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Marieke Kruidering-Hall PhD

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University of California, San Francisco

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In these medicine examples buy lumigan 3ml with amex, insulin receptor response is decreased while insulin production may be normal symptoms walking pneumonia discount lumigan 3 ml without prescription, increased or decreased medications metabolized by cyp2d6 discount 3ml lumigan. Sudden shock medicine ubrania buy lumigan american express, trauma or tragic event in the family, heredity and excess body weight are contributory factors. The onset is gradual and the ailment is detected during a routine medical check-up. If the diet is suitably modified and regular exercise is taken, these persons do not need insulin except during stressful days. Other types of Diabetes Mellitus: A third type of diabetes occurs in association with certain conditions. These include chronic pancreatitis or as a corollary to intake of some medications such as glucocorticoids, antihypertensives, etc. In this type the plasma glucose levels are higher than normal, but lower than those indicative of diabetes. The blood glucose returns to normal after delivery; but many of these women develop diabetes mellitus in later years. Nutrition in Diabetes Mellitus 295 Nutritional Care: is the cornerstone of diabetic therapy. The aim is to attain and then maintain a healthy weight for the body size and type. Such diets improve glucose tolerance control, often decreases insulin requirements and tends to lower serum cholesterol and triglyceride values. The soluble fibres (pectin, gums, hemicelluloses) present in fruits increase transit time, slow glucose absorption and lower serum cholesterol. Fenugreek seeds, recommended as addition to diabetic diet in ancient medical system, are valuable due to their high content of mucilaginous and total fibre. It also contains an alkaloid (trigonelline), which is known to lower blood sugar level. Of these saturated fats contribute about a fourth (7-10%), monounsaturated half (10-13%) and polyunsaturated about a fourth (8-10%) of the total energy. In a 2000 calorie diet, the calories from fat would thus be 400 to 600, which amounts to about 45 to 65 grammes of fat in the diet, a third of it is taken in hidden form. Hidden fats content of diet varies, but is estimated to provide about a third or more of the total fat in the diet. Thus the visible fat intake in the diet as butter, ghee and oil used in food preparation can be 30 to 40 grammes. In order 296 Fundamentals of Foods, Nutrition and Diet Therapy to control the saturated fat intake, the amounts of animal foods such as ghee, butter, cheese, eggs and meats must be monitored to provide less than 15 grammes of the total fat intake. Adolescent children, pregnant or nursing mothers need increased intake up to 15 to 20 per cent of total energy. Sweeteners: Use of artificial sweeteners in reasonable amounts is acceptable to control total calorie intake. Sodium: A moderate sodium intake of 1 gram/1,000 calories is recommended, because many diabetics are hypertensive or have hypertension. Foods containing sodium such as pickles, papads, and baked foods containing baking powder should be avoided. Alcohol: Alcohol is not a food and its use places an additional burden on the system. Its use is not advisable especially when oral hypoglycemic agents are to be taken as part of the therapy. Hence the meal plan should be based on her/his normal schedule, meal pattern, food acceptance, food preparation methods and facilities available. Meal plans should be realistic, attractive and flexible, within the limits of the diet prescriptions. Meal Distribution: It is important to distribute the carbohydrate foods in the meals through out the day. As these persons use insulin, the carbohydrate intake should coincide with the action time of the insulin used. Exchange Lists: the patient must study the food exchange lists available for planning diabetic diets (Table 28. Plan the menu by dividing the food exchanges into various meals according to the patient’s need and choice. Ensure that you include whole grain cereal preparations (chapatis, bhakari/roti, whole wheat preparations, etc. The sugar can be used in tea/coffee and jaggery can be used in food preparation, especially in dal, usal and vegetables. It is believed that it will prevent or postpone further complications of diabetes mellitus. If taken orally, it would be digested like any food protein and will not be able to regulate the use of blood glucose. The amount of insulin needed depends on the patient’s requirements; it can be reduced by exercise, while any infection or other stress may result in increased need. A number of types of insulins are available with different duration and speed of activity. Most diabetics, who need insulin, take one dose daily, while a few may need two doses per day. It has many beneficial effects: It helps to maintain weight, heart function, control of blood lipids and reduce adverse changes due to stress. These may increase the number of insulin receptor sites, thus improving glucose use. Monitoring Control: (a) Check blood glucose to keep day-today control (b) Check glycosylated hemoglobin to check long term index of control. Main value of this test is to confirm elevated blood glucose and monitor ketonuria. Some substances give false or negative results; these are megadoses of ascorbic acid, salicylates and levadopa. When a diabetic participates in games or increased activity without taking food, hypoglycemia may occur. Hypoglycemia may also occur, when a diabetic has diarrhoea or vomits, as this results in a decrease in blood sugar level. Hypoglycemia is accompanied by a feeling of weakness, giddiness and fainting, if not attended to promptly. If the person is conscious, he/she should be fed sugar, hard candy, fruit juice, sugar containing carbonated beverage or syrup, which give quick relief from symptoms. A diabetic should carry a medical identity card indicating that she/he is a diabetic and should be given intravenous glucose if she/he is unconscious due to hypoglycemia. Such immediate treatment can avert extended hypoglycemia, which causes damage to the central nervous system and the brain. There is an increase in lipolysis (breakdown of fats for energy) and production of fatty acids. In the diabetic state, liver oxidises fatty acids and produces acetone, acetoacetate and beta-hydroxybutyrate. Prevention is very essential and involves ensuring that carbohydrate is distributed in the daily meal to fit in with type of insulin, its dosage and time of injection. Long-term Complications Poorly controlled diabetes increases risks of long-term diabetic complications. These health problems relate mainly to tissue changes affecting blood vessels in vital organs. Neuropathy: these changes in the nerves involve injury and disease in the peripheral nervous system, especially in the legs and feet. Inadequate blood supply leaves the foot susceptible to injury, infection, gangrene and ultimately amputation. Hence the need to pursue the diet, exercise and if need be insulin, very methodically and avoid or delay complications. Retinopathy: the changes in the eyes include thickening of capillaries with small hemorrhages from broken arteries in the retina, with yellow waxy discharge or retinal detachment.

Parasympathetic nerves come from the brainstem and sacral spinal cord treatment hpv purchase lumigan 3ml mastercard, and sympathetic nerves (noradrenergic medications starting with p discount 3ml lumigan amex, adrenergic medications ending in pam generic lumigan 3ml on-line, and cholinergic) come from the thoracolumbar spinal cord symptoms in children purchase discount lumigan online. Parasympathetic nerves have long, myelinated pre-ganglionic and short, non-myelinated post ganglionic fibers. Sympathetic noradrenergic and cholinergic nerves have short, myelinated pre-ganglionic fibers and long, - 89 - Principles of Autonomic Medicine v. Sympathetic adrenergic nerves going to the adrenal medulla are myelinated fibers, but instead of post-ganglionic nerves the adrenal cells secrete adrenaline into the bloodstream. These chemicals act on receptors on target cells, such as heart muscle cells, and this changes body functions. The main chemical messengers of the autonomic nervous system are the neurotransmitters, acetylcholine and norepinephrine, and the hormone, adrenaline. The transmission of chemicals in the autonomic nervous system (neurotransmission) involves some common steps, although there are variations on the theme. Acetylcholine, norepinephrine, and adrenaline are stored in tiny - 92 - Principles of Autonomic Medicine v. Acetylcholine and adrenaline are produced in the cytoplasm (“cell juice”) and then are actively pumped into the vesicles. The neurotransmitter is released by a process called exocytosis, where the vesicle moves to the membrane surface of the cell, a hole forms at the junction of the vesicle with the cell membrane (microscopically, there is a little “omega sign”), and the messenger makes its way out of the cell. For instance, acetylcholine released from parasympathetic nerves in the heart binds to cholinergic receptors, and this causes the heart rate to decrease. It is the second messengers that actually change the functional state of the cells. Finally, activation or inhibition of the state of activity of the target cells alters information traveling to the central nervous system. Reflexive changes in traffic in the autonomic nerves complete a negative feedback loop. Because of the negative feedback loop, the level of an internal variable is kept within bounds. For example, when you exercise on a hot day, your core temperature tends to increase. Activation of a part of the autonomic nervous system (the sympathetic cholinergic system) releases the neurotransmitter acetylcholine from terminals of nerves supplying sweat glands, activating receptors on the cells - 94 - Principles of Autonomic Medicine v. This increases evaporative heat loss, which keeps the core temperature within bounds. This negative feedback loop is so rapid and efficient, exercising in the heat normally doesn’t elevate core temperature at all. They all contain a prominent, single nitrogen (N) atom—a quaternary ammonium ion in acetylcholine and an amine group in norepinephrine and adrenaline. And they are actively taken up into and stored in vesicles, which Chemical messengers of the autonomic nervous system acetylcholine, norepinephrine, and adrenaline (epinephrine) have a relatively acidic pH. Three types of chemical messengers— neurotransmitters, hormones, and autocrine/paracrine substances Automatic systems of the body use at least four types of chemical messenger. This means that only a relatively small amount of released neurotransmitter makes its way to the bloodstream unchanged. Two of the main neurotransmitters of the autonomic nervous system are norepinephrine and acetylcholine. Small amounts of norepinephrine are detectable in the plasma, and measurement of plasma norepinephrine is a common test in the evaluation of - 96 - Principles of Autonomic Medicine v. Acetylcholine released from nerves of the parasympathetic nervous system and from nerves of the sympathetic cholinergic system is so rapidly and efficiently broken down that acetylcholine is not normally detectable in the plasma. Therefore, tests of the parasympathetic and of the sympathetic cholinergic system rely on other types of measurements. Acetylcholine and norepinephrine are the main neurotransmitters of the autonomic nervous system. Hormones are released directly into the bloodstream and are delivered to all body organs. One of the most famous hormones, and the first whose structure was identified, is adrenaline, which is released into the - 97 - Principles of Autonomic Medicine v. Essentially all body organs take up circulating adrenaline; however, an exception is the brain, where an efficient blood-brain barrier prevents entry of catecholamines into most brain regions. A third type of chemical messenger is probably old in terms of evolution but new in terms of recognition by scientists. They are made in, released from, and act on the same or nearby target cells within the tissue. Autocrine/paracrine substances are made in, released by, and act on the same or nearby cells in an organ. Autocrine/paracrine substances are released just about as soon as they are made within the cells, unlike hormones and neurotransmitters, which are stored at particular sites within cells and are released from the storage sites in response to nerve - 98 - Principles of Autonomic Medicine v. Of several autocrine/paracrine substances in the body, one involves the catecholamine, dopamine. Dopamine released from the cells acts on dopamine receptors on the same or nearby cells, and this increases excretion of sodium and water. A large family of proteins called cytokines that are released from cells of the immune system exemplify a fourth type of chemical messenger. Cytokines play key roles in immunity and bodily responses to infection, inflammation, trauma, sepsis, and cancer. Neuroimmunology is a rapidly evolving field that focuses on - 99 - Principles of Autonomic Medicine v. A system involving the vagus nerve and cytokines regulates immune functions via a negative feedback loop. One example of neuroimmune interactions is regulation of cytokines by the vagus nerve. Acetylcholine released from parasympathetic nerves produces many effects in the body, including increasing the tone of the urinary bladder and bowel, increasing gastric acid secretion, stimulating salivation and tear production, and decreasing the rate and force of the heartbeat. Acetylcholine release from sympathetic cholinergic nerves acts at sweat glands, causing perspiration. Sweating responses have been classified as thermoregulatory (such as sweating when exercising in the heat), gustatory (sweating mainly on the forehead after eating, especially chili peppers), and emotional. The Search for the Omega Sign Once produced in the vesicles in autonomic nerves, neurotransmitters are released from the nerve terminals by the - 102 - Principles of Autonomic Medicine v. Exocytosis, a key element in the theory of chemical neurotransmission, was first proposed by Thomas Renton Elliott in 1904. Elliott was a student of Langley—the same Langley who coined the phrase, “autonomic nervous system. In a stroke of genius, he hypothesized that the similarity resulted from a chemical like adrenaline actually being released from the nerves and acting on nearby cells. His brief note, published in the Journal of Physiology, proposed “a mechanism developed out of the muscle cell, in response to its union with the synapsing sympathetic fibre, the function of which is to receive and transform the nervous impulse. Adrenalin(e) might then be a chemical stimulant liberated on each occasion when the impulse arrives at the periphery. As noted elsewhere, Loewi also thought he had obtained proof that adrenaline is the neurotransmitter of the sympathetic nerves—but he actually hadn’t. According to the exocytosis theory chemical neurotransmission results from physical movement of the bubble-like vesicles containing the neurotransmitter toward the cell membrane, fusion of the vesicle membrane with the cell membrane, pore formation at the site of fusion of the two membranes, and entry of the contents of the vesicles into the fluid outside the cell. Among those contents is the neurotransmitter, which diffuses a short way to reach receptors on the membrane of the target cells. If the vesicle membrane actually fused with the cell membrane and a hole formed at the junction, then if one looked under an electron microscope at the nerve terminal, one would see tiny “omega signs” or see the vesicle contents coming through the cell membrane. Recent highly sophisticated techniques have enabled such direct visualization; however, only a very small percentage of vesicles are actually found poking their way through the membrane surface. Concentrations of catecholamines can be measured in body fluids such as the plasma, urine, or cerebrospinal fluid. By assaying levels of catecholamines and their breakdown products, one can gain insights into the diagnosis of patients with complaints referable to the autonomic nervous system. Later on we will be dealing in depth about the many ways clinical catecholamine neurochemistry is important for diagnosis, understanding disease mechanisms, and treatment of dysautonomias. Measuring levels of catecholamines and related chemicals aids the workup of patients with dysautonomias.

Eur Arch Otorhinolaryngol 2010;267:1963-1967 [8] Michelotti A treatment abbreviation order lumigan 3ml with mastercard, Silva R treatment canker sore purchase lumigan with mastercard, Paduano S symptoms lead poisoning order lumigan 3 ml online, Cimino R medications like prozac order discount lumigan online, Farella M. Oromandibular dystonia and hormonal factors: twelve years follow-up of a case report. Eating dysfunction associated with oromandibular dystonia: clinical characteristics and treatment considerations Head & Face Medicine 2006, 2:47. Use of an oral sensory feedback device in the management of jaw opening dystonia. Otolaryngology – Head and Neck Surgery 2009;141:142-143 [21] Frucht S, Fahn S, Ford B. Oromandibular dystonia involving the lateral pterygoid muscles: four cases with different complexity. Impact on quality of life of botulinum toxin treatments for spasmodic dysphonia and oromandibular dystonia. Secondary nonresponsiveness to botulinum toxin type A in patients with oromandibular dystonia. Successful treatment of tardive lingual dystonia with botulinum toxin: Case report and review of the literature. Out-of-Hospital Lingual Dystonia Resulting in Airway Obstruction Prehosp Emerg Care. Botulism toxin management of spasmodic dysphonia: a 12-year experience in more than 900 patients. Botulinum for treating spasmodic dysphonia (laryngeal dystonia): a systematic Cochrane review. Spasmodic dysphonia and botulinum toxin: experience from the largest treatment series. Influence of age and gender on dose and effectiveness of botulinum toxin for laryngeal dystonia. Longitudinal follow-up of adductor spasmodic dysphonia patients after botulism toxin injection: quality of life results. Introduction Dystonia is generally referred to belong to the generic terms, muscle spasm and muscle stiffness. Muscle spasms would be any involuntary abnormal muscle contraction, regardless of whether it is painful or not, that cannot be usually terminated by voluntary relaxation. Muscle stiffness is an involuntary muscle shortening that usually lasts for seconds to minutes, but may be sustained. Sustained muscle contraction may lead to posturing and even pain as seen in tetany, dystonia, spasticity, and contracture. Whereas tetany is brisk, short-lived, and associated with paresthesiae, dystonia is a slow, more sustained co-contraction of the agonist and antagonist muscles, that may characteristically be task-specific and abolished by “sensory tricks. Limb dystonia may be focal (limited to a single body area), segmental (affecting at least two adjacent muscle groups), or a component of hemidystonia and generalized dystonia. It has been described in writers, typists, golfers, musicians, and many other occupations, and is often associated with markedly disabling loss of function. Focal hand dystonia was first recognized by its characteristic impairment of specific tasks. It has a tendency to cluster in those with particular occupations so that it was once thought of as psychogenic in origin. Embouchure’s dystonia, mainly affecting the lips, jaw and tongue, is included in this category. In task specific dystonia, primary sensory modalities are * Corresponding Author 44 Dystonia – the Many Facets intact, although impaired spatial or temporal discrimination may be identified if specifically sought(2). The neurological examination is essentially normal except for the dystonic movements. Actions eliciting the dystonia may be performed slowly and irregularly but there is no ataxia. This chapter aims to highlight the phenomenology, pathophysiology, clinical course and management of occupationally-related dystonias. Not only are these forms of dystonias characteristically mistaken to have psychogenic origins, but also that these disorders impinge on the profession and quality of life of the affected individuals. We cap this chapter with a peculiar illustrative case if only to emphasize the precepts of the phenomenology and management strategy of this kind of a dystonia. Phenomenology of task specific dystonias Focal dystonia, as with other dystonic disorders, have common characteristic features that distinguish it from other hyperkinetic movement disorders. There is co-contraction of agonists and antagonist groups of muscles and the contractions result in abnormal limb postures. The contraction is of relatively long duration and sustained as compared to that of chorea or athetosis and usually involves the same muscle groups. This involvement of the same muscle groups termed “patterned” movements may remain focal or may, in time, involve contiguous body parts. There is a directionality and predictability of the movements somehow being stereotypical in character. Another special characteristic of the dystonias is the response to certain “sensory tricks” whereby doing something else apart from the task may alleviate the dystonia such as chewing a gum while playing a wind instrument relieves the lip dystonia in some musicians. Sometimes, the dystonic contractions can occur rapidly and repeatedly mimicking a tremor. The feature that distinguishes it from the latter is the relatively irregular occurrence of the dystonic tremor, the apparent increase in the tremor when the muscles involved are pulled opposite to the direction of its contraction and activation of the muscles not required for maintenance of that particular posture(3). For this chapter, we focus our attention to task specific focal dystonias or those occurring in situations whereby repetitive skilled movements are essential to its development. The first symptom of focal hand dystonia is usually a feeling of tightness or loss of facility with a previously easily performed action, often accompanied by fatigue and aching in the affected arm and forearm that worsens with continued use. In the case of embouchure’s dystonia, there is initial feeling of tightness around the lip with somewhat difficulty in controlling lip and jaw movements. Pain, quite common in cervical dystonias, may not be as frequent in occupational dystonia. If indeed pain occurs, this could be part of muscle fatigue, myofascial pain component or corresponding joint changes. Overtime, there is involuntary posturing of the limb (or the lips, jaw or tongue in the case of embouchure’s dystonia) during the performance of the task. In due course, the abnormal movements may not only appear during the task but may also occur during other movements such as buttoning clothes, typing, holding a spoon. In some, Dystonia Arising from Occupations: the Clinical Phenomenology and Therapy 45 further progression may lead to the occurrence of some dystonic movements at rest however, this is not typical. Fixed dystonic postures are rare, and occurrence of “fixed posturing” puts psychogenic dystonia into the differential diagnosis. The most common task specific focal hand dystonia is writer’s cramp (4) whereby writing brings about a variety of combinations of dystonic posturing. Additionally, there is lack of muscle selectivity and prolonged muscle bursts in these patients. The abnormal movements start as soon as the hand holds the pen or after having written a few words. Patients normally describe an uncontrollable force that makes them grip the pen tightly, and as a result, normal fluidity of writing is lost and patients are unable to write undisturbed. A mirror image effect(4) may occasionally be observed whereby writing with the unaffected hand simulates or produces the dystonic posture on the affected hand. This emphasizes the importance of sensory input in the pathophysiology of focal dystonia as the phenomenon impacts on central motor programming. Sensory tricks such as touching the hand during writing may ameliorate the dytonia. It appears though that, as in cervical dystonia, the sensory trick may not abolish the dystonia when the disorder has become long standing. Patients who exhibit the dystonia only when writing are considered to have simple writer’s cramp whereas those having difficulties with other tasks are considered complex forms of the latter. As the symptoms of writer’s cramp progress, it may involve more proximal forearm muscles, elbow and the shoulder causing involuntary abduction. Phenomenology of musician’s dystonia In musician’s cramps, involuntary movements affect the limb while playing the instrument. Usually, the movements are similar as that of writer’s cramp whereby pain is not as striking as the loss of control.

Syndromes

Performing self-destructive behaviors, such as injuring themselves
Problems following directions that are spoken to them
You have a history of arthritis and are having new symptoms
Grows about 2 - 3 inches
Know what you are taking. Look at the list of ingredients and choose products that have fewer items listed.
Stool culture for Campylobacter jejuni
Distract your child with books, bubbles, games, hand-held video games, or other activities.
Wheezing
Decreased coordination, clumsiness, falls

With highly soluble blood and the gas phase along with its solubility and tissue reactiv gases medications errors purchase lumigan 3 ml online, the principal factor limiting the rate of absorption is respi ity medications that cause hair loss cheap lumigan 3ml amex. Because the blood is already removing virtually all gases after exposure to aerosols are the aerosol size and water solubility with a high solubility ratio from the lungs medicine rising appalachia lyrics order discount lumigan on line, increasing the blood of any chemical present in the aerosol medications equivalent to asmanex inhaler buy generic lumigan 3 ml on-line. The site of deposition of aerosols and particulates depends However, the rate can be accelerated greatly by increasing the largely on the size of the particles. In general, the smaller the particle, the further the blood carries the dissolved gas molecules to the rest of into the respiratory tree the particle will deposit (Fig. In each tissue, the gas molecules are transferred from the ranging from 5 μm or larger, described as “course particles” usually blood to the tissue until equilibrium is reached at a tissue concen are deposited in the nasopharyngeal region. Those deposited on the tration dictated by the tissue-to-blood partition coefﬁcient. After unciliated anterior or rostral portion of the nose tend to remain at releasing part of the gas to tissues, blood returns to the lungs to the site of deposition until they are removed by nose wiping, blow take up more of the gas. The mucous blanket of the ciliated nasal surface equilibrium between blood and each tissue according to the tissue propels insoluble particles by the movement of the cilia. This ticles and particles inhaled through the mouth are swallowed within equilibrium is referred to as steady state, and at this time, no net minutes. Soluble particles may dissolve in the mucus and be carried absorption of gas takes place as long as the exposure concentration to the pharynx or may be absorbed through the nasal epithelium remains constant. This ﬂow seems to depend on lymph ﬂow, capillary 165 referred to as “ﬁne particles” are deposited mainly in the tracheo action, the respiratory motion of the alveolar walls, the cohesive bronchiolar regions of the lungs, from which they may be cleared by nature of the respiratory tract’s ﬂuid blanket, the propelling power retrograde movement of the mucus layer in the ciliated portions of of the ciliated bronchioles, and the surface tension within the ﬂuid the respiratory tract (also known as the mucociliary escalator). Second, particles from the alveoli may be removed by phago rate of cilia-propelled movement of mucus varies in different parts cytosis. The principal cells responsible for engulﬁng alveolar debris of the respiratory tract, although in general it is a rapid and efﬁ are the resident alveolar macrophages. Toxicants or viral infections that dam found in large numbers in normal lungs and contain many phago age cilia may impair the efﬁciency of this process. Third, removal may occur sneezing greatly increase the movement of mucus and particulate via the lymphatics. Ultraﬁne or nanoparticles, particularly those that are approx system plays a prominent role in collecting high-molecular-weight imately 10 to 20 nm in size, have the greatest likelihood of deposit proteins leaked from cells or blood capillaries and particulate mat ing in the alveolar region. These extremely small particles may be ter from the interstitium and the alveolar spaces. Particulate matter absorbed into blood or cleared through the lymphatics after being may remain in lymphatic tissue for long periods, and this explains scavenged by alveolar macrophages (Oberdorster et al. The rate of clearance by the lungs can be increases along with the total surface area of the particles. The lower the tionship, illustrated in Table 5-7, indicates that nanoparticles have solubility, the lower the removal rate. Thus, it appears that removal the propensity to deliver high amounts of particulates to the lung. Some particles may remain in the alveoli indeﬁ be more important determinants of toxic potential than their size or nitely. Absorption of Toxicants Through the Skin the mechanisms responsible for the removal or absorption of Skin is the largest body organ and provides a relatively good barrier particulate matter from the alveoli are less clear than those respon for separating organisms from their environment. Overall, human sible for the removal of particles deposited in the tracheobronchial skin comes into contact with many toxic chemicals, but exposure tree. For example, there are several insecti ﬂuid layer of the alveoli are aspirated onto the mucociliary escala cides for which fatal exposures have occurred in agricultural work tor of the tracheobronchial region. From there, they are transported ers after absorption through intact skin (see Chap. The origin of the thin ﬂuid there are numerous chemicals that increase tumor development in layer in the alveoli is probably a transudation of lymph and secre other organs after dermal application. The skin comprises 2 major layers, the epidermis and der the alveolar ﬂuid ﬂows by an unknown mechanism to the terminal mis (Fig. The epidermis is the outermost layer and contains keratinocytes that are metabolically competent and able to divide. Proliferating keratinocytes in the stratum germinativum displace Table 5-7 maturing keratinocyte layers upward until they reach the outermost layer, the stratum corneum. The stratum corneum contains densely Particle Number and Surface Area for 10 μg/m3 packed keratinized cells that have lost their nuclei and are bio Airborne Particles logically inactive. Diagram of a cross section of human skin illustrating the various layers, cellular composition, and blood supply. Although the permeability of the skin also depends on both the diffusivity and the major anatomical area that controls absorption across the skin is thickness of the stratum corneum. Although the stratum corneum is the stratum corneum, compounds may also be absorbed through much thicker on the palms and soles (400–600 µm in callous areas) dermal appendages, including sweat and sebaceous glands and hair than on the arms, back, legs, and abdomen (8–15 µm), it has much follicles found in the dermis. These appendages account scrotum is characterized by a thin stratum corneum and a high dif for no more than 1% of the total cross-sectional area of the total skin fusivity. Consequently, as illustrated by the comparative absorption surface, and, in general, passage through these areas is much more of malathion across different human skin sites (Table 5-8), toxicants rapid than passage through the stratum corneum. Ultimately, to be are likely to readily cross scrotal skin, whereas absorption across absorbed a chemical must pass the barrier of the stratum corneum forehead skin is less extensive, and penetration across the palm is and then traverse the other six layers of the skin (Dugard, 1983; lowest because of the thickness of the stratum corneum and the lack Poet and McDougal, 2002). All toxicants move (stratum germinativum, spinosum, and granulosum) and the dermis. In general, lipo Despite possessing tight intercellular junctions, these cell layers are philic (fat-soluble) compounds are absorbed more readily across the stratum corneum, whereas the penetration of hydrophilic Table 5-8 (water-soluble) compounds is more limited. Nonpolar toxicants diffuse through the skin in a manner that is proportional to their Absorption of Malathion Across Different Human lipid solubility and inversely related to molecular weight. In contrast Dermal absorption has been studied in most laboratory ani 167 to the stratum corneum, they contain a porous, nonselective, aque mals including rats, mice, rabbits, guinea pigs, primates, and pig, ous diffusion medium. Toxicants pass through this area by diffusion and dermal absorption varies widely across these species. As a and enter the systemic circulation through the numerous venous and general rule, dermal absorption across rodent skin is greater than lymphatic capillaries in the dermis. The rate of diffusion depends on human skin, whereas the cutaneous permeability characteristics of blood ﬂow, interstitial ﬂuid movement, and perhaps other factors, guinea pigs, pigs, and monkeys are more similar to those observed including interactions with dermal constituents. Species differences in per There are several factors that can inﬂuence the absorption of cutaneous absorption account for the differential toxicity of insec toxicants through the skin, including (1) the integrity of the stratum ticides in insects and humans. Because much less toxic to mammals than to insects when it is applied to the the stratum corneum plays a critical role in determining cutaneous skin. Furthermore, insects have a much both lipid-soluble and water-soluble (Poet and McDougal, 2002). Caustic agents, such as acids and alkalis, that damage the stratum Species differences in dermal absorption of xenobiotics result corneum increase its permeability. The most frequently encountered from several anatomic, physiological, and biochemical factors penetration-enhancing damage to the skin results from burns and (Dugard, 1983; Poet and McDougal, 2002). Water also plays an extremely important role and thickness of the stratum corneum along with the nature of the in skin permeability. Under normal conditions, the stratum corneum dermal appendages are highly variable across species. This corneum is much thicker in humans than in most laboratory ani amount of water increases the permeability of the stratum cor mals, making human skin typically less permeable than animal skin. On contact with water, the stratum corneum sated for by a relatively thick hair cover, diminishing direct con can increase its weight of tightly bound water up to 5-fold, which tact of the skin with a xenobiotic. For example, eccrine sweat glands are the site of application will be covered with plastic wrap (occlusive located in the pads of the extremities of all mammals. The number of pilosebaceous ducts in humans and pigs by increasing dermal blood ﬂow. This is particularly important for is similar (about 40/cm2), but rodents may have up to 100 times occupational exposures to chemicals such as insecticides in which more. Another important potential rate-limiting step in the dermal agricultural workers are likely to be working strenuously at relatively absorption of chemicals is the cutaneous blood ﬂow. Such environmental conditions increase dermal the skin plays an important thermoregulatory function as opposed penetration and may increase the risk of systemic toxicity. Consequently, there is a much more extensive Solvents used to dissolve compounds of interest can also vasculature in humans than in most mammals (Calabrese, 1984). In general, lower absorption will be Biotransformation reactions in skin can also facilitate absorption, observed if a toxicant is highly soluble in the vehicle, whereas low and the presence of metabolizing enzymes is highly variable across solubility of the toxicant in the vehicle will tend to increase der species.

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