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Desiccants prevent moisture absorption from the air; for example asthma symptoms chest pain advair diskus 500mcg, they are used to qge031 asthma purchase 500mcg advair diskus otc prevent table salt from forming clumps asthma treatment vest proven 100 mcg advair diskus. The Delaney Clause, also enacted in 1958, states that "No additive may be permitted in any amount if tests show that it produces cancer when fed to man or animals or by other appropriate tests. Many of the complaints are about sulfite preservatives causing headaches, asthmatic reactions, and in some cases anaphylactic shock. RecaP Food additives are chemicals intentionally added to foods to enhance their color, flavor, texture, nutrient density, moisture level, or shelf life. Although there is continuing controversy over food additives, they are considered safe based on testing and use in the food industry or as a result of consensus among experts qualified by scientific training and experience. Persistent Organic Pollutants Can Cause Illness Many different organic chemicals are released into the atmosphere as a result of industry, agriculture, automobile emissions, and improper waste disposal. If a pollutant gets into the soil, a plant can absorb the chemical into its structure and can pass it on as part of the food chain. Fish and land animals can also absorb the pollutants into their tissues or can consume them when feeding on plants in the polluted water or soil. Bioaccumulation, the process by which increasing concentrations of pollutants are seen in species higher up the food chain, is illustrated in Figure 15. The chemicals can travel long Chapter 15 Food Safety and Technology: Impact on Consumers 605 1 Industrial wastes are released into water. As mercury is released into the environment, it falls from the air, eventually finding its way to streams, lakes, and the ocean, where it accumulates. Large predatory fish, such as swordfish, shark, king mackerel, and tilefish, tend to contain the highest levels of mercury. Lead, another naturally occurring element, can be found in the soil, water, and even the air. It also occurs as industrial waste from leaded gasolines, lead-based paints, and One of the ways mercury is released into the environment is by burning fossil fuels. Excessive lead exposure can cause learning and behavioral impediments in children and cardiovascular and kidney disease in adults. It is impossible to avoid lead residues completely, but because of the health implications, everyone should try to limit their exposure. Pesticides Protect Against Crop Losses Pesticides are a family of chemicals used in both the field and storage areas to help protect crops from weeds, insects, fungi, and other organisms, including birds and mammals. Rodents, for example, in addition to consuming food, also contaminate large quantities of food with their excreta. Pesticides also help reduce the number of microorganisms on crops, and increase overall crop yield and crop diversity. The three most common types of pesticides used in food production are insecticides, herbicides, and fungicides. Insecticides are used to control insects that can infest crops; herbicides are used to control weeds and other unwanted plant growth; and fungicides are used to control plant-destroying fungal growth. Biopesticides do not leave residues on crops-most degrade rapidly and are easily washed away with water. In nature, insects use pheromones, chemicals that act as signals, to attract mates. Synthetic pheromones are used to disrupt insect mating by attracting males into traps. Microbial biopesticides are derived from naturally occurring or genetically altered bacteria, viruses, or fungi. This is a common soil bacterium that is genetically altered to be toxic to several species of insects. Aside from biopesticides, many natural products such as salt, boric acid, dried blood, crushed egg shells, or diatomaceous earth (soil made up of a type of algae called diatoms) are used as pesticides. Ladybugs are bred and sold commercially to reduce aphids, and marigolds, mint, sage, garlic, chives, onion, and other strong-smelling plants can be placed among crops to deter a variety of insect pests. Examples of commonly used synthetic pesticides include thiabendazole (a fungicide used on potatoes) and fungicides commonly used to prevent apple diseases (such as dithane, manzate, and polyram). Bt bacteria produce crystals, shown here, that are a widely used microbial biopesticide.
The remaining single glucose residue attached in an (16) linkage is removed hydrolytically by the amylo-(16) glucosidase activity of debranching enzyme baby asthma symptoms uk buy advair diskus discount, releasing free glucose asthma definition ziggurat advair diskus 250mcg with amex. In the liver asthma treatment 1970 buy advair diskus pills in toronto, the phosphate is removed by glucose 6-phosphatase, releasing free glucose that can be used to maintain blood glucose levels at the beginning of a fast. A deficiency of the phosphatase causes glycogen storage disease Type 1a (Von Gierke disease). This disease results in an inability of the liver to provide free glucose to the body during a fast. Glycogen synthesis and degradation are reciprocally regulated to meet whole-body needs by the same hormonal signals (namely, an elevated insulin level results in overall increased glycogenesis and decreased glycogenolysis, whereas an elevated glucagon, or epinephrine, level causes increased glycogenolysis and decreased glycogenesis). Key enzymes are phosphorylated by a family of protein kinases, some of which are cyclic adenosine monophosphate dependent (a compound increased by glucagon and epinephrine). Phosphate groups are removed by protein phosphatase-1 (active when its inhibitor is inactive in response to elevated insulin levels). Glycogen synthase, phosphorylase kinase, and phosphorylase are also allosterically regulated to meet tissues needs. In the liver, glucose also serves an an allosteric inhibitor of glycogen phosphorylase. This allows the enzyme to activate glycogen phosphorylase, thereby causing glycogen degradation. Myophosphorylase deficiency prevents glycogen degradation in muscle, depriving muscle of glycogen-derived glucose, resulting in decreased glycolysis and its anaerobic product, lactate. Acid maltase [a(14)-glucosidase] deficiency prevents degradation of any glycogen brought into lysosomes. A variety of tissues are affected, with the most severe pathology resulting from heart damage. Glucose 6-phosphatase deficiency prevents the liver from releasing free glucose into the blood, causing severe fasting hypoglycemia, lacticacidemia, hyperuricemia, and hyperlipidemia. Both glycogen phosphorylase and glycogen synthase are activated by phosphorylation but at significantly different rates. Glycogen phosphorylase is inactivated by the resuting rise in calcium, whereas glycogen synthase is activated. Glycogen phosphorylase is phosphorylated and active, whereas glycogen synthase is phosphorylated and inactive. Epinephrine and glucagon both cause increased glycogen degradation and decreased synthesis in the liver through covalent modification (phosphorylation) of key enzymes of glycogen metabolism. Glycogen phosphorylase is phosphorylated and active ("a" form), whereas glycogen synthase is phosphorylated and inactive ("b" form). Ca 2+ released from the sarcoplasmic reticulum during exercise binds to the calmodulin subunit of phosphorylase kinase, thereby allosterically activating the "b" form of this enzyme. With Type Ia, the liver is unable to generate free glucose either from glycogenolysis or gluconeogenesis because both processes produce glucose 6-phosphate. However, two other monosaccharides, fructose and galactose, occur in significant amounts in the diet (primarily in disaccharides) and make important contributions to energy metabolism. The major source of fructose is the disaccharide sucrose, which, when cleaved in the intestine, releases equimolar amounts of fructose and glucose. Fructose is also found as a free monosaccharide in many fruits, in honey, and in high-fructose corn syrup (typically, 55% fructose/45% glucose), which is used to sweeten soft drinks and many foods. Fructose transport into cells is not insulin dependent (unlike that of glucose into certain tissues; see p. Phosphorylation of fructose For fructose to enter the pathways of intermediary metabolism, it must first be phosphorylated (Figure 12. Therefore, unless the intracellular concentration of fructose becomes unusually high, the normal presence of saturating concentrations of glucose means that little fructose is phosphorylated by hexokinase. Fructokinase provides the primary mechanism for fructose phosphorylation (see Figure 12.
The outermost layer is poorly defined and contains collagen fibers arranged in loose asthma symptoms 3 yr old order advair diskus 500mcg amex, longitudinal bundles interspersed with some elastic fibers asthma obesity purchase 100mcg advair diskus otc. The cells of the hair bulb are not arranged in layers but form a matrix of growing cells asthma 80 cheap advair diskus 100mcg line. The cyclic activity continues throughout life, but the phases of the cycle change with age. At about the fifth month of gestation, all the hairs are in anagen, a uniformity of growth not seen again. Between 8 and 10 weeks before birth, some hair sites have reached catagen and telogen phases. The frontal and parietal scalp areas show the first shedding events; in the occipital region, hairs remain in anagen until after birth. From about 6 weeks before birth, telogen hairs again appear in the frontal and parietal scalp, indicating a second cycle of hair growth. All hairs usually enter telogen immediately after birth, giving rise to a second period of shedding. About 18 weeks after birth, cycles are associated with individual hairs or groups of hairs. The total hair cycle in the scalp extends over 300 weeks, with telogen occupying 18 to 19 weeks. Generally, sebaceous glands are associated with hairs and drain into the upper part of the hair follicle, but on the lips, glans penis, inner surface of the prepuce, and labia minora, the glands open directly onto the surface of the skin, unrelated to hairs. The glands vary in size and consist of a cluster of two to five oval alveoli drained by a single duct. The secretory alveoli lie within the dermis and are composed of epithelial cells enclosed in a welldefined basement membrane and supported by a thin connective tissue capsule. Cells abutting the basement membrane are small and cuboidal and contain round nuclei. The entire alveolus is filled with cells that, centrally, become larger and polyhedral and gradually accumulate fatty material in their cytoplasm. Secretion is of the holocrine type, meaning the entire cell breaks down, and cellular debris, along with the secretory product (triglycerides, cholesterol, and wax esters), is released as sebum. Myoepithelial cells are not observed with sebaceous glands, but the glands are closely related to the arrectores pilorum muscle. Contraction of this smooth muscle bundle helps in the expression of secretory product from the sebaceous glands. In the nipple, smooth muscle bundles are present in the connective tissue between the alveoli of these glands. The short duct of the sebaceous gland is lined by stratified squamous epithelium that is a continuation of the outer epithelial root sheath of the hair follicle. Replacement of secretory cells of the alveolus comes mostly from division of cells close to the walls of the ducts, near their junctions with the alveoli. Collectively, the hair follicle, hair shaft, sebaceous gland, and erector pili muscle are referred to as the pilosebaceous apparatus. The pilosebaceous apparatus produces hair and sebum, the latter of which protects the hair and acts as a lubricant for the epidermis to protect it from the drying effects of the environment. Sebaceous glands become more active at puberty and are under endocrine control: androgens increase activity, estrogens decrease activity. Eccrine sweat glands are distributed throughout the skin except in the lip margins, glans penis, inner surface of the prepuce, clitoris, and labia minora. Elsewhere the numbers vary, being plentiful in the palms and soles and least numerous in the neck and back. The deep part is tightly coiled and forms the secretory unit located in the deep dermis. The secretory unit consists of a simple columnar epithelium resting on a thick basement membrane. These cells secrete glycoproteins, which have been identified in secretory vacuoles. Intercellular canaliculi extend between adjacent clear cells, which contain glycogen, considerable smooth endoplasmic reticulum, and numerous mitochondria but few ribosomes. Clear cells are thought to secrete sodium, chloride, potassium, urea, uric acid, ammonia, and water.
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The secretory phase is associated with development of a corpus luteum and is maintained as long as the corpus luteum remains functional asthma symptoms 8dpo buy advair diskus 100 mcg cheap. Progesterone secreted by the corpus luteum is the steroid primarily responsible for the secretory changes in the endometrium asthma definition race buy cheap advair diskus on-line. The ischemic (premenstrual) phase is characterized by intermittent constriction of the spiral arteries asthma treatment cats cheap advair diskus 500mcg with mastercard, resulting in vascular stasis and reduced blood flow to the functional layer. The outer zone of the endometrium is subjected to anoxia for hours at a time, resulting in breakdown of the stratum functionale. The spiral arteries also become necrotic, and blood is lost from the arteries and veins. Small lakes of blood form and coalesce, and overlying patches of mucosa are detached, leaving a denuded stromal surface. Sloughing of the endometrium continues until the entire functional layer has been discarded. The menstrual discharge consists of arterial and venous blood, autolyzed and degenerated epithelial cells, and glandular secretions. The straight arteries of stratum basale do not constrict during menstruation, thus preserving the basal layer to provide for restoration of the endometrium during the following new proliferative stage. The onset of the menstrual cycle coincides with the beginning involution of a corpus luteum. Little smooth muscle is present, and the cervical wall consists mainly of dense connective tissue and elastic fibers. The cervical canal is lined by a mucosa, the endocervix, which forms complex, branching folds. The epithelial lining consists of tall, mucus-secreting columnar cells along with a few ciliated columnar cells. Numerous large, branched cervical glands are present that are lined by mucus-secreting columnar cells similar to those of the lining epithelium. Occasionally the glands become occluded and filled with secretion, forming Nabothian cysts. The portion of the cervix that protrudes into the vaginal canal, the exocervix, is covered by a nonkeratinized stratified squamous epithelium whose cells contain much glycogen. The transition from the simple columnar epithelium of the cervical canal is abrupt and usually occurs near the external os. The cervical mucosa does not take part in the dramatic cyclic changes that occur in the endometrial lining of the body of the uterus and is not shed. At midcycle there is a copious secretion of a thin alkaline fluid, probably the result of increased stimulation by estrogen. After ovulation and establishment of a corpus luteum, the amount of secretion decreases and the mucus becomes thicker and more viscous. The lumen of the cervix is usually less than 1 cm in diameter but will expand to 10 cm or more at the time of birth. The dilatation is the result of increased elasticity and a softening of the cervical stroma during labor. The changes that occur within the cervical stroma are complex and not completely understood. However, changes are known to occur with regard to the making up of glycosaminoglycans in the ground substance during labor. Hyaluronic acid levels increase, binding more water, whereas concentrations of dermatan sulfate decrease, reducing the number of cross linkages between extracellular fibers within the stroma. In addition, the collagen and elastic fibers within the stroma are shortened and rearranged in such a way as to decreased tensile strength and resistance allowing the dilatation to occur. Deepest is the basal layer (stratum germinativum); followed by an intermediate (spinous) layer and a superficial layer (stratum corneum) from which cells are shed. Desquamated cervical cells can be recovered from vaginal secretions, or cells can be obtained more directly by gentle abrasion of the exocervix. In normal women, four types of cells usually are recognized cytologically, loosely corresponding to the layers of the cervicovaginal epithelium.
Especially favorable is the possibility of using standard equipment and operation conditions asthma attack symptoms 2 year old order advair diskus 500mcg with amex. In this procedure asthma symptoms not improving discount 250mcg advair diskus overnight delivery, small amounts of a stable isotope asthma pump discount 250 mcg advair diskus mastercard, typically a few milligrams, are included in the formulation. The labeled formulation is subsequently exposed to a neutron flux, and the stable isotope is thereby transformed to a radioactive isotope upon capture of a neutron. Several of the listed radionuclides are available in both enriched and natural forms; the use of the former, however, requires a less stable isotope to be included and/or less neutron radiation, at the disadvantage of higher costs. The main potential problem connected with neutron activation of dosage forms is the risk of affecting tablet function or causing degradation of the active compound as well as of excipients. Therefore, this has to be checked on a case-by-case basis before the start of in an in vivo study. Another potential problem is the creation of radionuclides, other than the intended one, which will obscure data interpretation and increase radiation exposure. If the undesirable isotopes have a significantly shorter half-life than the labeling isotope, this problem can be handled by waiting for a suitable time period such that the activity of the unintended isotope has declined, whereas significant activity remains for the desired radionuclide. One example of a common stable isotope that unintentionally can form radionuclides by neutron flux is sodium (24Na, t1/2 = 15 hours). Reviews of different applications of neutron activation in studies of dosage forms can be found in Digenis and Sandefer (1991). Conduct of In Vivo Studies Practical Procedures the subject is positioned in front of a g-camera, or between two cameras, one in front of the subject and one behind. The latter principle is needed when making quantifications of Biopharmaceutical Support in Formulation Development 283 Figure 14 A g-camera investigation with two opposite cameras. Systems with cameras that circulate around the subject for creation of three-dimensional images are also available, but their use in formulation studies in man are restricted by the higher amounts of radioactivity needed in the formulation to obtain reliable data. The data collection can be dynamic, that is, the subject is constantly located in front of the g-camera system, and signals are constantly gathered into images within very short time frames (often < 1 minute). In most cases, radiation is gathered over a finite time period to generate pictures. The time period for collecting radiation to one picture, typically 30 seconds to 1 minute, is mainly determined by quality requirements on picture/variability in quantitative data and the risk of moving artifacts. An example of the gastric emptying and colon transit time of a nondisintegrating tablet and small pellets after administration with a breakfast are given in Figure 15. Normally, it is possible to identify the stomach, terminal ileum, cecum, ascending/transversal/descending/sigmoidal colon, or rectum. Another approach for facilitating determination of position is to administer a radiolabeled reference solution, which will provide images of certain intestinal parts, such as the stomach. In the case of solid multiple particles, or liquid 284 Abrahamsson and Ungell Figure 15 Gastric emptying time after administration with breakfast (A) and colon residence time (B) for a nondisintegrating tablet and pellet formulation in eight individual subjects. This is exemplified in Figure 16, which shows the amount of food and a floating antacid remaining in the stomach at different times. The emptying or arrival processes from, or to, a certain region are determined by defining a region encompassing the area of interest. The number of counts obtained within this region is determined at several time points after correction for background radiation. The number of counts is often expressed as a percentage, defining the value obtained in the stomach immediately after administration as 100%. A rate constant, for example, the gastric emptying time, can then be determined from the emptyingtime profile by applying moment analysis (see sect. The gastric emptying of solids and liquids is often Biopharmaceutical Support in Formulation Development 285 Figure 16 the gastric emptying of a meal and a floating antacid formulation after concomitant administration. The two dashed vertical lines represent gastric emptying and colon arrival, respectively. The figures illustrate the correspondence between tablet erosion and drug absorption.