Showing papers in "Evidence-based Complementary and Alternative Medicine in 2004"

Complementary and Alternative Medicine, When Rigorous, can be Science

Abstract: In October 2003, during the 12th Congress of Oriental Medicine in Taipei, the National Palace Museum organized an enormously pertinent exhibit in Gallery 313 derived largely from the museum’s collection of ancient medical texts that includes classics on numerous topics. It is entitled Life is Worth More than Gold: A Special Exhibition of Ancient Medicinal Classics. In the English translation of the Chinese description clues are embedded that pertain to the origins of both Western medicine and the history of complementary and alternative medicine (CAM) as briefly described: “Disease has always been a great topic of concern in human society. From prayers and spells to the birth of medicine as a rational science, man has been able to develop all sorts of medical treatments to combat against different illnesses and ailments, because, as the Chinese proverb has it, ‘life is worth more than a thousand gold pieces.’ Towards the end of the Eastern Han (the 3rd century), typhoid was rampant in China, and the fatality rate was extremely high. Chang Chung-ching, with his extensive clinical experience, wrote the Treatise on Cold-Induced Febrile and Miscellaneous Diseases, and thereby established the foundations for ‘treatment based on differentiation of symptom-complex’ in traditional Chinese medicine. After that, as governments began setting up medical institutions and experiences of private doctors came to be valued, many important medicinal theories, treatments and much pharmaceutical knowledge were gradually organized systematically. Advancements in pharmacology were particularly notable. For example, the Newly-Revised Materia Medica issued by Emperor Kao-tsung of the T’ang dynasty in the 10th year of his reign (659) was the first pharmacological encyclopedia edited and published by the government, and a copy was taken to Japan by Japanese emissaries soon after its completion.”

Comparison of Radical Scavenging Activity, Cytotoxic Effects and Apoptosis Induction in Human Melanoma Cells by Taiwanese Propolis from Different Sources

Abstract: Propolis is a sticky substance that is collected from plants by honeybees. We previously demonstrated that propolins A, B, C, D, E and F, isolated from Taiwanese propolis (TP), could effectively induce human melanoma cell apoptosis and were strong antioxidant agents. In this study, we evaluated TP for free radical scavenging activity by DPPH (1,2-diphenyl-2-picrylhydrazyl). The phenolic concentrations were quantified by the Folin–Ciocalteu method. The apoptosis trigger activity in human melanoma cells was evaluated. TP contained a higher level of phenolic compounds and showed strong capability to scavenge free radicals. Additionally, TP1g, TP3, TP4 and TP7 exhibited a cytotoxic effect on human melanoma cells, with an IC50 of 2.3, 2.0, 3.3 and 3.3 μg/ml, respectively. Flow cytometric analysis for DNA fragmentation indicated that TP1g, TP2, TP3 and TP7 could induce apoptosis in human melanoma cells and there is a marked loss of cells from the G2/M phase of the cell cycle. To address the mechanism of the apoptosis effect of TP, we evaluated its effects on induction of apoptosis-related proteins in human melanoma cells. The levels of procaspase-3 and PARP [poly(ADP-ribose) polymerase] were markedly decreased. Furthermore, propolins A, B, C, D, E and F in TP were determined using HPLC. The results indicate that TP is a rich source of these compounds. The findings suggest that TP induces apoptosis in human melanoma cells due to its high level of propolins.

Neurobiology of Acupuncture: Toward CAM

Abstract: It has long been accepted that acupuncture, puncturing and scraping needles at certain points on the body, can have analgesic and anesthetic effects, as well as therapeutic effects in the treatment of various diseases. This therapy, including acupuncture anesthesia, has drawn the attention of many investigators and become a research subject of international interest around the world. Numerous studies have demonstrated that the nervous system, neurotransmitters, endogenous substances and Jingluo (meridians) may respond to needling stimulation and electrical acupuncture. An abundance of information has now accumulated concerning the neurobiological mechanisms of acupuncture, in relation to both neural pathways and neurotransmitters/hormonal factors that mediate autonomic regulation, pain relief and other therapeutics. Early studies demonstrated that the analgesic effects of electroacupuncture (EA) are mediated by opioid peptides in the periaqueductal gray. Recent evidence shows that nitric oxide plays an important role in mediating the cardiovascular responses to EA stimulation through the gracile nucleus-thalamic pathway. Other substances, including serotonin, catecholamines, inorganic chemicals and amino acids such as glutamate and α-aminobutyric acid (GABA), are proposed to mediate certain cardiovascular and analgesic effects of acupuncture, but at present their role is poorly understood. The increased interest in acupuncture health care has led to an ever-growing number of investigators pursuing research in the processes of the sense of needling touch, transduction of needling stimulation signals, stimulation parameters and placebos. In this Review, the evidence and understanding of the neurobiological processes of acupuncture research have been summarized with an emphasis on recent developments of nitric oxide mediating acupuncture signals through the dorsal medulla-thalamic pathways.

Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies

Abstract: Bromelain, an extract from the pineapple plant, has been demonstrated to show anti-inflammatory and analgesic properties and may provide a safer alternative or adjunctive treatment for osteoarthritis. All previous trials, which have been uncontrolled or comparative studies, indicate its potential use for the treatment of osteoarthritis. This paper reviews the mechanism of its putative therapeutic actions, those clinical trials that have assessed its use in osteoarthritis to date, as well as considering the safety implications of this supplement for osteoarthritis and reviewing the evidence to date regarding the dosage for treating this condition. The data available at present indicate the need for trials to establish the efficacy and optimum dosage for bromelain and the need for adequate prospective adverse event monitoring in such chronic conditions as osteoarthritis.

Drug Discovery, CAM and Natural Products

Abstract: This editorial is related to two papers in volume 1 issue 2 of eCAM and to others concerned with molecules derived from terrestrial and marine species (1‐15). These papers focus on natural products, especially those derived from the sea. Therefore, it is appropriate to apply the contributions of these papers, since they can offer a different perspective. It is, indeed, a matter of great coincidence that these papers are being published at a time when eCAM is making extensive efforts to highlight this subject, which occupies an important place in biomedicine and has enormous potential. This situation in which the focus, at least of publications, is on animal products, is in marked contrast to that of botanicals and herbals—qua plant-derived molecules, the available literature on which may be considered immense and sometimes focused in highly specialized journals. A recent issue of Science offers a veritable cornucopia of evidence concerned with new drugs, and it begins with an editorial entitled ‘Drug Discovery’ by Donald Kennedy Editor-in-Chief (16). This is followed by an introduction titled ‘Rethinking Drug Discovery (17) and a news essay, ‘Surviving the Blockbuster Syndrome; Orphan Drugs of the Future’ (18). Five reviews and viewpoints examine various aspects of molecular biology, organic chemistry and drug delivery systems (19‐23). If one explores the enormous wealth in this issue of Science in science’s next wave (www.nextwave.org), at least five presentations offer enormous potential for application (Bioprospecting beginning with ‘The Sweet Side of Venom and Practicing’ (24‐28). This sojourn into the world of drug discovery is, in my opinion, an area pertinent to complementary and alternative medicine (CAM). It is not remote but is closely related, relevant and highly visible, not to mention that it has rapidly increasing potential for wider distribution and understanding. This appears almost inevitable with the practice of western medicine shifting somewhat or, at least, bridging the divide between western and eastern medicine through the intervention of CAM. After all, many of these claims of healing have deep and everlasting recorded roots in the ancient world, most notably throughout Asia. The challenge will be to subject certain claims to the rigors of science and demand that conclusions be evidence-based (12). Otherwise, CAM will be unable to withstand the criticism of biologists and, sometimes, that of educated and skeptical public.

Modulation of Immune Functions by Foods.

Abstract: Evidence is rapidly accumulating as to the beneficial effects of foods. However, it is not always clear whether the information is based on data evaluated impartially in a scientific fashion. Human research into whether foods modulate immune functions in either intervention studies or randomized controlled trials can be classified into three categories according to the physical state of subjects enrolled for investigation: (i) studies examining the effect of foods in healthy individuals; (ii) studies analyzing the effect of foods on patients with hypersensitivity; and (iii) studies checking the effect of foods on immunocompromized subjects, including patients who had undergone surgical resection of cancer and newborns. The systematization of reported studies has made it reasonable to conclude that foods are able to modulate immune functions manifesting as either innate immunity (phagocytic activity, NK cell activity) or acquired immunity (T cell response, antibody production). Moreover, improvement of immune functions by foods can normalize the physical state of allergic patients or cancer patients, and may reduce the risk of diseases in healthy individuals. Therefore, it is valuable to assess the immune-modulating abilities of foods by measuring at least one parameter of either innate or acquired immunity.

Evidence-based Reconstruction of Kampo Medicine: Part II-The Concept of Sho.

Abstract: In this lecture, I would like to focus on and discuss what I think is the central concept of Kampo: the concept of Sho. It can be roughly translated into English as, for example, symptoms, signs or evidence, and I shall try to explain (though not define) it in more detail in the second section of this article. There are several reasons why I try to represent Kampo practice as based centrally on Sho, besides the fact that I believe it is really part of the essence of Kampo. First, many Western scientists and physicians are put off from the start if they are told that it is impossible for them to understand traditional Chinese medicine (TCM) or Kampo without grasping the full complexities of its basic concepts such as Ying-Yang, five elements, five organs, Qi, etc. If Western scientists and physicians are told that the TCM paradigm is so different from modern Western medicine that they should first switch the paradigm itself, they will be hopeless when they try to come to terms with any specific Kampo or TCM remedies. In some sense this is true and it is very risky for Western physicians to pick up any Kampo or TCM formulae outside the context of Kampo's cognitive paradigm. However, since saying that the paradigm should come first may only result in shutting the door against those who genuinely wish to enter the rich field of TCM or Kampo, I would think that it is more productive to first focus on what I think is the central medical concept of Kampo without going any deeper into its paradigm, philosophical foundations or the system itself. Secondly, I have to emphasize that TCM and Kampo are not monolithic ideological systems. They are broad systems of medical practice and thinking evolved over thousands of years. Therefore, the systems themselves have a rather wide variation. There have been many schools in TCM and Kampo and disputes among them are the rule, rather than the exception. Basic concepts like Yin-You (Ying-Yang in Chinese) or Ki (Qi in Chinese) have been held invariantly among different schools, but slightly different interpretations are common, even for such central concepts as Ying-Yang, and no less common are different emphases on more peripheral concepts. In the first article of this lecture series (1), I pointed out that Kampo could be seen as a simplified or practical version of TCM. Stated differently, Kampo is a sort of school or an important variant of TCM. In that article I stated that modern Kampo in Japan can be traced back to the 18th century Renaissance (or restoration) movement of the Koho (old formula) school of, for example, Yamawaki and Yoshimasu. Western readers may be astonished to know that Yoshimasu went so far as to suggest the irrelevance of the very concept of Ying-Yang, emphasizing, in effect, that anything should go as long as it is effective, regardless of philosophy. Though I should hastily add that such attitudes did not become orthodox in Japan, it cannot be denied that Kampo is less rigorous about its philosophical or ideological basis than the orthodox TCM. Thus, if I were asked by outsiders what the central concept held as consensus among Kampo practitioners in Japan is, I would say that it is Sho. Thirdly, it is very interesting to highlight the concept of Sho in this journal, Evidence-based CAM, because the Chinese character representing Sho can be translated in English to mean evidence. Also of interest is that the same word may have been differently represented in ancient Chinese character, the meaning of which in turn could be translated in English to mean symptom. Thus, the term Sho bears very interesting medical implications, unlike Ying-Yang or Qi, which would be of interest to any Western scientist or physician who wished to acquire medical knowledge about Kampo or TCM. Finally, there is a very practical reason peculiar to the Japanese situation surrounding Kampo. This is related to the government's policy on prescriptive drugs. In Japan, it is not possible for a physician to use TCM's three elements/eight categories interpretations in order for his/her Kampo formulae to be covered by the National Health Insurance System (NHIS). Thus, a Kampo formula, if it is to be covered by the NHIS, must be prescribed for disease entities expressed in terms of modern Western medicine, such as gastritis or atopic eczema. For rigorous practitioners of TCM this would be a great insult, as their diagnostic interpretations are not recognized as official or scientific categories of diseases. Thus, nowadays it has become more common for Japanese medical doctors to prescribe Kampo formula just by saying that the patient now has a condition which requires such formula. Though it has long been legitimate in Kampo to prescribe a formula as the patient is simply in its Sho, this tendency has become more prominent these days. For example, a patient can just be said to be Rikkunshi-To-Sho, regardless of his/her diagnosis in terms of modern western medicine. As I shall explain later, this situation arises in the Kampo system itself, where any symptoms (Sho) can be taken as evidence (Sho, again) for some formulae, and very often symptoms are called Sho-for-some Kampo formulae. As drugs covered by NHIS can only be prescribed by medical doctors trained in Western medicine in Japan, there is a tendency for them to use Kampo formula without paying much attention to the TCM interpretations of the symptoms of the patient. Therefore, I think the mainstream of Kampo is Sho-oriented, meaning that it does not rely so much on the rigorous interpretation of the disease state in terms of the basic TCM concepts as on the direct practical effects of a formula itself.

Evidence-based Reconstruction of Kampo Medicine: Part I-Is Kampo CAM?

Abstract: I would like to express my hearty congratulations at the launching of the new journal Evidence-based Complementary and Alternative Medicine (eCAM). I would also like to thank the Editors, Drs Tomio Tada, Edwin Cooper and Nobuo Yamaguchi, for inviting me to contribute a lecture series on the evidential basis of Kampo (Chinese herbal) medicine. This series will run for several issues with the following main topics (in this issue the first three topics are mainly covered): Is Kampo CAM? The historical background of Kampo What characterizes Kampo? Herbal compositions of Kampo medicines Composition and analysis of Kampo medicines Sho (symptoms) Construction of evidence for Kampo, based on Sho Various designs for clinical trials to construct an evidential basis for Kampo Outline of the existing evidence of using Kampo for the treatment of various diseases Preliminary notes for those who are not acquainted with Kampo: the term ‘Kampo’ is a Japanese name for Chinese herbal medicine. The difference between ‘Chinese’ Chinese herbal medicine and Kampo will be discussed in the historical overview section. Sho is broadly defined as Kampo diagnosis in the epistemic framework of Kampo's view of illness. The response to Kampo medicine is predicted by Sho.

Combination Effects of Herbs in a Multi-herbal Formula: Expression of Juzen-taiho-to's Immuno-modulatory Activity on the Intestinal Immune System

Abstract: Herbal formulas of traditional Japanese (Kampo), Chinese and Korean medicines usually comprise multiple herbs in a single formula. These medicines are expected to show their clinical effects by chemical, pharmacological and pharmaceutical combination effects of multi-herbs. However, little effort has been made so far to scientifically clarify the nature of such combination effects. Interestingly, for example, though a Kampo medicine Juzen-taiho-to (Shi-Quan-Da-Bu-Tang in Chinese) stimulates the immune functions of Peyer's patch cells, none of its single component herbs shows such activity. We thus examined the combination effect of herbs in the Juzen-taiho-to formula for the expression of its immuno-stimulating activity. Juzen-taiho-to, a composite formula of 10 herbs, has been generally considered to comprise two kinds of basic formula, each of which consists of four different herbs in addition to two others. The combinations of herbs based on these two basic formulas were evaluated for their stimulating activities on cytokine production from murine Peyer's patch cells both in vitro and ex vivo. Combined decoction of six among 10 herbs in Juzen-taiho-to is crucial for the expression of its stimulating activity on Peyer's patch cells. 3D-HPLC analysis of the ingredients in the fractions from the combined decoctions indicated that, in addition to quantitative changes of ingredients, alterations occur in their chemical composition by decoction of different herbs. The stimulating activity of Juzen-taiho-to on Peyer's patch cells results from the combination effect of its six essential component herbs. This combination effect is based on physicochemical interactions among the ingredients of the component herbs.

Complementary and Alternative Medicine: a Japanese Perspective

Abstract: The use of complementary and alternative medicine (CAM) is increasing rapidly. The World Health Organization (WHO) classifies 65–80% of the world's health care services as ‘traditional medicine’ (1). Therefore, from the viewpoint of the population ratio, more people use CAM than modern western medicine. Although much attention has been focused on CAM not only from physicians but also basic medical researchers, scientific evidence for most CAM is still sparse. Emergence of CAM as a new current of medicine depends on whether or not precise scientific evidence can be accumulated. Why has CAM become so popular among ‘consumers’? I think that the following factors are responsible: CAM is easy to understand and familiar CAM is non-invasive, with few side effects CAM helps improve quality of life (QOL) or activity of daily life (ADL) CAM helps one to maintain one's own health Western modern medicine does not fully correspond to the patients' demands the trend towards a more holistic medical approach ballooning medical expenses In this overview, I will describe and discuss the current status of CAM in Japan. The situation in Japan should be of much interest, since Japan is unique as a country in which highly advanced modern Western medicine coexists with traditional Asian medicine.

An Overview of Traditional Chinese Herbal Formulae and a Proposal of a New Code System for Expressing the Formula Titles

Abstract: Traditional Chinese herbal therapy can be characterized by the use of a large number of multi-herb formulae. To provide modern and Western scientists without knowledge of Chinese literature and cultural background easy access to information, a database with a total of 11 810 traditional Chinese herbal formulae was constructed. All the information was then translated into understandable scientific terms in English. While coining the formula titles in English, we discovered some principles governing the naming of titles by using computer analysis. In addition, we observed that about 92% of the formulae are in the range of single-herb formulae to thirteen-herb formulae. Most large number-herb formulae are formulated by combining pre-existing smaller number-herb formulae. The King herbs () with major therapeutic activity in a multi-herb formula were identified by the formulation concept using two parameters: the herbal dose and the herbal drug property (the degree of toxicity). Based on such analytical data, we established an English code system representing all formula titles written in ideographic Chinese characters: an array of important key words such as ‘Herbal name in Latin + Efficacy (Target organs) + Preparation form + Number of herbs.’ By searching the English version of the database with any of the above key words, a variety of information on the status of traditional Chinese herbal therapy can be accessed.

Traditional and Modern Biomedical Prospecting: Part II-the Benefits: Approaches for a Sustainable Exploitation of Biodiversity (Secondary Metabolites and Biomaterials from Sponges).

Abstract: The progress in molecular and cell biology has enabled a rational exploitation of the natural resources of the secondary metabolites and biomaterials from sponges (phylum Porifera). It could be established that these natural substances are superior for biomedical application to those obtained by the traditional combinatorial chemical approach. It is now established that the basic structural and functional elements are highly conserved from sponges to the crown taxa within the Protostomia (Drosophila melanogaster and Caenorhabditis elegans) and Deuterostomia (human); therefore, it is obvious that the molecular etiology of diseases within the metazoan animals have a common basis. Hence, the major challenge for scientists studying natural product chemistry is to elucidate the target(s) of a given secondary metabolite, which is per se highly active and selective. After this step, the potential clinical application can be approached. The potential value of some selected secondary metabolites, all obtained from sponges and their associated microorganisms, is highlighted. Examples of compounds that are already in medical use (inhibition of tumor/virus growth [arabinofuranosyl cytosine and arabinofuranosyl adenine]), or are being considered as lead structures (acting as cytostatic and anti-inflammatory secondary metabolites [avarol/avarone], causing induction of apoptosis [sorbicillactone]) or as prototypes for the interference with metabolic pathways common in organisms ranging from sponges to humans (modulation of pathways activated by fungal components [aeroplysinin], inhibition of angiogenesis [2-methylthio-1,4-napthoquinone], immune modulating activity [FK506]) are discussed in this study. In addition, bioactive proteins from sponges are listed (antibacterial activity [pore-forming protein and tachylectin]). Finally, it is outlined that the skeletal elements—the spicules—serve as blueprints for new biomaterials, especially those based on biosilica, which might be applied in biomedicine. These compounds and biomaterials have been isolated/studied by members of the German Center of Excellence BIOTECmarin. The goal for the future is to successfully introduce some of these compounds in the treatment of human diseases in order to raise the public awareness on the richness and diversity of natural products, which should be sustainably exploited for human benefit.

Ozone Therapy for Tumor Oxygenation: a Pilot Study.

Abstract: Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy. Ozone therapy is a non-conventional form of medicine that has been used successfully in the treatment of ischemic disorders. This prospective study was designed to assess the effect of ozone therapy on tumor oxygenation. Eighteen subjects were recruited for the study. Systemic ozone therapy was administered by autohemotransfusion on three alternate days over one week. Tumor oxygenation levels were measured using polarographic needle probes before and after the first and the third ozone therapy session. Overall, no statistically significant change was observed in the tumor oxygenation in the 18 patients. However, a significant decrease was observed in hypoxic values ≤10 and ≤5 mmHg of pO2. When individually assessed, a significant and inverse non-linear correlation was observed between increase in oxygenation and the initial tumor pO2 values at each measuring time-point, thus indicating that the more poorly-oxygenated tumors benefited most (rho = −0.725; P = 0.001). Additionally, the effect of ozone therapy was found to be lower in patients with higher hemoglobin concentrations (rho = −0.531; P < 0.034). Despite being administered over a very short period, ozone therapy improved oxygenation in the most hypoxic tumors. Ozone therapy as adjuvant in chemo-radiotherapy warrants further research.

Ozone Therapy on Cerebral Blood Flow: A Preliminary Report

Abstract: Ozone therapy is currently being used in the treatment of ischemic disorders, but the underlying mechanisms that result in successful treatment are not well known. This study assesses the effect of ozone therapy on the blood flow in the middle cerebral and common carotid arteries. Seven subjects were recruited for the therapy that was performed by transfusing ozone-enriched autologous blood on 3 alternate days over 1 week. Blood flow quantification in the common carotid artery (n = 14) was performed using color Doppler. Systolic and diastolic velocities in the middle cerebral artery (n = 14) were estimated using transcranial Doppler. Ultrasound assessments were conducted at the following three time points: 1) basal (before ozone therapy), 2) after session #3 and 3) 1 week after session #3. The common carotid blood flow had increased by 75% in relation to the baseline after session #3 (P < 0.001) and by 29% 1 week later (P = 0.039). In the middle cerebral artery, the systolic velocity had increased by 22% after session #3 (P = 0.001) and by 15% 1 week later (P = 0.035), whereas the diastolic velocity had increased by 33% after session #3 (P < 0.001) and by 18% 1 week later (P = 0.023). This preliminary Doppler study supports the clinical experience of achieving improvement by using ozone therapy in peripheral ischemic syndromes. Its potential use as a complementary treatment in cerebral low perfusion syndromes merits further clinical evaluation.

Antiprotozoan and Antiviral Activities of Non-cytotoxic Truncated and Variant Analogues of Mussel Defensin

Abstract: We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P) efficiently killed Trypanosoma brucei(ID50 4‐12� M) and Leishmania major(ID50 12‐45 � M) in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4� C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 � M. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs) contained in marine invertebrates.

CAM and NK Cells.

Abstract: It is believed that tumor development, outgrowth and metastasis are under the surveillance of the immune system. Although both innate and acquired immune systems play roles, innate immunity is the spearhead against tumors. Recent studies have revealed the critical role of natural killer (NK) cells in immune surveillance and that NK cell activity is considerably influenced by various agents, such as environmental factors, stress, foods and drugs. Some of these NK cell stimulants have been used in complementary and alternative medicine (CAM) since ancient times. Therefore, the value of CAM should be re-evaluated from this point of view. In this review, we overview the intimate correlation between NK cell functions and CAM agents, and discuss possible underlying mechanisms mediating this. In particular, neuro-immune crosstalk and receptors for CAM agents are the most important and interesting candidates for such mechanisms.

Study on Application of Static Magnetic Field for Adjuvant Arthritis Rats.

Abstract: In order to examine the effectiveness of the application of static magnetic field (SMF) on pain relief, we performed a study on rats with adjuvant arthritis (AA). Sixty female Sprague-Dawley (SD) rats (age: 6 weeks, body weight: approximately 160 g) were divided into three groups [SMF-treated AA rats (Group I), non-SMF-treated AA rats (Group II) and control rats (Group III)]. The SD rats were injected in the left hind leg with 0.6 mg/0.05 ml Mycobacterium butyrium to induce AA. The rats were bred for 6 months as chronic pain model. Thereafter, the AA rats were or were not exposed to SMF for 12 weeks. We assessed the changes in the tail surface temperature, locomotor activity, serum inflammatory marker and bone mineral density (BMD) using thermography, a metabolism measuring system and the dual-energy X-ray absorptiometry (DEXA) method, respectively. The tail surface temperature, locomotor activity and femoral BMD of the SMF-exposed AA rats were significantly higher than those of the non-SMF-exposed AA rats, and the serum inflammatory marker was significantly lower. These findings suggest that the pain relief effects are primarily due to the increased blood circulation caused by the rise in the tail surface temperature. Moreover, the pain relief effects increased with activity and BMD of the AA rats.

IL-12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll-like Receptor (TLR).

Abstract: Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various welldocumented medicinal properties. In the present study, we investigated the effects of hemicellulasederived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine-inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL-12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL-12 production by the CD14-positive cell population, consisting of monocytes/macrophages (Mo/M� ). Furthermore, the elim-+ -+ -+ -+

Prevention of Cancer Through Lifestyle Changes

Abstract: Cancer is the second leading cause of death in the USA and an abundance of evidence suggests that lifestyle factors including smoking, the typical high-fat, refined-sugar diet and physical inactivity account for the majority of cancer. This review focuses on diet and inactivity as major factors for cancer promotion by inducing insulin resistance and hyperinsulinemia. Elevated levels of serum insulin impact on the liver primarily, increasing the production of insulin-like growth factor I (IGF-I) while reducing the production of insulin-like growth factor binding protein 1 (IGFBP-1) resulting in stimulation of tumor cell growth and inhibition of apoptosis (programmed cell death). Adopting a diet low in fat and high in fiber-rich starch foods, which would also include an abundance of antioxidants, combined with regular aerobic exercise might control insulin resistance, reduce the resulting serum factors and thus reduce the risk for many different cancers commonly seen in the USA.

Shingles Immunity and Health Functioning in the Elderly: Tai Chi Chih as a Behavioral Treatment.

Abstract: Both the incidence and severity of herpes zoster (HZ) or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV)-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in older adults is associated with declines in VZV-responder cell frequency (VZV-RCF), an immunological marker of shingles risk. In this review, we discuss recent findings that administration of a relaxation response-based intervention, tai chi chih (TCC), results in improvements in health functioning and immunity to VZV in older adults as compared with a control group. TCC is a slow moving meditation consisting of 20 separate standardized movements which can be readily used in elderly and medically compromised individuals. TCC offers standardized training and practice schedules, lending an important advantage over prior relaxation response-based therapies. Focus on older adults at increased risk for HZ and assay of VZV-specific immunity have implications for understanding the impact of behavioral factors and a behavioral intervention on a clinically relevant end-point and on the response of the immune system to infectious pathogens.

Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy

Abstract: Exercise has been widely believed to be a preventive and therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease and cancer. A common problem associated with such pathologies is cachexia, characterized by progressive weight loss and depletion of lean and fat body mass, and is linked to poor prognosis. As this syndrome comprises changes in many physiological systems, it is tempting to assume that the modulation of the psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia progression in cancer patients. Cancer cachexia is characterized by a disruption in the rhythmic secretion of melatonin, an important time-conditioning effector. This hormone, secreted by the pineal gland, transmits circadian and seasonal information to all organs and cells of the body, synchronizing the organism with the photoperiod. Considering that exercise modulates the immune response through at least two different mechanisms—metabolic and neuroendocrine—we propose that the adoption of a regular exercise program as a complementary strategy in the treatment of cancer patients, with the exercise bouts regularly performed at the same time of the day, will ameliorate cachexia symptoms and increase survival and quality of life.

Traditional and Modern Biomedical Prospecting: Part I—the History: Sustainable Exploitation of Biodiversity (Sponges and Invertebrates) in the Adriatic Sea in Rovinj (Croatia)

Abstract: Nature, especially the marine environment, provides the most effective drugs used in human therapy. Among the metazoans, the marine sponges (phylum Porifera), which are sessile filter feeders, produce the most potent and highly selective bioactive secondary metabolites. These animals (or their associated symbiotic microorganisms) synthesize secondary metabolites whose activity and selectivity has developed during their long evolutionary history (evochemistry). The exploitation of these resources has become possible due to the progress in molecular and cell biology. BIOTECmarin, the German Center of Excellence follows this rationale. In the past, these animals have been successfully and extensively utilized to isolate bioactive compounds and biomaterials for human benefit. Pharmaceuticals prepared from marine animals, primarily sponges, have been applied since ancient times (Hippocrates, Aristotle and later Plinius). It has been reported that extracts and/or components from sponges can be used for the treatment of specific diseases. For a systematic and applied-oriented exploitation, the successful development of effective compounds largely depends on quality of the institutional infrastructure of marine stations and more so on the biodiversity. The Center for Marine Research in Rovinj (Croatia) fulfils these prerequisites. Founded in 1891, this institute has to its credit major discoveries related to exploitation of secondary metabolites/biomaterials from sponges for therapeutical application and to obtain biomaterials for general wellbeing.This is the first part of a review focusing on biomedical prospecting. Here, we have mainly described the historic background. The details of techniques, substances, approaches and outlooks will be discussed in the second part.

An Alternative Approach to Atopic Dermatitis: Part I—Case-Series Presentation

Abstract: Atopic dermatitis (AD) is a complex disease of obscure pathogenesis. A substantial portion of AD patients treated with conventional therapy become intractable after several cycles of recurrence. Over the last 20 years we have developed an alternative approach to treat many of these patients by diet and Kampo herbal medicine. However, as our approach is highly individualized and the Kampo formulae sometimes complicated, it is not easy to provide evidence to establish usefulness of this approach. In this Review, to demonstrate the effectiveness of the method of individualized Kampo therapy, results are presented for a series of patients who had failed with conventional therapy but were treated afterwards in our institution. Based on these data, we contend that there exist a definite subgroup of AD patients in whom conventional therapy fails, but the ‘Diet and Kampo’ approach succeeds, to heal. Therefore, this approach should be considered seriously as a second-line treatment for AD patients. In the Discussion, we review the evidential status of the current conventional strategies for AD treatment in general, and then specifically discuss the possibility of integrating Kampo regimens into it, taking our case-series presented here as evidential basis. We emphasize that Kampo therapy for AD is more ‘art’ than technology, for which expertise is an essential pre-requisite.

Phytochemical Assays of Commercial Botanical Dietary Supplements.

Abstract: The growing popularity of botanical dietary supplements (BDS) has been accompanied by concerns regarding the quality of commercial products. Health care providers, in particular, have an interest in knowing about product quality, in view of the issues related to herb-drug interactions and potential side effects. This study assessed whether commercial formulations of saw palmetto, kava kava, echinacea, ginseng and St. John's wort had consistent labeling and whether quantities of marker compounds agreed with the amounts stated on the label. We purchased six bottles each of two lots of supplements from nine manufacturers and analyzed the contents using established commercial methodologies at an independent laboratory. Product labels were found to vary in the information provided, such as serving recommendations and information about the herb itself (species, part of the plant, marker compound, etc.) With regard to marker compound content, little variability was observed between different lots of the same brand, while the content did vary widely between brands (e.g. total phenolic compounds in Echinacea ranged from 3.9-15.3 mg per serving; total ginsenosides in ginseng ranged from 5.3-18.2 mg per serving). Further, the amounts recommended for daily use also differed between brands, increasing the potential range of a consumer's daily dose. Echinacea and ginseng were the most variable, while St. John's wort and saw palmetto were the least variable. This study highlights some of the key issues in the botanical supplement market, including the importance of standardized manufacturing practices and reliable labeling information. In addition, health care providers should keep themselves informed regarding product quality in order to be able to appropriately advise patients utilizing both conventional and herbal medicines.

Evidence-based Reconstruction of Kampo Medicine: Part-III-How Should Kampo be Evaluated?

Abstract: In the previous two lectures, I tried to explain in detail that the paradigm of Kampo is basically different from that of modern Western medicine, focusing especially on the concept of Sho. Kampo has been developed to cope with Sho, not with the disease entities understood in terms of modern Western medicine. Thus, there is little point asking, for example, ‘Are there any Kampo remedies effective for lung cancer (or type C hepatitis, or essential hypertension)?’ This question, asked wrongly, however, highlights two important issues, one intriguing and long term, and the other important and short term. The former is that the effects of Kampo herbs have so far not been tested properly against any of the specific disease entities defined in the framework of modern Western medicine. The latter is that we urgently need some methods to accommodate evaluation of the clinical effects of Kampo remedies in the framework of evidence-based medicine of the West.

Functional Somatic Syndromes: Emerging Biomedical Models and Traditional Chinese Medicine

Abstract: The so-called functional somatic syndromes comprise a group of disorders that are primarily symptom-based, multisystemic in presentation and probably involve alterations in mind-brain-body interactions. The emerging neurobiological models of allostasis/allostatic load and of the emotional motor system show striking similarities with concepts used by Traditional Chinese Medicine (TCM) to understand the functional somatic disorders and their underlying pathogenesis. These models incorporate a macroscopic perspective, accounting for the toll of acute and chronic traumas, physical and emotional stressors and the complex interactions between the mind, brain and body. The convergence of these biomedical models with the ancient paradigm of TCM may provide a new insight into scientifically verifiable diagnostic and therapeutic approaches for these common disorders.

Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling.

Abstract: Previous studies have shown that the traditional herbal complex Gosha-jinki-gan (GJG) improves diabetic neuropathy and insulin resistance. The present study was undertaken to elucidate the molecular mecha- nisms related with the long-term effects of GJG administration on insulin action in vivo and the early steps of insulin signaling in skeletal muscle in streptozotocin (STZ) diabetes. Rats were randomized into five subgroups: (1) saline treated control, (2) GJG treated control, (3) 2-unit insulinsaline treated diabetic, (4) salineGJG treated diabetic and (5) 2-unit insulinGJG treated diabetic groups. After seven days of treatment, euglycemic clamp experiment at an insulin infusion rate of 6 mU/kg/min was performed in overnight fasted rats. Despite the 2-unit insulin treatment, the metabolic clearance rates of glucose (MCR, ml/kg/min) in diabetic rats were significantly lower compared with the controls (11.4 � 1.0 vs 44.1 � 1.5; P � 0.001), and were significantly improved by insulin combined with GJG or GJG alone (26 � 3.2 and 24.6 � 2.2, P � 0.01, respectively). The increased insulin receptor (IR)-� protein content in skeletal mus- cle of diabetic rats was not affected by insulin combined with GJG administration. However, the decreased insulin receptor substrate-1 (IRS-1) protein content was significantly improved by treatment with GJG. Additionally, the increased tyrosine phosphorylation levels of IR-� and IRS-1 were significantly inhibited in insulin combined with GJG treated diabetes. The present results suggest that the improvement of the impaired insulin sensitivity in STZ-diabetic rats by administration of GJG may be due, at least in part, to correction in the abnormal early steps of insulin signaling in skeletal muscle.

Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

Abstract: We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.

An Alternative Approach to Atopic Dermatitis: Part II—Summary of Cases and Discussion

Abstract: In the first part of this Review, we presented case-series where Kampo treatment was introduced for those atopic dermatitis (AD) patients who had failed with conventional therapy, in an attempt to prove that there exists a definite subgroup of AD patients for whom Kampo treatment is effective. In this second part, we will first provide the summary of the results for 140 AD patients we treated in 2000. The results suggest that Kampo treatment is effective for more than half of AD patients who fail with conventional therapy. In the Discussion, we will examine the evidential basis for conventional AD therapy and discuss how Kampo treatment should be integrated into the guidelines for AD therapy. We contend that Kampo treatment should be tried before systematic immunosuppressive agents are considered. As each Kampo treatment is highly individualized, it should be regarded more as ‘art’ than technology, and special care should be taken to assess its efficacy in clinical trial.

Designations of Medicines.

Abstract: With the proliferation of medicines vying for recognition in modern health care systems, we are in some cases faced with the problem of what to call them. One has only to consider the terms ‘complementary’ and ‘alternative’, which appear in the title of this journal, to gain a sense of the problem. The two terms are virtually synonymous in their referents. Nevertheless, they differ markedly in their connotations, since they imply different roles in their relationship with the medicine that has come to dominate health care over the planet. What is more, they are considered by some as inappropriate designations for traditional medicines such as Chinese, Arabic and Ayurvedic medicine on the grounds that these cannot be defined in terms of an alien medical system of much more recent vintage. Many other terms used to designate medicines are also the subject of disagreement. Hence, clarification of their connotations may help to contribute to their understanding and thereby promote the development of a rational nomenclature. Before embarking on an investigation of terms used to refer to complementary and alternative medicines, it is as well to consider the confusing welter of terms that have arisen to denote the medicine with respect to which they are considered complementary or alternative. Modern Western Biomedicine The medicine that is taught in medical colleges was, until recently, the absolutely dominant medicine in the West and beyond. Hence it was simply referred to as ‘medicine’. The word ‘medicine’ has been used to refer to numerous different forms of healing that have existed over the centuries. It derives from the Latin medicina, which is related to medico, ‘to heal’ or ‘cure’. The word ‘medicine’ thus essentially means the art of healing. It is only over recent centuries that ‘medicine’ has come to denote specifically the medicine that is based on a wide gamut of natural sciences with biology at its core, since biology explains the workings not only of the human body, but also the microorganisms that account for a large portion of human suffering. This medicine, by its seemingly incomparable achievements, has attained dominance not only its in Western homeland, but also beyond. Even though it is not necessarily the main provider of health care in every country, Western medicine is the arbiter of health matters for the government of virtually every nation of the world. Because of this, its right to be simply called ‘medicine’ was, for the greater part of the 20th century at least, almost uncontested. It was only in the final decades of the last century that dissatisfaction with this medicine caused certain sectors of the Western population to turn to alternative forms of medicine, giving rise to the need for a term by which to distinguish the dominant medicine from the alternatives. Unfortunately, not one, but many, terms denoting this body of medical knowledge have come into use. ‘Western medicine’ labels the medicine it denotes by its origin. It is commonly used particularly in contexts in which non-Western medicines such Chinese, Arabic and Ayurvedic medicine are discussed. Some consider ‘Western medicine’ inappropriate because this medicine is now used across the globe and because it has major contributors outside the West. ‘Modern medicine’ is arguably a good term since it denotes a body of medicine that although it has roots in antiquity, is most precisely definable by its scientific stringency, which is of comparatively recent origin. It is a term commonly used in contexts where an ancient medicine (e.g. Chinese medicine or Indian medicine) is also discussed. In , there is a strong schol