By G. Cronos. Missouri Tech. 2019.

There are also approaches that will help you to change the underlying mechanisms at the root of your unhappiness buy cheap celebrex 100 mg on-line. I’m looking forward to sharing with you what I have found to be personally helpful for both my patients and myself 100 mg celebrex sale. Hopefully, this will provide you with your own insight into how to live in this world with greater peace and satisfaction. I believe that all of us are connected through our shared humanity and our universal mental suffering. Stress affects every human being on the road of life, but you’re in the driver’s seat now. Phil Blustein Calgary, Alberta December, 2014 1 What Your Body Has in Mind When You Don’t Mind Your Body tress is not the only cause of illness but it can certainly make what you do have worse. People get sick for multiple reasons, Swhich include genetics, lifestyle issues and environmental toxins. Stress is something that all people experience and it can lead to physical problems as well. Western medicine is fantastic at identifying and treating physical ailments, but it doesn’t emphasize and prioritize the contribution of underlying stress to these medical issues. I’d like to introduce you to some of my actual patients so you can start to connect the dots for yourself: Larry is a big man. He has a long-standing history of Crohn’s disease (an inflammatory condition of the bowel) and had already undergone surgery. When I inquired, he told me about having to care for his father who had recently died, and that he was laid off from a job that he had been working at for the last ten years. His diarrhea and abdominal pain had become progressively worse and worse until he ended up with a bowel obstruction that could only be corrected by yet another surgery. He had ignored a growing problem for a long time 5 6 • Mindfulness Medication but his body hadn’t. I was frustrated that I could only try to fix the damage done after the fact, instead of helping Larry learn how to interfere with the progression of his disease while he still had a chance to avoid the knife. She had left her family back home and they were depending on her to send back money to support them. Clearly under tremendous pressure, she began to experience problems with abdominal pain and an irregular bowel pattern with alternating diarrhea and constipation, gas and bloating. She also began having difficulty sleeping and was experiencing headaches and fatigue, which are often some of the first symptoms of ongoing stress. All of her medical tests came back normal and I diagnosed her with Irritable Bowel Syndrome. Again, Mika’s body was reacting to the levels of stress in her life and I was forced to just help her treat her symptoms, knowing that until she lowered her stress levels, she was in for more suffering, pain and grief. What’s common to both of these patients and many others, is that their symptoms are really secondary to, or aggravated by, the stress in their lives. If they had been able to understand what their stress levels were doing to their bodies before it made them sick and if they also had some help to then reduce their stress, perhaps I may never have met them at all! Let’s start by taking a look at what both Eastern and Western philosophies have to say about how you create and deal with stress. Rather than seeing them as separate, I have tried to integrate the tools and concepts that I have found to be most useful, regardless of point of origin. This integrative approach merges the best of Eastern and Western philosophy, medicine, and psychology as a means to understand the mind, how each of us creates stress, and how you can best learn to manage and minimize it. What Your Body Has in Mind • 7 Autonomic Physical and Psychological Responses Have you ever had to consciously tell your heart to beat, or your lungs to breathe, in order to make sure that they were doing their jobs? Your heartbeat and breathing are both examples of what scientists call autonomic involuntary behaviours. That’s a fancy way of saying that these biological activities carry on independently, without you having to be actively aware of what’s going on. The same can be said for a lot of the mental activities that carry on in your life. As an example, see if any of the following scenarios are familiar to you: • Have you ever had an experience where you drove from one spot to another and have suddenly realized that you don’t recall driving the last few blocks, or even the whole trip sometimes? Your mind is constantly thinking, evaluating and judging, as well as going over what happened in the past and your plans for the future. It’s what it does naturally, but unlike the moment-to-moment activities of the heart, or the lungs, the automatic thoughts that go through your head are something that can be observed, examined, changed and released. Your thoughts are the product of your experiences, your history, your biology and most importantly, your habits. External events conspire with the internal workings of your mind to create stress. Because your mind has the ability to literally think about itself, you can often find ways in which your habitual patterns of thought are maintaining a stress response.

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You need to accept and embrace both the possibility of productive change as well as the chance that your partner may remain stuck buy celebrex 200mg on-line. Accepting your partner is especially important when your efforts to help ✓ Result in an argument ✓ Seem ineffective 278 Part V: Helping Others with Anxiety ✓ Aren’t well-received by your partner ✓ Seem merely to increase your partner’s anxiety even after multiple expo- sure trials What does acceptance do? Acceptance allows you and your loved one to join together and grow closer safe celebrex 100mg, because acceptance avoids putting pressure on the one you care about. This message frees your loved one to ✓ Take risks ✓ Make mistakes ✓ Feel vulnerable ✓ Feel loved Change requires risk-taking, vulnerability, and mistakes. When people feel that they can safely goof up, look silly, cry, or fail miserably, they can take those risks. Giving up anxiety and fear takes tremendous courage in order to face the risks involved. Letting go of your need to see your partner change helps bol- ster the courage needed. When you take on the role of a helper, it doesn’t mean that your worth is at stake. Chapter 19 Recognizing Anxiety in Kids In This Chapter ▶ Seeing what’s making kids so scared ▶ Knowing when to worry about your kids’ anxiety ▶ Recognizing the usual anxieties of childhood ▶ Looking at the most common anxiety disorders among kids any adults can recall childhood as being a time of freedom, explora- Mtion, and fun. Not too many years ago, kids rode bikes in the street and played outside until dark. Now, anxious parents wait with their children at bus stops until they’re safely loaded. In this chapter, you discover the dif- ference between normal and problematic anxiety in kids. We explain that some childhood fears are completely normal, while others require interven- tion. If you’re concerned about a particular child, we urge you to seek professional diagno- sis and treatment. Numerous studies confirm this alarming development, but one in particular is a shocker. Psychologist Jean Twenge compared symptoms 280 Part V: Helping Others with Anxiety of anxiety in today’s kids with symptoms in seriously disturbed kids receiv- ing hospital treatment in 1957. She reported in the Journal of Personality and Social Psychology (December 2000) that boys and girls today report a greater number of anxiety symptoms than psychiatric inpatient children in 1957. The statistics are bad enough in their own right, but when you consider the fact that anxiety disor- ders often precede the development of depression later on, it raises concerns that the consequences of childhood anxiety could worsen in the years to come. Of course, we all know the complexities and tensions of the world today — longer work hours, rapidly developing technologies, violence on television, and even terrorism. We also suspect that certain types of parenting hold par- tial responsibility, as we discuss in Chapter 20. For the moment, what you as a parent need to know is how to distinguish the normal anxieties of childhood from abnormal suffering. Realize that the vast majority of kids feel anxious at various times to one degree or another. After all, one of the primary tasks of childhood is to figure out how to overcome the fears that life creates for everyone. Successful resolution of those fears usually results in good emotional adjustment. You just need to know whether your children’s fears represent normal development or a more sinister frame of mind that requires help. Look at Table 19-1 to get an idea of the anxiety that you can expect your children to experience at one time or another during their youth. Anxiety Problem When Anxiety Is When Anxiety Should Go Normal Away Fear of separation Common between If this continues with no from mother, father, or the ages of 6 months improvement after 36 to 48 caregiver and 24 months. Chapter 19: Recognizing Anxiety in Kids 281 Anxiety Problem When Anxiety Is When Anxiety Should Go Normal Away Fear of unfamiliar Common from age 2 If this continues without peers until around 3 years showing signs of reduc- old. Fear of animals, dark- Common between If these fears don’t start to ness, and imaginary ages 2 and 6 years. School phobia Mild to moderate This should decline and school or day-care cause no more than minimal phobia is common problems after age 6. A brief from ages 3 to 6; it reemergence at middle can briefly reappear school is okay, but it should when moving from quell quickly. Fear of evaluation by This fear almost It should gradually reduce others defines adolescence. But Most teens worry it’s not uncommon for it to a fair amount about last through the late teens. Table 19-1 gives you some general guidelines about so-called normal child- hood fears.

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We have a lymphatic system common to the entire body cheap celebrex 100 mg visa, which may be a source of disease cheap celebrex 200mg on-line. The apparatus for the removal of waste, is also to be taken into the estimate, for we have here sources of general disease. And finally we have to take into consideration the condition and forces of life - heat, electricity, and formative force. The reader will notice that classification grows more difficult as we progress, and calls for closer study, and more thought. But it has this in its favor, that it brings out all we know of medicine, and enables us to classify our own knowledge and that of the books, so as to make them useful. When we study local remedies we find that they may be classified in a similar manner, some of them readily, others with difficulty. We have remedies that influence the respiratory organs, the digestive apparatus, the urinary apparatus, the excretory apparatus - skin, kidneys, bowels - the brain, etc. We find also that some remedies may be classified as they influence special tissues - mucous membranes, serous membranes, connective tissue, bones, etc. Let us call this the first study of remedies, a study that recalls and fixes that which we know, and that gathers from books the essential facts, or what seems to us essential facts of drug action. It is work, but I will guarantee that the physician comes out of it stronger in mind, and very much better able to prescribe for disease. There are some things which can only be learned by experiment, and I would urge every one to some effort in this direction. You have your own bodies, and though you may value them highly, it will do little harm to test some medicines upon your own person. There is nothing in medicine that I would not test on my own person, if I was engaged in studying its action. Very certainly if the physician has occasion to take medicine for any disease, he should carefully note its effects from hour to hour. Let us call this the second method of studying remedies, it is the Homœopathic method, though employed to some extent by all classes of physicians. It gives most excellent and reliable results, and we can not afford to dispense with it. The third method is by carefully studying the effects of remedies administered for disease. This study can only be made to advantage where notes are kept, when care is used in the diagnosis, and when single remedies, or remedies that act in the same way, are employed, It is true that we can carry something in our memories, and by repeated observations facts will become familiar, but it is not a good plan to trust the memory too far. There are two things we want to know - the expression of disease, and the action of remedies - and in so far as we can, we want to associate them together. We may keep a record of cases with but little writing, if we have a plan to commence with. One word will sometimes express the condition of disease, it will rarely require more than a line. Now when giving remedies we may note nearly as briefly the reason why we have selected the remedy. Pulse small, frequent - Aconite; pulse frequent, sharp - Rhus; veins full - Podophyllum; tissues full, œdematous - Apocynum; muscular pain - Macrotys; nervous, free from fever - Pulsatilla; periodicity - Quinine; dull, stupid, sleepy - Belladonna; pain of serous membranes - Bryonia; dusky coloration of surface or mucous membranes - Baptisia; mucous membranes deep red - Acids; mucous membranes pale - Alkalies; feeble heart - beef-tea; strong circulation, high temperature - boiled milk. I give examples as my memory recalls them, but I think that the majority can have a record in about as many words. We do not want to write a book for other persons, but to make such notes as will enable us to recall the entire history of the disease, with its expressions that have suggested the use of the remedies employed. The reader will see that the record of the effect of the medicine can be easily kept. A 0 will tell the story of no effect, and a group of half a dozen adjectives will note the more important influences that we wish to record. In making a study of our working materia medica, it is well to note the advantages of carrying remedies, and of extemporaneous prescription at the bedside. The advantages are threefold - to the physician, to the patient, and to the friends. To the physician in that he learns his remedies better, and prescribes with greater certainty. To the patient, that the remedies are given in less doses, are promptly administered, and are not admixed with unpleasant vehicles, and are of more certain value and action. I have no special love for retail druggists, and many unpleasant experiences have shown me that it is quite possible to procure the poorest drugs in the market from them, and that it is quite uncertain what you will get in any given case. Of course there are many exceptions, but this is applicable to the druggist in ordinary, who makes it a rule to buy cheap, and sell dear.

The incidence of any investigator-reported musculoskeletal adverse event by the 1-year post-treatment follow-up in 487 ciprofloxacin-treated patients was 13% (64 patients) buy 100mg celebrex visa. The incidence of any neurologic event by 6 weeks of follow-up in ciprofloxacin­ treated patients was 7 buy celebrex 100 mg without prescription. Earlier hospital discharge or avoidance of hospital admission could become options for more patients, which in turn holds the potential to improve their quality of life. Myalgia is less frequently reported, but also found in a few case reports in the published literature. These safety concerns and the subsequent restriction of the use of fluoroquinolones in pediatric patients emanated from findings of cartilage damage in the weight- bearing joints of juvenile experimental animals. To date, there is little evidence that fluoroquinolone-associated arthropathy as described in experimental animals 1 correlates with the same phenomenon in humans. Fluoroquinolone-associated arthropathy in children has been described in the literature as a separate clinical phenomenon, distinct from that observed in laboratory animals and without damage 2 to cartilage. The available clinical information describing joint toxicity in humans comes largely from case reports, compassionate-use protocols, and worldwide clinical safety 3-6 databases. A large proportion of the patients included in these studies and reports 8 had cystic fibrosis, which may itself be associated with arthropathy. Tendinopathy appears to be a more significant adverse event associated with fluoroquinolone therapy that can 12 result in tendon rupture. Fluoroquinolone-associated tendinopathy appears to be more common in patients with tendons under high stress, and may pose a risk to those who 13,14 participate in sports or exercise. Other risk factors also have been identified, 15 including age, concomitant steroid therapy, and renal disease. The incidence of neurological side effects such as seizures, hallucinations, tremor, restlessness, dizziness, and headache was reported as approximately 0. Severe central nervous system adverse events such as psychotic reactions, hallucinations, depressions and grand mal convulsions occur at an incidence of less than 0. The primary objective of the studies included in the Written Request was to evaluate the long-term musculoskeletal and neurologic adverse events in pediatric patients (1 to 17 years) who received ciprofloxacin therapy. The current application was submitted in response to the Written Request issued September 23, 2003. It consists of two clinical trials in pediatric patients, a population pharmacokinetic analysis, and an animal toxicology study. Effective therapeutic intervention for children presenting with pyelonephritis is necessary because there may be a correlation between the degree of scarring and renal damage resulting from an infection when it is inappropriately treated. Although a number of patients are treated with long-term antibiotic prophylaxis, appropriate bowel management and a timed voiding schedule, recurrent infections often occur. In particular, illnesses such as nasal congestion, pharyngitis, anorexia or vomiting which alter fluid intake may make voiding less frequent and not forceful enough to clear away any bacteria that has made its way to the urethra and an infection may develop. Patients that experience more chronic infections or develop breakthrough infections while receiving antimicrobial prophylaxis often have isolates of enterococci, Proteus species, Pseudomonas species or Candida species. As a class, fluoroquinolones produce arthrotoxicity in juvenile dogs following 7 to 14 days of oral dosing. Pathological evidence of arthrotoxicity was observed at an oral dose level of 30 mg/kg/day. The study conducted by the sponsor examined multiple weight bearing joints during two weeks of dosing with ciprofloxacin at oral dose levels of 10, 30, and 90 mg/kg/day. Recovery and latent arthrotoxicity potential were examined in the recovery groups which were maintained for a period of five dose-free months; a period that covered complete musculoskeletal development. No evidence (clinical and histopathological) of arthrotoxicity was observed in male and female juvenile dogs dosed for 14 days at the 10 mg/kg/day dose level at the 24­ hour post-dosing terminal sacrifice and in male and female dogs held for the 5-month dose-free recovery period. The 30 mg/kg/day dose level did not result in clinical evidence of arthrotoxicity at any time during the study. Half of the juvenile dogs at the terminal sacrifice exhibited gross pathological and/or histopathological evidence of articular cartilage arthrotoxicity. The incidence and severity of the pathological and histopathological observations were reduced but still present in the 5-month post-dose recovery animals. Clinical evidence of arthrotoxicity was observed in 10 of 12 juvenile dogs at the 90 mg/kg/day dose level. These symptoms were resolved by Week 8 (six weeks into the post-dose recovery phase). All juvenile dogs exhibited articular cartilage lesions based upon gross pathology and histopathology at the terminal sacrifice (24 hours following the final dose). Similarly, all animals at the 5­ month post-dose recovery sacrifice from the 2-week, 90 mg/kg/day dosing routine exhibited both gross pathological and histopathological evidence of articular cartilage lesions.

Another Note: the citric acid kills bacteria purchase 100mg celebrex amex, while the car- bonation brings relief celebrex 100mg with mastercard. Squeeze 1 slice of lemon and 1 whole orange into an 8 ounce bottle that has a tight lid. Food Recipes Despite the presence of aflatoxins, benzopyrenes, and sol- vents in many foods, it is possible to have a delicious and safe diet. Help yourself to lots of butter, whipping cream, whole milk, avocados, and olive oil. Remember, when you are recovering from a major illness it is essential not to diet to lose weight. Change brands every time you shop to prevent the same pollutants from building up in your body. Be sure to drink plenty of plain water from your cold faucet throughout the day, especially if it is difficult for you to drink it with your meals. Never drink water that has been run through a water softener or copper plumbing or has traveled through a long plastic hose. To further improve flavor and to dechlorinate attach a small faucet filter made of carbon only. Because commercial cold cereals are very convenient, but have solvents, here are two replacements. If you would like to add nuts to your granola recipes, rinse them in cold tap water first, to which vitamin C powder has been added (¼ tsp. This will probably be the most heavenly peanut butter your mouth has ever experienced. Although I am prejudiced against all sugar from a health standpoint, my testing revealed no benzene, propyl alcohol, wood alcohol. However it does contain sorghum mold and must be treated with vitamin C to detoxify it. Get at least 4 flavors for variety: linden blossom, orange blossom, plain clover and local or wild flower honey. Add just enough water to keep the fruit from sticking as it is cooked (usually a few tablespoons). Soups All home made soups are nutritious and safe, provided you use no processed ingredients (like bouillon), or make them in metal pots. Always add a dash of vitamin C or tomato juice or vinegar to draw out calcium from soup bones for you to absorb. It can be taken straight from the freezer, rinsed, and placed in ¼ inch of milk (unboiled is fine) in the frying pan. Seven Day Sample Menu Because processed foods have many toxins, you must cook as much from scratch as possible. Or you could make a hot soup for dinner, refrigerate, and eat the leftovers for lunch. Try baking several potatoes at one time, refrigerate and put them in a salad the next night. Variety is the spice of life, so combine the allowed foods in the most creative ways you can imagine. Too Sick To Cook, Too Tired To Eat Pick three meals from the sample menu that need no cooking and eat them every day. Even if you have dry skin, difficult hair or some other unique requirement, just pure borax will satisfy these needs. A part of every skin problem is due to the toxic elements found in the soaps themselves. It does this by impregnating the skin and attracting water, giving the illusion of moist skin. In fact you simply have moist aluminum stuck in your skin which your immune system must remove. When you have used it down to the undissolved granules, add more water and shake again. It does not contain cobalt (the blue or green gran- ules) which causes heart disease and draws cancer parasites to the skin. It is the main ingredient of non- chlorine bleach and has excellent cleaning power without fading colors. For bleaching (only do this occasionally) use original chlorine bleach (not “new improved” or “with special brighteners”, and so forth). Any dish soap that you use should be safe enough to eat because nothing rinses off clean. Start each day by steril- izing your sponge (it harbors Salmonella) or with a new one while the used one dries for three full days. It does not lather but goes right to work removing sweat and soil without stripping your color or natural oils. Hair gets squeaky clean so quickly (just a few squirts does it) that you might think nothing has happened! Only citric acid is strong enough to get the borax out, lemon juice and vinegar are not.

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Tubes ssowed no gas productions at the end of 24+2 hours are reincubated and examined at the end of 48±3hrs celebrex 200 mg with visa. Confirmed test 362 ‚ All fermentation tubes showing gas production in presumptive 0 tests within 48 hours at 35 C shall be utilized in the confirmed test ‚ Eosin methylene blue( E celebrex 200 mg otc. B ) agar, Endo agar or brilliant green lactose bile broth fermentation tubes may be used in the test ‚ A loop-full of culture from each positive fermentation tubes is streaked over the surface of E. Development of typical colonies (nucleated, with or without metallic sheen) or atypical colonies (opaque, nonucleated mucoid, pink) the confirmed test may be considered positive ‚ If no colonies develop with in the incubation period the confirmed test may considered negative. B or Endo agar to lactose fermentations tubes and nutrient agar slants and incubate at appropriate temperature for a period not to exceed 48hours ‚ If Brilliant green lactose bile broth is used in the confirmed test, an E. B or Endo agar plate is streaked from each fermentation 363 tube showing gas and all plates should be incubated at appropriate temperature and period The purpose of the completed test is to determine ‚ The colonies developing on E,M. B or Endo agar are again capable fermenting lactose with the formation of acid and gas. Apparatus and Glassware a) Test tubes (18mmx180mm) b) Durham tubes (10mmx75mm) c) Pipettes 1(total-flow) 0 0 d) Incubators, 35±1 C, 37±1 C 0 e) Water bath, 45. B agar or Endo agar from each positive tubes in a way to obtain discrete colonies and incubate o for 18-24 hours at 35 C. Gram stains Procedure Preparation of food homogenate Prepare as described as above Dilution Prepare as described above. Incubation 0 Incubate the plates at 30 C for 20-24hours Counting of the colonies (presumptive B. Confirmation a) From typical colonies make smear and stain with Gram and examine microscopically. Nitrate broth tube: after 24 hours incubation at 35 0 C test for the reduction nitrate to nitrite iii. These media are simply reconstituted by weighing the required quantities and by adding distilled water, as per the manufacturer’s instructions. The quantity of agar given in the formulae of media may have to be changed depending upon the quality of agar used. The concentration varies from batch to batch and should be such that will produce a sufficiently firm surface on solidification. In some laboratories media are prepared by individual measurement of ingredients and then mixing the same. Hence the method of preparation is given likewise: 375 Nutrient broth Meat extract 10. Dissolve the agar in nutrient broth and sterilize by autoclaving at 121°C for 15 minutes. Glucose broth Nutrientbroth 900ml Glucose (10% solution) 100 ml • Dissolve 9 gm glucose in distilled water and sterilize by tyndallisation. Blood agar Nutrient agar 100 ml Sheep blood (defibrinated) 10 ml • Melt the sterile nutrient agar by steaming, cool to 45°C. Loeffler serum medium Nutrientbroth 100ml Serum(sheeporhorseorox) 300ml Glucose 1. Distribute in 100 ml quantities in a bottle and autoclave at 121°C for 15 minutes. Glycerolated blood tellurite mixture Sterile defibrinated sheep blood 14 ml Sterileglycerol 6 ml Sterile potassium tellurite solution (1% in water) 4 ml • Sterilize the glycerol in hot air oven at 160°C for 60 minutes and the tellurite solution by autoclaving at • 115°C for 20 minutes. One per cent solution of • good quality tellurite is sufficient but 2% of some batches may be required. Preparation of complete medium Glycerolated blood tellurite mixture 24 ml Agar base 100 ml 380 Melt the agar, cool to 45°C, add blood and tellurite and pour in sterile petri dishes. A-1 Medium Tryptone 20 g Lactose 5 g NaCl 5 g *Triton X-100 (Rohm & Haas) 1 ml Salicin 0. Dispense 10 ml portions of single strength broth into 18 x 150 mm tubes containing inverted fermentation vials. For double strength broth, use 22 x 175 mm tubes containing inverted fermentation vials. Dispense 15 ml into 20 x 150-mm screw-cap tubes and sterilize by autoclaving for 15 min at 121°C. Alkaline Peptone Agar Peptone 10 g NaCl 20 g Agar 15 g Distilled water 1 liter Boil to dissolve ingredients. Alkaline Peptone Water Peptone 10 g NaCl 10 g Distilled water l liter 383 Adjust pH so that value after sterilization is 8. Medium must be reduced before inoculation by 24 h anaerobic incubation in anaerobic glove box or GasPak jar. Anaerobic Egg Yolk Agar Agar base Yeast extract 5 g 384 Tryptone 5 g Proteose peptone 20 g NaCl 5 g Agar 20 g Distilled water 1 liter Autoclave 15 min at 121°C.

The advances in robotics allow assays to be fully automated and run continually day and night with minimal operator intervention cheap 100 mg celebrex amex. Molecular biology has provided the means to clone human receptors in a variety of cells and express different enzymes in model systems buy 200mg celebrex otc. Other detection systems use radioactive ligands, bioactivated fluorescent markers or fluorescent quenching approaches in which the interaction with the test compound causes a reduction in the fluorescence of a plate bound enzyme/receptor-conjugate. Novel, rapid methods of detecting both drug- ligand interations and receptor/enzyme activation are continually being developed in order to provide more rapid and sensitive detection systems. These lead compounds are then isolated and characterized, if necessary, before production and optimization on a larger scale. With the developments in high-throughput screening the issues of bioavailability and drug metabolism can be addressed at the earlier stages in the drug discovery/development program ultimately allowing the pharmaceutical industry to select compounds for development with acceptable bioavailability and metabolic profile, and reducing the development costs associated with developing a suitable means of delivering such agents. Nowhere is the impact of this new science more dramatic than in medicine and pharmaceutical drug discovery. Previously “invisible” traditional drug targets are today being examined in detail at the molecular level through the systematic analysis of the genes and proteins which encode them. Coupled with powerful approaches to determining protein structure, such as X-ray crystallography and Fourier-transform two- dimensional electron microscopy, their detailed molecular architecture and the molecular mechanisms by which they work are also being revealed. This molecular information, when coupled with a detailed knowledge of the pharmacological behavior of the same receptors in specific tisssues, gives pharmacologists and medicinal chemists new starting points for drug discovery and optimization, leading to more selective and potentially safer medicines. Currently, very few examples of the successful ab initio design of effective drugs exist, let alone their specific optimization for delivery. However, with the definition of robust molecular approaches for building specific delivery and activation characteristics into broad classes of drug, there is an increasing opportunity for converting already known drugs with limited selectivity into highly targeted agents. As the search for safer, more effective medicines continues, the availability of routine methods for optimizing delivery is one stage of the development process which offers considerable commercial potential. It has been a stimulating period for molecular biology, with a raft of innovative technologies providing the basis for profound advances in our appreciation of the inner workings of cells, tissues and, increasingly, whole organisms. A heady mixture of scientific opportunism and commercial exploitation has led us to the point where virtually all the genes in the human genome are now known. However, as unfair as it may seem, this genetic heritage is not yet available to all scientists. A small number of companies still hold the keys to the majority of these genes, 364 and, with recent developments, it looks as though the same may prove true for the framework sequence of the entire genome. Potentially more frustrating for the academic scientist, the patenting of such information may lock away the fruit of genomics for decades to come. From this it has proved possible to survey the majority of the genes expressed in a particular cell or tissue. The broad applicability of such techniques not only to tissues but also to established cell lines and model cell systems is illustrated in Figure 15. The latter effort is still under way in companies as well as in public institutions. The economies of scale provided by industrial-scale sequencing have hastened progress to the point where at least two companies now have the majority of expressed human genes in their freezers. This has certainly had the effect of restricting access to key therapeutic genes, but on the other hand subscribers to these proprietary databases have early access to information which would not otherwise be available. At the moment, the main beneficiaries of this commercial effort are pharmaceutical and biotech companies who see such access as conferring a significant competitive advantage on their research and development activities. Although there are as yet no methodologies for real-time gene expression observations, the attempt by companies such as Incyte and Affymetrix to place whole genomes on silicon chips, together with the advent of continuous flow hybridization approaches, promises a much greater depth to temporal analysis of complex biological processes than hitherto possible, bringing with it new opportunities for defining appropriate therapeutic intervention points in complex biological cascades. This information can now be complemented by hybridization array approaches, in which the expression of defined subsets of genes (or indeed the expression of entire genomes) can be carefully monitored at high volume across specific time courses and dose regimens, providing a degree of accuracy and reproducibility in determining the level of gene expression which sequencing alone cannot achieve. Together, sequencing and arraying techniques can be used to provide information on both the biology of disease and the behavior of compounds as they impact a biological system. The scientific basis of hybridization arraying as a technique for the determination of gene expression levels is shown in Figures 15. A full description of these hybridization arraying approaches has been published and is also available on the Web (see Table 15. Access to comprehensive sequence databases and the bioinformatics tools to analyze them plays a central role in these gene expression monitoring approaches, illustrating their “reach-through” impact in genomics in general. A further technique which holds considerable promise for evaluating individual gene expression at the histological or cellular level is in situ hybridization. This provides a cellular level of resolution to gene expression analysis which complements that of microarray analyses. All the above techniques have major potential applications in drug delivery, from defining new members of key transporter and receptor gene families and their expression, to providing experimental systems for evaluating the efficacy of new delivery systems. Similar databases will undoubtedly emerge from mammalian systems as mammalian cell genome closure and proteomics advance. Systematic approaches to biological function are encompassed within the broad area of “functional genomics”. For most of this century, our knowledge of cell biology has been primarily descriptive, reproducible in vitro work dating only from the 1960s.