DiseaseComps: a metric that discovers similar diseases based upon common toxicogenomic profiles at CTD

The Comparative Toxicogenomics Database (CTD) is a free resource that describes chemical-gene-disease networks to help understand the effects of environmental exposures on human health. The database contains more than 13,500 chemical-disease and 14,200 gene-disease interactions. In CTD, chemicals and genes are associated with a disease via two types of relationships: as a biomarker or molecular mechanism for the disease (M-type) or as a real or putative therapy for the disease (T-type). We leveraged these curated datasets to compute similarity indices that can be used to produce lists of comparable diseases ("DiseaseComps") based upon shared toxicogenomic profiles. This new metric now classifies diseases with common molecular characteristics, instead of the traditional approach of using histology or tissue of origin to define the disorder. In the dawning era of "personalized medicine", this feature provides a new way to view and describe diseases and will help develop testable hypotheses about chemical-gene-disease networks. AVAILABILITY: The database is available for free at http://ctd.mdibl.org/     

Humanised models of cancer in molecular medicine: the experimental control of disanalogy

This paper explores the epistemology of extrapolation from model organisms to humans in molecular medicine. We take into account two common views on the issue, the homology view and the disanalogy view. In response to both interpretations, we argue that the foundational basis of extrapolations cannot simply be provided by homology and that relevant disanalogies can, thanks to the techniques of molecular biology, be experimentally controlled and exploited to allow useful and reliable extrapolations. The case of "humanised mice" in the context of cancer stem cell research provides evidence of how animal models can be construed to approximate bona fide causal analogue models of human diseases. To supplement this view we show how the epistemology of model organisms needs to take into account the engineering side of molecular medicine. Model organisms are often manipulated to create analogies or remove disanalogies with the target system. We maintain that highlighting this feature is fundamental to explain what warrants extrapolation in the search for the molecular causes of disease.     

肺与大肠相表里的微生态学解释

“肺与大肠相表里”、“肺在志为悲（忧）”均是传统中医所特有的思维,现代临床实践也发现肠道疾病与肺部疾病常相伴而发,而情志失调常为肺肠疾病的诱因。但没有物质基础的经脉如何联系肺与肠,用经脉络属或是五行理论来解释的“肺在志为悲（忧）”观点有没有明确的物质基础仍有待研究。目前各项研究发现肺与大肠在解剖及生理病理过程方面存在相似性,而菌群在肺—肠联系中起着重要的作用,很可能是经脉联系肺肠的物质基础之一,随着对肠道菌群研究的进一步深入,其与抑郁症等情志障碍疾病的潜在关系被逐渐揭示,也让“肺在志为悲（忧）”的观点获得认同和深化,借助最新研究成果深度认识理论术语与客观实在的关系,是中医发展的必由之路。     

Ethnomedicine of the Kagera Region, north western Tanzania. Part 2: The medicinal plants used in Katoro Ward, Bukoba District

Background

The Kagera region of north western Tanzania has a rich culture of traditional medicine use and practices. The dynamic inter-ethnic interactions of different people from the surrounding countries constitute a rich reservoir of herbal based healing practices. This study, the second on an ongoing series, reports on the medicinal plant species used in Katoro ward, Bukoba District, and tries to use the literature to establish proof of the therapeutic claims.

Methodology

Ethnomedical information was collected using Semi-structured interviews in Kyamlaile and Kashaba villages of Katoro, and in roadside bushes on the way from Katoro to Bukoba through Kyaka. Data collected included the common/local names of the plants, parts used, the diseases treated, methods of preparation, dosage, frequency and duration of treatments. Information on toxicity and antidote were also collected. Literature was consulted to get corroborative information on similar ethnomedical claims and proven biological activities of the plants.

Results

Thirty three (33) plant species for treatement of 13 different disease categories were documented. The most frequently treated diseases were those categorized as specific diseases/conditions (23.8% of all remedies) while eye diseases were the least treated using medicinal plants (1.5% of all remedies). Literature reports support 47% of the claims including proven anti-malarial, anti-microbial and anti-inflammatory activity or similar ethnomedical uses. Leaves were the most frequently used plant part (20 species) followed by roots (13 species) while making of decoctions, pounding, squeezing, making infusions, burning and grinding to powder were the most common methods used to prepare a majority of the therapies.

Conclusion

Therapeutic claims made on plants used in traditional medicine in Katoro ward of Bukoba district are well supported by literature, with 47% of the claims having already been reported. This study further enhances the validity of plants used in traditional medicine in this region as resources that can be relied on to provide effective, accessible and affordable basic healthcare to the local communities. The plants documented also have the potential of being used in drug development and on farm domestication initiatives.     

Diseases of amphibians

The development and refinement of amphibian medicine comprise an ongoing science that reflects the unique life history of these animals and our growing knowledge of amphibian diseases. Amphibians are notoriously fastidious in terms of captive care requirements, and the majority of diseases of amphibians maintained in captivity will relate directly or indirectly to husbandry and management. Investigators have described many infectious and noninfectious diseases that occur among various species of captive and wild amphibians, and there is considerable overlap in the diseases of captive versus free-ranging populations. In this article, some of the more commonly reported infectious and noninfectious diseases as well as their etiological agents and causative factors are reviewed. Some of the more common amphibian diseases with bacterial etiologies include bacterial dermatosepticemia or "red leg syndrome," flavobacteriosis, mycobacteriosis, and chlamydiosis. The most common viral diseases of amphibians are caused by the ranaviruses, which have an impact on many species of anurans and caudates. Mycotic and mycotic-like organisms cause a number of diseases among amphibians, including chytridiomycosis, zygomycoses, chromomycoses, saprolegniasis, and ichthyophoniasis. Protozoan parasites of amphibians include a variety of amoeba, ciliates, flagellates, and sporozoans Common metazoan parasites include various myxozoans, helminths (particularly trematodes and nematodes), and arthropods. Commonly encountered noninfectious disease etiologies for amphibians include neoplasia, absolute or specific nutritional deficiencies or overloads, chemical toxicities, and inadequate husbandry or environmental management.     

兽医中药在宠物临床上的应用

本文系统综述了我国兽医中药在宠物临床上的应用历史及概况。从兽医中药起源,到中药在宠物临床上的古今应用。重点针对宠物临床中常见病、多发病如犬猫皮肤寄生虫病、皮肤真菌病、胃肠道疾病、传染病、肝胆疾病、心肺疾病、腰病以及虚弱性疾病等等进行了归纳总结。同时指出,随着宠物饲养社会功能的变化,宠物中药将会伴随着宠物市场的扩大迎来更大的发展空间。     

The Determinants of Traditional Medicine Use in Northern Tanzania: A Mixed-Methods Study

Introduction

Traditional medicines are an important part of healthcare in sub-Saharan Africa, and building successful disease treatment programs that are sensitive to traditional medicine practices will require an understanding of their current use and roles, including from a biomedical perspective. Therefore, we conducted a mixed-method study in Northern Tanzania in order to characterize the extent of and reasons for the use of traditional medicines among the general population so that we can better inform public health efforts in the region.

Methods

Between December 2013 and June 2014 in Kilimanjaro, Tanzania, we conducted 5 focus group discussions and 27 in-depth interviews of key informants. The data from these sessions were analyzed using an inductive framework method with cultural insider-outsider coding. From these results, we developed a structured survey designed to test different aspects of traditional medicine use and administered it to a random sample of 655 adults from the community. The results were triangulated to explore converging and diverging themes.

Results

Most structured survey participants (68%) reported knowing someone who frequently used traditional medicines, and the majority (56%) reported using them themselves in the previous year. The most common uses were for symptomatic ailments (42%), chronic diseases (15%), reproductive problems (11%), and malaria/febrile illnesses (11%). We identified five major determinants for traditional medicine use in Northern Tanzania: biomedical healthcare delivery, credibility of traditional practices, strong cultural identities, individual health status, and disease understanding.

Conclusions

In order to better formulate effective local disease management programs that are sensitive to TM practices, we described the determinants of TM use. Additionally, we found TM use to be high in Northern Tanzania and that its use is not limited to lower-income areas or rural settings. After symptomatic ailments, chronic diseases were reported as the most common reason for TM use which may be particularly important in Northern Tanzania where non-communicable diseases are a rapidly growing burden.     

Association studies on human mitochondrial DNA: methodological aspects and results in the most common age-related diseases

Mitochondrial DNA (mtDNA) follows direct maternal inheritance and, as such, can be used in phylogenetic studies to determine a human lineage tree. The presence of common polymorphisms allows a classification of mtDNA in haplogroups and sub-haplogroups, according to the branch they belong to. Thanks to the rapidly growing number of mtDNA sequences available, this classification is being corrected and redefined to be more accurate. In parallel with this process, several studies are trying to identify an association between common mtDNA polymorphisms and common complex traits, as hypothesized by the common disease-common variant theory. Here we review the associations already reported with the main age-related complex diseases and we identify the critical points (sample size, size of the recruiting area, careful matching between cases and controls regarding geographical origin and ethnicity, data quality checking) to be taken in account in planning such studies. On the whole, this research area is opening a new perspective as an important component of "mitochondrial medicine", capable of identifying new molecular targets for the diagnosis, prevention and treatment of common complex diseases.     

Skeletal muscle adaptation to exercise: a century of progress.

Skeletal muscle physiology and biochemistry is an established field with Nobel Prize-winning scientists, dating back to the 1920s. Not until the mid to late 1960s did there appear a major focus on physiological and biochemical training adaptations in skeletal muscle. The study of adaptations to exercise training reveals a wide range of integrative approaches, from the systemic to the molecular level. Advances in our understanding of training adaptations have come in waves caused by the introduction of new experimental approaches. Research has revealed that exercise can be effective at preventing and/or treating some of the most common chronic diseases of the latter half of the 20th century. Endurance-trained muscle is more effective at clearing plasma triglyceride, glucose, and free fatty acids. However, at the present time, most of the mechanisms underlying the adaptation of human skeletal muscle to exercise still remain to be discovered. Little is known about the regulatory factors (e.g., trans-acting proteins or signaling pathways) directly modulating the expression of exercise-responsive genes. Because so many potential physiological and biochemical signals change during exercise, it will be an important challenge in the next century to move beyond "correlational studies" and to identify responsible mechanisms. Skeletal muscle metabolic adaptations may prove to be a critical component to preventing diseases such as coronary heart disease, type 2 diabetes, and obesity. Therefore, training studies have had an impact on setting the stage for a potential "preventive medicine reformation" in a society needing a return to a naturally active lifestyle of our ancestors.     

Meeting report: membrane proteins in health and disease.

This article summarizes the scientific presentations made at a Canadian Society of Biochemistry and Molecular & Cellular Biology Symposium on "Membrane Proteins in Health and Diseases" and two satellite meetings on "Bicarbonate Transporters" and "Nucleoside Transporters" held in Banff, Alberta, 20-24 March 2002. Membrane proteins are encoded by about 1/3 of genes and are involved in a wide range of essential functions, including the transport of nutrients, ions, and waste products across biological membranes. Mutations or changes in the expression of these genes cause an equally wide range of diseases. Membrane proteins are also common drug targets or provide drug entry mechanisms. The importance of membrane proteins in biology and medicine was highlighted by the presentations made at this exciting meeting by an international group of experts.     

Selecting SNPs for association studies based on population frequencies: a novel interactive tool and its application to polygenic diseases

Common complex polygenic diseases as autoimmune diseases have not been completely understood on a molecular level. While many genes are known to be involved in the pathways responsible for the phenotype, explicit causes for the susceptibility of the disease remain to be elucidated. The susceptibility to disease is thought to be the result of genetic epistatic interactions between common polymorphic genes. This polymorphism is mostly caused by single nucleotide polymorphisms (SNPs). Human subpopulations are known to differ in the susceptibility to the diseases and generally in the distribution of single nucleotide polymorphisms. The here presented approach retrieves SNPs with the most divergent frequencies for selected human subpopulations to help defining properties for the experimental verification of SNPs within defined regions. A web-accessible program implementing this approach was evaluated for multiple sclerosis (MS), a common human polygenic disease. A link to a summary of data from "The SNP Consortium" (TSC) with sex-dependencies of SNPs is available. Associations of SNPs to genes, genetic markers and chromosomal loci are retrieved from the Ensembl project. This tool is recommended to be used in conjunction with microarray analyses or marker association studies that link genes or chromosomal loci to particular diseases.     

基于脑-肠-微生物轴的肠易激综合征机制与治疗研究进展

肠易激综合征(irritablebowelsyndrome,IBS)是常见的功能性肠病之一,目前尚缺乏可用器质性疾病解释的临床特征,最新研究将其机制描述为脑-肠-微生物轴紊乱,强调了肠道微生物群在调节脑肠互动中的中介作用,而中医药对于脑肠稳态调节有着悠久广泛的治疗经验并取得了良好疗效,但两者关联性缺乏论述。因此,本文以脑肠轴为切入点,以肠道微生物作为介质,基于脑肠轴-中医药的良性互动,结合我们相关工作,综述了目前与脑-肠-微生物轴相关的IBS的中西医研究,为同行提供参考。     

Common opossum (<Emphasis Type="Italic">Didelphis marsupialis</Emphasis>Linnaeus, 1758): food and medicine for people in the Amazon

Background

In the Amazon rainforest, biodiversity is a significant resource for traditional communities, as it can be used as a relevant source of protein and it has a promising zootherapeutic potential. Studies on knowledge and ways how local peoples use the fauna are still incipient. This paper presents both the knowledge on and food and medicinal uses of common opossum (Didelphis marsupialis) by riverine communities in an Amazon floodplain region.

Methods

The study was conducted with riverine communities in the municipality of Abaetetuba, Pará, Brazil. The main methods used were structured and semi-structured interviews, the “snowball” technique, and participant observation.

Results

The study showed that D. marsupialis has an undeniable cultural significance for the local community, both in terms of food and medicine. Its meat is prized by inhabitants as it is classified as tasty, soft and, in some cases, it is designated as the best bushmeat in the region. The interviewees have demonstrated a thorough knowledge on various aspects of the animal’s biology, such as its diet, behavior, and places of occurrence. The hunting activity is practiced by men, but the preparation of meat and medicinal oil are tasks mainly performed by women. In medical terms, common opossum is used in the treatment of various diseases, such as rheumatism, asthma, sore throat, and inflammation. Given the importance of this species, its meat or live individuals are often sold in the city fair at prices that can reach R$ 40.00 (U$D 18,00) per individual.

Conclusions

D. marsupialis is an important source of protein for riverine communities in the region studied. Its fat is used as a traditional medicine and it is indicated for many types of diseases. Although the species concerned is treated with hostility in various Brazilian regions, in the case of Abaetetuba this animal is strongly prized due to the good quality of its meat. However, despite the value assigned to the species, its consumption should be the subject of further studies, as this marsupial species has been described as a reservoir for parasites that cause severe diseases.

     

Traditional ancient Egyptian medicine: A review

The ancient Egyptians practiced medicine with highly professional methods. They had advanced knowledge of anatomy and surgery. Also, they treated a lot of diseases including dental, gynecological, gastrointestinal, and urinary disorders. They could diagnose diabetes and cancer. The used therapeutics extended from different plants to include several animal products and minerals. Some of these plants are still used in the present day. Fortunately, they documented their life details by carving on stone, clay, or papyri. Although a lot of these records have been lost or destroyed, the surviving documents represent a huge source of knowledge in different scientific aspects including medicine. This review article is an attempt to understand some information about traditional medicine in ancient Egypt, we will look closely at some basics, sources of information of Egyptian medicine in addition to common treated diseases and therapeutics in this great civilization.     

Molecular genetics of human prion diseases in Germany

Human prion diseases may be acquired as infectious diseases, they may be inherited in an autosomal dominant fashion or occur sporadically. Mutations and polymorphisms in the sequence of the coding region of the prion protein gene (PRNP) have been established as an important factor in all of these three types of prion diseases. Therefore, a total of 578 patients with suspect prion diseases referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit over a period of 4.5 years have been examined for mutations and polymorphisms in the coding region of PRNP. We found 40 cases with a missense mutation previously reported as pathogenic. Amongst these, the aspartate to asparagine change at codon 178 (D178N) was the most common mutation. All of these cases carried the D178N mutation in coupling with methionine at codon 129, resulting in the typical fatal familial insomnia (FFI) genotype. Most cases with pathogenic mutations were not found in the group of clinically "probable" cases according to established clinical criteria, supporting the notion that inherited prion diseases often exhibit atypical features. Two novel missense mutations (T188R and P238S) and several silent polymorphisms were found, demonstrating the quality of our screening procedure based on a modified version of the single-stranded conformational polymorphism technique. In "definite" CJD cases with no pathogenic mutation, the patients clinically classified as "probable" were mostly homozygous for methionine at the common polymorphism at codon 129, whereas there was a marked over-representation of patients homozygous for valine amongst those clinically classified as "possible". This large study on suspect cases of human prion diseases in Germany clearly shows that PRNP genetics is essential for a comprehensive analysis of prion diseases.     

Foods and liver health

Chronic liver damage is a worldwide common pathology, characterised by an inflammatory and fibrotic process that leads to a progressive evolution from chronic hepatitis to cirrhosis and hepatocellular carcinoma (HCC). A major role for fats and oxidative stress has been recently demonstrated in the pathogenesis of liver diseases. In the clinical practice, dietary recommendations in the management of chronic diseases often rely on denying patients certain foods, which results in a severe reduction of quality of life. In this paper a new perspective based on the development of Food intended for Specific Medical Purposes (FSMP) containing highly bioavailable antioxidant compounds or polyunsaturated-fatty acids, has been highlighted as a tool for preventive and curative medicine, to be associated to pharmacological treatments.     

Perceptions and uses of Chinese medicine among the chinese in Hong Kong

The present paper was based on both qualitative observations and quantitative survey data. Major findings are as follows: (1) The sacred or magical-religious tradition of Chinese medicine is accepted by a relatively small portion (roughly one-fifth) of the ordinary Chinese people in urban Hong Kong, and is relatively more popular among women or less educated people. (2) Both the classical-professional and the local-empirical traditions of secular medicine are resorted to by many Chinese people (over one half) either for treating diseases or for strengthening their constitution. The acceptance of secular Chinese medicine does not vary significantly among different sex, age, education, or income groups. It should be noted that secular Chinese medicine is often used in addition to or in combination with modern Western medicine. (3) It appears that most people are more confident in the Chinese medical tradition than in Chinese-style practitioners in Hong Kong, and that people's confidence in secular Chinese medicine has been increasing in recent years. (4) There are reasons for the confidence in secular Chinese medicine. Chinese medicine is generally perceived to be better than or as good as Western, scientific medicine in some ways, such as for tonic care, for fewer side effects, for curing the cause (not symptoms) of diseases, and for treating certain diseases. Therefore, to ordinary Chinese people, Chinese and Western medicine may perform either equivalent or complementary functions. (5) As regards the process of seeking medical care, most people seem to follow the pattern of moving from self-medication, using Chinese and/or Western home remedies, to Western-style doctors, to Chinese-style practitioners, and finally to a Western medical hospital. Policy and theoretical implications of these findings are discussed.     

Evidence-based medicine,opinion-based medicine,and real-world medicine

The freedom of a doctor to treat an individual patient in the way he believes best has been markedly limited by the concept of evidence-based medicine. Clearly all would wish to practice according to the best available evidence, but it has become accepted that "evidence-based" means that which is derived from randomized, and preferably double-blind, clinical trials. The history of clinical trial development, which can be traced to the use of oranges and lemons for the treatment of scurvy in 1747, has reflected a progressive need to establish whether smaller and smaller effects of treatment are real. It has led to difficult concepts such as "equivalence" and aberrations such as "meta-analysis." An examination of evidence-based practice shows that it has usually been filtered through the opinions of experts and journal editors, and "opinion-based medicine" would be a more appropriate term. In the real world of individual patients with multiple diseases who are receiving a number of different drugs, the practice of evidence-based (or even opinion-based) medicine is extremely difficult. For each patient a judgment has to be made by the clinician of the likely balance of risks and benefits of any therapy. Good practice still requires clinical freedom for doctors.