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Alberto Gobbi
João Espregueira-Mendes
John G. Lane
Mustafa Karahan
Editors
Bio-orthopaedics
A New Approach
Bio-orthopaedics
Alberto Gobbi • João Espregueira-Mendes
John G. Lane • Mustafa Karahan
Editors
Bio-orthopaedics
A New Approach
Editors
Alberto Gobbi John G. Lane
O.A.S.I. Bioresearch Foundation NPO Musculoskeletal and Joint Research
Milan Foundation
Italy San Diego
California
João Espregueira-Mendes USA
Clínica do Dragão, Espregueira-Mendes
Sports Centre – FIFA Medical Centre of Mustafa Karahan
Excellence Department of Orthopedics
Porto Acibadem University
Portugal Istanbul
Turkey
© ISAKOS 2017
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, express or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The ability of injured tissues to heal is the fundamental basis on which the
practice of surgery is predicated. As noted by Girdlestone and Hippocrates,
tissue healing is not guaranteed and is governed by a variety of local and
systemic factors. While advances in cellular and molecular biology over the
last two decades have significantly improved our understanding of the basic
biological processes involved in tissue healing, the ability to ensure, opti-
mize, or enhance this repair process in all tissues has not progressed at the
same rate.
Classically, the orthopedic surgeon’s control over tissue healing was often
limited to optimizing the biomechanical environment (i.e., reattaching a ten-
don, replacing a ligament, stabilizing a broken bone) and limiting additional
tissue damage. Mother Nature and the patient were then left to do the rest.
Confounding systemic factors such as diabetes, smoking, hypercholester-
emia, and age, as well as local factors (poor vascularity, tissue degeneration,
cell death, etc.) can hamper this healing response and lead to poor clinical
outcomes. Over the past several years, the orthopedic community has begun
to explore ways to enhance the biologic response of connective tissues in an
effort to optimize the repair process and improve clinical outcomes. These
advances have come in the form of cell-based therapies, cytokine-based ther-
apies, and scaffold-based therapies. This text, Bio-Orthopaedics: A New
Approach, provides an excellent snapshot of the current status of these thera-
pies in orthopedics.
Professor Alberto Gobbi has been a key figure in the evolution and clinical
application of biologics in orthopedics and sports medicine. As the editor of
Bio-Orthopaedics: A New Approach, Prof. Gobbi has gathered together a
stellar collection of clinicians and basic scientists to share their insight, expe-
rience, and expertise in the scientific rationale and clinical application of a
variety of innovative modalities designed to optimize connective tissue heal-
ing. The importance of a strong scientific foundation on which to predicate
the rationale of bio-orthopedics is skillfully put forth in the early chapters of
this text. This is followed by a balanced and comprehensive review of clinical
vii
viii Foreword
I would like to thank Jane Elizabeth Hayward for helping me in the process
of selection, editing, and keeping up the pressure on me, the co-editors, and
all the contributors of this book.
—Alberto Gobbi
I would like to thank all my research and development team which provided
a valuable help in the development of this book, to my co-editors which
supervised and organized the book contents, and to all the book’s contribu-
tors. With them, this book became a useful source of knowledge.
—Prof. Espregueira-Mendes
The guiding influence and direction of my mentor Prof. David Amiel and the
meticulous work of Frances Shepherd.
—John G. Lane
I had help from many of my students, residents, and fellows throughout the
preparation of the book. I especially want to thank Assoc. Prof. Sarper Gursu
and Dr. Ersin Erçin for their invaluable help.
—Mustafa Karahan
ix
Introductory Commentary
xi
xii Introductory Commentary
clearly documented that MSCs were derived from perivascular cells, peri-
cytes, which brought together a huge array of information that clearly indi-
cated that the in situ MSCs were derived from perivascular cells and did not
function as a multipotent progenitor in vivo. In fact, the detail that MSCs did
not arise from stroma (i.e., connective tissue) opened up new logics and
explanations for both the immunomodulatory and trophic capabilities of
these cells once they were reintroduced to injury sites [4]. These new facts
also caused an explosion of clinical trials that exploited these MSC properties
for use in a large spectrum of non-orthopedic clinical problems ranging from
GVHD, ALS, MS, diabetes, kidney transplantation, etc. We have recently
reviewed all of the new cellular and molecular information related to MSCs
and summarized much of it in a poster for Nature Protocols [5]. It follows
that some of the released molecules form biologic products that both release
the MSCs from their perivascular anchorages and stimulate and sustain their
control over regenerative activities.
Bone marrow has been used since the days of Aristotle to provide a boost
to bone reconstructions. The assumption is that there are osteo-progenitors
that add value and participate in bone formative and natural regenerative
events. There are such osteo-progenitors in bone marrow (see poster, [5]), but
it may be that the therapeutic capacity of marrow in skeletal reconstructive
events is due to the array of secreted molecules from both MSCs [6] and
hematopoietic progenitors in marrow since it has long been known that both
cell types have strong paracrine functionalities.
These paracrine capabilities and the actions of multiple secreted bioactive
molecules bring into focus the modern view of skeletal reconstruction events
with emphasis on both cells and the multitude of informational molecules
that are synthesized and organized at local regenerative tissue sites. These
bioactive factors are in, on, and outside of cells and in, on, and bound to the
extracellular matrix and released upon injury and trauma and as a natural
function of local microenvironment that these cells experience. Indeed, these
complex events described above are the bio of the bio-orthopedics and are the
basis of many of the chapters in this book. The bio is not new, but it is now a
key component in the practice of modern orthopedics. This book contains the
emphasis on bio-orthopedics and its central and timely discussion as a basis
for the new standard of care in orthopedics. The use of biologics in a variety
of injured skeletal tissues has been slow to start, but now appears to be the
time when these new materials and logics will be implemented. This book
has many chapters which focus on the new logics of biologic (BIO)
orthopedics.
References
1. Caplan AI. Adult mesenchymal stem cells: when, where, and how. Stem
Cells Int. 2015;2015:628767.
2. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641–50.
3. Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal
stem cells in multiple human organs. Cell Stem Cell. 2008;3:301–13.
4. Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol.
2009;217:318–24.
5. Somoza RA, Correa D, Caplan AI. Roles for mesenchymal stem cells as
medicinal signaling cells. Nat Protoc 2015; 11.
6. Meirelles Lda S, Fontes AM, Covas DT, et al. Mechanisms involved in the
therapeutic properties of mesenchymal stem cells. Cytokine Growth
Factor Rev. 2009;20:419–27.
Contents
Part I Overview
xv
xvi Contents
Part II Muscle
Part IV Ligaments
Part V Menisci
Part VI Bone
45 Orthokine���������������������������������������������������������������������������������������� 561
Ron Arbel
46 Joint Congruence Restoration in Osteochondral Defects:
The Use of Mesenchymal Stem Cells with the “Sandwich”
Technique���������������������������������������������������������������������������������������� 571
Boguslaw Sadlik and Mariusz Puszkarz
47 Biological Reconstruction in Patients with Osteochondral
Defects: Postoperative Management and MRI
Monitoring�������������������������������������������������������������������������������������� 587
Boguslaw Sadlik, Mariusz Puszkarz, and Adrian Blasiak
48 The Role of Biological Treatments in Spine Disorders�������������� 599
José Fábio Santos Duarte Lana, Edilson Silva Machado,
Renato Bender Castro, João Lopo Madureira Junior,
Paulo David Fortis Gusmão, Nivaldo Evangelista Teles,
Luiz Felipe Chaves Carvalho, João Paulo Bezerra Leite,
Bruno Tavares Rabello, and Ozório de Almeida Lira Neto
49 Cell Culture Methods�������������������������������������������������������������������� 619
Alain da Silva Morais, F. Raquel Maia, Rui L. Reis,
and Joaquim M. Oliveira
50 Evolving Perspectives in Orthobiologic Approaches
to Articular Cartilage Regeneration�������������������������������������������� 637
Lorenzo Brambilla, Celeste Scotti, Alberto Gobbi,
and Giuseppe M. Peretti
51 Comprehensive Approach to Patellofemoral Chondral
Lesion Treatments�������������������������������������������������������������������������� 651
Luiz Felipe Morlin Ambra, Andreas H. Gomoll,
Eildar Abyar, and Jack Farr
52 Partial Anterior Cruciate Ligament Lesions: A Biological
Approach to Repair ���������������������������������������������������������������������� 665
Graeme P. Whyte, Alberto Gobbi, and Dawid Szwedowski
53 Osteochondral Repair Using a Hybrid Implant
Composed of Stem Cells and Biomaterial ���������������������������������� 671
Kazunori Shimomura, Hiromichi Fujie, David A. Hart,
Hideki Yoshikawa, and Norimasa Nakamura
Index�������������������������������������������������������������������������������������������������������� 683
Part I
Overview
The Optimization of Natural
Healing
1
Christopher Rogers and Alberto Gobbi
Contents
1.1 Introduction
1.1 Introduction 3
1.2 The Phases of Tissue Healing 4 The doctor of the future will give no medicine, but
1.2.1 Hemostasis Phase 4 will interest his patients in the care of the human
1.2.2 Inflammation Phase 5 frame, in a proper diet, and in the cause and pre-
1.2.3 Proliferation Phase 5 vention of disease.
1.2.4 Remodeling Phase 5 —Thomas Edison (1847–1931)
1.3 Impaired Tissue Healing 6
Since Edison’s day, a mountain of scientific
1.4 actors That Contribute to Impaired
F evidence has been created that supports this asser-
Healing 7
tion. The benefits of a healthy diet, regular physi-
1.4.1 Obesity 7
1.4.2 Drugs 7 cal activity, and avoidance of substances known
to promote disease have essentially become com-
1.5 Factors That Improve Natural Healing 9
1.5.1 Sleep 9 mon knowledge. When it comes to using “natu-
1.5.2 Circadian Rhythms 10 ral” remedies for the treatment of musculoskeletal
1.5.3 Nutrition 11 conditions, there seems to be no shortage of rec-
1.5.4 Dietary Supplements 13 ommendations; however, many of these remedies
1.5.5 Physical Activity 15
1.5.6 Cognitive Control/Biofeedback 17 remain incompletely evaluated in the medical lit-
erature. These treatments do not always assure
Conclusion 17
safety or efficacy, simply because they are “natu-
References 17 ral.” Regenerative medicine physicians rely upon
the peer-reviewed medical literature for guidance
to maximize clinical outcomes.
Recent estimates conclude that the average
adult human is composed of 37.2 trillion cells [1]
and, perhaps, as many bacteria [2]. The word cell
derives from the Latin word cella, meaning “small
C. Rogers, M.D. room.” In 1665, Robert Hooke discovered and
San Diego Orthobiologics Medical Group, 6125 Paseo named them for their resemblance to monastery
Del Norte, Suite 100, Carlsbad, 92011 CA, USA
cells inhabited by Christian monks [3]. In these
A. Gobbi, M.D. (*) “small rooms,” all of the amazing properties of life
Orthopedic Arthroscopic Surgery International
are found. The cell serves such vital functions as
(O.A.S.I.) Bioresearch Foundation, Gobbi Onlus,
Milan, Italy energy production, protein synthesis, and the repair
e-mail: gobbi@cartilagedoctor.it of all the tissues of the musculoskeletal system.
© ISAKOS 2017 3
A. Gobbi et al. (eds.), Bio-orthopaedics, DOI 10.1007/978-3-662-54181-4_1
4 C. Rogers and A. Gobbi
The human body is in a continual state of Regenerative medicine is the clinical transla-
renewal. In the average adult, more than 1.1 mil- tion of cellular biology and tissue engineering to
lion new platelets and 2.4 million erythrocytes replace, rejuvenate, or regenerate human cells,
are produced every second [4, 5]. Bone and mus- tissues, and organs in order to restore normal
cle cells turnover at a much slower rate, but will function. This emerging field of medicine is
be completely replaced several times throughout changing the face of orthopedics at an ever-
an individual’s life span [6]. The viability of accelerating rate. Our expanding knowledge of
these cells, and therefore our health, is influenced cellular biology, human genetics, and tissue engi-
by the activities we do daily and the environment neering and the clinical translation of this new
in which we do those activities. Behaviors that understanding will likely continue to evolve for
optimize health will naturally lead to optimal the foreseeable future. As clinicians and scien-
healing. Optimizing healing is therefore nothing tists, we and our patients will have an increasing
more than the facilitation of optimizing one’s number of treatment options to consider as we
overall health. strive to eliminate musculoskeletal pain and dys-
In the clinical context, healing can manifest in function. With cellular-based therapy, patients
three forms: “healing better,” “feeling better,” and may finally be relieved of having to deal better or
“dealing better.” Healing in the truest sense merely feel better and will be enabled to actually
implies that injured, degenerated, or diseased tis- heal better. Regenerative medicine holds great
sue is repaired and normal function is restored. promise and has already begun to deliver on that
However, very little effort extended in current promise.
medical practice achieves this high standard. Up
until recently, complete tissue healing either
occurs naturally or not at all. Corticosteroid injec- 1.2 The Phases of Tissue Healing
tions for the treatment of chronic inflammation,
analgesics for unresolving pain, and even surgical Healing is the process whereby tissues repair them-
repair of damaged tendons or joints often provide selves in response to disease or trauma. Tissue
only temporary relief and rarely restore normal healing is a dynamic process involving the coordi-
tissue function [7–9]. Yet, these treatment options nated actions of both resident and migratory cells
have remained the standard of care in orthopedics within the extracellular matrix leading to the repair
for decades. For many patients, simply achieving of injured tissues. The healing process is not only
relief of their symptoms is sufficient. They simply complex but also fragile, and it is susceptible to
wish to feel better. They understand the limita- interruption or failure leading to chronic nonheal-
tions of medical care and are often content with a ing tissue that may cause pain or loss of function.
quick fix to alleviate symptoms. Factors contributing to incomplete healing include
In cases where all efforts have failed to alleviate diabetes, arterial disease, infection, and metabolic
symptoms, patients are offered pain management deficiencies [10]. The tissue healing process can be
which may include supportive counseling, behav- divided into four distinct phases: hemostasis,
ioral modification, and education. There is no inflammation, proliferation, and remodeling.
doubt that these efforts have enabled patients to
better cope with their otherwise unmanageable
condition. Oftentimes, simply educating the 1.2.1 Hemostasis Phase
patient and taking time to listen to their concerns
will result in a therapeutic benefit. Empowering In the hemostasis phase, platelets in the blood
the patient to control emotional responses and become activated and adhere to the injured site
enhancing cognitive awareness and the impact that within minutes following injury. Injured vessels
the environment has on their symptoms can allow constrict and the coagulation cascade is activated
these benefits to be maintained over long periods limiting blood loss. Platelets release cytokines to
of time [10]. promote clotting by the activation of fibrin, which
1 The Optimization of Natural Healing 5
exogenous sources of free radicals which include related quality of life scores and better function
ionizing radiation, lead, pesticides, cadmium, alco- scores. Regardless of which etiological factors
hol, cigarette smoke, ultraviolet light, asbestos, have the greatest effect on knee osteoarthritis, a
automobile exhaust, microwave radiation, and air reduction in excess body weight is the primary
pollution from fires or volcanic activity [30, 31]. risk factor that can be modified to reduce knee
Oxygen-derived free radical reactions have been osteoarthritis pain [34, 48].
associated with several diseases including
Alzheimer’s disease, Parkinson’s disease, multiple
sclerosis, amyotrophic lateral sclerosis, atheroscle- 1.4.2 Drugs
rosis, hypertension, ischemic heart disease,
asthma, chronic obstructive pulmonary disease, More than one billion people worldwide smoke
rheumatoid arthritis, renal failure, and lung, breast, tobacco products. Smoking is the leading cause
and hematologic cancers [32, 33]. of preventable death and causes 480,000 deaths
each year in the United States alone [49]. The US
Department of Health and Human Services
1.4 Factors That Contribute reports that cigarettes contain at least 250 chemi-
to Impaired Healing cals known to be harmful in humans, including
hydrogen cyanide, carbon monoxide, and ammo-
1.4.1 Obesity nia. Among the known harmful chemicals, at
least 69 can cause cancer [49, 50].
Excess body weight is the primary modifiable Nicotine, present in all tobacco products, is
factor influencing the development of knee osteo- addictive and reduces cutaneous blood flow by
arthritis [34, 35]. Knee pain from osteoarthritis vasoconstriction, stimulates release of proteases
correlates strongly with body mass index (BMI) that may accelerate tissue destruction, suppresses
in studies performed all over the world [36–44]. the immune response, and leads to an increased
Knee osteoarthritis occurs about seven times risk of infection [51]. Almost every clinical study
more frequently in obese individuals than in non- on the effects of smoking in patients undergoing
obese individuals [45]. Garver et al. found that orthopedic surgery for cartilage or ligament inju-
individuals in the highest BMI class had signifi- ries demonstrates negative outcomes in patients
cantly more pain and poorer function than those who smoke [52]. In patients undergoing rotator
with lower BMIs, even after controlling for cuff repair, there is decreased tendon repair quality,
radiographic osteoarthritis severity [46]. decreased biomechanics, poorer clinical outcomes,
Increasing low-level activity, especially and impaired healing of small to medium tears as
among inactive individuals, alleviates knee pain assessed by magnetic resonance imaging in
and reduces the risk of disability from knee patients who smoke [53]. In cases of fracture heal-
osteoarthritis [34]. Randomized controlled trials ing, smoking tobacco is a contributory factor in
show that exercise is safe and effective for over- delayed unions and prolonged healing times [54].
weight and obese adults with osteoarthritis [47]. Smoking cessation is the single most effective
Messier et al. [48] studied the effects of knee intervention to improve healing. Heart rate, blood
pain and body weight reduction by diet, with or pressure, carbon monoxide levels, oxygenation, and
without exercise in 399 older adults (>55 years) blood circulation can normalize within a few weeks
with knee osteoarthritis and body mass index of of quitting. Smoking cessation restores the tissue
27–41. After 18 months, lean weight loss was microenvironment rapidly and the inflammatory
11.4% for the diet/exercise group, 9.5% for the cellular functions within 4 weeks, but the prolifera-
diet-alone group, and 2% for the exercise group. tive response remains impaired [51]. Smoking ces-
Pain levels and IL-6 serum concentrations were sation just 4 weeks prior to surgery can significantly
lower in the diet/exercise group when compared reduce complication rates [55]. Long-term effects
with the diet-alone or exercise-alone groups. The of quitting include decreased risk of cancer, heart
diet/exercise group also had better physical health- disease, and pulmonary disease [56]. Assistance for
8 C. Rogers and A. Gobbi
patients who choose to quit smoking can be found failed to induce chondrotoxicity in low-dose
at the National Cancer Institute’s quit line, exposures [68].
1-800-QUIT-NOW (www.smokefree.gov). Clinical trials in humans do not demonstrate
Alcohol is one of the most widely used drugs adverse effects in patients receiving a single-dose
in the world. The Substance Abuse and Mental steroid injection following surgery [69]. And a
Health Services Administration reported rates of review of the human literature found that high-
alcoholism are as high as 10% in the North dose corticosteroid administration for less than 10
American population. Alcohol is a central ner- days has no clinically important effect on wound
vous system depressant with wide-ranging and healing, but in patients taking chronic corticoste-
detrimental systemic effects [57]. Increased insu- roids for at least 30 days before surgery, wound
lin resistance and higher serum sugar levels with complication rates are increased up to five times
alcohol consumption impair healing [58]. [64]. Further studies are required to determine the
Chronic alcohol abuse is associated with a effects of a single-dose steroid injection versus
high risk of malnutrition which results in prolonged steroid use on healing in patients receiv-
decreased inflammatory and immune responses ing regenerative medicine therapies.
to tissue injury, decreased fibroblast migration, Nonsteroidal anti-inflammatory drugs
angiogenesis, and decreased type I collagen pro- (NSAIDs) are commonly used for their analgesic
duction [59]. Alcohol also reduces bone quality and anti-inflammatory effects. Cyclooxygenases
and delays fracture repairs [60, 61]. (COX-1 and COX-2) catalyze the conversion of
Glucocorticosteroids, including prednisone and arachidonic acid to prostaglandins which plays a
dexamethasone, have been used to treat inflamma- significant role in normal bone healing, osteo-
tion in rheumatoid and osteoarthritis since 1951. clastic activity, bone formation, and angiogenesis
However, long-term use can delay healing by [70]. These drugs have been hypothesized to
interfering with inflammation, fibroblast prolifera- affect the healing process of bone fractures and
tion, collagen synthesis and degradation, deposi- orthopedic surgical sites. Nonsteroidal anti-
tion of connective tissue ground substances, inflammatory drugs (NSAIDs) have been shown
angiogenesis, wound contraction, and re-epitheli- to have a depressant effect on wound healing
alization [62]. Subcutaneous injection of dexa- while simultaneously decreasing the granulocytic
methasone strongly interferes with both the inflammatory reaction [71]. NSAIDs have an
synthesis and degradation of type I collagen and antiproliferative effect on blood vessels and skin,
type III collagen [63]. Animal studies show a 30% thereby delaying wound healing rates [72].
reduction in wound tensile strength with perioper- The role of NSAIDs in orthopedics remains
ative corticosteroids at 15–40 mg/kg/day [64]. controversial because of unclear effects on heal-
Local administration of glucocorticoid has sig- ing [73]. Delayed fracture healing and spinal
nificant negative effects on tendon cells in vitro, fusion inhibition have been described in associa-
including reduced cell viability, cell proliferation, tion with traditional NSAID use [74–77]. Several
and collagen synthesis. The mechanical properties experimental models of bone, ligament, and ten-
of tendon are also significantly reduced [65]. don repair have assessed the effects of these
Corticosteroid injections inhibit collagen tendon drugs in animals with variable outcomes [78].
repair and are a predictor of future tendon tear [66]. Celecoxib, a COX-2-specific NSAID, and indo-
Long-term use or high-dose intra-articular methacin significantly inhibit tendon-to-bone
administration of glucocorticosteroids may also healing in a rat model [79]. However, in a recent
induce apoptosis in chondrocytes impairing carti- review of the literature, the short-term use of low-
lage homeostasis [67]. Increased chondrocyte dose NSAIDs and COX-2 inhibitors did not
autophagy has been described as an adaptive appear to have a detrimental effect following soft
response to protect chondrocytes from short-term tissue injuries [73]. Most studies on the effects of
glucocorticosteroid exposure, whereas prolonged NSAIDs on healing have been completed in ani-
exposure decreases autophagy and increases apop- mal models making it difficult to translate these
tosis in vitro [67]. Yet, in vitro dexamethasone has results to the clinical setting.
1 The Optimization of Natural Healing 9
associated with poor quality sleep, increased 4. Take a hot bath less than 3 h before bedtime.
sleep latency, predominance of light slow-wave The core body temperature drops after a hot
sleep, diminution of deep slow-wave sleep, and bath and signals that it is time to sleep.
a reduction in rapid eye movement (REM) 5. After a hot bath, spend 10 min stretching or
sleep [101]. Shorter sleep time is associated massaging muscles to minimize the likeli-
with higher levels of the inflammatory markers hood of pain that triggers awakenings.
interleukin 6 (IL-6) and C-reactive protein 6. Avoid watching TV or using a computer at
[102]. The highest elevations are found in least an hour before going to bed. These
patients with sleep apnea and high body mass devices emit blue light reducing the produc-
index (BMI) [103]. Magnesium supplementa- tion of melatonin and can disrupt circadian
tion has demonstrated improved sleep quality rhythms, affecting cell cycle regulation and
in adults older than 51 years of age [104]. metabolism. In addition, modern television
The NIH recommended daily allowance rarely offers content conducive to a good
(RDA) of magnesium is 420 and 320 mg for men night’s sleep.
and women older than 50 years of age, respec- 7. Install low-wattage yellow, orange, or red
tively. It is estimated that 38% of adults have light bulbs for a light source to navigate at
daily magnesium intakes less than the recom- night. These wavelengths do not impair mel-
mended allowance [105]. Magnesium deficiency atonin production to the same degree as blue
is considered when serum magnesium concen- light.
trations are lower than 0.75 mmol/L. Patients 8. Sleep in complete darkness, cover the win-
with malabsorption (Crohn’s, celiac disease, his- dows with drapes, or wear an eye mask.
tory of intestine surgery), type 2 diabetes, Light controls melatonin production in the
chronic alcoholism, and renal disease or those pineal gland, and even a small amount of
taking diuretics are at increased risk of magne- light from a clock radio can interfere with
sium deficiency. Green leafy vegetables, nuts, sleep.
legumes, and whole grains are rich sources of 9. Maintain bedroom temperature to less than
magnesium. Dietary supplementation with mag- 70 °F (21 °C). The optimal room tempera-
nesium glycinate 300 mg is preferred to other ture for sleep is between 60 and 68 °F
forms of supplemental magnesium due to (15.5–20 °C).
increased bioavailability and reduced risk of 10. Move all electronics away from the bed at
side effects. Magnesium overdose can result in night. Electromagnetic fields found in elec-
diarrhea, hypotension, lethargy, confusion, and tronic devices such as a computer or router
cardiac rhythm abnormalities. can disrupt the pineal gland and its melato-
Sleep hygiene education is a safe and cost- nin production.
effective method for managing sleep disturbance. 11. Avoid using loud alarm clocks and, if possi-
Patients suffering from sleep disturbance should ble, do not use them at all.
be given the following advices: 12. If you find that your mind is racing, consider
writing your ideas down on a notepad or
1. Get 10–15 min of morning sunlight each day. even spend a few minutes attending to the
The circadian system needs bright light to issue of concern.
reset itself. More sunlight exposure is
required as you age.
2. Get a daily dose of bright sun exposure during 1.5.2 Circadian Rhythms
the day to optimize melatonin production.
3. Avoid drinking caffeinated beverages several These are essentially endogenous physiological
hours before bedtime. Some people do not oscillations occurring at 24-h interval. These
metabolize caffeine properly and should rhythms are maintained by circadian clocks
avoid caffeine altogether. which are located in every functional cell type,
1 The Optimization of Natural Healing 11
including the immune system. The immune sys- thritic cartilage. [115]. In tissue cultures of carti-
tem and its regulation play a vital role in tissue lage explants, nitrotyrosine staining, chondrocyte
healing, and disorders of immune system have a telomere length, and glycosaminoglycans (GAG)
direct effect on efficacy of tissue healing. Most remaining in the cartilage tissue were decreased
immune cells through their expression of circa- in cartilage exposed to reactive oxygen species
dian clock genes display profound impacts on (ROS). However, in cartilage treated with the
cellular functions, including a daily rhythm in the anti-oxidative, ascorbic acid, a tendency to main-
synthesis and release of cytokines, chemokines, tain chondrocyte telomere length and proteogly-
and cytolytic factors [106]. can was seen in the cartilage explants, suggesting
Alteration of circadian rhythms through clock that oxidative stress induces chondrocyte telo-
gene mutation in many animal studies has shown mere instability and catabolic changes in carti-
altered immune response states [106]. A rat model lage matrix structure and composition [115].
study has shown that rats with circadian rhythm Increased reactive oxygen species (ROS)
disorder showed poor collagen synthesis and inhibit mesenchymal stem cell (MSC) prolifera-
impaired effect of interleukin (IL)-1, IL-6, trans- tion, increase senescence, enhance adipogenic
forming growth factor α, and stress hormones on differentiation, reduce osteogenic differentiation,
fibroblasts [107]. A recent molecular level study and inhibit MSC immunomodulation [116, 117].
has also shown that cardiac neutrophil oscilla- Furthermore, oxidative stress reduces their
tions have a direct effect on myocardial infarct ex vivo expansion capabilities [117]. MSCs may
size and healing [108]. Melatonin, a key hormone have low innate antioxidant activity and are more
promoting circadian rhythm, has shown to have a sensitive to oxidative stress compared to more
direct effect on skin wound healing in a mouse differentiated cell types [118, 119].
model. This mouse model study found transplan- Antioxidants are substances capable of scav-
tation of umbilical cord blood (UCB)-MSCs pre- enging free radicals and preventing cellular dam-
treated with melatonin-enhanced wound closure, age. Increased consumption of whole foods such
granulation, and re- epithelialization at mouse as fruits and vegetables containing natural anti-
skin wound sites [109]. oxidants may offer health benefits [120, 121].
In the present era, circadian rhythm disorder Nonenzymatic antioxidants are classified as
influences healing in people who travel great dis- metabolic or nutrient antioxidants. Metabolic
tances across the globe and in athletes or workers antioxidants are produced by endogenous cellu-
who are subjected to work night shifts. Further lar metabolism and include coenzyme Q10, mel-
research in the area of human chronobiology can atonin, uric acid, bilirubin, l-arginine, transferrin,
help in better understanding of the role of circa- and glutathione.
dian rhythm and its influence on tissue healing in Nutrient antioxidants are provided in the diet
humans. and include selenium, manganese, zinc, flavo-
noids, vitamins E and C, and omega-3 and
omega-6 fatty acids. The oxygen radical
1.5.3 Nutrition absorbance capacity (ORAC) assay measures the
degree of inhibition of peroxy-radical-induced
The development of various chronic and degen- oxidation by nutrient antioxidants. A review of
erative diseases, such as cancer [110], heart dis- the antioxidant activity in 326 selected foods
ease [111], and neuronal degeneration [112, 113], reveals high activity in many fruits, vegetables,
may be attributed to oxidative stress. Oxidative herbs, and spices [122]. Foods with higher ORAC
stress has also been implicated in the process of values include blueberries, raspberries, strawber-
aging [114] and in the pathogenesis of osteoar- ries, cranberries, blackberries, apples, pears, cit-
thritis [115]. Oxidative stress induces telomere rus fruits, gooseberries, figs, onions, broccoli,
genomic instability, replicative senescence, and artichokes, eggplant, asparagus, garlic, thyme,
dysfunction of chondrocytes in human osteoar- oregano, basil, peppermint, black pepper, ginger,
12 C. Rogers and A. Gobbi
cinnamon, curry powder, cumin, paprika, pea- almost every cell in the body. Vitamin D supple-
nuts, almonds, pecans, walnuts, pistachios, mentation also significantly inhibits human mes-
beans, and peas. enchymal stem cell (MSC) apoptosis and delays
Nutritional deficiencies have been long recog- the development of replicative senescence in
nized as an indicator of poor health. Patients with long-term cultures [125].
decreased albumin or zinc levels demonstrate The optimal serum level is controversial and
delayed healing and greater incidence of compli- has been reported from 25 to 80 ng/mL with defi-
cations following orthopedic surgery. Greene ciency defined as less than 30 ng/mL [126]. By
reported that patients with albumin level less than this standard, nearly 90% of healthy US adults
3.5 g/dL showed a sevenfold increase in the risk are vitamin D deficient [127]. The prevalence of
of major wound complications following hip or vitamin D insufficiency has been measured in
knee arthroplasty [123]. Low albumin levels may 52.3% of sports medicine patients and 66.1% of
be due to kidney or liver disease, poor nutrient trauma patients [128].
absorption, or low protein diets. After total hip arthroplasty, patients with vita-
Decreased protein intake can negatively min D deficiency have lower postoperative Harris
impact healing due to decreased collagen produc- hip scores [129]. Up to 83% of chronic lower
tion, angiogenesis, and fibroblast proliferation. back patients have abnormally low vitamin D
The essential amino acids histidine, isoleucine, levels, and clinical improvement is seen with
leucine, lysine, methionine, phenylalanine, tyro- vitamin D supplementation [130]. Vitamin D
sine, threonine, tryptophan, and valine are not insufficiency also plays a critical role in children
produced in the body and are only supplied by undergoing hematopoietic stem cell transplanta-
the diet. They serve as enzymes, hormones, cyto- tion for malignancy. Hansson et al. demonstrated
kines, growth factors, and components of anti- a more rapid increase in neutrophil granulocyte
bodies. Inadequate protein intake impedes both levels, decreased rejection, and increased sur-
tissue maintenance and healing. Insufficient pro- vival rates in children who were vitamin D suffi-
tein intake can be assessed utilizing serum albu- cient [131].
min, pre-albumin, or total lymphocyte count. The Vitamin D is synthesized from 7-dehydro
recommended daily allowance for protein in cholesterol in the skin through exposure to sun-
healthy adults more than 20 years of age is 80 mg light. Many individuals do not get enough sunlight
per kg of body weight. Malnourished patients exposure, and those living in colder climates are
may require up to 1.5 g per kg of body weight at even greater risk for vitamin D deficiency.
[59]. Excellent sources of digestible protein Therefore, vitamin D supplementation is recom-
include eggs, milk, cheese, meat, fish, rice, mended for most adults. Singh et al. studied the
wheat, oatmeal, peanut butter, and beans. effect of vitamin D supplementation on serum
Zorrilla demonstrated that patients with zinc vitamin D levels. They noted serum concentra-
levels less than 95 μg/dL had almost 12-fold tions are influenced by age, body mass index
increased risk for wound complications in (BMI), and serum albumin concentration [132].
patients undergoing hip hemiarthroplasty for They recommend 5000 IU/day for 3 months to
fracture [124]. The daily recommended dose for correct vitamin D deficiency. After 3 months,
zinc is 11 and 8 mg/day in men and women older they advise repeating the vitamin D serum con-
than 50 years, respectively. Good sources of zinc centration test. Once the deficiency has been cor-
include meats, seafood, milk, cheese, nuts, rected, a maintenance dose of 2000 IU/day is
legumes, and whole grains. recommended.
The active form of vitamin D, 1,25-dihydroxy- Vitamin C (l-ascorbic acid) is an essential
vitamin D3, is essential for normal bone growth, water-soluble vitamin required for the biosynthe-
maintenance, and repair. It is probably essential sis of collagen, protein metabolism, and wound
for the health of most nonskeletal tissues as well healing. It is also an important antioxidant shown
as the vitamin D receptor has been identified on to regenerate antioxidants in the body, including
1 The Optimization of Natural Healing 13
vitamin E (alpha-tocopherol) [133]. Good reduce pain although a high level of between trial
sources of vitamin C include citrus fruits, toma- inconsistency was observed. The single most
toes, potatoes, peppers, broccoli, strawberries, important explanation was product brand. Twelve
Brussel sprouts, and cantaloupe. When neces- trials using the Rottapharm/Madaus product
sary, vitamin C supplementation of 1 g/day is resulted in significant pain reduction although a
recommended. At doses above 1 g/day, absorp- sensitivity analysis showed less promising
tion falls to less than 50%, and unmetabolized results.
ascorbic acid is excreted in the urine [133]. Each A large National Institutes of Health (NIH)
vitamin and mineral has a specific role to play in study compared glucosamine hydrochloride,
health, and once sufficient amounts of that nutri- chondroitin, both supplements together, cele-
ent to perform those roles are obtained, there is coxib, or a placebo in patients with mild knee
no benefit to consume more. osteoarthritis. Those who received the celecoxib
Manganese, vitamin B6 (pyridoxine), and had better short-term pain relief at 6 months than
vitamin E (alpha-tocopherol) are also linked to those who received the placebo. Those who
good tendon health; however, deficiency of these received glucosamine and chondroitin supple-
nutrients in well-nourished individuals is exceed- ments did not receive significant improvement in
ingly rare. These essential nutrients are found in knee pain or function, although the investigators
seafoods, nuts, whole wheat, seeds, tofu, chicken, saw evidence of improvement in a small subgroup
turkey, and green leafy vegetables. of patients with moderate-to-severe pain who
took glucosamine and chondroitin together [137,
138]. The American College of Rheumatology
1.5.4 Dietary Supplements indicates that there is insufficient evidence of effi-
cacy and does not recommend glucosamine or
The term “nutraceutical” was derived from the chondroitin sulfate for patients with hand, hip, or
words “nutrition” and “pharmaceutical” and is knee osteoarthritis [139].
defined as a food that offers health benefits [134]. Fusini et al. performed a critical review of nutra-
The term, however, is not recognized by the US ceutical supplements in the management of tendi-
Food and Drug Administration (FDA) which uses nopathy [140]. They concluded that results were
the term “dietary supplement” instead. The FDA encouraging but were unable to confirm a benefit
states that supplements are not intended to treat, from glucosamine, chondroitin sulfate, vitamin C,
diagnose, prevent, or cure diseases. Therefore, type I collagen, arginine alpha-ketoglutarate, bro-
companies that produce them cannot make health melain, curcumin, boswellic acid, or methylsulfo-
claims. nyl-methane (MSM). Numerous supplements have
Despite strong evidence of the health benefits been proposed to reduce chronic inflammation
of consuming a diet rich in whole fruits, vegeta- associated with joint diseases such as osteoarthritis
bles, whole grains, and lean protein, there is little and rheumatoid arthritis. In a review by Ghasemian
evidence for the multitude of dietary supplements et al., ginger, rosemary, borage, Boswellia serrata,
offered to patients with orthopedic injuries. and urtica dioica (stinging nettle) have demon-
Despite this fact, approximately 62.5% of adults strated preclinical or clinical evidence of efficacy
with arthritis reported taking at least one dietary and safety [141].
supplement. Glucosamine and chondroitin sul- Osteoarthritis is a multifactorial process that
fate are the most common supplements used by includes articular cartilage catabolism, synovial
patients with osteoarthritis [135]. tissue inflammation, and subchondral bone resorp-
Eriksen et al. performed a systematic review tion. These pathological changes are associated
and stratified meta-analysis of randomized with an excessive production of pro-inflammatory
placebo-controlled trials on the efficacy of glu- molecules such as interleukin 1-β (IL-β) and tumor
cosamine in the treatment of painful arthritis necrosis factor alpha (TNF-α). A review of current
[136]. Glucosamine was shown to moderately nutraceuticals in the management of osteoarthritis
14 C. Rogers and A. Gobbi
summarized the biologic effects of several nutra- thromboxane A2 and modulation of immune cell
ceuticals consumed by patients [142]. surface adhesion molecules [155]. Phlogenzym
Pomegranate juice (Punica granatum) has (which contains 90 mg bromelain, trypsin, and
strong antioxidant properties due to their high rutin) is compared favorably to diclofenac 100–
content of hydrolyzable tannin and anthocyanins, 150 mg by reducing pain 80% in patients with
a polyphenolic compound that exhibits antioxi- knee osteoarthritis during a 4-week trial [156].
dant and anti-inflammatory capabilities. In osteo- No serious adverse events were reported.
arthritic chondrocytes, pomegranate fruit extract Phlogenzym (which contains 540 mg bromelain)
(PFE) has been shown to suppress COX-2 showed significantly better pain relief in patients
enzyme activity and IL-1β-induced prostaglandin with moderate-to-severe knee osteoarthritis than
E2 (PGE2) and nitric oxide (NO) production diclofenac 100–150 mg during a 12-week trial
[143]. Interleukin 1-β (IL-1β)-induced expres- [157]. Again, no serious adverse events were
sion of matrix metalloproteinase (MMP)-1, noted. Although bromelain has demonstrated
MMP-3, and MMP-13 has been reduced by PFE clinical efficacy, the optimum dosage remains
in osteoarthritic chondrocytes as well [144]. unclear.
Clinical studies of PFE efficacy in treating OA Cat’s claw (Uncaria tomentosa and Uncaria
inflammation have not yet been performed. guianensis) is a vine found near the Amazon
Green tea (Camellia sinensis) contains cate- River with anti-inflammatory properties. U.
chins which have demonstrated anticancer, anti- tomentosa inhibits COX-1 and COX-2, TNF-α,
inflammatory, antibacterial, and neuroprotective PGE2, nitric oxide production, and lipopolysac-
effects [142]. In particular, epigallocatechin-3- charide (LPS)-induced iNOS gene expression
gallate (EGCG) decreases reactive oxygen spe- [158, 159]. Pain with daily activities due to
cies (ROS)-mediated cytotoxicity in human Kellgren–Lawrence grade 2–3 knee osteoarthritis
chondrocytes [145]. Several inflammatory medi- was significantly reduced in a 4-week placebo-
ators of inflammatory joint disease are inhibited controlled trial of cat’s claw bark extract; how-
by EGCG as well including IL-1β, TNF-α, IL-6, ever, night pain was not improved [160].
nitric oxide, and PGE2 in human chondrocytes Devil’s claw (Harpagophytum procumbens) is
[146, 147]. Encouraging evidence from in vitro a desert plant found in southern Africa which
and animal studies demonstrates the potential claims benefits for digestion and joint and lower
anti-inflammatory and antiarthritic effects of back pain. A dose-dependent analgesic and anti-
green tea; however, controlled clinical trials have inflammatory effect have been demonstrated in
not yet been completed. rats [161]. Devil’s claw inhibits PGE2 produc-
Frankincense oil is an aromatic resin obtained tion, TNF-α, IL-1β, IL-6, MMPs, and nitric oxide
from trees of the genus Boswellia. Boswellia ser- [162–164]. Significant pain relief has been
rata (B. serrata) in vitro has been reported to achieved with harpagoside 360 mg daily [165],
inhibit leukotriene biosynthesis [148], collagen harpagoside 57 mg daily [166], and harpagoside
IV and elastin hydrolysis [149], IL-1β-induced 100 mg daily [167] when compared to placebo in
cartilage matrix breakdown, and nuclear factor patients with osteoarthritis or nonspecific lower
kappa β (NFKB) in human chondrocytes [150]. back pain.
Pain reduction, swelling, and disability have been Turmeric (Curcuma longa) comes from the
demonstrated in human clinical trials using a her- C. longa root and contains curcuminoids (cur-
bomineral formulation containing B. serrata cumin, demethoxycurcumin, bis-demethoxycur-
[151, 152], B. serrata extract with Aflapin or cumin) which are natural polyphenols with strong
Laxin [153], or B. serrata 1000 mg daily [154] antioxidant capacity. A randomized double-blind
when compared with placebo. placebo-controlled trial investigated the ability of
Bromelain is derived from the pineapple curcuminoids to reduce systemic oxidative bur-
plant stems and immature fruit. Bromelain influ- den in patients suffering from knee osteoarthritis
ences inflammation by decreasing PGE2 and [168]. Forty mild-to-moderate knee osteoarthritis
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The theatre was a large barn-like structure; and it was filled with an
audience who sat in its boxes, or small, square divisions marked off
by narrow boards, where they arranged themselves for the most part
as they were assorted by domestic or friendly ties. Although they
obviously kept fully aware of what was going on upon the stage, and
at times seemed to look and to listen intently, or to break forth into
irrepressible applause, the most exciting scenes did not appear
greatly to interrupt their incessant smoking and indulgence in various
kinds of cheap drinks and eatables. Incessant tea-drinking went on
as a matter of course.
The principal play on this occasion celebrated the daring and
unflinching loyalty of a confidential servant to his Samurai master.
The purposes of the master were by no means wholly honourable as
judged by our Western standards of morals; and the means
contrived by the servant for carrying out these purposes were
distinctly less so. Especially was this true of the heartless and base
way in which the servant, in furtherance of his master’s interests,
treated the daughter of his master’s enemy, who had trusted him
with her love and her honour. I am sure that for this sort of behaviour
the rascal would have been hissed off the stage of even the lowest
of the Bowery theatres. But when he was detected and caught by the
father of the girl, the servant who was so despicably base toward
others, remained still so splendidly loyal to his master, that the
climax of the entire drama was reached and successfully passed in a
way to astonish and disgust the average audience in Western and
Christian lands. For he cheerfully bares his neck and, kneeling,
stretches it out to catch fully the blow of the father’s sword,—
protesting that he esteems it an honour and a joy to die in this
honourable manner for his lord and master. So impressed, however,
is the would-be executioner with the rascal’s splendid exhibition of
the noblest of all the virtues, that he raises the betrayer of his
daughter from his knees, pardons him, praises him unstintedly for his
honourable excellence, makes peace with the servant’s master, and
gladly bestows upon the servant his own beloved daughter in
honourable marriage.
As I have already said, it was undoubtedly the influence of such
dramas which helped to keep alive the extreme and distorted views
of the supreme excellence of loyalty as a virtue, in the narrower
significance of the terms, that went far toward securing the
remarkable character for self-sacrificing courage and endurance of
the Japanese private soldier during the late war with Russia. It would
not be fair, however, to infer from this, or other similar experiences,
the inferiority of the Japanese as a race in either ethical maxims or
moral practice. For, has not an extravagant and perverted
conception of the Christian virtue of “love” served in Occidental lands
to obscure and overshadow the even more fundamental virtues of
courage, endurance, and a certain necessary and divine sternness
of justice? And, with all its restrictions and deficiencies, the
Japanese Bushidō has hitherto resisted the temptations to avarice
and a selfish indulgence in luxury, on the whole, rather better than
anything which these Western nations have been able to make
effective in its stead. But when Japan gets as far away from the
Knightly spirit of Feudalism as we have for a long time been, its
moral doctrines and practices of the older period are likely to
undergo changes equally notable with those which have taken place
in Europe since feudal times prevailed there.
It was not until my second visit, in 1899, that I enjoyed the
opportunity of seeing Japan’s then most celebrated actor, Ichikawa
Danjuro. “Danjuro” is the name of a family that has been eminent in
the line of histrionic ability for nine or ten generations. Ichikawa, of
that name, was especially remarkable for combining the several
kinds of excellence demanded of the actor by Japanese dramatic art.
He had very uncommon histrionic power; even down to his old age
he was able almost equally well to take all kinds of parts, including
those of women and boys; and he had “marvellous agility as a
dancer.” As respects his ideals and characteristic style—making due
allowance for the wide differences in language and in the traditions
and requirements of the stage in the two countries—Danjuro has
been called “The Irving of Japan,” not altogether unaptly.
On this occasion I had not my usual good fortune of being in the
company of an intelligent and ready interpreter, who could follow
faithfully and sympathetically, but critically, every detail of the
scenery and the wording of the plays, as well as of the performance
of the actors. But the two of the three plays in which Danjuro took
part, between the rising of the curtain at eleven o’clock and our
departure from the theatre at about four in the afternoon, were quite
sufficient to impress me with the high quality of his acting. I need
scarcely say that he gave me that impression of reserve power and
of naturalness which only the greatest of artists can make. But,
indeed, reserve, and the suggestiveness which goes with it and is so
greatly intensified by it, is a chief characteristic of all the best works
of every kind of Oriental art.
It was a still different exhibition of Japanese histrionic skill which I
witnessed on the afternoon and evening of October 15, 1906. In the
most fashionable theatre of Tokyo a Japanese paraphrase of
Sardou’s “La Patrie” was being given by native actors. It was in
every way a most ambitious and even daring attempt to adopt
outright rather than to adapt, foreign dramatic models, in all their
elaborate details. How far would it be—indeed, how far could it be—
successful? I could see and judge for myself; since I was to have the
best of interpreters. The advertised time for the rising of the curtain
was five o’clock; but the actual time was a full half-hour later. The
entire performance lasted for somewhat more than five hours. The
scenery and stage settings were excellent. The scene of the meeting
of the Prince of Orange and the Count of Flanders in the woods by
moonlight was as artistically charming and beautiful a picture as
could be set upon the stage anywhere in the world. Much of the
acting, considering the difficulty of translating the motifs and the
language, was fairly creditable; but the Japanese have yet a great
deal to learn before they can acquire the best Western and modern
style of the dramatic art. Indeed, why should they try? The stilted
stage-manners of their own actors in the past, and the extravagance
of posturing and gesturing for the expression of strong emotions, still
hamper them greatly in this effort. Why then should they spend time
and money on the attempt at this reproduction of foreign models,
rather than in the reproduction and development of the best of their
own dramatic art? Certainly, artistic success in such an endeavour,
even if it could easily be attained, could not have the same influence
upon the conservation of the national virtues which have
distinguished their past that might reasonably be hoped for by a
more strictly conservative course. As a piece of acting the attempt to
reproduce the French play was a failure. The performance of the
drama was followed by a very clever farce called “The Modern
Othello,” which was written by a business man of Tokyo, a friend of
our host on this occasion.
For witnessing the latest developments of the highest-class dramatic
art of Japan, it was a rare opportunity which was afforded by a series
of performances lasting through an entire fortnight in November of
1906. The occasion was a “Memorial,” or “Actor’s Benefit,”
commemorative of the life-work of Kan-ya Morita, who, in a manner
similar to the late John Augustin Daly, had devoted himself to the
improvement and elevation of the theatre. All the best actors in
Tokyo, including the two sons of Morita, took part in these
performances, which consisted of selected portions of the very best
style of the dramas of Old Japan. I cannot, therefore, give a more
graphic picture of what this art actually is, and what it effects by way
of influence upon the audience, than to recite with some detail our
experiences as members of a theatre party for one of these all-day
performances.
A former pupil of mine and his wife were the hosts, and the other
guests, besides my wife and myself, were Minister and Madam U
——, and Professor and Mrs. U——. Since we were the only
foreigners among the members of the party, our hostess came to
conduct us to the tea-house, through which, according to the
established custom, all the arrangements for tickets, reserved seats,
cushions, hibachis, refreshments, and attendance, had been made.
There we met the husband, who had come from his place of
business; and after having tea together, we left our wraps and shoes
at the tea-house, and, being provided with sandals, we shuffled in
them across the street into the theatre. Four of the best boxes in the
gallery, from which a better view of the stage can be obtained than
from the floor, had been thrown into one by removing the partitions of
boards; and every possible provision had been made for the comfort
of the foreigners, who find it much more difficult than do those to the
manner born to sit all day upon the floor with their legs curled up
beneath them. The native audience—and only a very few foreigners
were present—was obviously of the highest class, and was in
general thoroughly acquainted with the myths, traditions, and
histories, which were to be given dramatic representation. As the
event abundantly showed, they were prepared to respond freely with
the appropriate expressions of sentiment. It is an interesting fact that
Japanese gentlemen and ladies, whom no amount of personal grief
or loss could move to tears or other expressions of suffering in
public, are not ashamed to be seen at the theatre weeping copiously
over the misfortunes and sorrows of the mythical divinities, or the
heroes of their own nation’s past history.
The curtain rose at about eleven o’clock; and the first play was a
scene from an old Chinese novel, and bore the name “zakwan-ji.” It
represented three strong men who, meeting in the night, begin to
fight with one another. Snow falls, while the battle grows more fierce.
Two of the men are defeated; and the victor, in his arrogance, then
attacks the door of a shrine near by. But the spirit of the enshrined
hero appears and engages the victor of the other men in combat. Of
course, the mere mortal is easily overcome by his supernatural foe;
but when he yields, all parties speedily become friends. The acting
was very spirited and impressionistic; but no words were spoken by
the actors. The story was, however, sung by a “chorus” consisting of
a single very fat man, who sat in a box above the stage; but the
language was so archaic that even our learned friend, the professor,
could not understand much of it.
The second play was a version of the celebrated story of the Giant
Benkei and the warrior Yoshitsune. It differed materially from the
version given by Captain Brinkley in his admirable work on Japan. In
this scene, when Yoshitsune and Benkei have arrived at the “barrier,”
disguised as travelling priests, and are discussing the best means of
procedure, three country children appear with baskets and rakes to
gather pine leaves. On seeing the priests, the children warn them
that yesterday and the day before two parties of priests have been
killed by the soldiers at the barrier, on suspicion of their being
Yoshitsune and his followers in disguise. Benkei then comes forward
and asks of the boys the road the travellers ought to take. In very
graceful dances and songs the children give a poetical description of
this road. Benkei then takes an affectionate leave of his master, and
goes up to the gate to ask for passports of its guardian. It is agreed
that the signal for danger shall be one sound of Benkei’s horn; but
that if the horn is sounded three times, it shall mean “good news.”
Soon the horn is sounded once, and Yoshitsune rushes to the
rescue of his faithful attendant. At this point the stage revolves, and
the next scene presents the guardian of the gate seated in his
house, while in the foreground Benkei is being tortured to make him
confess. Yoshitsune attempts to rescue Benkei, but the latter
prevents his master from disclosing his identity. The guardian,
however, suspects the truth; but since he is secretly in favour of
Yoshitsune, he releases Benkei, and after some hesitation grants the
coveted passports and sends the whole party on their way.
The third play, like the first, was also Chinese; it was, however, much
more elaborate. A Tartar General, while in Japan, has married a
beautiful Japanese girl, and has taken her back with him to live in
China. After a great battle the General returns to his home, and an
old woman among the captives is introduced upon the stage to plead
for the release of her son, a Captain in the Japanese army, who had
also been taken captive. The old woman proves to be the step-
mother of the young wife and the Japanese Captain is her brother.
When the wife recognises her mother, she is much overcome, and
joins in pleading for the life of both the captives. The husband
becomes very angry and threatens to kill both mother and daughter;
but the mother, although her arms are bound, throws herself before
him and saves her daughter. The daughter then goes to her room,
and according to a prearranged signal with her brother, opens a vein
and pours the blood into a small stream that runs below. The brother,
who is in waiting on a bridge over the stream, sees the signal and
hurries to the rescue of his sister. He reaches the palace and
compels the men on guard to carry his sword within; it requires eight
men to accomplish this stupendous task, so exceedingly strong is
the swordsman! He overcomes the Tartar General and gets himself
crowned Emperor; but he comes out of the palace in time to see his
sister die of her self-inflicted wound. The aged mother, thinking it
would be dishonourable to allow her step-daughter to make the only
great sacrifice, stabs herself and dies to the sound of doleful music
long drawn-out.
During the intermission which followed this impressive but crudely
conceived and childish tragedy, we enjoyed an excellent Japanese
luncheon in the tea-house near by.
When the curtain rose for the next performance, it disclosed a row of
ten or twelve actors clothed in sombre Japanese dress, all on their
knees, who proceeded to deliver short speeches eulogistic of the
deceased actor in whose memory this series of plays was being
performed. The next play represented Tametomo, one of the twenty-
three sons of a famous Minamoto warrior, who with his concubine,
three sons, his confidential servant, and some other followers, had
been banished to an island off the coast of Japan. The astrologers
had prophesied that he and his oldest son would die; but that his
second son would become the head of a large and powerful family.
Not wishing his future heir to grow up on the barren island, he
manages to get a letter to a powerful friend on the mainland, who
promises that if the boy is sent to him, he will treat him as his own
son and educate him for the important position which he is destined
to fill in the world. But the father does not wish to disclose his plan to
the rest of the family. He therefore bids the two older boys make a
very large and strong kite; and when it is finished and brought with
great pride to show to the father, he praises the workmanship of
both, but calls the younger of the two into the house and presents
him with a flute. The child is much pleased with the gift and at once
runs away to show it to his brother, but stumbles and falls at the foot
of the steps and breaks the flute. This is considered a very ill omen,
and Tametomo pretends to be very angry and threatens to kill his
son. The mother, the old servant, and the other children plead for the
life of the boy; and at last the father says that he will spare his son,
but since he can no longer remain with the rest of the family, he will
bind him to the kite and send him to the mainland. A handkerchief is
then tied over the boy’s mouth and he is bound to the huge kite and
carried by several men to the seashore. Then follows a highly
emotional scene, in which the mother and brothers bewail the fate of
the boy and rebuke the hard-hearted father. The wind is strong, and
all watch the kite eagerly; while the father reveals his true motive for
sending away his son, and the youngest of the brothers, a babe of
four years old, engages in prayer to the gods for the saving of his
brother. The servant announces that the kite has reached the shore;
and soon the signal fire is seen to tell that the boy is safe. Tametomo
then assures his wife that the lives of the family are in danger from
the enemy, whose boats are seen approaching the island. At this the
wife bids farewell to her husband and takes the two children away to
kill them, with herself, before they fall into the hands of the enemy.
Tametomo shoots an arrow at one of the boats, which kills its man;
but the others press forward, and just as they are about to disembark
on the island the curtain falls.
On this lengthy and diversified programme there follows next a
selection of some of the most celebrated of dramatic dances. The
first of these was “The Red and White Lion Dance.” Two dancers
with lion masks and huge red and white manes trailing behind them
on the floor, went through a wild dance to represent the fury of these
beasts. The platforms on which they rested were decorated with red
and white tree-peonies; for lions and peonies are always associated
ideas in the minds of the Japanese. Another graceful dance
followed, in which the dancers, instead of wearing large masks,
carried small lion heads with trailing hair, over the right hand. The
masks of these dancers had small bells, which, as they danced,
tinkled and blended their sound with the music of the chorus. Then
came a comic dance, in which two priests of rival sects exhibited
their skill,—one of them beating a small drum, while his rival
emphasised his chant by striking a metal gong.
The seventh number on the programme was very tragic, and drew
tears and sobbing from the larger part of the audience, so intensely
inspired was it with the “Bushidō,” and so pathetically did it set forth
this spirit. Tokishime, a daughter of the Hōjō Shōgun, is betrothed to
Miura-no-Suké. The young woman goes to stay with the aged
mother of her lover, while he is away in battle. The mother is very ill,
and the son, after being wounded, returns home to see his mother
once more before she dies. The mother from her room hears her
son’s return and denounces his disloyal act in leaving the field of
battle even to bid her farewell; she also sternly forbids him to enter
her room to speak to her. The young man, much overcome, turns to
leave, when his fiancée discovers that his helmet is filled with
precious incense, in preparation for death. She implores him to
return to his home for the night only, pleading that so short a time
can make no difference. When they reach the house, a messenger
from her father in Kamakura presents her with a short sword and
with her father’s orders to use it in killing her lover’s mother, who is
the suspected cause of the son’s treachery. Then ensues one of
those struggles which, among all morally developed peoples, and in
all eras of the world’s history, furnish the essentials of the highest
forms of human tragedy. Such was the moral conflict which
Sophocles set forth in so moving form in his immortal tragedy of
“Antigone.” The poor girl suffers all the tortures of a fierce contention
between loyalty and the duty of obedience to her father and her love
for her betrothed husband; who, when he learns of the message,
demands in turn that the girl go and kill her own father. The daughter,
knowing her father to be a tyrant and the enemy of his country, at
last decides in favour of her lover, and resolves to go to Kamakura
and commit the awful crime of fratricide. After which she will expiate
it by suicide.
The closing performance of the entire day was a spectacle rather
than a play. It represented the ancient myth of the Sun-goddess, who
became angry and shut herself up in a cave, leaving the whole world
in darkness and in sorrow. All the lesser gods and their priests
assembled before the closed mouth of the cave and sang enticing
songs and danced, in the hope of inducing the enraged goddess to
come forth. But all their efforts were in vain. At last, by means of the
magic mirror and a most extraordinarily beautiful dance, as the cock
crows, the cave is opened by the power of the strong god, Tajikara-
o-no-miko-to; and the goddess once more sheds her light upon the
world.
At the close of this entire day of rarely instructive entertainment it
remained only to pick at a delicious supper of fried eels and rice
before retiring,—well spent indeed, but the better informed as to the
national spirit which framed the dramatic art of the Old Japan. It is in
the hope that the reader’s impressions may in some respect
resemble my own that I have described with so much detail this
experience at a Japanese theatre of the highest class.
CHAPTER VIII
THE NO, OR JAPANESE MIRACLE-PLAY