By A. Bozep. The Rockefeller University.

Until recently order diabecon 60 caps online, life has been highly focused on training generic diabecon 60caps on-line, but now the resident has begun to realize that they are lonely 60caps diabecon visa. This resident has few friends, has not dated anyone in sev- eral years, and has no real interests outside of training. The resident wonders if they are depressed, even though their mental and physical health have previously been excellent. Introduction Conceptual frameworks can help us to quickly grasp the re- lationships among complex ideas and to clarify the terms of a discussion. This guidebook uses such a framework to pro- pose a common understanding of the essential components of physician health, and in fact to broaden the defnition of Physician enfranchisement is another complex area, given the physician health. This framework is represented schematically position of physicians as private practitioners or contractors. The ensuing discussion will describe its Our advocacy skills are often put to the test in our relation- main components. Yet the resulting exchange, negotia- Systemic issues tion, debate and interchange helps build a better system for Physicians are educated and work within a medical system that all. It is essential that such communication not only continue, has an identity, a regulatory code, a set of expectations, unique but be encouraged. It is important to acknowledge their advocacy skills for only so long before they feel forced that physicians have little immediate control over “the system,” into a diffcult choice such as leaving their practice or, worse, and to a considerable degree are controlled by it. The system and the profession need to system has strengths that contribute to physicians’ professional acknowledge that they nurture and sustain each other, and that health. Canadian health care embodies generally held values of they achieve far more synergistically than they do as adversar- universal access to health services, protection of society’s most ies. Physicians can promote their own health and well-being by vulnerable members, and the notion of collective contributions being actively involved in medical policy and decision-making, to the health of the nation. Physicians are thus part of the very volunteering with their medical associations and colleges, and fabric that defnes the Canadian ethos, and this fact in itself using their advocacy skills to promote a vision of a healthy sustains many of us during our most challenging hours. The physician’s white coat serves many pur- some physicians struggle to remain connected to friends and poses, including facilitating professional detachment from the family and to sustain personal pursuits while juggling the tragedy, horror and pain encountered on a daily basis. However, it is important to maintain important that we remain in touch with who we are, how we non-professional ties. Multiple social connections promote feel, our methods of responding and reacting to our world, and emotional resilience and good health, while isolation fosters our ideas about what makes us healthy—or not. Like all other human beings, physi- can make our responses more compassionate to similar stories cians are in a continuous process of personal change. The better we understand our physical selves need care and maintenance, their sexual self inner selves, the better we can manage our own strengths and matures and evolves, and their use of health services increases. In general, mental resilience increases over time while vulner- abilities retreat. People with mental illness still experience cians are always growing and developing. Stagnation is rare, social stigma, and even within the house of medicine mental ill- and where it exists may signal ill-health. Although attitudes others, many of life’s challenges centre on transitions: from are changing, the medical profession must continue to address residency to practice, from one career stage to another, from the stigmatization of mental illness as an essential aspect of one personal milestone to the next. At certain times—such as during train- Case resolution ing, major professional or personal transitions, or when deal- In the absence of other symptoms, it is unlikely that the ing with complaints or litigation—physicians are particularly resident is mentally ill. By openly talking about such vul- experiences led to a pessimistic view of adult relationships nerabilities, ensuring safe and rapid access to support services and for the resident to be overly self-reliant. By sacrifcing and programs, and promoting resilience, medical schools and many aspects of normal development (e. Professionally, this has led to For example, weight gain is common issue among students isolation from colleagues and perhaps patients; personally, and residents and usually occurs in the context of a shift in it has resulted in loneliness and potential despair. The challenges posed by chronic health conditions In some ways, the resident needs to complete adolescence are also important to acknowledge, as are the needs of trainees and early adulthood. Students and residents with disabilities have self, identify two or three activities to pursue during free rights that require respect and consideration, and training time (e. Medicine is a profession based In turn, this connection and insight will help promote on interpersonal relationships. The ability to form a meaning- self-resilience and promote a sustainable practice. Conceptual Framework Learning ineness, humour, empathy, insight and compassion are typical Object. This section will It identifes the elements that are typically considered essential • consider the meaning of medical professionalism, to the physician’s Professional Role. Defning professionalism • propose ways to build resiliency in the Professional Role. Case While working in a hospital, a fourth-year resident is con- tacted by a community pharmacist who wants to clarify the dose of narcotic prescribed for a physician colleague and friend.

Wearable e-skins Measuring easily quantifiable data is the key to a better health order 60caps diabecon overnight delivery, therefore the future belongs to digestible cheap diabecon 60 caps with amex, embedded and wearable sensors buy generic diabecon 60caps on line; the latter working like a thin e-skin. These sensors will measure all important health parameters and vital signs from temperature, and blood biomarkers to neurological symptoms 24 hours a day transmitting data to the cloud and sending alerts to medical systems when a stroke is happening real time. Examples include hydration sensors for athletes and intelligent textiles that change color indicating diseases. Whether you are a patient or a medical professional, follow the 1 main trends and try to be up-to-date by using digital methods. Constantly look for solutions to improve your practice as a 2 medical professional or your health as a patient. Embrace digital in a comfortable way and use techniques that 3 make your life easier and your work more efficient. No matter how important role digital will play in our lives, human 8 touch is and will always be the key in the doctor-patient relationship. You Tomorrow This work is licensed under the Creative Commons Attribution-NonCommercial- NoDerivs 3. The formation of the Ghana Psychic and Traditional Healers Association in 1961 and the establishment of the Centre for Scientific Research into Plant Medicine in 1975 attest to this fact. Also in 1991 the government established a unit for the coordination of Traditional Medicine (which is now Traditional and Alternative Medicine Directorate) which was followed by the setting up of the Food and Drugs Board in 1992, which among others, is to certify the sale of Traditional Medicine products to the public. Although all these documents provide a legal policy framework for the development of Traditional Medicine, there is no single document that coordinates the general policy direction of government in the area of traditional medicine. It cuts across sectoral boundaries and provides a national position for which all sectors have to buy into. Almost all the relevant traditional medicine institutions and organizations were involved in the process of developing the document. Others included were Sociology and Biochemistry Departments of the University of Ghana and the Faculty of Pharmacy of the Kwame Nkrumah University of Science and Technology. It is hoped that the document will be relevant to all government institutions working towards the development of Traditional Medicine. The potential of traditional medicine has been recognized by successive governments. The establishment of the Traditional and Alternative Medicine Directorate of the Ministry of Health is to coordinate the activities of policy initiation and implementation. For the Directorate to work effectively there is the need for a general policy direction for coordinating activities in the area of traditional medicine. The objective is to provide a general policy direction or framework within which government short to long term plans on Traditional Medicine would be based. The policy cuts across sectoral boundaries and provides a national position for which all sectors have to use as a basis for developing plans for traditional medicine development. It provides employment to indigenous people and there is the need to improve the practice. The main problems affecting the practice of Traditional Medicine include the lack of information on practitioners including their qualification, registration, educational background, location, number and the products used in their practices. Other problems include inappropriate premises for practice, inadequate record keeping by practitioners, inadequate facilities for diagnosis and the use of un-standardized products. In most cases there are no recognized locally accredited training institutions and/or professional bodies. The purpose is to offer patients/clients options of health service from which to choose. Individual association appears not to be well represented at the grassroots level and there is often misunderstanding and lack of information sharing amongst stakeholders. Suspicion between members of different groups, personality projections, and power and ego clashes are not uncommon. The management of the organization of practitioners shall be decentralized to the regional, district, sub-district and community levels. Traditional Medicine Practice Council will be required to regulate practices particularly in the private sector. Also, personnel at these levels would have to provide management support for the organization of the associations. The structure for managing and regulating practitioners would have to be formalized through a national legislation that will lead to formation of a regulatory Council. Among practitioners there is ignorance about the meaning, implication and workings of patent laws and rights as well 4 as the availability of trademark registers and protection. It is worth nothing that plants cannot be patented but knowledge of use of plants and formulation of the plant products can be patented. The next step is to design training programme and schedule that would fit the convenience of the practitioners given that they have other economic interests.

He intro- duced magnetic feld gradients and by analysis of the characteristics of the emitted radio waves generic diabecon 60 caps line, he was able to determine their origin discount 60 caps diabecon otc. In 1973 206 he demonstrated how it was possible to see the difference between tubes flled with water from an environment of heavy water buy generic diabecon 60 caps line. These very frst experiments showed that one could use a set of simple linear gradients, oriented in three dimensions and slowly build up a picture. Peter Mansfeld showed how the radio signals could be mathematically analyzed, which made it possible to develop a useful imaging technique. This snap-shot technique meant that in principle complete two-dimensional images could be achieved in extremely short times like 20 – 50 ms. They are rapidly turned on and off (which causes that banging noise), and the gradient magnets allow the scanner to image the body in slices. The transverse (or axial, or x-y) planes slice you from top to bottom; the coronal (x-z) plane slice you lengthwise from front to back; and the sagittal (y-z) planes slice you lengthwise from side to side. Y Coil Z Coil X Coil Transceiver Patient An illustration of the feld gradient coils. Mansfeld showed how the radio signals can be mathematically analyzed, and thus made the image possible. Echo-planar imaging allows T weighted im- 2 ages to be collected many times faster than previously possible. The electromagnets consist of a so- lenoid cooled down to about 4 K by liquid helium. At such temperatures superconduction is attained and it is possible to send large currents through the solenoid and thus get the large magnetic felds required. For parts of the body with bones it is dif- fcult to use x-rays to study the tissue around – because the bones absorb the x-rays much more than the tissue. This is a Lanthanide element (atomic number 64) that is paramagnetic and has the effect that it strongly decrease the T1 relaxation times of the tissues. These compounds are taken up by, and accumulate in, glycolytically active cells, such as rapidly dividing tumor cells. These compounds also bind to albumin in the blood, allowing for the assessment of blood volume at tumor sites prior to cellular uptake (similar to imaging with gadolinium), a valuable diagnostic indicator and tool for treatment response in its sur- roundings. Formation of ultrasound In 1880 Pierre Curie and his brother Jacques discovered that certain crystals (the socalled piezoelec- tric crystals) can produce a pulse of mechanical energy (sound pulse) by electrically exciting the crystal. Furthermore, the crystals can produce a pulse of electrical energy by mechanically exciting the crystal. This ultrasound physics principle is called the piezoelectric effect (pressure electricity). Crystalline materials with piezoelectric properties are quartz crystals, piezoelectric ceramics such as barium titanate or lead zirconate titanate. A device that converts one form of energy into another is called a “transducer” – and they can be used for production and detection of diagnostic ultrasound. We are not going into more details about the equipment here, but it is possible to use ultrasound tech- nique to produce pictures of the inside of the body. Since ultrasound images are captured in real-time, they can show the structure and movement of the body’s internal organs, as well as blood fowing through the blood vessels. Ultrasound imaging is a noninvasive medical test that helps physicians diagnose and treat medical conditions. A short history The origin of the technology goes back to the Curies, who frst discovered the piezoelectric effect. Attempts to use ultrasound for medical purposes startet in the 1940s when they used a contineous ultrasonic emitter to obtain images from a patient`s brain. The use of Ultrasonics in the feld of medicine had nonetheless started initially with it’s applications in therapy rather than diagnosis, utilising it’s heating and disruptive effects on animal tissues. An excellent review of the history of ultrasound can be found in the following address: http://www. The transducer is coupeled to the body by a gel and the pulse of ultrasound goes into the soft tissuse (speed of about 1500 m per second). The transducer will then sense the refected, weaker pulses of ultrasound and transform them back into electrical signals. These echoes from different organs are amplifed and processed by the receiver and sent to the computer, which keeps track of the return times and amplitudes. You can see how arms and legs of a fetus move, or see the heart valve open and close. Computer Receiver A lot of technology is involved in the different parts Transducer of the ultrasound technique. Let us shortly mention that the transducer, that trans- mits and receives the ultrasound energy into and from the body is a key component. It is built up of hundreds of transducers in order to take a high reso- The main components of ultrasound lution real-time scan. The many transducers create a wavefront and the angle of the wavefront can be altered by fring the transducers one after another. By changing the angle of the wavefront, a three-dimensional image can be built up over a large area.

Serum cholesterol diabecon 60 caps overnight delivery, blood pressure cheap 60 caps diabecon with visa, cigarette smoking diabecon 60caps sale, and death from coronary heart disease. Changes in cholesterol synthesis and excretion when cholesterol intake is increased. Effect of dietary egg on variability of plasma cholesterol levels and lipoprotein cholesterol. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. Effects of dietary cholesterol on the regulation of total body cholesterol in man. Tissue storage and control of choles- terol metabolism in man on high cholesterol diets. Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity. Control of serum cholesterol homeostasis by choles- terol in the milk of the suckling rat. The role of orphan nuclear receptors in the regula- tion of cholesterol homeostasis. Genetic factors influence the atherogenic response of lipoproteins to dietary fat and cholesterol in nonhuman primates. U-shape relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness and evidence for extreme inter- individual variation in dietary cholesterol absorption in humans. Is relationship between serum choles- terol and risk of premature death from coronary heart disease continuous and graded? Dietary palmitic acid results in lower serum cholesterol than does a lauric-myristic acid combination in normolipemic humans. The effect of increased egg consump- tion on plasma cholesteryl ester transfer activity in healthy subjects. Dietary fats and lung cancer risk among women: The Missouri Women’s Health Study (United States). Tzonou A, Kalandidi A, Trichopoulou A, Hsieh C-C, Toupadaki N, Willett W, Trichopoulos D. A prospective cohort study on dietary fat and the risk of postmenopausal breast cancer. Dietary oxysterols are incorporated in plasma triglyceride-rich lipoproteins, increase their suscepti- bility to oxidation and increase aortic cholesterol concentration of rabbits. Apolipoprotein A4-1/2 polymorphism and response of serum lipids to dietary cholesterol in humans. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: A meta-analysis. Total and high density lipoprotein cholesterol as risk factors for coronary heart disease in elderly men during 5 years of follow-up. Egg yolk and serum-cholesterol levels: Impor- tance of dietary cholesterol intake. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants. Dietary choles- terol, fat, and lung cancer incidence among older women: The Iowa Women’s Health Study (United States). Effect of egg choles- terol and dietary fats on plasma lipids, lipoproteins, and apoproteins of normal women consuming natural diets. Proteins also function as enzymes, in membranes, as transport carriers, and as hormones; and their component amino acids serve as precursors for nucleic acids, hormones, vitamins, and other important molecules. For amino acids, isotopic tracer methods and linear regression analysis were used whenever possible to deter- mine the requirements. The estimated average requirements for amino acids were used to develop amino acid scoring patterns for various age groups based on the recommended intake of dietary protein. Moreover, the constituent amino acids of protein act as precursors of many coenzymes, hormones, nucleic acids, and other molecules essential for life. Thus an adequate supply of dietary protein is essential to maintain cellular integrity and function, and for health and reproduction. Proteins in both the diet and body are more complex and variable than the other energy sources, carbohydrates and fats. The defining char- acteristic of protein is its requisite amino (or imino) nitrogen group. The average content of nitrogen in dietary protein is about 16 percent by weight, so nitrogen metabolism is often considered to be synonymous with protein metabolism. Carbon, oxygen, and hydrogen are also abundant elements in proteins, and there is a smaller proportion of sulfur.

Post delivery deaths from all causes dropped 95%+ when delivery attendants buy cheap diabecon 60caps, midwives cheap diabecon 60 caps amex, and physicians started washing their hands with soap purchase diabecon 60caps mastercard. You can also finger sweep the mouth or in a pinch put your mouth over the baby’s mouth and nose and suck gently. Clean cord, cloth strips, or cord clamps to tie off the cord, and a sterile (if possible – otherwise immaculately clean) instrument/blade/scissors to cut the cord. Neonatal tetanus from cord cutting with dirty instruments accounts for ¾ of all tetanus deaths worldwide. Do you know why they always run around boiling water & ripping up sheets in old movies featuring a delivery? The hot water is, of course, wanted for washing hands and instruments, but also hot moist packs can be placed against mom’s perineum to help relax the muscles and tissue, and allow them to stretch easier with less chance of - 111 - Survival and Austere Medicine: An Introduction tearing. This is a technique which is completely lost in modern obstetrics that works well. Also ensure that you have a hand basin immediately available for frequent hand washing. Problems are more likely to arise with the first baby, with older mothers, mothers with previous delivery complications and/or multiple previous deliveries. There are several areas where problems arise; the following is just an overview of the more common: Obstructed labour/slow progress: Midwives are experts at encouraging slowly progressing labour without medical interventions. Currently if labour fails to progress it is augmented with oxytocin or a caesarean section. When there is no prospect of vaginal delivery due to obstructed labour or malpresentation then there are two options for delivery: Forceps/suction delivery or caesarean section. The reality for most is that in a primitive situation this will be beyond the midwife; if the baby is unable to be delivered the mother will die. Breech presentations: This is where the baby is coming bottom first rather than normal headfirst. During normal birth the head moulds itself and slowly stretches the birth canal to a size it can pass through. As a consequence there is a risk of the head becoming stuck or the baby being asphyxiated before the head can be delivered. There are a number of measures, which are well described in the references aimed at delivering breech babies. If the baby dies during the birth process they can usually still be delivered without endangering the mother’s health. Infection: One of the biggest killers relating to childbirth prior to the last century was infection. It is not uncommon today particularly with more complicated deliveries but fortunately it is very responsive to antibiotics. You need to pay very close attention to antisepsis, ensure that if possible sterile gloves are worn, sterile instruments are used, and if gloves are not available that you wash your hands very thoroughly with soap and water. Early bleeding is caused by failure of the uterine muscles to contract and close off the connection site of the placenta; lacerations of the cervix especially the anterior lip, vagina, vulva; retained fragments or pieces of placenta; abnormal location of the placenta during the pregnancy (like all the way into the uterine muscle); rupture of the uterus; inversion/prolapse of the uterus; bleeding disorders & coagulopathies (blood clotting problems) either as a result on inheritance or pre-eclampsia/eclampsia. The most common cause is failure of the uterine muscles to clamp down (atony), lacerations especially the cervix, and retained placental fragments. Blood loss after delivery is normal in this amount, and assuming that mom was healthy and not severely anaemic before delivery is not a problem. Also it is normal for bleeding to continue in small amounts after the delivery, and bloody mucus (lochia) can continue for some time. But continued bright red bleeding like a heavy period or greater amounts, increasing size of the uterus (womb), etc. Palpate the fundus (the top of the uterus); is the uterus firm and small (so well contracted and probably not the source of bleeding), soft and small (possibly not well contracted – maybe bleeding, or soft and big or getting bigger (not contacted and probably filled with blood)? Use gloves and examine outer vulva & rectum for tears, examine inside vagina for same, examine anterior cervical lip. Bleeding will either be coming from a visible source, or out of the cervix with no visible tears and, therefore, intrauterine – coming from within the uterus. If the cause of bleeding is an obvious external or vaginal laceration manage appropriately with a repair. Consult the reference sections for more details on the basics of obstetric repairs. Most heavy bleeding occurs simply because the uterus will not contract or a piece of placenta is left behind. Nipple stimulation either through breastfeeding or direct stimulation releases the hormone oxytocin which stimulates contractions and is the first treatment choice. If large and soft, firm pressure on the fundus may expel accumulated blood clots and assist contraction.

The course proved to be very successful and was deemed by participants to have fully achieved its objectives and their personal objectives also order diabecon 60 caps mastercard. A variety of capture techniques were taught with the main focus on the advanced technique of cannon netting order diabecon 60 caps overnight delivery. Cannon netting has the potential to allow the capture of large numbers of ducks (the main target for avian influenza surveillance) and is of particular use in areas where other trapping methods cannot be used buy discount diabecon 60 caps on line. Duplicate sets of avian influenza cloacal and oropharyngeal swab samples were taken from trapped (1) waterbirds, one set for in-country analysis at the National Veterinary Research Institute, Vom, Nigeria, and one set for the New FluBird partner University of Kalmar, Sweden. Cannon netting is a technical, complex and potentially hazardous trapping technique and successful cannon netters and cannon netting teams require certain key attributes. Many of the already experienced participants proved themselves to be very technically adept and capable bird trappers and with a little extra training within existing experienced cannon netting teams should be competent at being part of a regional cannon netting team capable of both national and international wild bird surveillance programmes. Epidemic/epizootic West Nile virus in the United States: guidelines for surveillance, prevention, and control. Proceedings of the 2nd Technical Meeting of the Scientific Task Force on Avian Influenza & Wild Birds, Avian Influenza & Wildlife Workshop on ‘Practical Lessons Learned’, Aviemore, Scotland: 26 – 28 June 2007. Manual on the preparation of national animal disease emergency preparedness plans. Key questions to ask when a disease is detected: geographic range, wetland characteristics, host range, seasonality, transmission, field signs and potential impacts. Factsheets on a selection of diseases currently impacting wetlands providing a brief description of the disease and the methods used for prevention and control. For the purposes of this Manual a wetland disease is considered to be one that either occurs in wetlands or is caused by agents that depend on wetlands. Diseases with water-borne pathogens and/or aquatic hosts such as amphibian chytridiomycosis, crayfish plague and epizootic ulcerative syndrome are obvious diseases of wetlands. There are numerous other diseases (such as bovine tuberculosis and some of the tick- borne diseases) which, at first consideration, would seem to be unrelated directly to water and wetlands. This may, for example, relate to seasonal rainfalls, heralding temporary wetlands, flushes of vegetation attracting high densities of waterbirds or grazing ungulates and conditions for hatch-off of large numbers of invertebrate vectors. The diversity and density of both wetland triggers, thus, result in ‘seasonal’ disease – and terrestrial hosts at wetlands allows us to related to water and wetlands. Considering understand how these ‘meeting places’ allow disease wetlands, temporary or permanent, as emergence and transmission. One of the greatest central causes of disease problems in wetlands is the issue of faecal contamination in wastewaters from both humans and livestock. The problem is particularly great where there are intensive animal rearing facilities or high densities of people with poor or little sanitation and sewage treatment. The shared nature of so many infectious diseases across the sectors of humans, livestock and wildlife [►Figure 2-3] illustrates how inadequate or breakdowns in water management, hygiene and sanitation, can lead to wider infection in hosts of other sectors which can then perpetuate infection cycles and spillback into the original sector. Instead, the Manual focuses on principles and practices of disease management with specific information on only a sub-set of priority animal diseases of wetlands. Prioritisation of important diseases is not as easy as it sounds as ‘importance’ may depend on personal, cultural or organisational perspectives. Taking an ecosystem approach to health helps ensure that diseases are seen, and dealt with, from a broader perspective with an understanding and appreciation of the interconnectivities. An experts workshop was held in 2010 to perform a disease prioritisation exercise and identify which diseases were of greatest importance, for which specific factsheets would be produced. The aim of the workshop was to identify approximately 30 of these priority animal diseases of wetlands which also impact humans, ensuring that this subset contained at least some diseases of each animal taxa, and for all regions of the world, to help maximise the utility of the Manual. The first task of the workshop drew up a long list of animal diseases associated with wetlands. Each disease’s relevance to wetlands was scored, priority being given to those diseases where either the host, pathogen/toxin or vector was entirely dependent on wetlands. Diseases were then scored according to their impact on: Wildlife health (data were often lacking so expert judgements were made); Livestock health; Human health; and Livelihoods. A number of diseases, such as tick-borne diseases were grouped together as many of the practical approaches to managing them were similar. The scoring was then summed, using a weighting towards relevance to wetlands and impacts on wildlife. This decision was made given the focus of the Manual and the available information already in existence regarding livestock diseases. Ultimately, the factsheets that were produced and presented within this chapter, cover a broad range of priority animal diseases in wetlands, and together cover at least some diseases of all taxa, in various geographical regions. Points for consideration The reader must appreciate that the factsheets presented within this chapter represent information on only a sub-set of diseases and thus must not constraint thinking with respect to trying to diagnose a disease. Animal health expertise should always be sought when making decisions on priority diseases of particular wetlands. It is also worth understanding that many disease problems are multifactorial and a single disease may not be responsible. The causes of lesser flamingo mortality events appear to be multifactorial and not due to one specific disease.

Modern biotechnology makes use of the technique to block metabolic pathways in the body involved in disease pro- cesses cheap diabecon 60caps mastercard. Like other therapeutic proteins order diabecon 60caps without prescription, antibodies must there- fore assume the correct molecular arrangement to be effective purchase 60 caps diabecon amex. Biopharmaceuticals: This structural sensitivity also causes problems biological instead of because proteins do not always automatically as- chemical production sume the required structure during the produc- tion process. Long chains of amino acids in solu- tion spontaneously form so-called secondary structures, arranging themselves into helical or sheetlike structures, for ex- ample. However, this process rarely results in the correct overall shape (tertiary structure) – especially in the case of large pro- teins where the final structure depends on the interactions of several, often different, amino acid chains. During natural biosynthesis of proteins in the body’s cells, a se- ries of enzymes ensure that such ‘protein folding’ proceeds cor- rectly. The enzymes prevent unsuitable structures from being Drugs from the fermenter 29 Diverse and changeable: the structure of proteins primary structure } A chain of up to twenty different amino acids (primary struc- ture – the variable regions are indicated by the squares of dif- ferent colours) arranges itself into three-dimensional struc- secondary tures. The position of these secondary structures in rela- tion to one another determines the shape of the protein, i. Often, a number of proteins form func- tional complexes with quaternary structures; only when arranged in this way can they perform their intended func- tions. When purifying proteins, it is extremely difficult to retain such protein complexes in their original form. These strictly controlled processes make protein production a highly complex process that has so far proved impossible to replicate by chemical means. Instead, proteins are produced in and isolated from laboratory animals, microorganisms or special cultures of animal or plant cells. Natural sources limited Biological production methods do, however, have several disadvantages. The straightforward ap- proach, isolating natural proteins from animals, was practised for decades to obtain insulin (see article ‘Beer for Babylon’). But the limits of this approach soon became apparent in the second half of the 20th century. Not only are there not nearly enough slaughtered animals to meet global demands for insulin, but the animal protein thus obtained differs from its human counter- part. The situation is similar for virtually every other biophar- maceutical, particularly since these molecules occur in animals in vanishingly small amounts or,as in the case of therapeutic an- tibodies, do not occur naturally in animals at all. Most biopharmaceuticals are therefore produced in cultures of microorganisms or mammalian cells. Simple proteins can be 30 Little helpers: the biological production of drugs The bacterium Escherichia coli is relatively easy to cultivate. For complicated substances consisting of several proteins or for substances that have to be modified by the addition of non-protein groups such as sugar chains, mam- malian cells are used. To obtain products that are identical to their human equivalents, the appropriate human genes must be inserted into the cultured cells. These genetically manipulated cells then contain the enzymes needed to ensure correct folding and processing of the proteins (especially in the case of mam- malian cells) as well as the genetic instructions for synthesising the desired product. In this way a genetically modified cell is obtained which produces large quan- tities of the desired product in its active form. Biotech production: each But multiplying these cells poses a technological facility is unique challenge, particularly when mammalian cells are used to produce a therapeutic protein. Cells are living organisms, and they react sensitively to even tiny changes in their environment. From the nutrient solution to the equip- ment, virtually every object and substance the cells touch on their way from, say, the refrigerator to the centrifuge can affect them. Drugs from the fermenter 31 High-tech cell cultivation: biotechnological production facility in Penzberg Large-scale industrial production facilities for biopharma- smallest impurity can render a batch useless. These factors determine not only the yield of useful product but also the quantity of interfering or undesired byproducts and the structure of the product itself. As a result, each biopharmaceu- tical production plant is essentially unique: Changing just one of hundreds of components can affect the result. Focus on Chinese Laboratories and manufacturers around the hamster cells world work with standard cell lines to produce biopharmaceuticals, enzymes and antibodies. These cell lines are used because they are well researched and, as far as is possible with living organisms, are amenable to stan- dardisation. Biotech researchers insert structural and control genes into the cells of these and similar lines to produce the desired pharma- ceutical. This establishes a new cell line, which is usually treated as a closely guarded company secret.