The document discusses an international surgical conference held in Yokohama, Japan in August 2011. It then provides an overview of Kampo medicine, which is traditional Japanese herbal medicine that is prescribed by doctors in Japan and covered by national health insurance. In particular, it focuses on Daikenchuto (TU-100), one of the most commonly prescribed Kampo medicines which is used to improve gastrointestinal motility and prevent postoperative complications. The manufacturing process and quality control of TU-100 are then described in detail.
This document discusses drug therapy and administration methods for asthma. It describes various drug classes used to treat asthma, including β2 agonists, corticosteroids, leukotriene modifiers, and others. It outlines administration routes, devices, and techniques for delivering asthma medications via inhalers, nebulizers, and orally. Side effects of different drug classes are also summarized. Methods for studying the effects of bronchoconstrictors and bronchodilators on isolated guinea pig trachea are then outlined.
Salbutamol inhalers are safe and effective for treating conditions like asthma when used as directed. They provide quick relief from breathing problems when needed. Doctors usually also prescribe a preventative inhaler to use daily. Before using a salbutamol inhaler, it's important to tell your doctor about any medical conditions you have or other medications you're taking. Potential side effects are minor but include tremors, headache, and palpitations.
This document discusses drugs that act on the respiratory system. It covers categories like anti-tussives, expectorants, and drugs for conditions like asthma and tuberculosis. It describes the mechanisms and types of cough, including productive and non-productive cough. It then examines the mechanisms, classifications, and examples of different drug classes for treating cough and related conditions, including anti-tussives like codeine; expectorants that liquefy secretions; mucolytics; antihistamines; bronchodilators; and demulcents for the throat. It notes important considerations like adverse effects and contraindications for these drug classes.
Japan has a unique culture that has developed in isolation due to its mountainous and island geography. Some notable aspects of Japanese culture include haiku poetry consisting of 17 syllables, anime accounting for 60% of animated entertainment worldwide, and traditions such as origami, ikebana flower arrangement, and traditional Japanese gardens which create miniature landscapes. The document provides 10 facts about various cultural aspects of Japan to inform people traveling to Japan for the 2020 Summer Olympics or those with an interest in Japanese culture.
Nepal's capital is Kathmandu. The name Nepal is derived from the word "Nepa" which referred to the ancient Newar Kingdom in the Kathmandu Valley. Local legends say a Hindu sage named "Ne" established himself in the valley and the name Nepal means "the place protected by Ne". Nepal is divided into three physiographic regions - Mountain, Hill and Terai plain bordering India. The official currency is the Nepalese rupee. Hinduism is practiced by 80% of the population while Buddhism, Islam, and Christianity make up the remainder. Carpets are Nepal's most important export product and the country is known for its mountain scenery and festivals like Dashain.
Bhutan is known as the Land of the Thunder Dragon. It has a rich Buddhist cultural heritage dating back to the 7th century when Buddhism was introduced. Notable figures include Guru Rinpoche who established many sacred sites and Ngawang Namgyal who unified Bhutan as a nation in the 1630s. Today Bhutan remains deeply spiritual with Buddhism shaping its unique culture and traditions. Traditional architecture, cuisine like ema datshi, and festivals like the sacred naked dance honor this heritage amid modernization. Outdoor activities like trekking among stunning Himalayan scenery and whitewater rafting have also become popular ways to experience Bhutan.
Japan is an island country made up of over 4000 small islands, with four main islands. Tokyo is the capital and largest city, with a population of over 126 million people. The Japanese currency is the yen. Japan has a highly developed economy and culture, with traditions like cherry blossom viewing, shrines, and anime/manga being an important part of society. Strict social norms and politeness are deeply ingrained in Japanese culture.
This document discusses drug therapy and administration methods for asthma. It describes various drug classes used to treat asthma, including β2 agonists, corticosteroids, leukotriene modifiers, and others. It outlines administration routes, devices, and techniques for delivering asthma medications via inhalers, nebulizers, and orally. Side effects of different drug classes are also summarized. Methods for studying the effects of bronchoconstrictors and bronchodilators on isolated guinea pig trachea are then outlined.
Salbutamol inhalers are safe and effective for treating conditions like asthma when used as directed. They provide quick relief from breathing problems when needed. Doctors usually also prescribe a preventative inhaler to use daily. Before using a salbutamol inhaler, it's important to tell your doctor about any medical conditions you have or other medications you're taking. Potential side effects are minor but include tremors, headache, and palpitations.
This document discusses drugs that act on the respiratory system. It covers categories like anti-tussives, expectorants, and drugs for conditions like asthma and tuberculosis. It describes the mechanisms and types of cough, including productive and non-productive cough. It then examines the mechanisms, classifications, and examples of different drug classes for treating cough and related conditions, including anti-tussives like codeine; expectorants that liquefy secretions; mucolytics; antihistamines; bronchodilators; and demulcents for the throat. It notes important considerations like adverse effects and contraindications for these drug classes.
Japan has a unique culture that has developed in isolation due to its mountainous and island geography. Some notable aspects of Japanese culture include haiku poetry consisting of 17 syllables, anime accounting for 60% of animated entertainment worldwide, and traditions such as origami, ikebana flower arrangement, and traditional Japanese gardens which create miniature landscapes. The document provides 10 facts about various cultural aspects of Japan to inform people traveling to Japan for the 2020 Summer Olympics or those with an interest in Japanese culture.
Nepal's capital is Kathmandu. The name Nepal is derived from the word "Nepa" which referred to the ancient Newar Kingdom in the Kathmandu Valley. Local legends say a Hindu sage named "Ne" established himself in the valley and the name Nepal means "the place protected by Ne". Nepal is divided into three physiographic regions - Mountain, Hill and Terai plain bordering India. The official currency is the Nepalese rupee. Hinduism is practiced by 80% of the population while Buddhism, Islam, and Christianity make up the remainder. Carpets are Nepal's most important export product and the country is known for its mountain scenery and festivals like Dashain.
Bhutan is known as the Land of the Thunder Dragon. It has a rich Buddhist cultural heritage dating back to the 7th century when Buddhism was introduced. Notable figures include Guru Rinpoche who established many sacred sites and Ngawang Namgyal who unified Bhutan as a nation in the 1630s. Today Bhutan remains deeply spiritual with Buddhism shaping its unique culture and traditions. Traditional architecture, cuisine like ema datshi, and festivals like the sacred naked dance honor this heritage amid modernization. Outdoor activities like trekking among stunning Himalayan scenery and whitewater rafting have also become popular ways to experience Bhutan.
Japan is an island country made up of over 4000 small islands, with four main islands. Tokyo is the capital and largest city, with a population of over 126 million people. The Japanese currency is the yen. Japan has a highly developed economy and culture, with traditions like cherry blossom viewing, shrines, and anime/manga being an important part of society. Strict social norms and politeness are deeply ingrained in Japanese culture.
This document provides a catalogue of 17 units that summarize key aspects of Chinese culture. The units cover topics such as Chinese geography, history, ethnic groups, festivals, language, zodiac signs, religions, Confucianism, kung fu, tea culture, food, calligraphy, paintings, music, traditional medicine, opera, and names. Each unit provides subsections that delve deeper into the cultural topic at hand.
Learn how, over the centuries, Japan changed from a nation that possessed ancient cultural traditions to become one of the most economically and technologically advanced societies in the world.
The document provides an overview of North East India, describing its seven sister states - Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, and Tripura - as well as Sikkim. It discusses the geography, population, and official recognition of the region. It then provides more detailed descriptions of each individual state, covering their history, demographics, culture, economy and tourism. The states are characterized as diverse, with lush landscapes, unique tribes and traditions, and significant biodiversity.
Singapore is an island country located in Southeast Asia with a population of 5.26 million people. It has a highly developed market economy and ranks highly in terms of economic competitiveness and human development. The flag features red, white, and crescent moon/stars which symbolize brotherhood, purity, and the nation's ideals. The document provides details on Singapore's demographics, geography, history, culture, government, economy, and some of its young entrepreneurs.
Paraguay is a landlocked country located in central South America, bordered by Argentina, Brazil, and Bolivia. It lies on both banks of the Paraguay River, which runs through the center of the country. Paraguay was ruled by Spain for around 300 years before gaining independence in 1811. In the late 19th century, Paraguay engaged in the disastrous Triple Alliance War against Argentina, Brazil, and Uruguay, which devastated the country. More recently, Paraguay fought and won the Chaco War against Bolivia from 1932 to 1935 to gain control over disputed border lands. The country has two official languages, Spanish and Guarani. Agriculture is the primary economic activity, with crops like
This document provides an overview of Turkmenistan with sections on basic information, history, politics, economy, and culture. It notes that Turkmenistan was historically located along the Silk Road and was conquered by various empires throughout its history. In the 20th century, it became part of the Soviet Union before gaining independence in 1991. Today, Turkmenistan has a presidential republic government structure led by President Gurbanguly Berdimuhamedow. The economy relies heavily on natural gas exports, with China becoming a major buyer. Cultural aspects highlighted include carpets, horses, dresses, and foods. Turkey is also described as one of Turkmenistan's largest trading partners and first to recognize its independence and neutrality.
Afghanistan has a long history of invasion and conflict due to its strategic location. Islam was introduced in the 7th century and various empires controlled Afghanistan until the Pashtuns established power in the 1700s. Afghanistan is predominantly Sunni Muslim and the largest ethnic groups are Pashtun, Tajik, Uzbek, and Hazara. The culture centers around family, religion, traditional gender roles, and cuisine like pilaf and tea. Leisure activities include buzkashi, wrestling, and children's games despite ongoing conflict.
Natural region of Pakistan has some of the most beautiful natural places in the world, located primarily in the northern areas and Kashmir region. These areas are famous for their sky high mountains, lush green valleys, rivers, lakes, and wildlife. Some of the top natural places to visit include the Neelum Valley, known for its greenery, springs, and mountains; the Hunza Valley, with places like the Rakaposhi Base Camp and Atta Abad Lake; and the Swat Valley, called the "Mini Switzerland of Pakistan" with sites like Mahodand Lake. Other highlights mentioned are the Kalash Valley with its unique culture, the Kaghan Valley known for sites like Lake Saiful Muluk
China has a long history spanning thousands of years. Early societies developed agriculture and pottery making as evidenced by artifacts from the Yangshao period and oracle bones from the Shang Dynasty. Imperial rule was established through a dynastic system with emperors viewed as the "Son of Heaven" ruling with the "Mandate of Heaven." Key dynasties included the Qin which first unified China, the Han which was a golden age, the Tang which expanded Chinese territory, and the Ming which was a stable period. In the early 20th century, the Qing Dynasty fell and the Republic of China was established, but civil war erupted between the Nationalists and Communists with Mao Zedong founding the People's Republic of
Here is some feedback on the lecture:
- The information provided was very thorough, covering the key topics of emergency management of poisoning, common toxins, diagnosis and treatment plans.
- The duration of the lecture was appropriate to cover all the important material.
- There was opportunity for discussion and questions throughout, which helped with understanding and retention of the concepts.
- The presentation style was clear with effective use of visual aids to support the spoken content.
- The pace of speaking was good - not too fast or slow.
- Lecturer demonstrated strong command of the subject matter and was able to discuss different cases knowledgeably.
- There was active participation by both the lecturer and attendees in the
The document discusses several common beliefs in Japanese folk medicine about preventing and treating colds and illnesses. These include keeping the body warm in winter, eating easy to digest foods that warm the body when sick, taking medicine with warm water, wearing a mask, gargling everyday, and applying a cold wet towel to the forehead for fever. Some practices like keeping warm and eating soft foods may provide comfort, but there is mixed or no evidence that others like gargling or putting onions on the throat work. Hand washing is encouraged by doctors worldwide.
Islamic medicine 1000 years ahead of its times [from www.metacafe.com]Abdrabu Abdallah
Within a century after the death of Prophet Muhammad, Islamic medicine had advanced significantly, establishing hospitals with separate wards, licensing physicians, and advancing practices in various medical fields like surgery and ophthalmology. By the 9th century, the hospital in Baghdad incorporated innovations like treating patients with music and allowing free care, setting standards for modern hospitals. Islamic medicine made major advances in medical education, establishing teaching hospitals and licensing physicians through examinations over 1000 years before similar systems developed in Europe.
Islamic cultures made many important scientific and medical contributions despite being burned in Europe:
They developed navigational tools like the astrolab and compass which enabled long sea voyages and discovery. Astronomers like Al-Biruni discussed theories of Earth's rotation centuries before Galileo.
Medicine advanced with discoveries in anatomy, use of anesthesia and cauterization in surgery, and linking disease to human contact. Figures like Ibn Sina and Al-Razi wrote influential medical encyclopedias and treatises. Hospitals were also established.
Other fields like optics, sociology, and physics also saw innovations through scholars such as Ibn al-Haytham,
Zhejiang University- School of Medicine- PPTSaju Bhaskar
Zhejiang University is one of the oldest universities in China, established in 1897. It has grown significantly over time and now has six campuses across various disciplines like engineering, science, medicine, agriculture and more. It is a comprehensive research university with over 41,000 students and strong academic programs and international partnerships.
Medicine And Medical Education In Islamic Historyzakir2012
- Islamic medical schools were built following the model of Jundi-Shapur medical school in Persia, which had a teaching hospital and university. Students received clinical and lecture-based training, and were expected to examine patients and record observations.
- Basic sciences like anatomy, pharmacology and herbal medicine were taught through lectures, illustrations and dissections. Students then received clinical training by examining patients under experienced physicians.
- Hospitals established under Islamic rule were the first to provide free care to all citizens, conduct medical research and train students. They had inpatient and outpatient wards, libraries and facilities for various specialties.
- Surgery and clinical practice were advanced through innovations like the use of
Highlights of the History of Medicine Divisionbelgrade18
The document provides an overview of the collections held by the History of Medicine Division, including monographs, serials, manuscripts, prints, photographs, and audiovisual materials covering the history of medicine from the 13th century to before 1970. It notes important early works such as Isagoge Johannitii in Tegni Galeni from the 13th century and Vesalius' De fabrica from 1543. The division also holds collections on East Asian medicine including 3,000 pre-1900 printed books, manuscripts, and ephemera from China, Japan, and Korea. Archives, personal papers, bound manuscripts, and oral histories are accessible to the public during business hours.
ICD Revision Beta 2013 - Internal MedicineBedirhan Ustun
This is a presentation on ICD Revision current status in Internal Medicine TAG summarizing the latest developments in Beta Phase including the Review Process, Field Trials and next steps
This document provides an overview of Islamic medicine. It discusses the history of Islamic medicine from the 8th to 13th centuries when major Muslim physicians and scholars made significant contributions to the field. Modern medicine, Islamic medicine, homeopathy and traditional medicine do not need to be in conflict. Islamic medicine is flexible, universal, and embraces growth and development. It should be guided by the teachings of the Quran and Hadith and bring people closer to God. The ethical foundations of Islamic medicine are discussed regarding issues like reproduction, contraception, and organ replacement. The conclusion emphasizes that Islamic medical practitioners should focus on teaching and practicing good medicine and substantive research to substantiate Islamic medicine as the right approach.
The document provides an overview of Islamic medicine between the 11th and 15th centuries. It discusses how Islamic ideas influenced the understanding of disease causation and led to advances in hospitals, surgery, anatomy, and chemistry. Key individuals mentioned include Rhazes, who distinguished between smallpox and measles, and Avicenna, whose Canon of Medicine was influential in Europe. Hospitals were established in Baghdad and other cities, and surgeons like Albucasis described various surgical procedures. While dissections were forbidden, observations challenged some of Galen's anatomical theories. Arab scientists also made advances in distillation and developed new drugs.
Japanese encephalitis is a mosquito-borne viral disease that is common in parts of Asia. It is transmitted to humans via bites from infected Culex mosquitoes. While most infections cause mild symptoms or no symptoms, approximately 1 in 250 infections result in encephalitis, which can be fatal in 30% of cases. Survivors often face permanent neurological impairments. Control efforts focus on vaccination programs and reducing mosquito populations in areas like rice paddies where they breed.
Muslim Contributions in Medicine-Geography-AstronomyAli Usman
The document summarizes many of the contributions of Muslim scientists to medicine and astronomy throughout history. It shows that Muslim physicians between the 7th-13th centuries established the first hospitals, medical schools, and quarantine practices. Scientists like al-Razi, Ibn Sina, and al-Zahrawi made breakthroughs in surgery, anesthesia, pharmacology, and pathology that influenced Western practices for centuries. Muslim geographers and astronomers also made advances in map-making, navigation, optics, and understanding the motions of celestial bodies before their European counterparts. Their work laid the foundations for modern science.
This document provides a catalogue of 17 units that summarize key aspects of Chinese culture. The units cover topics such as Chinese geography, history, ethnic groups, festivals, language, zodiac signs, religions, Confucianism, kung fu, tea culture, food, calligraphy, paintings, music, traditional medicine, opera, and names. Each unit provides subsections that delve deeper into the cultural topic at hand.
Learn how, over the centuries, Japan changed from a nation that possessed ancient cultural traditions to become one of the most economically and technologically advanced societies in the world.
The document provides an overview of North East India, describing its seven sister states - Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, and Tripura - as well as Sikkim. It discusses the geography, population, and official recognition of the region. It then provides more detailed descriptions of each individual state, covering their history, demographics, culture, economy and tourism. The states are characterized as diverse, with lush landscapes, unique tribes and traditions, and significant biodiversity.
Singapore is an island country located in Southeast Asia with a population of 5.26 million people. It has a highly developed market economy and ranks highly in terms of economic competitiveness and human development. The flag features red, white, and crescent moon/stars which symbolize brotherhood, purity, and the nation's ideals. The document provides details on Singapore's demographics, geography, history, culture, government, economy, and some of its young entrepreneurs.
Paraguay is a landlocked country located in central South America, bordered by Argentina, Brazil, and Bolivia. It lies on both banks of the Paraguay River, which runs through the center of the country. Paraguay was ruled by Spain for around 300 years before gaining independence in 1811. In the late 19th century, Paraguay engaged in the disastrous Triple Alliance War against Argentina, Brazil, and Uruguay, which devastated the country. More recently, Paraguay fought and won the Chaco War against Bolivia from 1932 to 1935 to gain control over disputed border lands. The country has two official languages, Spanish and Guarani. Agriculture is the primary economic activity, with crops like
This document provides an overview of Turkmenistan with sections on basic information, history, politics, economy, and culture. It notes that Turkmenistan was historically located along the Silk Road and was conquered by various empires throughout its history. In the 20th century, it became part of the Soviet Union before gaining independence in 1991. Today, Turkmenistan has a presidential republic government structure led by President Gurbanguly Berdimuhamedow. The economy relies heavily on natural gas exports, with China becoming a major buyer. Cultural aspects highlighted include carpets, horses, dresses, and foods. Turkey is also described as one of Turkmenistan's largest trading partners and first to recognize its independence and neutrality.
Afghanistan has a long history of invasion and conflict due to its strategic location. Islam was introduced in the 7th century and various empires controlled Afghanistan until the Pashtuns established power in the 1700s. Afghanistan is predominantly Sunni Muslim and the largest ethnic groups are Pashtun, Tajik, Uzbek, and Hazara. The culture centers around family, religion, traditional gender roles, and cuisine like pilaf and tea. Leisure activities include buzkashi, wrestling, and children's games despite ongoing conflict.
Natural region of Pakistan has some of the most beautiful natural places in the world, located primarily in the northern areas and Kashmir region. These areas are famous for their sky high mountains, lush green valleys, rivers, lakes, and wildlife. Some of the top natural places to visit include the Neelum Valley, known for its greenery, springs, and mountains; the Hunza Valley, with places like the Rakaposhi Base Camp and Atta Abad Lake; and the Swat Valley, called the "Mini Switzerland of Pakistan" with sites like Mahodand Lake. Other highlights mentioned are the Kalash Valley with its unique culture, the Kaghan Valley known for sites like Lake Saiful Muluk
China has a long history spanning thousands of years. Early societies developed agriculture and pottery making as evidenced by artifacts from the Yangshao period and oracle bones from the Shang Dynasty. Imperial rule was established through a dynastic system with emperors viewed as the "Son of Heaven" ruling with the "Mandate of Heaven." Key dynasties included the Qin which first unified China, the Han which was a golden age, the Tang which expanded Chinese territory, and the Ming which was a stable period. In the early 20th century, the Qing Dynasty fell and the Republic of China was established, but civil war erupted between the Nationalists and Communists with Mao Zedong founding the People's Republic of
Here is some feedback on the lecture:
- The information provided was very thorough, covering the key topics of emergency management of poisoning, common toxins, diagnosis and treatment plans.
- The duration of the lecture was appropriate to cover all the important material.
- There was opportunity for discussion and questions throughout, which helped with understanding and retention of the concepts.
- The presentation style was clear with effective use of visual aids to support the spoken content.
- The pace of speaking was good - not too fast or slow.
- Lecturer demonstrated strong command of the subject matter and was able to discuss different cases knowledgeably.
- There was active participation by both the lecturer and attendees in the
The document discusses several common beliefs in Japanese folk medicine about preventing and treating colds and illnesses. These include keeping the body warm in winter, eating easy to digest foods that warm the body when sick, taking medicine with warm water, wearing a mask, gargling everyday, and applying a cold wet towel to the forehead for fever. Some practices like keeping warm and eating soft foods may provide comfort, but there is mixed or no evidence that others like gargling or putting onions on the throat work. Hand washing is encouraged by doctors worldwide.
Islamic medicine 1000 years ahead of its times [from www.metacafe.com]Abdrabu Abdallah
Within a century after the death of Prophet Muhammad, Islamic medicine had advanced significantly, establishing hospitals with separate wards, licensing physicians, and advancing practices in various medical fields like surgery and ophthalmology. By the 9th century, the hospital in Baghdad incorporated innovations like treating patients with music and allowing free care, setting standards for modern hospitals. Islamic medicine made major advances in medical education, establishing teaching hospitals and licensing physicians through examinations over 1000 years before similar systems developed in Europe.
Islamic cultures made many important scientific and medical contributions despite being burned in Europe:
They developed navigational tools like the astrolab and compass which enabled long sea voyages and discovery. Astronomers like Al-Biruni discussed theories of Earth's rotation centuries before Galileo.
Medicine advanced with discoveries in anatomy, use of anesthesia and cauterization in surgery, and linking disease to human contact. Figures like Ibn Sina and Al-Razi wrote influential medical encyclopedias and treatises. Hospitals were also established.
Other fields like optics, sociology, and physics also saw innovations through scholars such as Ibn al-Haytham,
Zhejiang University- School of Medicine- PPTSaju Bhaskar
Zhejiang University is one of the oldest universities in China, established in 1897. It has grown significantly over time and now has six campuses across various disciplines like engineering, science, medicine, agriculture and more. It is a comprehensive research university with over 41,000 students and strong academic programs and international partnerships.
Medicine And Medical Education In Islamic Historyzakir2012
- Islamic medical schools were built following the model of Jundi-Shapur medical school in Persia, which had a teaching hospital and university. Students received clinical and lecture-based training, and were expected to examine patients and record observations.
- Basic sciences like anatomy, pharmacology and herbal medicine were taught through lectures, illustrations and dissections. Students then received clinical training by examining patients under experienced physicians.
- Hospitals established under Islamic rule were the first to provide free care to all citizens, conduct medical research and train students. They had inpatient and outpatient wards, libraries and facilities for various specialties.
- Surgery and clinical practice were advanced through innovations like the use of
Highlights of the History of Medicine Divisionbelgrade18
The document provides an overview of the collections held by the History of Medicine Division, including monographs, serials, manuscripts, prints, photographs, and audiovisual materials covering the history of medicine from the 13th century to before 1970. It notes important early works such as Isagoge Johannitii in Tegni Galeni from the 13th century and Vesalius' De fabrica from 1543. The division also holds collections on East Asian medicine including 3,000 pre-1900 printed books, manuscripts, and ephemera from China, Japan, and Korea. Archives, personal papers, bound manuscripts, and oral histories are accessible to the public during business hours.
ICD Revision Beta 2013 - Internal MedicineBedirhan Ustun
This is a presentation on ICD Revision current status in Internal Medicine TAG summarizing the latest developments in Beta Phase including the Review Process, Field Trials and next steps
This document provides an overview of Islamic medicine. It discusses the history of Islamic medicine from the 8th to 13th centuries when major Muslim physicians and scholars made significant contributions to the field. Modern medicine, Islamic medicine, homeopathy and traditional medicine do not need to be in conflict. Islamic medicine is flexible, universal, and embraces growth and development. It should be guided by the teachings of the Quran and Hadith and bring people closer to God. The ethical foundations of Islamic medicine are discussed regarding issues like reproduction, contraception, and organ replacement. The conclusion emphasizes that Islamic medical practitioners should focus on teaching and practicing good medicine and substantive research to substantiate Islamic medicine as the right approach.
The document provides an overview of Islamic medicine between the 11th and 15th centuries. It discusses how Islamic ideas influenced the understanding of disease causation and led to advances in hospitals, surgery, anatomy, and chemistry. Key individuals mentioned include Rhazes, who distinguished between smallpox and measles, and Avicenna, whose Canon of Medicine was influential in Europe. Hospitals were established in Baghdad and other cities, and surgeons like Albucasis described various surgical procedures. While dissections were forbidden, observations challenged some of Galen's anatomical theories. Arab scientists also made advances in distillation and developed new drugs.
Japanese encephalitis is a mosquito-borne viral disease that is common in parts of Asia. It is transmitted to humans via bites from infected Culex mosquitoes. While most infections cause mild symptoms or no symptoms, approximately 1 in 250 infections result in encephalitis, which can be fatal in 30% of cases. Survivors often face permanent neurological impairments. Control efforts focus on vaccination programs and reducing mosquito populations in areas like rice paddies where they breed.
Muslim Contributions in Medicine-Geography-AstronomyAli Usman
The document summarizes many of the contributions of Muslim scientists to medicine and astronomy throughout history. It shows that Muslim physicians between the 7th-13th centuries established the first hospitals, medical schools, and quarantine practices. Scientists like al-Razi, Ibn Sina, and al-Zahrawi made breakthroughs in surgery, anesthesia, pharmacology, and pathology that influenced Western practices for centuries. Muslim geographers and astronomers also made advances in map-making, navigation, optics, and understanding the motions of celestial bodies before their European counterparts. Their work laid the foundations for modern science.
Muslims made many important contributions to the field of geography from the 7th century onwards. Key Muslim geographers and their works included Al-Khwārizmī who wrote one of the earliest books on geography, Al-Masudi who compiled travel observations in his book Meadows of Gold, and Al-Idrisi who created a detailed world map and geographical encyclopedia. Ibn Majid advanced navigation and oceanography through his books on marine science and ship movements. Muslim geographers accumulated knowledge through travel, study, and the needs of pilgrimage and trade, and their works informed both Eastern and Western understanding of geography for centuries.
Japanese civilization was shaped by cultural influences from China and the rise of feudalism under military rulers. The Yamato clan took control in the 400s and named emperors to rule, though sometimes in name only. Buddhism spread from China and mixed with existing Shinto practices. In the late 700s, the capital moved to Heian where an refined aristocratic culture developed, illustrated by The Tale of Genji. However, as central power declined in the 1000s, large landowners built private armies and established feudal rule over smaller landowners seeking protection. The Minamoto family established the Kamakura shogunate in 1192, placing a military dictator or shogun in power supported by samur
the presentation will help you in understanding diffrent terms of islamic banking. also it will help you in finding the answers of your critics about islamic banking.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central19various
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central
1. International Surgical Week
August 29, 2011 Yokohama, Japan
What is traditional Japanese Kampo medicine
An Overview of Basic and Clinical Challenges
Asahikawa
Toru Kono
Division of Gastroenterologic and General Surgery
Department of Surgery, Asahikawa Medical University
Tokyo
Mt. Taisetu National Park, Asahikawa
(Scenery from the window of my office)
3. Herbal medicinal products in the world
China and other countries
• Many doctors are concerned about the
quality of herbal medicinal products
• One reason is that some herbal medicinal
products are contaminated with
unexpected pharmaceutical ingredients
(e.g. antibiotics, pesticides)
• EBM is not enough
4. What is Kampo ?
• Kampo is traditional Japanese medicine
• Kampo is prescribed by Japanese medical
doctors
• Kampo is covered by the National Health
Insurance
• Kampo products from Tsumura are not
considered as CAM products in Japan
5. Kampo
• Over the last few years, FDA began
shifting its focus on Kampo because of its
exceptionally high quality and
standardized ingredients
• Kampo is primarily extract granules and
their pharmacological actions have been
elucidated at the molecular level
6. What is daikenchuto (DKT, TJ-100) ?
- TU-100 in the US -
Most frequently prescribed Kampo medicine
Approved in 1986 by the Japanese government
Improves gastrointestinal motility and
prevents postoperative adhesion and paralytic
ileus after abdominal surgery
7. Annual sales of Daikenchuto (TU-100)
sales
X 100 80 200 packages
million yen X 10000
60
40
20
0
2005 2006 2007 2008 2009 2010
8. What is daikenchuto (TU-100) ?
Composed of 3 medicinal herbs
* Japanese pepper
* Processed ginger
* Ginseng radix
and maltose powder
9. Manufacturing process of TU-100
Japanese Pepper Processed Ginger Ginseng Radix
Mix herbs spray drying via addition of heat (203ºF) extract powder
Maltose powder
Extracted powder TU-100
Mixture of extract powder and maltose powder is at a ratio of 1:8
10. TU-100 final components
Extract of 3 medicinal herbs
( Japanese pepper,
Magnesium stearate (lubricant processed ginger,
ginseng radix )
Lactose hydrate
Maltose powder
Clinical dose of TU-100 per day: 7.5 to 15g
weights in parentheses show doses per day
11. O
MeO O
MeO
How to check the quality HO
6-shogaol HO (10-shogaol)
hydroxy-α-sanshool
of TU-100 MeO
O
NH HO
8-shogaol
hydroxy MeO
O OH O
HO
O OH
α-sanshool
HO
6-gingerol 6-shogaol
MeO
HO 10-gingerol
ginsenoside Rg1
Glc
O ginsenoside Rb1
Circled ingredients are the
HO 6
Glc-Glc
HO
O
MeO
O OH
characteristic markers
hyperoside
HO O
OH HO
O-Glc 2
Glc-Glc O
HO
8-gingerol for quality control of TU-100
OH
O Gal quercitrin OH
OH O
HO O
OH
OH O
O Rha
ginsenoside
Rb1
No unexpected pharmaceutical ingredients
No toxins, pesticides, microbes and heavy metals
(impurity) O OH
MeO
α-sanshool O
NH
HO 10-gingerdion
H
γ-sanshool NH
OH O
N O
H MeO
O N
hydroxy-β-sanshool HO
10-dehydrogingerdion
β-sanshool O HO
Three-dimensional high-performance liquid chromatography of TU-100
Confidential data in TSUMURA
Kono T. et al J Gastroenterology 2011 (in press)
15. TU-100 reports of adverse effects
from 1986 to 2006
Only 46 cumulative cases during 20 years
Annual sales of > 9 million packages
All AEs are not severe and patients have
fully recovered
• liver dysfunction
• liver damage
• jaundice
• pneumonitis
• pancytopenia
• oral mucositis
17. TU-100 Main Clinical Applications and Mechanism
• Prevention and treatment of paralytic
bowel obstruction after abdominal
surgery, orally or through ileus tube
Shibata C, et al. Surgery 1999;126(5): 918-24
Nagano T, et al. Biol Pharm Bull 1999;22(10):1131-3
Jin XL, et al. Dig Dis Sci 2001;46(6):1171-6
Sato Y, et al. Biol Pharm Bull 2004;27(11): 1875-77
Several important neuronal factors are involved in the
mechanism, one of which is calcitonin gene-related peptide
(CGRP), a neuropeptide produced in the nervous tissue
by the sensory neurons.
18. TU-100 Main Clinical Applications and Mechanism
• Improvement in intestinal blood flow
• Beneficial effects are due to the mobilization of
endogenous calcitonin family of peptides and their
receptor-associated factors
• Calcitonin gene-related peptides (CGRP
• Adrenomedullin (ADM
Murata P, et al. Life Sci 2002;70:2061-2070
Kono T, et al. J Surgical Res 2008;150:78-84
Kono T, et al. Surgery 2009;146(5):837-840
Kono T, et al. J Crohn’s and Colitis 2010;4:161-170
Kono T, et al. J Gastroenterology 2011 (in press)
19. CGRP and ADM: Physiological Effects
Gastrointestinal motility (CGRP)
Vasodilation (CGRP, ADM)
Secretion (CGRP)
Anti-inflammatory cytokine (CGRP, ADM)
Anti-microbe (ADM)
CGRP and ADM play pivotal roles in
understanding TU-100’s effects
20. CGRP and ADM
Different sites of production and expression
CGRP is synthesized almost exclusively in neuronal tissues
(e.g. nerve terminals)
ADM is mainly distributed in non-neuronal tissues (e.g.
epithelial cells, smooth muscle cells, etc.)
Dawn in Tokyo
21. Sensory nerve fibers positive for CGRP in
intestinal mucosa
CGRP
Mucosa (crypt)
CGRP
22. ADM production by intestinal epithelial cells
Small Intestine Large Intestine
Rat
Small Intestine Large Intestine
Human
24. TU-100 injection site
Practical experiment scenery
A tube was inserted
via the cecum into
the proximal colon
TU-100 is dissolved
Laser probe
Cecum
Distal Colon
Recording site
Plastic wrap to keep warm and to prevent colon
the tissue from becoming dehydrated.
25. Effect of TU-100 intraluminal administration on Colonic
Vascular Conductance (VC; index of blood flow)
The time-course of changes in colonic VC
0.24
TU-100
0.20
100 mg/kg
300 mg/kg
0.16
10 mg/kg
Vehicle
0.12
0.08
0.04
0.00
0 15 30 45 60 75 90
Kono T., et al., J. Surg Res 2008
26. Next, we examined the mechanism of
vasodilation using blocker drugs:
CGRP receptor blocker (CGRP8-37)
Nitric oxide synthase inhibitor (L-NAME)
Vasoactive intestinal polypeptide (VIP)
receptor blocker ([4-Cl-DPhe6, Leu17]-VIP)
Substance P (SP) receptor blocker (spantide)
28. TU-100 increases blood flow of the
small intestine as well as colon
0.25
D.W. 5 mL/kg (N=7)
TJ-100 2700 mg/kg (N=6)
TU-100 100
## ##
0.20 ** *
#
VC
0.15
0.10
0.05
0 15 30 45 60 75 90 105 120
Time (min)
Two-way ANOVA: treatment, [F(1, 99)=32.96 p<0.0001], time, [F(8, 99)=3.69,
p=0.0008]. *P<0.05, **p<0.01 versus pre-administration (0 min) (Dunnett’s test).
#, ## p<0.05, 0.01 versus D.W. group (Student’s t-test).
29. Some of you may be wondering
if TU-100 works like capsaicin............
Kyoto, Genkoan
30. TU-100 does not work like capsaicin
BCTC did not abolish TU-100 effect
BCTC: selective anti-capsaicin
200 200 BCTC (3mg/kg, i.v.) + D.W. (5 mL/kg, i.d.)
BCTC (3mg/kg, i.v.) + TJ-100 (900 mg/kg, i.d.)
160 Capsaicin (3 mg/kg, i.d.) 160
BCTC (3mg/kg, i.v.) + Capsaicin (3 mg/kg, i.d.)
120 120
VC (%)
VC (%)
80 80
40 40
0 0
-40 -40
0 15 30 45 60 75 90 0 15 30 45 60 75 90
Time (min) Time (min)
31. TU-100-induced vasodilation is observed by
in vivo dynamic microscopy
Before After
The difference in background color (yellow) is due to TU-100 infusion
Arrows are pointing to the same area TU-100
32. What is the correlation between
CGRP and ADM receptors?
Autumn in Kyoto, Shodaji temple
33. ADM and CGRP antagonists, both receptor
blockers abolished TU-100-induced blood flow
DKT alone (N=8)
DKT + ADM22-52 (N=7)
DKT + CGRP 8-37 (N=6)
CVC
Time (min)
34. CGRP and ADM receptors are very unusual
Calcitonin receptor-like receptor (CRLR)
is an immature receptor.
Only when RAMP (receptor activating
membrane protein) binds to CRLR does
it mature into a “real” receptor that is capable
of binding ADM and/or CGRP.
35. Association of CRLR with a RAMP dictates the specificity of ligand binding
CRLR CRLR CRLR
N N N
C C C
RAMP1 RAMP2 RAMP3
N N N N N N
C C C
C C C
CGRP receptor ADM receptor ADM/CGRP receptor
36. TU-100 up-regulates CGRP and its receptor components mRNA
TU-100 1.5
CRLR *
- + 1
CRLR 504 bp 0.5
0
DKT(-) DKT(+)
Ramp-1 230 bp
1.5
Ramp-1
1
*
CGRP 102 bp
0.5
GAPDH 249 bp 0
DKT(-) DKT(+)
1
Evaluation of RNA from the rat colon CGRP *
0.75
after TU-100 administration using RT-PCR.
0.5
0.25
0
DKT(-) DKT(+)
Kono T., et al., J. Surg Res 2008
The intensity of each band was normalized to
that of the corresponding band of GAPDH.
The data are presented as mean ± SE (n = 4).
Bars show SEM. Compared with control, *p < 0.05.
37. TU-100 up-regulates RAMP2, 3 (ADM/CGRP receptor)
CRLR RAMP2 RAMP3
N N RAMP2
C
C
N N
RAMP3
Cont TU-100 Cont TU-100 Cont TU-100
C
C
CGRP GAPDH
ADM receptor
ADM/CGRP receptor
Cont TU-100 Cont TU-100
38. ADM production by epithelial cell line of rat small intestine
IEC-6 cell
ADM (green)
Dashed line: Isotype Control Ab (rabbit IgG)
Red line: Anti-ADM Ab
IEC-6 cell (rat intestinal epithelial cell line) was stained with anti-ADM antibody, and
analyzed by flow cytometer using FACScalibur and by immunocytochemistry.
Kono, J Crohn’s Colitis 2010
39. TU-100 enhances ADM production by intestinal epithelial
cell lines in a time-dependent manner
900 µg/ml TU-100
ADM concentration ( pg/ml )
Control
Culture time ( hour )
IEC-6 cell was cultured with or without 900 µg/ml of DKT for 12, 24, 48, 72, or 96 h.
N=3. *, **: p<0.05, 0.01 vs. no TU-100 control, respectively.
Kono, J Crohn’s Colitis 2010
40. TU-100 enhances ADM production by intestinal epithelial
cell lines in a dose-dependent manner
a) IEC-6 b) IEC-18
ADM concentration ( pg/mL )
ADM concentration ( pg/mL )
TU-100 concentration (µg/ml )
TU-100 was added to IEC-6 (a) and IEC-18 (b) cells at concentrations of 90, 270, 900 or 2700
mg/ml. N=4.
*, **: p<0.05, 0.01 vs. no TU-100 control, respectively.
41. TU-100 increases ADM production from
small and large intestinal epithelial (IE) cells
Cells TU-100 concentration (µg/ml)
IE cells of small intestine
IE cells of large intestine
Intestinal epithelial (IE) cells were isolated from the small or large intestine of normal
mice and stimulated with TU-100 (90, 270, or 900 µg/ml) at 1 x106 cells/ml in 96-well
round plates for 24 h. Concentrations (pg/ml) of adrenomedullin (ADM) in culture
fluids were determined using the EIA method. N=4-6, *, **: p<0.05, 0.01 versus no
TU-100 control, respectively.
Kono, J Crohn’s Colitis 2010
42. Which of the active ingredients in TU-100?
Kyoto Darumaji
43. Ingredient Analysis of TU-100
• TU-100 is composed of only 4 components:
Japanese pepper 2.2%
processed ginger 5.6%
ginseng radix 3.3%
maltose powder 88.9%
44. Japanese pepper and processed ginger are
key components for ADM release
ADM release ( ng/ml )
Cont. 80 800 10 100 10 100 10 100 ( µg/mL )
Maltose Processed Ginseng Japanese
Ginger radix pepper
Components of TU-100
Epithelial cell line of rat small intestine, IEC-6, was plated in 96-well flat plates at 1 x104 cells/well. The next
day, culture fluids were replaced with fresh medium containing test sample. Cells were allowed to incubate
an additional 24 h, and the supernatants were harvested. Concentrations (pg/ml) of adrenomedullin (ADM)
in culture fluids were determined using the EIA method. Maltose syrup and extracts of three medicinal herbs
(processed ginger, ginseng radix, and Japanese pepper) were evaluated at concentrations described in
figure. N=3. **: p<0.01 versus control (Dunnett test)
Kono, J Crohn’s Colitis 2010
46. Mechanism of TU-100-induced hyperemia
6-shogaol, hydroxy- -sanshool
Lumen
How do
they
Microvascular
stimulate?
vessel
Neuronal tissue
(Sensory nerve) Non-Neuronal tissue
(Epithelial cells)
ADM
Nerve endings CGRP
vasodilatation Improvement in
Microvascular Vessel microcirculation
47. Role of TU-100 as
TRP Channel Activator
Activation of transient receptor potential A1 expressed
in intestinal epithelial cell increases intestinal blood flow
via release of adrenomedullin
Inhibition of postoperative adhesion formation by Daikenchuto, a releaser
of endogenous adrenomedullin in intestinal tract
Florida
48. What is a Transient Receptor Potential (TRP)
channel?
TRP channel is a 6-transmembrane Ca2+ channel
49. Natural ligands like mint, cinnamon and chili pepper
stimulate specific TRP channels
AITC (mustard oil)
Menthol (mint) Capsaicin (‘hot’ chili peppers)
CNA (cinnamon)
Do the crude drugs (or constituents) in Kampo stimulate also?
TRPA1 channel
TRPM8 channel TRPV1 channel
C
N
TRP channel
Figure modified from David D. McKemy. Molecular Pain. 2005;1:16.
50. Hypothesis
TU-100 and TRP channels
Pharmacological effects of Kampo may
be defined by TRP channel activity
keywest
51. Do the TU-100 active ingredients,
hydroxy- -sanshool and 6-shogaol,
activate
TRP channels?
Florida
52. Hydroxy- -sanshool, 6-shogaol are TRPA1, TRPV1 agonists
Molecular biological profiles of hydroxy- -sanshool
Molecular biological profiles of 6-shogaol
54. Intestinal epithelial cells express TRPA1 and ADM
but not TRPV1
IEC-6 DRG
Fig.6. intestinal epithelial cell line IEC-6 TRPA1
expressed mRNA of TRPA1 and ADM
RT-PCR analysis was performed for TRPA1, TRPV1, TRPV1
ADM and β-Actin in IE-6 cell, and dorsal root ganglion
(DRG) isolated from normal rats using KOD PCR kit ADM
(Toyobo). The PCR products of 30-cycle amplification
of the mRNAs were resolved on a 2% agarose gel. β-Actin
DDW2011 poster presentation
55. TRPA1 expression in intestinal epithelial cells
The nucleus is dyed blue by DAPI
56. Hypothesis
TU-100
(6-shogaol, hydroxy- -sanshool
Stimulation
TRPA1
in intestinal epithelial cells
Enhanced ADM release from
intestinal epithelial cells
57. TRPA1 agonist only stimulates ADM production in IEC-6 cell
ADM release ( pg/mL )
TRPV1, CB1,CB2 TRPA1 TRPV1 TRPV1-V3
KCNK3
-
(Cont.) anandamide allyl capsaicin 2-aminoethoxy
Isothiocyanate diphenyl borate
(mustard oil)
Various TRP agonists were dissolved in DMSO and added at concentrations of 0.3, 3, 30 mol/L to
cultivation of IEC-6 cell (rat intestinal epithelial cell line). DMSO concentration was 0.3% in all wells. Next
day, ADM concentrations in culture fluid were measured by the EIA method. Data are shown as average/SE
of 3 well. ** : P<0.01 significant at the Dunnett determination
58. Treatment of TRPA1 siRNA diminishes
ADM enhancing activity of TU-100
300 2000
TU-100 TRPA1 agonist
allyl isothiocyanate (AITC)
Percentage to no stimulus control
Cinnamaldehyde (CNA)
1500
ADM production
200 1000
500
100
0
NC A1 NC A1
No stimulus No stimulus
IEC-6 cell was incubated for 3 days in presence of 0.3 μmol/L siRNA specific to TRPA1. Culture fluids were replaced with
fresh medium containing the respective siRNA and stimulus (900, 2700 μg/ml DKT, 30 μmol/L AITC or 100 μmol/L CNA).
ADM concentrations in the 24 h culture fluids were measured by the EIA method. N=3 to 4, NC: Negative control siRNA,
A1: TRPA1 siRNA,
59. Hypothesis: Mechanism of TU-100`s effect in promoting colonic blood flow
TU-100
(Hydroxy- -sanshool, 6-shogaol)
Increased
Intestinal epithelial cells concentration
in blood
TRPA1 (absorption)
ADM up-regulation
ADM release in blood
Vasodilatation
60. How does TU-100
behave inside the
Epithelial body ?
cell
adrenomedullin
Improvement of
Microvascular
Circulation
Hydroxy sanshool
Shogaol
Gingerol
62. The number of Crohn's disease patients has steadily
increased over the past 30 years in Japan
Incidence
Japan
30,000
Patients/100,000 people/Year
Over 500,000 Crohn’s patients in USA
63. Distribution of Crohn’s disease patients in Japan
Asahikawa
(my home)
Low High incidence
Tokyo
Emergency helicopter transport of
IBD patient from rural area to Asahikawa
Ministry of Health, Labour and Welfare, 2000
64. Overnight workshop at the hot springs hosted annually for
patients of IBD Friendship Society of Asahikawa
Once a year doctors and patients get together to enjoy hot spring
65. CGRP and ADM in Crohn’s disease
CGRP in the intestine of Crohn’s disease
patients is decreased compared with that of
normal intestine.
Decrease of CGRP contributes to microvascular
dysfunction in Crohn’s disease patients.
66. Submucosal neuronal network, including CGRP, in the
intestine of Crohn’s disease patients was decreased
compared with normal intestine
Normal ileum Crohn’s disease ileum
Neuronal marker, PGP9.5 (red) and DAPI (blue
67. Selective loss of neuropeptide CGRP, but not ADM,
in Crohn’s disease model and human
Kono T. et al J Gastroenterology 2011 (in press)
It has been reported that blood flow is decreased by more than
50% in the terminal ileum and colon of Crohn’s disease patients
Gastroenterology. 1977;72:388-96. Gut. 1986;27:542-9.
68. Measurement of colonic blood flow in TNBS-treated rat
0.14
normal colon
0.12
TNBS treated colon
0.10
0.08
CV
0.06
0.04
0.02
0.00
0 15 30 45 60 75 90
min
The involved segment of the ischemic colon (VC value: ≤ 0.06)
in TNBS-induced colitis rats was identified by measurement of colonic blood flow,
while that of control rats was indicated as 0.10±0.01.
Kono T. et al J Gastroenterology 2011 (in press)
69. CGRP and ADM in Crohn’s disease (CD)
Several investigators have reported therapeutic
effects of CGRP in experimental CD models.
ADM has been reported to have therapeutic
effects in experimental CD models as well.
Can exogenous CGRP and ADM be candidate
therapeutic agents for CD ?
Answer is NO!
70. Exogenous CGRP and ADM cannot be
therapeutic agents for Crohn’s disease
First, metabolic clearance is too fast
Second, administration of both peptides in
excess may induce decrease in peripheral
vascular resistance
Third, it is difficult to control delivery of both
peptides to diseased intestine
Therefore, it is desirable to develop an agent that
increases endogenous CGRP and ADM such as TU-100
71. TU-100 and Crohn’s disease
Our hypothesis is that TU-100 acts as an
endogenous CGRP and ADM enhancer and
exerts therapeutic effects on CD via endogenous
CGRP and ADM
• Improves intestinal blood flow
• Suppresses anti-inflammatory cytokine production
• Anti-microbial
Specifically, ADM can be targeted instead of decreased-CGRP
in CD
72. TU-100 improves colonic blood flow
in ischemic colon
0.20 TU-100, 900 mg/kg (N=7) TU-100
Distilled Water (N=5) +ischemic
Distilled Water (Normal; N=6) †† colon
††
†† ** ††
0.15 ** **
†† † **
* *
Normal
VC
0.10
0.05 ischemic
colon
0.00
0 15 30 45 60 75 90
Time (min)
The basal colonic vascular conductance (VC) of the ischemic colon indicated 0.06 or less which was lower than that of the
normal colon (0.10 ± 0.01). Changes of the VC induced by test sample are expressed as the mean ± S.E.M. (a) DKT (900
mg/kg) and vehicle (distilled water) were evaluated. Factorial two-way ANOVA analysis revealed significant effects of group
[F(4, 144)=21.17 p<0.0001] and time [F(5, 144)=3.95, p=0.0022]. *p<0.05, **p<0.01 versus pre-administration (0 min)
(Dunnett’s test). †, ††: p<0.05, 0.01 versus the vehicle control, respectively (Student’s t-test).
Kono T. et al J Gastroenterology 2011 (in press)
73. Effect of TU-100 on colonic blood flow
in ischemic colon
Before After
How about TU-100’s effect on hyperemic colon?
Does TU-100 exert an effect or NOT?
74. TU-100 increases VC in ischemic lesion (CV < 0.6) only
and never in hyperemic lesion (active) (CV > 0.2)
0.40 0.40
Vascular Conductance 0.35 0.35 大建中湯 100 mg/kg (N=7)
Vascular Conductance
大建中湯 100 mg/kg (N=7)
0.30 0.30
0.25 0.25
0.20 ischemic 0.20
0.15 0.15 hyperemic
0.10 0.10
0.05 0.05
0.00 0.00
In hyperemic segments, endogenous ADM and CGRP
0 15 30 45 60 75 90 0 15 30 45 60 75 90
Time (min) Time (min)
have been used up so there is nothing left
200 200
大建中湯 100 mg/kg (N=7)
for TU-100 to act on
Vascular Conductance (%)
Vascular Conductance (%)
160 160 大建中湯 100 mg/kg (N=7)
120 120
80 80
40 40
0 0
-40 -40
0 15 30 45 60 75 90 0 15 30 45 60 75 90
Time (min) Time (min)
Kono T. et al J Gastroenterology 2011 (in press)
76. TU-100 directly induced blood flow increase
in Crohn’s disease ( colon artificial anus)
Thermographs
before after
colon artificial anus
a b c skin temp
33
32
31
30
29
28
27
26
DKT sprinkled on the artificial anus
25
78. Blood flow is a very important factor
in pathogenesis of Crohn’s disease
Ileal ulcers tend to occur along the
mesenteric margin of the bowel wall in CD
and experimental models of CD
J Clin Pathol. 1997;50:1013-7.
Aliment Pharmacol Ther. 1999;13:531-5.
Aliment Pharmacol Ther. 2000;14:241-5.
79. Crohn’s disease ileum
Mesenteric side
Mesenteric side
Mesenteric side
stenosis
stenosis
80. Who can answer the prepotency of
the Crohn’s disease?
Hypothesis:
Primary pathological abnormality
in Crohn’s disease is in the
mesenteric blood supply
Lancet. 1989;2:1057-62.
81. Schematic diagram of human small intestine in Crohn’s disease
Normal Remission Mucosal barrier Active
flora
vessel
bacteria
inflammation
* granuloma ulcer
Mesenteric Mesenteric
margin margin
long artery
short artery
CGRP glanulomatous
Blood flow vasculitis
Lancet. 1989;2:1057-62.
No connection between the submucosal plexuses derived from short artery and
* long artery The association might well be explained in terms of granulomatous vasculitis
affecting small end-arteries that specifically supply the mesenteric margin
82. Is TU-100 an effective treatment for
Crohn’s disease?
Adelaide, Australia
83. Crohn’s disease model
• 2,4,6-TRINITROBENZE SULFONIC ACID (TNBS)-
INDUCED COLITIS:Th1-mediated response
Intestinal inflammation induced by intrarectal administration of hapten reagent
TNBS in ethanol solution. Simultaneous administration of TNBS and ethanol is
required to induce TNBS colitis, because ethanol disrupts the epithelial layer and
exposes the underlying Lamina propria to bacterial components.
Intestinal inflammation induced by intrarectal administration of TNBS
has many of the characteristic features of CD in humans
85. Experimental Schedule
Assessment of colonic damage was performed
on day 3 by macroscopic/microscopic observations
and cytokine contents.
Kono T, et al. J Crohn’s and Colitis 2010
86. TU-100 decreases mucosal cytokines
TNF and IFN in CD model
Concentrations of cytokines in protein extracts of the colonic mucosa were determined by ELISA.
N = 6. *, **: p<0.05, 0.01 versus colitis control, respectively.
Kono T, et al. J Crohn’s and Colitis 2010
87. TU-100 treatment protects against development of
TNBS-induced mucosal damage in colon
Representative photographs
Vehicle TU-100
(water) (900mg/kg)
Macroscopically visible damage was evaluated 3 days after TNBS instillation.
Mucosal damage was scored on a 0-8 scale.
TU-100 was given orally at 900 mg/kg. Clinical severity was monitored by mucosal damage score,
necrotic area of colonic mucosa. N=9 (Naive), 13 (colitis groups). *, **: p<0.05, 0.01 versus TNBS/Water
(colitis vehicle control), respectively.
Kono T, et al. J Crohn’s and Colitis 2010
88. TU-100 decreases
systemic inflammatory responses
Concentrations of cytokines in protein extracts of the colonic mucosa were determined by ELISA.
N = 6. (b) Serum amyloid A (SAA) concentration in plasma was determined by ELISA. n = 11.
SAA of naive and vehicle (50% EtOH) control mice were less than 0.001 mg/ml, respectively.
*, **: p<0.05, 0.01 versus colitis control, respectively.
Kono T, et al. J Crohn’s and Colitis 2010
89. Crohn’s disease model
• Oxazolone:Th2-polarized type colitis
6
Significant at P = 0.03
Score ( Max: 11 )
4
2
0
Water Water TJ-100
50%EtOH ir OXN ir ( Colitis )
90. ADM inhibits production of cytokines including
IFN and TNF by rat immune cells
γ α
Splenocytes
Concentration
Peritoneal macrophages
ADM addition ( μmol/L )
Splenocytes (upper) and peritoneal macrophages (lower) were isolated from normal SD rats, and cultured in presence of 1 µg/ml
LPS. ADM was added at final concentrations of 0.01, 0.1, or 1 µmol/L. N=3. *, **: p<0.05, 0.01 vs. LPS control, respectively.
91. ADM does not work like infliximab: it inhibits TNF production
infliximab binds TNF infliximab releases TNF
from the target cell membrane
infliximab
infliximab
infliximab kills TNF cell ADM inhibits TNF production
infliximab
Membrane binding TNF Membrane binding TNF
ADM
92. Antimicrobial effect of ADM
PAMP>ADM=Human b-defensin-2>human neutrophil peptide-1
Adrenomudullin (ADM) Proadrenomudullin N-terminal 20 peptide
(PAMP)
brush border membrane
Intestinal
TRPA1 Epithelial cell
O
N
OH Anti-TNF
Hydroxy- -sanshool
Anti-IFN-
O
O
vasodilatation
HO
6-Shogaol Microvascular Vessel
ADM
ADM, PAMP release
release
Enteric flora can be controlled by TU-100 via ADM
93. Conclusions
• TU-100 is an endogenous CGRP and
ADM enhancer via TRPA1 channel
• TU-100 improves intestinal blood flow
but is unlikely to be a direct vasodilator
• ADM inhibits TNF and IFN
production from immune cells
• ADM suppresses systemic
inflammatory responses (CRP)
• ADM exerts influence on enteric flora
• TU-100 ameliorates both Th-1 and Th-2
polarized type animal CD models
94. Strategy
• TU-100 may be a new type of medication for
Crohn’s disease
• Unlike infliximab, TU-100 is not for severe
conditions
• TU-100 is mainly effective in moderate or
mild or conditions
• TU-100 may help prolong remission periods
after infliximab-induced remission
• TU-100 may help decrease the frequency
and dosage of antibody treatment
Kono T, et al. Surgery 2009;146(5):837-840
95. This work
was performed
in collaboration
with
Dr Kaneko
Dr Omiya
Dr Koseki
Dr Suzuki
Dr Hira
Dr Watanabe
Dr Ebisawa
Dr Chisato
Dr Chiba
Polar bear is the main attraction Thank you for your
at Asahiyama Zoo in Asahikawa, attention
the most popular zoo in Japan