The 2011 Medical Molecular Hydrogen Symposium: An Inaugural Symposium of The Journal Medical Gas Research

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Ohta et al.

Medical Gas Research 2011, 1:10


http://www.medicalgasresearch.com/content/1/1/10 MEDICAL GAS
RESEARCH

COMMENTARY Open Access

The 2011 Medical Molecular Hydrogen


Symposium: An inaugural symposium of the
journal Medical Gas Research
Shigeo Ohta1*, Atsunori Nakao2 and Kinji Ohno3

Abstract
This report summarizes a brief description/history of the Hydrogen Research Meetings as well as key presentations/
oral abstracts delivered in the most recent symposium. Additionally, we introduced 38 diseases and physiological
states for which hydrogen exhibits beneficial effects.

Introduction This report summarizes a brief description/history of


Novel medical gases are expected to provide us with the Hydrogen Research Meetings as well as key presen-
more effective therapeutic interventions and preventive tations/oral abstracts delivered in the most recent
medicine. In the past decades, there has been extraor- symposium.
dinary, rapid growth in our knowledge of gaseous mole-
cules, including nitric oxide, carbon monoxide, and First Medical Molecular Hydrogen Research
hydrogen sulfide, which have been known to play Meeting, 2009
important roles in biological systems. Additionally, since The first scientific meeting organized by Dr. Ohta was held
Dr. Shigeo Ohtas groups pioneering paper was pub- on February 7, 2009 in Tokyo. 42 scientists and clinicians
lished in the June 2007 Nature Medicine showing the from 30 individual institutes were invited. The aim of the
potency of hydrogen as a therapeutic gas for oxidative meeting was to unite innovative investigators to discuss
stress-mediated diseases including cerebral infarction and propagate medical hydrogen research. Dr. Ohta deliv-
[1], basic and clinical hydrogen research has resurfaced. ered the keynote presentation, in which he gave a brief his-
In Japan, the birthplace of hydrogen gas research, Dr. tory of hydrogen medicine and emphasized the huge
Ohta (Nippon Medical School), who is currently serving impact of his report published in Nature Medicine. He
as an Associate Editor of Medical Gas Research, orga- pointed out the great interest in the field, expressed in
nized annual Medical Molecular Hydrogen Research more than 30 personal communications with investigators,
Meetings in 2009 and 2010 to provide investigators and the resulting need to widen the scope of basic/clinical
with focused opportunities to share their rapid scientific research to the whole world. He mentioned the successful
progress. Most recently, we organized the Medical application of hydrogen gas in a rat neonatal hypoxic brain
Molecular Hydrogen Symposium on February 18-19, injury model in collaboration with Dr. Xuejun Sun (Second
2011 at the Nagoya University Hall (Figure 1). The latest Military Medical School, Shanghai, China) [2], who is cur-
meeting is a kick-off inaugural meeting for the newly rently serving as an Associate Editor. Dr. Atsunori Nakao
launched journal Medical Gas Research (MGR), which (Department of Surgery, University of Pittsburgh), who is
aims to promote the exchange and dissemination of the also an Associate Editor, presented the promising prelimin-
latest scientific findings. ary results of a collaborative study with Dr. Ohtas group in
which hydrogen water was applied in a rat kidney trans-
plant model. Dr. Nakaos report clearly showed survival
* Correspondence: ohta@nms.ac.jp benefits for transplant recipients. He received a research
1
Department of Biochemistry and Cell Biology, Institute of Development and award at this meeting and his report was later published in
Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396
Kosugi-machi, Nakahara-ku, Kawasaki-city, Kanagawa 211-8533, Japan
Kidney International [3,4]. Dr. Takahisa Kawai (Forsythe
Full list of author information is available at the end of the article Research Institute, Boston, MA, USA), who is an editorial
2011 Ohta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Ohta et al. Medical Gas Research 2011, 1:10 Page 2 of 7
http://www.medicalgasresearch.com/content/1/1/10

editorial board member, and held in Nagoya on Feb 18-


19, 2011. This symposium mainly focused on molecular
hydrogen and covered a wide-range of therapeutic gases,
including hydrogen sulfide (H2S), nitric oxide (NO), and
carbon monoxide (CO). A total of 98 academic and 53
corporate registrants attended the meeting from Japan
(144), USA (5), Korea (1), and Taiwan (1). The meet-
ings timetable, titles, and speakers are summarized in
Table 1. We also introduced 38 diseases and physiologi-
cal states for which hydrogen exhibits beneficial effects
(Table 2).

Hydrogen
Dr. Ohta gave a keynote lecture and introduced a num-
ber of hydrogens potent efficacies on a broad spectrum
Figure 1 A snap shot of the Medical Molecular Hydrogen of diseases in animal and human models, as well as the
Symposium in 2011.
emerging molecular bases of hydrogens effects. He
emphasized the following points: (i) In the three and a
board member, focused on hydrogen generated by intest- half years since the first hydrogen paper was published
inal bacteria. His initial studies elegantly demonstrated the in Nature Medicine, more than 70 original papers have
critical physiological roles of gut microflora-derived hydro- been published in leading biological/medical journals.
gen [5]. There was a general consensus that both clinicians Based on cumulative knowledge, beneficial biological
and researchers in the field of molecular hydrogen research effects of hydrogen have been established with no
should gather and exchange accumulating knowledge in doubt. (ii) There are several ways to intake or consume
future annual meetings. hydrogen, including inhaling hydrogen gas, drinking
water dissolved with hydrogen (hydrogen water), taking
Second Medical Molecular Hydrogen Research a hydrogen bath, injecting hydrogen saline, dropping
Meeting, 2010 hydrogen saline into the eye, and increasing production
The second meeting was also organized by Dr. Ohta on of intestinal hydrogen by bacteria. (iii) Hydrogen shows
February 3, 2010 in Tokyo. 47 basic scientists and clinical not only anti-oxidative stress effects, but also has var-
physicians, as well as 23 corporate participants were ious anti-inflammatory and anti-allergic effects. (iv) The
invited and shared the latest developments in medical primary molecular target of hydrogen remains unknown.
issues related to hydrogen. This meeting hosted a keynote In their first report published in 2007 [1], Dr. Ohtas
lecture, an invited lecture, two special lectures, and twelve group indicated that cells cultured in H2-rich medium
platform presentations. After Dr. Ohta began his keynote were protected against oxidative stress by the hydroxyl
lecture by remarking on the impressive progress over the radical-scavenging activity of H2; however, recent evi-
last year, Dr. Sun gave an invited lecture and introduced dence clearly shows that the scavenging property is not
the great effects of intraperitoneal administration of saline the only explanation for the potent beneficial effects of
dissolved with H2 in several model animals. Dr. Takashi hydrogen. For example, the amount of orally adminis-
Asada (Department of Psychiatry, Tsukuba University), an tered H2 may not be enough to scavenge hydroxyl radi-
authority on Alzheimer disease, presented the results of cals. In addition, it is likely that the dwell time of H2 in
clinical studies involving patients with mild cognitive the body is too short to scavenge a large amount of
impairment (MCI). He started clinical intervention studies hydroxyl radicals that are continuously generated. (v)
on MCI patients by orally administering hydrogen water; Several reports demonstrate an effect on the regulation
the project is still in progress. Dr. Toru Yoshikawa (Kaoh- of gene expressions and protein-phosphorylations; how-
siung Medical University, Taiwan) also gave a special lec- ever, the transcriptional factors and kinases involved in
ture on the physical aspects of hydrogen effects. He the functions afforded by H2 have not been identified. It
presented the physical characteristics of molecular hydro- also remains unknown whether the regulations are
gens interaction with water in biological systems. directly performed by H2. (vi) The amount of adminis-
tered H2 is independent of the extent of effects. Intest-
Third Medical Molecular Hydrogen Research inal bacteria seem to produce more than 1 liter of H2
Meeting, 2011 gas per day, whereas the amount of H2 originating from
The third meeting was organized by Dr. Kenji Ohno drinking hydrogen water is less than 50 ml. Neverthe-
(Nagoya University Graduate School of Medicine), an less, additional H 2 in drinking hydrogen water is
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Table 1 Scientific Program of the Medical Molecular Hydrogen Symposium in 2011


Feb. 18, 2011 Title Speaker
13:00 Opening Remarks Kinji Ohno, Nagoya Univ.
13:05 Keynote Lecture Recent progress towards hydrogen medicine Shigeo Ohta, Nippon Medical Sch.
13:35 Scientific Session I
1. Effects of hydrogen-rich water on kidney functions in SHR.Cg-Leprcp/NDmcr rat - a Michio Hashimoto, Shimane Univ.
metabolic syndrome model rat
2. Hydrogen-rich UW solution attenuates renal cold ischemia reperfusion injury Toyofumi Abe, Osaka Univ.
3. Therapeutic effect of maternal hydrogen water administration in a rat model of fetal Yukio Mano, Nagoya Univ.
brain damage
4. Effects of hydrogen water on human skin and hair Yoshiaki Kurita, Hosei Univ.
14:23 Coffee Break
14:50 Scientific Session II
5. Consumption of hydrogen water prevents memory impairment accompanying Ikuroh Ohsawa, Metropolitan Instittue of
neurodegeneration in transgenic mice Gerontology
6. Appearance of hydrogen gas in the human skin after the ingestion of hydrogen-rich Kazutoshi Nose, National Cerebral and
water and inhalation of hydrogen gas Cardiovascular Center
7. Effectiveness of long-term intake of hydrogen rich water in a patient with MELAS Mikio Hirayama, Kasugai Municipal
Hospital
8. Effectiveness of hydrogen rich water on myopathy Tohru Ibi, Aichi Medical Univ.
9. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/ Tomohiro Kawamura, Univ. of Pittsburgh
reperfusion injury in rats
15:50 Invited Lecture I Deadly gas can save a life! -Preclinical studies using carbon Atsunori Nakao, Univ. of Pittsburgh
monoxide/hydrogen-
16:30 Break
16:40 Invited Lecture II Medical Gas Research John Zhang, Loma Linda Univ.
17:20 Invited Lecture III A hypothesis on biological protection from space radiation through Michael P. Schoenfeld, NASA Marshall
the use of therapeutic gases Space Flight Center
18:10 Banquet
Feb. 19, 2011
9:30 Symposium I CO as a therapeutic modality Organizer: Atsunori Nakao, Univ. of
Pittsburgh
S1-1. Is exhaled carbon monoxide a marker of oxidative stress? Tohru Takahashi, Okayama Prefecture
Univ.
S1-2. A tracer analysis study demonstrates redistribution of endogenous carbon Makoto Sawano, Saitama Medical Univ.
monoxide from blood to tissue in human body
S1-3. Translational research of carbon monoxide therapy using miniature swine Hisashi Sahara, Kagoshima Univ.
10:30 Special Lecture Function of hydrogen sulfide and its therapeutic applications Hideo Kimura, National Center of
Neurology and Psychiatry
11:10 Break
11:20 Scientific Session III
10. Hydrogen from intestinal bacteria is protective for Con A-induced Hepatitis Mikihito Kajiya, The Forsyth Institute
11. Abnormal breath hydrogen production by ingestion of lactulose in Parkinsons Masaaki Hirayama, Nagoya Univ.
disease
12. A new portable breath hydrogen analyzer and its clinical application Akito Shimouchi, National Cerebral and
Cardiovascular Center
13. Application of hydrogen water in the dental field Noriyuki Tanaka, Uchida Dental Clinic
12:08 Lunch
12:45 Symposium II Biological Effects of NO Hirosuke Kobayashi, Kitasato Univ.
S2-1. NO-ROS cellular signaling mediated via nitrated cyclic nucleotide Hideshi Ihara, Osaka Prefecture Univ.
S2-2. Relationship between protein S-nitrosylation and neuronal death Takashi Uehara, Wakayama Mediccal Univ.
S2-3. Role of nitrosative stress in chronic obstructive pulmonary disease Ryujiro Sugimoto, Iwakuni Clinical Center
S2-4. Effects of simultaneous inhalation of nitric oxide and hydrogen on mouse Hirosuke Kobayashi, Kitasato Univ.
myocardial ischemia-reperfusion injury
14:15 Scientific Session 4
14. Effect of hydrogen rich water against a progression of disease and a formation of Daisuke Kawai, Okayama Univ.
liver tumor in NASH model mouse
15. The dynamic movement of H2 in a liver and its effects Naomi Kamimura, Nippon Medical Univ.
16. Molecular hydrogen effectively protects cereulide-induced liver injury by suppressing Sayaka Sobue, Chubu Univ.
apoptosis
14:51 Closing Remarks Kinji Ohno, Nagoya Univ.
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Table 2 Thirty-eight diseases and physiological states for Table 2 Thirty-eight diseases and physiological states for
which hydrogen effects are reported which hydrogen effects are reported (Continued)
Disease/Physiology Species Source of H2 Reference Cancer
Brain Tongue carcinoma cells medium [45]
Cerebral infarction rodent gas [1] Inflammation and allergy
Superoxide in brain rodent water [6] Allergy type I rodent water [46]
Neonatal brain hypoxia rodent gas [2,7] Sepsis rodent gas [47]
rodent saline [8] Zymosan-induced inflammation rodent gas [47]
pig gas [9] Others
Restraint-induced dementia rodent water [10] Multipotent stromal cells cells gas [48]
Alzheimers disease rodent saline [11] Radiation injury cells medium [49,50]
Senile dementia rodent water [12] Although the observations are not directly relevant to diseases, Turmeric [51]
Parkinsons disease rodent water [13,14] and acarbose [52] increase hydrogen production by intestinal bacteria in
humans.
Hemorrhagic cerebral infarction rodent gas [15]
Traumatic brain injury rodent gas [16]
Spinal cord unambiguously effective. Many mysteries of hydrogen
Spinal cord injury rodent saline [17] therapy remain unsolved. He closed his talk by empha-
Eye sizing that the molecular mechanisms underlying the
Glaucoma rodent eye drop [18] amazing effects of a very small amount of H 2 remain
Corneal alkali-burn rodent eye drop [19] elusive.
Ear Sixteen platform speakers presented clinical and basic
Hearing disturbance rodent medium [20] aspects of the medical application of molecular hydro-
rodent gas [21] gen. Among them were three treatments for patients
rodent water [22] with neurological and dental diseases. Dr. Mikio Hir-
Lung ayama (Department of Neurology, Kasugai City Hospi-
Lung cancer Cells medium [23] tal) and his colleagues presented their clinical report of
Oxygen-induced lung injury rodent saline [24,25] treatment for a patient with mitochondrial encephalo-
Lung transplantation rodent gas [26] myopathy, lactic acidosis, and stroke-like episode
Heart (MELAS) syndrome. He reported that a 33-year-old
Myocardial infarction rodent gas [27] female patient was successfully treated by drinking
rodent saline [28] hydrogen-containing water for one and half years, which
Heart transplantation rodent gas [29] reduced the frequency of episodic cerebral ischemia. Dr.
Irradiation-induced heart injury rodent water [30] Tohru Ibi (Department of Neurology, Aichi Medical
Liver School) conducted an open label trial on mitochondrial
Hepatic ischemia rodent gas [31] disorders and inflammatory myopathies, and demon-
Hepatitis rodent bacteria [5] strated a remarkable reduction of several serum markers
Obstructive jaundice rodent saline [32] specific for myelopathy. He also conducted a double-
Kidney blind crossover trial; however, the trial showed no sig-
Cisplatin nephropathy rodent gas, water [33] nificant effects, which was likely due to a small amount
rodent water [34] of hydrogen water and to a short observation period.
Hemodialysis human dialysis [35,36] Both reports suggest that oral administration of hydro-
Kidney transplantation rodent water [4] gen water is likely to be effective for mitochondrial dis-
Pancreas eases. Dr. Noriyuki Tanaka (Uchida Dental Clinic)
Acute pancreatitis rodent saline [37] reported that direct dental application of hydrogen
Intestine water on injured regions reduced inflammation and pro-
Intestinal graft rodent gas [3] moted healing in dental operations, including tooth
rodent saline [38,39] extraction.
Ulcerative colitis rodent gas [40] Medical Gas Researchs editor-in-chief Dr. John
Blood vessel Zhang (Department of Neurosurgery, Loma Linda Uni-
Atherosclerosis rodent water [41] versity, CA) gave a greeting talk, introducing the aims
Metabolism and scope of the journal. Dr. Zhang pointed out the
Diabetes mellitus type 2 human water [42] importance of stimulating medical gas research and
Metabolic syndrome human water [43] collaborating with a wide-range of people in various
Obesity/Diabetes rodent water [44] fields.
Ohta et al. Medical Gas Research 2011, 1:10 Page 5 of 7
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Dr. Michael P. Schoenfeld from NASA gave a special devices to measure H2 gas in breath. Takaoka Co Ltd.
lecture on the potential application of H 2 to protect demonstrated a tiny home apparatus to produce hydro-
astronauts from radiation-mediated injury during long gen water. Doctors Choice Co Ltd. demonstrated pow-
space travel. Cosmic radiation induces serious oxidative ders to prepare a hydrogen bath at home using a new
stress, which is one of the major issues to be resolved material that releases H2 gas. These new products will
by hydrogen research. help expand our knowledge and applicability of hydro-
gen research.
Other Medical Gases (NO, CO, and H2S)
Mammals produce NO, CO, and H 2 S by their native
Acknowledgements
enzymes; however, mammals lack an enzyme to produce We would like to express our sincere thanks to all the meeting participants
H 2 . All four gases modulate signaling pathways and and staff, especially Dr. Mikako Ito at Nagoya University, who conducted the
have some therapeutic effects. Thus, we invited leading meeting.

NO, CO, and H2S researchers to the symposium. Author details


Dr. Hideo Kimura (National Center of Neurology and 1
Department of Biochemistry and Cell Biology, Institute of Development and
Psychiatry), an editorial board member, gave a special Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396
Kosugi-machi, Nakahara-ku, Kawasaki-city, Kanagawa 211-8533, Japan.
lecture on hydrogen sulfide (H2S). Dr. Kimura discov- 2
Thomas E Starzl Transplantation Institute, Department of Surgery, University
ered biological roles for H2 S. He reviewed studies on of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
3
H2S from past to present and emphasized the potential Division of Neurogenetics, Center for Neurological Diseases and Cancer,
Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku,
for actual medical applications. Nagoya 466-8550, Japan.
Dr. Nakao organized a mini-symposium on carbon
monoxide (CO). In the mini-symposium, the discre- Received: 9 March 2011 Accepted: 7 June 2011 Published: 7 June 2011

pancy between the animal and human models was dis-


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doi:10.1186/2045-9912-1-10
Cite this article as: Ohta et al.: The 2011 Medical Molecular Hydrogen
Symposium: An inaugural symposium of the journal Medical Gas
Research. Medical Gas Research 2011 1:10.

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