, also concentrate and store ATP. [5] It is possible that PD might be a local product of regional or systemic cause of a decline in energy charge including the translocation of endotoxin and the cytokines it releases. Other gut bacteria, such as E coli, are present in the gut in larger numbers and may contain and release far more endotoxin than HP and would be eradicated or reduced in number by the antibiotics used to achieve HP eradication. The increase of l-dopa absorption observed in this study may have little or no relation to HP eradication. References 1. Pierantozzi M, Pietroiusti A, Brusa L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology 2006;66:1824-1829. 2. Richard G Fiddian-Green H Pylori: cause or effect? http://www.gutjnl.com/cgi/eletters/35/8/1033#385, 8 Apr 2004 3. Otte JA, Geelkerken RH, Oostveen E, Mensink PB, Huisman AB, Kolkman JJ. Clinical impact of gastric exercise tonometry on diagnosis and management of chronic gastrointestinal ischemia. Clin Gastroenterol Hepatol 2005;3:660-666. 4. Richard G Fiddian-Green Irreversible shock, gastric intramucosal pH and energy charge. http://adc.bmjjournals.com/cgi/eletters/78/2/155#1417, 12 Mar 2005 5. Mark F. Bear, Barry W. Connors, Michael A. Paradiso. Neuroscience: Exploring the Brain. Third Edition, Lippincott Williams and Wilkins, 2006. Disclosure: The author reports that Tonometric patents have been issued in his name.
Reply from the Authors 4 December 2006
Antonio Pietroiusti, Univeristà di Roma Tor Vergata Viale Oxford 81, 00133 Rome, Italy, Mariangela Pierantozzi, Antonio Pietroiusti, Livia Brusa, Salvatore Galati, Alessandro Stefani, Gianluigi Lunardi, Ernesto Fedele, Giuseppe Sancesario, Antonio Bergamaschi, Andrea Magrini, Paolo Stanzione, and Alberto Galante Send Correspondence to journal: Re: Reply from the Authors pietroiusti{at}med.uniroma2.it Antonio Pietroiusti, et al.	Dr. Fiddian-Green states that "Helicobacter pylori(HP)infection might have been the result of a systemic metabolic abnormality that was the primary cause of Parkinson’s Disease (PD) and gut dysfunction as in peptic ulceration." We did not address this issue because the objective of our study focused on the reversible HP- induced interference with l-dopa intestinal absorption in infected patients with PD. We think Dr. Fiddian-Green's assertion is unlikely. He believes that events such as chronic mesenteric ischemia or metabolic stress are necessary predisposing conditions for HP infection given the peculiar metabolic needs of the organism. This hypothesis in not supported by epidemiology and pathophysiology data on HP infection. Epidemiologic studies unequivocally show that HP infection is acquired during childhood [6] when the predisposing events hypothesized by Dr. Fiddian-Green (i.e. chronic mesenteric ischemia or "metabolic stress") are highly improbable. Concerning the high pCO2 levels required for the organism survival, there is compelling evidence that they are produced by the strong urease activity present on the organism surface which use the urea of the gastric acid environment as substrate to produce ammonia and CO2 thus creating the optimal conditions for HP survival in the gastric lumen. [7] In addition, Dr. Fiddian-Green comments that HP infection itself may represent an innocent bystander and that the improvement of pharmacokinetic and clinical response to l-dopa that we found after eradication may be partially due to the efficacy of HP eradication therapy on organisms other than HP. This hypothesis cannot be excluded. Nevertheless, as we reported, the relationship between the HP-related gastritis/duodenitis relief and the significant clinical improvement observed in HP-eradicated patients with PD is certain. We do consider the possibility that gastrointestinal motility alterations, as frequently found in l-dopa treated PD patients, [8] may allow bacterial overgrowth even in the stomach. [9] These bacteria which are generally able to metabolize neutral amino acids [10] might in turn directly affect l-dopa intestinal absorption and their elimination due to anti-HP antibiotic treatment. Consequently, this could induce a better l-dopa adsorption but this hypothesis needs to be further evaluated. References 6. Rowland M, Daly L, Vaughan M, Higgins A, Bourke B, Drumm B. Age- specific incidence of Helicobacter pylori. Gastroenterology 2006; 130: 65- 72. 7. Sachs G, Weeks DL, Wen Y, Marcus EA, Scott DR, Melchers K. Acid acclimation by Helicobacter pylori. Physiology 2005; 20: 429-38. 8. Hardoff R, Sula M, Tamir A, et al. Gastric emptying time and gastric motility in patients with Parkinson’s disease. Mov Disord 2001; 16: 1041-47. 9. Dominquez-Munoz JE. Testing the abnormalities of gastroduodenal function in functional dyspepsia. Dig Dis 2001; 19: 195-200. 10. Barker HA. Amino acid degradation by anaerobic bacteria. Annu Rev Biochem 1981; 50:23-40. Disclosure: The authors report no conflicts of interest.