The other type is rare and only 1 in 10 order vasodilan without a prescription arteriogram,000 to 1 in 100 best order for vasodilan blood pressure normal lying down,000 persons may be affected purchase vasodilan paypal blood pressure medication olmetec. Mutant alleles at a single gene locus are the best studied individual risk factors for adverse drug reactions, including the genes for N-acetyltransferases, thiopurine methyltransferase, dihydropyrimidine dehydro- genase, and cytochrome P450. However, pharmacogenetic factors rarely act alone; rather they produce a phenotype in concert with other variant genes such as those for receptors and with environmental factors such as cigarette smoking. Most idiosyncratic drug reactions are unpredictable and because of their rarity my not show up in patients during clinical trials with a few thousand patients. They may ﬁrst surface when the drug has been taken by hundreds of thousands of patients in the post-marketing phase. Pharmacogenetics, by individualizing treatment to patients for whom it is safe, provides a rational framework to minimize the uncer- tainty in outcome of drug therapy and clinical trials and thereby should signiﬁcantly reduce the risk of drug toxicity. Topiramate, an anticonvulsant medication, is an efﬁcacious treatment for alcohol dependence. Future studies in larger samples are needed to more fully establish these preliminary ﬁndings. In other situations, it may help in the adjustment of dose of the drug such as in warfarin therapy. Clinical signs include unexplained elevation of end-tidal Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 119 carbon dioxide, muscle rigidity, acidosis, tachycardia, tachypnea, hyperthermia, and evidence of rhabdomyolysis. However, it is invasive, requiring skeletal muscle biopsy and is not widely available. Researchers have begun to map mutations within the ryanodine receptor gene (chromosome 19q13. Pharmacogenetics of Clozapine-Induced Agranulocytosis Clozapine has long been accepted as one of the most effective medications for treat- ing schizophrenia but has had limited utilization due to the risk of inducing agranu- locytosis, a life-threatening decrease of white blood cells that requires frequent blood testing of patients. This raised the hope for a one-time genetic test may obviate the need for continuous blood monitoring for the majority of clozapine- treated patients. These ﬁndings have uncovered new clues to the underlying biological and physiologic mechanisms of drug-induced agranulocytosis and provide a starting point for eluci- dating a common mechanism across drugs from different classes that carry this rare but devastating side effect. The sensitivity and selectivity of these biomarkers could support further development of a diagnostic test. However, no genetic test is currently available for clozapine-induced agranulo- cytosis. Candidate gene studies have failed to identify a strong, replicated genetic variant that substan- tially increases risk of clozapine-induced agranulocytosis. Combined analysis of such studies may identify associated genetic variants that can be rapidly translated to clinical practice. Universal Free E-Book Store 120 4 Pharmacogenetics Role of Pharmacogenetics in Warfarin Therapy Warfarin (Coumadin) is the most commonly prescribed oral anticoagulant for the treatment and prevention of thromboembolic events. The correct mainte- nance dose of warfarin for a given patient is difﬁcult to predict, the drug carries a high risk of toxicity, and variability among patients means that the safe dose range differs widely between individuals. Recent pharmaco- genetic studies indicate that the routine incorporation of genetic testing into warfa- rin therapy protocols could substantially ease both the ﬁnancial and health risks currently associated with this treatment (Reynolds et al. The labeling update is a milestone that brings personalized medicine to the main- stream. To this end, there are numerous studies currently ongoing looking at outcomes when genetic tests are incorporated into warfarin treat- ment. The Harvard Partners Center for Genetics and Genomics, Medco and the Mayo Clinic, Clinical Data and PharmaCare, and the University of Utah under the Critical Path Initiative, are all researching the clinical utility of pharmacogenetics-based war- farin dosing. Mutations in three speciﬁc genes can increase an individual’s risk for dangerous blood clots and their leading complication, and is an indication for warfarin therapy. The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are signiﬁcantly closer to the required sta- ble therapeutic dose than those derived from a clinical algorithm or a ﬁxed-dose approach (The International Warfarin Pharmacogenetics Consortium 2009). Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 121 A genome-wide association study found gene polymorphisms that affect the anticoagulant effect of warfarin (Takeuchi et al. These results provide justiﬁcation for conducting large-scale trials assessing patient beneﬁt from genotype-based forecasting of warfarin dose. Role of Pharmacogenetics in Antiplatelet Therapy The antiplatelet agent clopidogrel (Plavix) is used in the management of cardiovas- cular disease and stroke, but genetic mutations may reduce the effect of this drug. Persons with these gene variants carry double or triple the risk of death, myocardial infarction or stroke, compared with people with the normal metabolism alleles. It is currently in a clinical trial Universal Free E-Book Store 122 4 Pharmacogenetics in Canada, and the data from the pharmacogenomic study will help support regula- tory ﬁlings for the combined use of the test with Plavix. In patients undergoing coronary stent placement, a single *17 gene variant resulted in about a twofold increase in the incidence in bleeding within 30 days fol- lowing stent placement. Patients with the double *17/*17 genotype exhibited a dose-response fourfold increase in bleeding (8 %). The most striking ﬁnding was that among the patients tested, 35 % had the single *17 variant and another 5 % had the *17/*17 genotype. According to the recommendation from the American College of Cardiology on genotyping for clopidogrel, genotyping may be considered for identifying poor metabolizers in “moderate to high risk patients” as alternate therapies are available (Holmes et al. In response to this publication, cardiologists from Scripps Health as well as colleagues from Vanderbilt University and Hôpital Pitié-Salpetrière in Paris pointed out what they see as ﬂaws in the review analysis. Moreover, the meta-anal- ysis did not test for heterogeneity among patients who underwent stenting versus those who were medically treated. It is obvious that a metal implant in a coronary artery would pose a particular vul- nerability to inadequate platelet suppression. Role of Pharmacogenetics in Statin Therapy Lowering low-density lipoprotein cholesterol with statin therapy results in substan- tial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger beneﬁts. In 10–20 % of cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications and is a reason for discontinuation. The ﬁnding raises hope that a test could be developed to screen patients to ﬁnd out who is at greatest risk for developing this adverse reaction. Although there is a statin-gene association for myopathy in the case of some statins, the usefulness of this information still needs to be proven (Giorgi et al. The problem is that it will take thousands and thousands of patients to screen in order to validate a particular marker. Because of the rarity of such events, the prospect of predicting them by genetic biomarkers is viewed as not only daunting but unlikely. The Critical Path is also linking the Association of Clinical Research Organizations with the Clinical Data Interchange Standards Consortium to form the Clinical Data Acquisition Standards Harmonization project. Areas of focus in this effort are bioinformatics and data standards, biomarkers, establishing public-private partnerships, and developing guidance and regulations. It is also partnering with researchers at Duke University to look for rare variants corre- sponding to adverse reactions to the antipsychotic drug clozapine.
Patients with little life expectancy or who have a poor functional status may beneﬁt by incorporating palliative or hospice care into their treatment plan 20 mg vasodilan with mastercard heart attack under 30. External beam chemoradiotherapy may be helpful when the disease is locally advanced and causing signiﬁcant morbidity buy vasodilan 20mg on-line prehypertension in young adults. Debulking surgery has no role in the treatment of ad- vanced pancreatic cancer since the risk of the procedure is similar to that of a curative resection and offers no survival beneﬁt purchase vasodilan pills in toronto blood pressure chart calculator. In carotenoderma, the ingested pigment is predominantly deposited in the palms, soles, forehead, and nasolabial folds. When there is jaundice, skin pigment deposition does not depend on sun expo- sure. Over time, with bilirubin deposition, sun exposure oxidizes bilirubin to biliverdin causing a green discoloration of the skin in light-skinned patients. Transcutaneous biopsy carries with it the theoretical risk of seeding the surrounding tissues as the needle is passed. Endoscopic ultrasound-guided ﬁne-nee- dle aspiration is increasing being utilized for biopsies as there is less risk of intraperito- neal spread of tumor. A negative biopsy or ﬁne-needle aspiration may not be sufﬁcient to rule out a neoplasm when the lesion is small. The dismal prognosis for advanced disease calls for prompt surgical referral for potentially curable lesions. She has taken over- currently describes it as periumbilical and radiating into his the-counter nonsteroidal anti-inﬂammatory drugs with- groin and legs. She wants to know what is wrong with her knee also had episodic severe testicular pain, bowel urgency, nau- and what may have caused it. His past medical history is signiﬁcant the following represents the most potent risk factor for of hypertension that has recently become difﬁcult to control. Previous joint injury normal ﬁrst and second heart sounds without murmurs, and an S4 is present. Abdominal palpation demonstrates minimal diffuse other past medical history and takes no medications. No masses are examination is signiﬁcant for an intact neurologic exami- present, and the stool is negative for occult blood. His Laboratories show a normal white blood cell count, he- neurologic examination is intact. Microscopic polyangiitis ploratory laparoscopy for acute abdominal pain and pre- D. Polyarteritis nodosa 345 Copyright © 2008, 2005, 2001, 1998, 1994, 1991, 1987 by The McGraw-Hill Companies, Inc. A 58-year-old female presents complaining of right the hospital for congestive heart failure, renal failure, and shoulder pain. Physical examination on admission was notes that she feels that the shoulder has been getting notable for these ﬁndings and raised waxy papules in the progressively more stiff over the last several months. The patient’s past medical history is ocrit was 24%, and white blood cell and platelet counts also signiﬁcant for diabetes mellitus, for which she takes were normal. Further evaluation included right shoulder is not warm or red but is tender to touch. A 44-year-old woman presents for evaluation of dry plaining of painful arthritis that is worse in the mornings eyes and mouth. She was recently evaluated by an years ago and the symptoms have worsened over time. A recent lab- She describes her eyes as gritty-feeling, as if there were oratory report shows an erythrocyte sedimentation rate sand in her eyes. Which of the following will be helpful in dis- that it is difﬁcult to be outside in bright sunlight. In addi- tinguishing relapsing polychondritis from rheumatoid tion, her mouth is quite dry. Relapsing polychondritis will present with high-titer changes, her dentist has had to place ﬁllings twice in the rheumatoid factor. A 66-year-old woman with a history of rheumatoid She takes no medication regularly and does not smoke. Her oral mucosa is dry heart rate is 110 beats/min, blood pressure is 104/78 with thick mucous secretions, and the parotid glands are mmHg, and oxygen saturation is 97% on room air. Laboratory examination reveals posi- left knee is swollen, red, painful, and warm. She has tion, her chemistries reveal a sodium of 142 mEq/L, evidence of chronic joint deformity in her hands, knees, potassium 2. A 32-year-old African-American woman presents to her which the patient states have been there for many months. Which protein do you expect to ﬁnd on immu- about 6 months ago, and at that time, a complete blood nohistochemical staining? Fibrinogen α-chain She has also developed joint stiffness and pain in her hands, C. Immunoglobulin light chain wrists, and knees that is present for about 1 h upon awaken- D. A 41-year-old female presents to your clinic with 3 she intermittently developed painful mouth ulcerations that weeks of weakness, lethargy. She also reports a severe “sun- notes increasing difﬁculty with climbing steps, rising from burn” on her face, upper neck, and back that occurred after a chair, and combing her hair. The patient also notes some past medical history is positive for two spontaneous vaginal dyspnea on exertion and orthopnea. She is taking oral contraceptive pills and has no tions, and the past medical history is otherwise uninfor- allergies. The physical examination is notable for an beats/min, respiratory rate 12 breaths/min, SaO2 98% on elevated jugular venous pressure, an S , and some bibasilar room air. This area has an atrophic center proximal muscle weakness in the deltoids and biceps and with hair loss and is erythematous with a hyperpigmented the hip ﬂexors. Her conjunctiva are pink and no scleral icterus is examination and reﬂexes are normal. The oropharynx shows a single 2-mm aphthous ul- remarkable except for a negative antinuclear antibody ceration on the buccal mucosa. All the following clinical condi- The patient is incapable of closing her hands tightly. In addi- tions may occur in polymyositis except tion, there is warmth and a possible effusion in the right knee and tenderness with range of motion in the left knee. A 64-year-old man with congestive heart failure pre- Mean corpuscular hemoglobin count 32 g/dL sents to the emergency room complaining of acute onset of Platelet 98,000/mL severe pain in his right foot. The pain began during the night The differential is 80% polymorphonuclear cells, 12% lym- and awoke him from a deep sleep.
In the authors view there is no doubt that untreated caries in the primary dentition causes abscesses order vasodilan 20mg hypertension unspecified, pain discount vasodilan 20 mg on line blood pressure medication drug test, and suffering in children proven vasodilan 20mg blood pressure chart pdf download. This can then need hospital admission and invasive treatment, sometimes under general anaesthesia, whereas a simple restoration, at the time when the caries was diagnosed, would have prevented this extremely distressing episode for the child. It is therefore essential for all dentists involved in the care of young children to learn restorative techniques that give the best results in primary teeth and this should always be alongside excellent preventive programmes, and this chapter is devoted to the discussion of such techniques. A treatment philosophy which the authors believe is effective in the management of caries in children is shown in Table 8. High quality restorative care is supplemented with prevention in the form of sealants placed in other molars deemed to be susceptible to future carious attack. Such an approach can be justified where it is likely that remineralization would occur or the tooth maintained in a state, free from pain or infection until exfoliation. More work is required on this concept but the following sections discuss conflicting reasons to treat or not to treat particular carious lesions. However conservative the technique it is inevitable that some sound tooth tissue has to be removed when operative treatment is undertaken. This weakens the tooth and makes it more likely that problems such as cracking of the tooth or loss of vitality of the pulp may occur in the future. Key Point • Every time that a restoration is replaced more sound tissue has to be removed, putting the tooth at further risk. It is almost inevitable when treating an approximal lesion that the adjacent tooth will be damaged. The outer surface has a far higher fluoride content than the rest of the enamel so that even a slight nick of the intact surface will remove this reservoir of fluoride. Additionally, it has been shown that early lesions that remineralize are less susceptible to caries than intact surfaces and these areas of the tooth are all too easily removed when preparing an adjacent tooth. It is virtually impossible to avoid damaging the interdental papillae when treating approximal caries. The papillae can be protected by using rubber dam and/or wedges and if well-fitting restorations are placed the tissues will heal fairly rapidly, but long-term damage can be more critical. Many adults can be seen to be suffering from overenthusiastic treatment of approximal caries in their youth; and while the relative import-ance of poor margins compared to bacterial plaque can be debated, the potential damage from approximal restorations is sufficient reason to avoid treatment unless a definite indication is present. Poor restoration of the teeth can, over time, lead to considerable alteration of the occlusion. However, this can allow the teeth to erupt into contact again or the interocclusal position to change and alter the occlusion. Often this is felt to be of little concern, but there are a large number of adults where the cumulative effect of many poorly restored teeth has severely disturbed the occlusion, thus making further treatment difficult, time consuming, and expensive. Even when coarse criteria such as those developed for the United Kingdom Child Dental Health Surveys are used, there is wide variation between examiners. It is not just variations between examiners that need to be considered as there is also a marked difference between the same examiner on different occasions. The implications need to be considered in relation to the decision to treat or not. Caries usually progresses relatively slowly, although some individuals will show more rapid development than others. The majority of children and adolescents will have a low level of caries and progress of carious lesions will be slow. In general, the older the child at the time that the caries is first diagnosed the slower the progression of the lesion. In addition, it is now accepted that the chief mechanism whereby fluoride reduces caries is by encouraging remineralization, and that the remineralized early lesion is more resistant to caries than intact enamel. Although it is difficult to show reversal of lesions on radiographs, many studies have demonstrated that a substantial proportion of early enamel lesions do not progress over many years. Surveys of dental treatment have often shown a rather disappointing level of success. In general, 50% of amalgam restorations in permanent teeth can be expected to fail during the 10 years following placement. Some studies have shown an even poorer success rate when looking at primary teeth, and this has been put forward as a reason for not treating these teeth. The fact that the treatment of approximal caries can cause damage to the affected tooth, the adjacent tooth, the periodontium, and the occlusion is a valid reason to think twice before putting bur to tooth. But, of course, a case could equally well be made that the neglect of treatment will cause as much or more damage. Lack of treatment can, and all too often does, lead to loss of contact with adjacent and opposing teeth, exposure of the pulp resulting in the development of periapical infection, and/or loss of the tooth. At worst, the child may end up having a general anaesthetic for the removal of one or more teeth. While it is true that the rate of attack is usually slow, it is quite possible for the rate in any one individual to be rapid so that any delay in treatment would not then be in the best interests of the child. Because of the normally slow rate of attack it is difficult to be sure if a lesion is arrested or merely developing very slowly. It is true that remineralization will arrest and repair early enamel lesions, but there is, in fact, little evidence that remineralization of the dentine or the late enamel lesion is common. Some of these dentists have published their results, which show that the great majority of their restorations in primary teeth survive without further attention until they exfoliate. The treatment procedures used are not particularly difficult in comparison to others that dentists attempt on adults, and it is difficult to avoid the conclusion that the reasons for poor results in some studies are due to poor patient management and lack of attention to detail. It should be the aim of the profession to develop better and more effective ways of treating the disease rather than throwing our hands up in surrender. Small restorations are more successful than large, and therefore if a carious lesion is going to need treatment it is better treated early rather than late. The fact that small restorations are often more successful makes for difficult decisions when the management of caries involves preventive procedures, which need both time to work and time to assess whether they have been effective. Each child is an individual and treatment should be planned to provide the best that is possible for that individual. Too often treatment is given which is the most convenient for the parent or, more likely, the dentist. Is it really in the best interest of the child to remove a tooth which could be saved? In the United Kingdom, general anaesthesia is still widely used for removing the teeth of young children despite the risks of death, its unpleasantness, and the cost involved. However, if the pulp of a carious permanent tooth is exposed then a considerable amount of treatment may be required to retain it, and the prognosis for the tooth would still be poor. Primary teeth are often considered by parents and some dentists as being disposable items because there comes a time when they will be exfoliated naturally. Losing a tooth early gives a message to the child that teeth are not valuable and not worth looking after. A well-restored primary dentition can be a source of pride to young children and an encouragement for them to look after the succeeding teeth.
Even the most useful disease biomarkers such as prostate-speciﬁc antigen vasodilan 20mg for sale arteria tapada del corazon, are proteins order 20 mg vasodilan with amex arrhythmia consultants. The pathomechanism-based medicine of the future will require input from proteomics for the understanding of how protein pathways link genes to diseases order 20mg vasodilan with mastercard blood pressure ranges by age. It is important to understand how the protein function gets deranged in order to design molecules that will correct the aberrant protein. After a lead molecule is identiﬁed, one needs to conﬁrm the efﬁcacy of the drug through the expected mechanism. Proteomics can be used to study the mode of action of drugs by comparing the proteome of the cells in which the drug target has been eliminated by molecular knockout techniques or with small molecule inhibi- tors believed to act speciﬁcally on the same target. Proteomic techniques enable study of protein expression levels, modiﬁcations, location and function in high throughput automated systems. Because proteome analysis can produce comprehensive molecular description of the differences between normal and diseased states, it can be used to compare the effect of candi- date drugs on the disease process. Proteomics can be integrated into the drug discov- ery process along with the genomic and chemical drug discovery. Proteomics may emerge as a powerful approach for directly identifying highly predictive pharma- cogenomic biomarkers in blood or other body tissues. Deﬁnition and validation of drug targets by proteomics will have the following advantages for drug discovery: • Fewer dropout compounds in the developmental pipeline • Rational drug design of compounds with fewer side effects Role of Proteomics in Clinical Drug Safety Clinical chemistry endpoints for routine animal toxicity testing and clinical trial safety monitoring have been used for over 25 years. Drug-induced damage to the liver is the most common type of toxicity that results in a treatment being withdrawn from clinical trials or from further marketing. Similarly, cardiotoxicity is a frequent occurrence in patients undergoing cancer chemotherapy. However, the currently available biomarkers for these common types of drug-induced toxicities have lim- ited sensitivity or predictive value. The proteomic tools available today are enabling us to tap into the wealth of genome sequence information to discover and carefully investigate associations of thousands of proteins with drug-induced toxicities that are now not easily monitored. Toxicoproteomics Proteomics can increase the speed and sensitivity of toxicological screening by identifying protein markers of toxicity. Proteomics studies have already provided insights into the mechanisms of action of a wide range of substances, from metals Universal Free E-Book Store 166 6 Pharmacoproteomics to peroxisome proliferators. Current limitations involving speed of throughput are being overcome by increasing automation and the development of new techniques. Toxicoproteomics involves the evaluation of protein expression for the under- standing of toxic events. Transcriptional proﬁling and proteomics are used to com- pile toxicology predictors. Afﬁnity-based biosensor technology is being investigated to proﬁle lead compound-protein interactions. Immobilized artiﬁcial membrane chromatography is being evaluated to predict oral compound absorption. Some examples of application of proteomics in toxicology are given in the following sections. Hepatotoxicity Studies on the rodent liver proteome show that several compounds cause increased proliferation of peroxisomes and liver tumors. Peroxisome proliferators are found to induce protein expression changes as a distinct protein signature. Experimental evi- dence suggests that activation of acetaminophen and subsequent formation of protein adducts are involved in hepatotoxicity. Most of the changes caused by acet- aminophen occur in a subset of the proteins modiﬁed by acetaminophen. Many of the proteins that show changed expression levels are involved in the regulation of mechanisms that are believed to drive acetaminophen-induced hepatotoxicity. Complementary strategies of 2D gel electrophoresis, coupled either with database spot mapping or protein isolation and amino acid sequencing, have successfully identiﬁed a subset of proteins from xenobiotic-damaged rodent livers, the expres- sion of which differs from controls. Lovastatin treatment is associated with signs of toxicity as reﬂected by changes in a heterogeneous set of cellular stress proteins involved in functions such as cytoskeletal structure, calcium homeostasis, protease inhibition, cell signaling or apoptosis. These results present new insights into liver gene net- work regulations induced by lovastatin and illustrate a yet unexplored application of proteomics to discover new targets by analysis of existing drugs and the pathways that they regulate. Mitochondrial respiration is a useful parameter of cytotoxicity for in vitro hepatotoxicity screening, as cytotoxicity can be detected during an early stage of exposure. In addition to the conventional biomarkers, several protein biomarkers, which relate to oxidative stress and metabolism-regulation, can also be detected. Further comprehensive analysis of deﬁned proteins would be necessary to estimate more sensitive toxicology biomarkers. Nephrotoxicity An example of dose-related nephrotoxicity is that caused by cyclosporine A which has proven beneﬁcial effects in organ transplantation. This shows that proteomics can provide essential information in mechanistic toxi- cology. Monitoring of proteins in the urine enabled a more detailed understanding of the nature and progression of the proteinuria associated with glomerular nephrotoxicity than was previously possible. Neurotoxicity Neurotoxicant-induced changes in protein level, function, or regulation could have a detrimental effect on neuronal viability. Direct oxidative or covalent modiﬁcations of individual proteins by various chemicals or drugs are likely to lead to disturbance of tertiary structure and a loss of function of neurons. The proteome and the func- tional determinants of its individual protein components are, therefore, likely targets of neurotoxicant action and resulting characteristic disruptions could be critically involved in corresponding mechanisms of neurotoxicity. Proteomics, therefore, offers a comprehensive overview of cell proteins, and in the case of neurotoxicant exposure, can provide quantitative data regarding changes in corresponding expression levels and/or post-translational modiﬁcations that might be associated with neuron injury. Universal Free E-Book Store 168 6 Pharmacoproteomics Applications of Pharmacoproteomics in Personalized Medicine Examples of clinical applications of proteomic technologies will be given in various chapters dealing with therapeutic areas. Advantages of use of pharmacoproteomics in personalized medicine are: • Pharmacoproteomics is a more functional representation of patient-to-patient variation than that provided by genotyping. Personalized medicine in the age of pharmacoproteomics: a close up on India and need for social science engagement for responsible innovation in post- proteomic biology. Reverse-phase protein microarrays: application to biomarker discovery and translational medicine. Universal Free E-Book Store Chapter 7 Role of Metabolomics in Personalized Medicine Metabolomics and Metabonomics The human metabolome is best understood by analogy to the human genome, i. In a systems biology approach, metabolo- mics provides a functional readout of changes determined by genetic blueprint, regulation, protein abundance and modiﬁcation, and environmental inﬂuence. Metabolomics is the study of the small molecules, or metabolites, contained in a human cell, tissue or organ (including ﬂuids) and involved in primary and interme- diary metabolism. By deﬁnition, the metabolome should exclude enzymes, genetic material and structural molecules such as glycosaminoglycans, and other polymeric units that are degraded to small molecules but do not otherwise participate in meta- bolic reactions. According to the Metabolomics Society, “Metabolomics is the study of meta- bolic changes. It encompasses metabolomics, metabolite target analysis, metabolite proﬁling, metabolic ﬁngerprinting, metabolic proﬁling, and metabonomics”.