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Any alteration in mucus rheology that compromises clearance can predispose the individual to airway disease and infection cheap 8mg ondansetron with mastercard medications jock itch. In addition order 4 mg ondansetron visa treatment for pink eye, the state of mucus hydration (or mucin concentration) will affect the properties of the gel purchase 8mg ondansetron free shipping symptoms 9 dpo. Two mucin subunits order ondansetron 8mg online treatment integrity checklist, each about 500 nm in length, are joined end to end via disulfide bonds (S-S) and consist of oligosaccharide-rich regions (represented by the thickened line) and folded domains stabilized by disulfide bonds (represented by the knots). An increase in mucus viscoelasticity is also thought to occur in asthma, chronic bronchitis, chronic obstructive pulmonary disease and acute respiratory distress syndrome. The mucus blanket (c) is always propelled in the same direction as the effective stroke (d) 9. Rest phase At the end of the effective stroke the cilium disengages from the mucus gel and enters the rest phase where it lies parallel to the epithelium pointing in the direction of mucus flow. Recovery stroke The cilium “unrolls” within the periciliary fluid ready for the next effective stroke. Undergoing the recovery stroke beneath the mucus layer prevents retrograde mucus transport (Figure 9. They are packed at a density of 6–8 cilia per μm2 and cannot move without affecting neighbouring cilia. In order to perform an unhindered beat cycle the movement of each cilium is slightly out of phase with that of its neighbor, leading to a phenomenon termed “ciliary metachrony”. Metachrony results solely from hydrodynamic coupling between adjacent cilia and provides the necessary cooperation within a field of cilia to permit them to transport mucus. Each cilium is bounded by an evagination of the plasma membrane and, as shown diagrammatically (Figure 9. Each outer doublet microtubule consists of an A subfiber which is circular in cross-section, and an incomplete B subfiber, which is C-shaped in cross-section. The inner and outer dynein arms of the A subfiber project towards the B subfiber of the adjacent microtubule. Since the microtubules are constrained at the ciliary tip, it is possible to imagine how the sliding of microtubules on one side of the cilium might cause the cilium to bend. How such sliding is translated into a full beat cycle is still the subject of extensive research. A wide number of agents are able to alter the rate of ciliary beating; this can either be via a non-specific, toxic effect, e. However, data concerning the role of cyclic guanosine 5′-phosphate-dependent protein phosphorylation on ciliary beat frequency are conflicting. Increases in the intracellular concentration of Ca2+ ([Ca2+] ) increases ciliary beat frequency possibly via i protein phosphorylation induced by calcium/calmodulin kinase. Ciliated cells also respond to mechanical stimulation by increasing their beat frequency, an effect which spreads to surrounding cells (5–7 cells in all directions) and is mediated by an increase in [Ca2+]. Such intercellular signaling provides the opportunity for cooperative cellular activity which would be advantageous to the ciliated epithelium in its efforts to transport mucus. Airway cilia may be able to upregulate their beat frequency in response to an increase in the mucus load. As with most sites of drug absorption, the bioavailability of a drug is affected by the area available for absorption, the contact time between the drug and the absorption site, metabolism of the drug prior to and during absorption and the pathology of the absorbing tissue. The area available for absorption is enhanced2 by: • the convolutions of the turbinates, and • the microvilli present on the surface of the ciliated and unciliated cells of the respiratory epithelium. However, the effective surface area for absorption is influenced by the type of dosage form from which the drug is administered, as described below. Molecules (% loss) Degradation 0–15 0–5 Clearance a 0–30 20–50 Deposition (anterior loss) 10–20 10–20 Health status and environment 10–20 10–40 Membrane permeability ab 0–30 20–50 Mucus layer <1 <1 adepends on excipients bdepends on physicochemical characteristics of the drug, e. This property facilitates its physiological role in heat exchange and also potentially, drug absorption. The rich blood supply means that drugs absorbed via the nasal route have a rapid onset of action, which can be exploited for therapeutic gain. In the nasal cavity this is influenced by the rate at which the drug is cleared from the absorption site by mucociliary clearance and by metabolism. While the mucociliary clearance of deposited particles is advantageous if the particles are likely to be hazardous, the clearance of a deposited drug is clearly not beneficial if it prevents absorption. The site of deposition in the nasal cavity profoundly affects the rate of mucociliary clearance of a drug moiety: • Particles deposited on ciliated regions (for example, the turbinates) of the mucosa are immediately available for clearance. As described above, clearance of the bulk of the mucus from the nose to the nasopharynx occurs over 10–20 minutes. This is probably because most of the spray has deposited on non-ciliated regions of the nasal cavity. Deposition site; □ Turbinates; ▲ Nasopharynx ● The implications of this for drug absorption are that administration of a drug as drops may only be suitable if the drug molecule is rapidly absorbed. Those drug molecules which diffuse across the nasal epithelium more slowly will need a longer contact time and may be better administered as sprays. The absorption rate of certain drugs may be so slow that therapeutically active plasma levels are not attained. Such conditions include rhinitis, the common cold, hayfever, sinusitis, asthma, nasal polyposis, Sjogren’s and Kartagener’s syndromes. In addition, environmental factors such as humidity, temperature and pollution can also affect the rate of nasal clearance. The common cold consists of two distinct phases: mucus hypersecretion, followed by nasal congestion. It has been shown that during the former phase, less than 10% of a dose administered as a nasal spray will remain in the nasal cavity after 25 minutes. In contrast, almost all the administered dose will still be present at the site of deposition up to 90 minutes after administration during the nasal congestion phase. This would clearly lead to unpredictable absorption of an administered drug which would be unacceptable for a potent drug with a narrow therapeutic window. The inclusion of a vasoconstrictor such as oxymetazoline in the formulation might relieve such symptoms and provide more reproducible drug absorption. This would be likely to affect drug absorption but not necessarily in a reproducible manner. It has been suggested that the low bioavailabilities of some nasally administered peptides results from their enzymatic degradation in the nasal cavity. The nasal mucosa and fluids have been shown to possess a variety of exopeptidases and endopeptidases (see Section 1. The actions of intracellular enzymes will not be significant if the peptide is absorbed by the paracellular route (see Section 9. Small peptides are relatively resistant to the action of endopeptidases but their activity is significant for large peptides. Although enzymatic activity is present in the nasal cavity, this activity is generally lower than the enzymatic activity of the gastrointestinal tract, making this route an attractive alternative to the oral delivery of enzymatically labile drugs such as therapeutic peptides and proteins. These enzymes are capable of metabolizing inhaled pollutants into reactive metabolites which may induce nasal tumors.
Table 3-3 Prefixes of Number and Measurement This table lists commonly used prefixes of number and measurement along with their meanings and word analyses ondansetron 4mg with mastercard medications not to take after gastric bypass. Table 3-4 Prefixes of Direction This table lists commonly used prefixes of direction as well as their meanings and word analyses discount 4 mg ondansetron otc in treatment online. It is time to review prefixes by completing Learning Activities 3–1 order ondansetron 8 mg fast delivery medicine head, 3–2 cheap ondansetron 8 mg free shipping medicine jar, and 3–3. Complete each activity and review your answers to evaluate your understanding of the chapter. Learning Activity 3-1 Identifying and Defining Prefixes Place a slash after each of the following prefixes and then define the prefix. Levels of Organization • Identify the cavities, quadrants, and regions of the Cell body. Cell Membrane and Cytoplasm • List and identify the terms related to direction, Nucleus position, and planes of the body. Tissue Organ • Recognize, pronounce, spell, and build words related System to body structure and identify common Organism abbreviations. Anatomical Position • Describe diagnostic and therapeutic procedures and Planes of the Body other terms associated with body structure. Body Cavities • Demonstrate your knowledge of this chapter by Abdominopelvic Divisions completing the learning and medical record activities. These terms are an This chapter provides the basic foundation for essential part of medical terminology and are used understanding the body system chapters that fol- in all body systems. It presents the basic structural and functional and terminology associated with the disease organization of the body—from the cellular level process are also provided. It also presents terms used to ents and describes terms associated with diagnos- describe planes of the body, body cavities, quad- tic and therapeutic procedures. Body Structure Key Terms This section introduces important terms associated with body structure, along with their defini- tions and pronunciations. In each pair of chromosomes, one chromosome is inherited from the father and the other from the mother. Each of these levels builds on the traits as hair color, body structure, and metabolic previous level, and contributes to the structure and activity. The levels of organization from least to most com- plex are: Tissue • cell Groups of cells that perform a specialized activity • tissue are called tissues. Between the cells that make up tissues are • system varying amounts and types of nonliving, intercellu- • organism. More than 200 cell types compose four Cell major tissues of the body: The study of the body at the cellular level is called • Epithelial tissue covers surfaces of organs, cytology. The cell is the structural and functional lines cavities and canals, forms tubes and unit of life. Body cells perform all activities associ- ducts, provides the secreting portions of ated with life, including utilizing food, eliminating glands, and makes up the epidermis of the waste, and reproducing. It is composed of cells arranged in a membrane that encloses cytoplasm and a nucleus. Cell Membrane and Cytoplasm • Connective tissue supports and connects The cell membrane acts as a barrier that encloses other tissues and organs. It controls the transport of many diverse cell types, including fibroblasts, fat substances to and from the cell. Nucleus The nucleus is responsible for metabolism, growth, Organ and reproduction. This blueprint is found in Organs are body structures that perform special- a complex molecule called deoxyribonucleic acid ized functions. When the cell is ready to divide, made up of connective tissue, muscle tissue, chromatin forms chromosomes, which carry thou- epithelial tissue, and nervous tissue. In the human, there are about 31,000 genes that Epithelial and connective tissue cover the inner determine unique human characteristics. Abdominopelvic Divisions 43 penetrates the epithelial lining of the stomach and Table 4-1 Planes of the Body its muscular wall to stimulate the release chemicals for digestion and contraction for peristalsis. System Plane Anatomical Division A body system is composed of varying numbers of Midsagittal (median) Right and left halves organs and accessory structures that have similar or Coronal (frontal) Anterior (ventral) and related functions. For example, organs of the gas- posterior (dorsal) trointestinal system include the esophagus, stom- aspects ach, small intestine, and bowel. Some of its accesso- ry structures include the liver, gallbladder, and Transverse Superior (upper) and pancreas. The purpose of this system is to digest (horizontal) inferior (lower) aspects food, remove and use its nutrients, and expel waste products. Other body systems include the reproduc- tive, respiratory, urinary, and cardiovascular systems. Thus, structural abnormalities and body The highest level of organization is the organism. All complex organisms, scanning devices that show images taken in sever- including humans, are made up of several body al body planes. Body Cavities Anatomical Position Medical professionals locate structures or abnor- The anatomical position is a body posture used to malities by referring to the body cavity in which locate anatomical parts in relation to each other. The lower • dorsal (posterior), including the cranial and limbs are parallel, with toes pointing straight spinal cavities ahead. No matter how the body is actually • ventral (anterior), including the thoracic and positioned—standing or lying down, facing for- abdominopelvic cavities. Divisions The abdominopelvic area of the body lies beneath Planes of the Body the diaphragm. It holds the organs of digestion (abdominal area) and the organs of reproduction To identify the different sections of the body, and excretion (pelvic area). Two anatomical meth- anatomists use an imaginary flat surface called a ods are used to divide this area of the body for plane. The most commonly used planes are mid- medical purposes: sagittal (median), coronal (frontal), and trans- verse (horizontal). Current imaging a means of locating specific sites for descriptive procedures, such as magnetic resonance imaging and diagnostic purposes. Pain, lesions, abrasions, Spine punctures, and burns are commonly described as The spine is divided into sections corresponding to located in a specific quadrant. These also identified by using body quadrants as the divisions are: method of location. For example, the stomach is located in the left example, the kidneys are superior to the urinary hypochondriac and epigastric region; the appen- bladder. The directional phrase superior to denotes dix is located in the hypogastric region.
Syndromes
- Heroin
- High LDL cholesterol and low HDL cholesterol
- Stroke
- Normal aging process
- Body position
- Rocky Mountain spotted fever
- Umbilical (connection between the navel and gut)
- Kyphotic curves refer to the outward curve of the thoracic spine (at the level of the ribs).
- Kidney
With additional insight purchase ondansetron 4 mg free shipping medicine interactions, you can bring empathy purchase 8mg ondansetron with visa medications that cause tinnitus, support and love to the process of trying to change ondansetron 8 mg medicine 3 sixes. You can thereby diminish the power that your inner child has over your present day-to-day experiences cheap ondansetron 4 mg with amex treatment resistant schizophrenia. It will give you more control, more perspective and that elusive peace of mind that we all dream about. The next time you become aware of an inner voice or conversation with yourself that’s going something like, “Oh I shouldn’t have done that…” look for clues that it’s really a child talking. When you become aware of your inner child, extend compassion and understanding to the child you once were and use the occasion as an opportunity to explore why you think and act the way you do. Summary • You have an inner voice that’s always commenting to you during times of stress and directing the action to be taken next. This refers to childhood events, which were very emotionally traumatic and may have related to loss, rejection, abandonment, humiliation, betrayal and/or a sense of having been overwhelmed. If you were to develop mindfulness in relation to your own thoughts, you would Adiscover that you have an inner voice that is always talking to you, usually criticizing, comparing and judging everything that arises internally and externally. In this chapter, you’ll learn a helpful stress-reducing technique, which is how to talk to your inner voice. The purpose of the inner-child dialogue is to: • discover the underlying core belief system of the inner child • examine if the core belief system is true • identify the inner child’s feelings This is an important progression that ultimately helps you to change the limiting and painful belief system of the inner child. The inner-child dialogue is a useful technique for really understanding yourself and your stress, but if you’re new to it, it’s going to seem a little strange at first. Remember, you can’t continue to handle things the way you always have and expect a different result. The other advantage of the inner-child dialogue is that, through this technique, you can truly understand that your inner voice is your inner child just trying to be safe. This understanding makes it easier to allow your thoughts to pass through your mind without taking any ownership of their content. The inner voice is really your protector, the voice that recognizes when you have strayed from your created belief system. You should view the voice as that of your beautiful inner child who is trying to help you. If you keep this in mind, it may be easier to bring a sense of self-compassion to any conversations that you have with your inner child. There is the surface level on which you, as an adult, have numerous worries and concerns in response to stressful events. However, it’s the underlying realm of the inner child that truly gives a stressful event its motivational drive. Have you ever noticed that in some situations there’s an emotional or psychological intensity that appears disproportionate to what’s actually happening? This is why connecting with the inner child, and truly understanding the experience from the inner child’s perspective, can be so useful. Talking to Yourself You’re directly and intimately feeling the emotions and physical sensations that the inner child is experiencing and so you can authentically understand and express support to the inner child. The initial process of dialoguing follows this sequence: Dialogue: A Friendly Chat with Your Inner Child • 167 1. Inquire: Time to ask some questions Mindfulness: Bring Awareness to Your Inner Voice Initially, to start an inner-child dialogue, you’ll want to bring mindful- ness into play. When practicing mindfulness, you bring your attention to the present moment without trying to change it and are simply present to whatever is being experienced. You’re bringing awareness to what’s being said, and what’s felt emotionally and physically. When a more emotionally charged thought arises and you notice your inner voice commenting, create some space around that sensation. Just observe it; notice what it’s saying to you from a place of awareness, acceptance, non-judgment, non-attachment and compassion. It can be very difficult not to identify with what the inner voice is saying and you may want to even amplify, or add to, what you’re hearing. The initial ability to let the voice say what it needs to say, for as long as it needs to say it, without interfering, is the first step. When you’re upset, you probably feel like talking to a friend and sharing with him or her what it is that you’re experiencing. The opportunity just to be heard is likely more helpful than necessarily having your friend offer a solution. You can truly experience mentally, emotionally and physically what the inner child is experiencing first hand, without having to guess at what’s happening. In many situations, just listening and allowing the mind to speak will bring a stressful moment to a close without needing to do anything further. The child has normally felt neglected, marginalized and unimportant and finally there’s some recognition. This starts with really listening to the child, without interrupting, as it talks to you. Be completely open to feeling the emotional state 168 • Mindfulness Medication of the child mentally and physically. Actively bring your attention to feeling the mental trauma and anxiety conveyed by your inner child, as well as any accompanying physical sensations, such as rapid or shallow breathing, racing heart rate, twisting sensations in the abdomen, shaking of the head or body, etc. Sitting in the fire of the emotional trauma of the child, and not running from it or avoiding it, will allow a transformation to occur. By directly experiencing what the child is feeling, you will be able to really determine, and then express, what it is that the child needs. When you first begin the inner-voice conversations, you will tend to view the inner voice as completely “who you are. It helps to create some space, away from the intensity of the inner voice, by clarifying the fact that who you are is not the voice. Remember that it’s the voice of your inner child and this will allow you to keep your distance and listen to the inner voice with a sense of compassion. What happens typically is that when the inner child starts to talk to you about its anxieties and concerns, your present-day awareness identifies with what’s being said and amplifies what’s being expressed. You react to the initial thoughts and have additional reactive thoughts that in-turn create more tension. Dialogue: A Friendly Chat with Your Inner Child • 169 To avoid this, be careful not to identify with your inner voice by saying to yourself, “It’s just my mind. This gives your mind a job to occupy itself so that it doesn’t have the chance to react and get more emotionally and/or actively involved. Engage: Start a Conversation with Yourself So you’ve observed that your inner voice (the voice of your inner child) has something to say. It’s used to being the one in charge and you don’t usually challenge it, especially during times of stress when you function on autopilot and are very reactive rather than responsive. Inquire: You’re in the Driver’s Seat, Ask the Questions • Remind yourself, once again, of the fact that this is a conversation with your inner child by opening the inquiry with, “My dear child…” • The questions you pose to your inner child should be in the form of an open-ended question.
This simple 360 3×3×3 combinatorial split and mix approach generates a library of beads containing 27 different compounds in only 6 coupling reactions cheap ondansetron 8 mg free shipping treatment plan for depression. A10×10×10×10×10 split and mix reaction scheme will produce 10 4 mg ondansetron with mastercard symptoms 20 weeks pregnant,000 compounds in only 50 reactions ondansetron 4mg on-line treatment uterine cancer. It is therefore clear that these strategies can produce large libraries of compounds of wide molecular diversity order ondansetron 4 mg fast delivery medications kidney disease. As each resin bead contains only a single molecule the beads can be screened individually for bioactivity by either screening for activity of bound peptide in the biological assay or by cleaving the resultant peptide from the bead before undertaking the bioanalysis. The identity of any active compounds can then be determined by using mass spectrometry to sequence the active peptide. These involve the synthesis of a large number of combinatorial libraries making it possible to identify the sequence of the active agent from the identification of the libraries containing the active agent. For example, if we were interested in a 5 amino acid peptide we could use an indexed library approach. This approach involves the initial synthesis of 20 combinatorial libraries using 20 different amino acids as the first amino acid. By screening these libraries we would be able to identify a library containing the most active peptide against a therapeutic target—this library would indicate which amino acid is required in the first position of the peptide. If we then, keeping the first amino acid constant, synthesize a further 20 libraries using 20 different amino acids in the second position we will be able to identify the second amino acid required for optimal activity. Such a process allows the most active agent to be identified from a potential pool of 3. Parallel array libraries use a similar strategy but the libraries are all synthesized in parallel. For example, if we were looking for a small molecule drug which could be synthesized from three basic building blocks A, B and C each of which had 12 different possible variants (e. The first set of libraries would each contain a known variant of A, the second set of libraries a known variant of B and the third set of libraries a known variant of C. By screening all the libraries and identifying the most active library from each set it is immediately possible to identify the structure of the most active compound, as only one compound will be common to the libraries (e. All these approaches assume that the only a single compound will be synthesized on each bead at each coupling stage, that there are no side-reactions and that other members of the libraries do not interfere with the binding of the most active compound to the ligand of interest during screening. Although these limitations may seem highly significant, these techniques have been successfully validated using combinatorial techniques to identify known endogenous receptor ligands. These techniques provide a wide range of molecularly diverse molecules with potential therapeutic applications. In addition, the field of combinatorial chemistry has led to the development of (i) a vast range of clean chemical reactions which give rise to a single products, (ii) novel linker technologies allowing molecules to be readily linked to solid supports and subsequently cleaved on completion of the coupling reactions, (iii) novel protecting strategies and (iv) novel chemistries which allow the synthesis of a diverse range of molecules including benzodiazepines, saccharides and lactams, in addition to the more traditional peptides and oligonucleotides on solid supports. The recent developments in molecular biology and robotics have provided the impetus for such technology. However, more recently the industry has been considering 384 and even 1,536 microwell plates. The advances in robotics allow assays to be fully automated and run continually day and night with minimal operator intervention. Molecular biology has provided the means to clone human receptors in a variety of cells and express different enzymes in model systems. 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.
