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The corona radiata is an outer layer of follicular (granulosa) cells that form around a developing oocyte in the ovary and remain with it upon ovulation proven levitra extra dosage 40mg. The underlying zona pellucida (pellucid = “transparent”) is a transparent buy levitra extra dosage 40mg line, but thick, glycoprotein membrane that surrounds the cell’s plasma membrane. As it is swept along the distal uterine tube, the oocyte encounters the surviving capacitated sperm, which stream toward it in response to chemical attractants released by the cells of the corona radiata. This initiates a process called the acrosomal reaction in which the enzyme-filled “cap” of the sperm, called the acrosome, releases its stored digestive enzymes. Finally, a single sperm makes contact with sperm-binding receptors on the oocyte’s plasma membrane (Figure 28. The plasma membrane of that sperm then fuses with the oocyte’s plasma membrane, and the head and mid-piece of the “winning” sperm enter the oocyte interior. Some sperm undergo a spontaneous acrosomal reaction, which is an acrosomal reaction not triggered by contact with the zona pellucida. The digestive enzymes released by this reaction digest the extracellular matrix of the corona radiata. Rather, hundreds of sperm cells must undergo the acrosomal reaction, each helping to degrade the corona radiata and This OpenStax book is available for free at http://cnx. If you consider the loss of millions of sperm between entry into the vagina and degradation of the zona pellucida, you can understand why a low sperm count can cause male infertility. When the first sperm fuses with the oocyte, the oocyte deploys two mechanisms to prevent polyspermy, which is penetration by more than one sperm. This is critical because if more than one sperm were to fertilize the oocyte, the resulting zygote would be a triploid organism with three sets of chromosomes. The first mechanism is the fast block, which involves a near instantaneous change in sodium ion permeability upon binding of the first sperm, depolarizing the oocyte plasma membrane and preventing the fusion of additional sperm cells. The fast block sets in almost immediately and lasts for about a minute, during which time an influx of calcium ions following sperm penetration triggers the second mechanism, the slow block. In this process, referred to as the cortical reaction, cortical granules sitting immediately below the oocyte plasma membrane fuse with the membrane and release zonal inhibiting proteins and mucopolysaccharides into the space between the plasma membrane and the zona pellucida. Zonal inhibiting proteins cause the release of any other attached sperm and destroy the oocyte’s sperm receptors, thus preventing any more sperm from binding. The mucopolysaccharides then coat the nascent zygote in an impenetrable barrier that, together with hardened zona pellucida, is called a fertilization membrane. The unneeded complement of genetic material that results is stored in a second polar body that is eventually ejected. The two haploid nuclei derived from the sperm and oocyte and contained within the egg are referred to as pronuclei. The pronuclei then migrate toward each other, their nuclear envelopes disintegrate, and the male- and female- derived genetic material intermingles. This step completes the process of fertilization and results in a single-celled diploid zygote with all the genetic instructions it needs to develop into a human. However, in approximately 1 percent of ovulation cycles, two eggs are released and both are fertilized. Because dizygotic twins develop from two eggs fertilized by two sperm, they are no 1322 Chapter 28 | Development and Inheritance more identical than siblings born at different times. Although the zygote can split as early as the two-cell stage, splitting occurs most commonly during the early blastocyst stage, with roughly 70–100 cells present. These two scenarios are distinct from each other, in that the twin embryos that separated at the two-cell stage will have individual placentas, whereas twin embryos that form from separation at the blastocyst stage will share a placenta and a chorionic cavity. In vitro, which in Latin translates to “in glass,” refers to a procedure that takes place outside of the body. For example, a woman may produce normal eggs, but the eggs cannot reach the uterus because the uterine tubes are blocked or otherwise compromised. A man may have a low sperm count, low sperm motility, sperm with an unusually high percentage of morphological abnormalities, or sperm that are incapable of penetrating the zona pellucida of an egg. A normal ovulation cycle produces only one oocyte, but the number can be boosted significantly (to 10–20 oocytes) by administering a short course of gonadotropins. Right before the ova would be released from the ovary, they are harvested using ultrasound-guided oocyte retrieval. If there are severe problems with the sperm—for example, the count is exceedingly low, or the sperm are completely nonmotile, or incapable of binding to or penetrating the zona pellucida—a sperm can be injected into an egg. In the United States, fertilized eggs are typically cultured to the blastocyst stage because this results in a higher pregnancy rate. The period of time required for full development of a fetus in utero is referred to as gestation (gestare = “to carry” or “to bear”). A developing human is referred to as an embryo during weeks 3–8, and a fetus from the ninth week of gestation until birth.

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Finally best levitra extra dosage 60mg, it is hydrolyzed into choline and acetate by acetyl cholinesterase enzyme and thereby the action of the transmitter is terminated discount levitra extra dosage 60 mg online. Cholinergic receptors are classified into muscarinic and nicotinic cholinergic receptors. The response of most autonomic effector cells in peripheral visceral organs is typically muscarinic, whereas the responses in parasympathetic and sympathetic ganglia, as well as responses of skeletal muscle are nicotinic. The effect of parasympathetic nervous system activity in an organ may be produced either by stimulation of a parasympathetic nerve fibers supplying the organ or by the application of acetylcholine or other parasympathomimetics to the effector cells. Noradrenaline is the neurotransmitter released by post ganglionic sympathetic nerves to elicit its effect on effectors cells. Sympathetic nerve activity may be demonstrated by sympathetic nerve stimulation or by application of noradrenaline or adrenaline or other sympathomimetics, i. Adrenergic neuron terminals synthesize noradrenaline, store it in vesicles and release it to effector cells upon stimulation of the nerve. The transmitter is synthesized from precursor tyrosine (amino acid) through several processes which are potential sites of drug action. Termination of noradrenergic transmission results from several processes such as reuptake into the nerve terminal (reuptake1), diffusion away from the synaptic cleft and subsequent reuptake into the perisynaptic glia or smooth muscle (reuptake2) or degradation by enzymes. Reuptake into the nerve terminal is the most important mechanism for termination of the effects of noradrenaline. Receptors that respond to adrenergic nerve transmitter are termed adrenergic receptors. These receptors are subdivided into alpha and beta adrenoreceptor types on the basis of both agonist and antagonist selectivity. These are synthesis, storage, release, activation of receptors and termination of the action of the transmitter. Drugs acting on the sympathetic nervous system a) Sympathomimetics or adrenergic drugs: are drugs that mimic the effects of sympathetic nerve stimulation. Drugs acting on the parasympathetic nervous system a) Parasympathomimetics or cholinergic drugs: are drugs which mimic acetylcholine or the effects of parasympathetic nerve stimulation. Administration of these drugs will result in an increase in the parasympathetic activities in the systems innervated by cholinergic nerves. Direct-acting: bind to and activate muscarinic or nicotinic receptors (mostly both) and include the following subgroups: a. Irreversible: Organophosphate compounds; echothiophate The actions of acetylcholine may be divided into two main groups: - 1. Nicotinic actions- those produced by stimulation of all autonomic ganglia and the neuromuscular junction 2. It functions as a neurotransmitter at all cholinergic sites in the body; because of its unique pharmacokinetic properties, it has never been used in medical therapeutics; the discussion which follows is for academic exercise. Pharmacokinetics Acetylcholine is poorly absorbed from the gastric mucosa; therefore it is ineffective if given orally. In the blood it is rapidly hydrolyzed by the enzyme cholinesterase into acetic acid and choline; this makes its duration of action very short and unreliable for therapeutic purposes. Pharmacodynamics As mentioned earlier it has two types of actions: nicotinic and muscarinic; the muscarinic actions are of main interest and are discussed below. These are synthetic derivatives of choline and include metacholine, carbachol and betanechol. These drugs have the following advantages over acetylcholine: • They have longer duration of action, • They are effective orally as well as parenterally, and • They are relatively more selective in their actions. Bronchial asthma because they may induce bronchial constriction and increase bronchial secretions 2. Coronary insufficiency because the hypertension produced will further compromise coronary blood flow 5. Pharmacodynamics The drug directly stimulates the muscarinic receptors to bring about all the muscarinic effects of acetylcholine. Pharmacodynamics Inhibits the enzyme cholinesterase; therefore, it increases and prolongs the effect of endogenous acetylcholine at the different sites. Pharmacodynamics Just like physostigmine, it inhibits cholinesterase enzyme; but unlike physostigmine, it has a direct nicotinic action on skeletal muscles. Indications • Myasthenia gravis • Paralytic Ileus • Reversal of effect of muscle relaxants, e. Poisoning with organophosphates is an important cause of morbidity and mortality all over the world. It usually results from: • Occupational exposure as in persons engaged in spraying insecticides, • Accidental exposure, and 39 • Ingestion of any of these compounds with suicidal intent. Antinicotinics which include ganglion blockers such as hexamethonium, trimethaphan, etc. Antimuscarinics include tertiary amines such as atropine, scopolamine, tropicamide, etc, andquaternary amines such as propantheline, ipratropium, benztropine, etc.

The other major category of ganglia are those of the autonomic nervous system buy discount levitra extra dosage 60 mg on-line, which is divided into the sympathetic and parasympathetic nervous systems purchase 40mg levitra extra dosage visa. The sympathetic chain ganglia constitute a row of ganglia along the vertebral column that receive central input from the lateral horn of the thoracic and upper lumbar spinal cord. Three other autonomic ganglia that are related to the sympathetic chain are the prevertebral ganglia, which are located outside of the chain but have similar functions. The neurons of these autonomic ganglia are multipolar in shape, with dendrites radiating out around the cell body where synapses from the spinal cord neurons are made. The neurons of the chain, paravertebral, and prevertebral ganglia then project to organs in the head and neck, thoracic, abdominal, and This OpenStax book is available for free at http://cnx. Another group of autonomic ganglia are the terminal ganglia that receive input from cranial nerves or sacral spinal nerves and are responsible for regulating the parasympathetic aspect of homeostatic mechanisms. These two sets of ganglia, sympathetic and parasympathetic, often project to the same organs—one input from the chain ganglia and one input from a terminal ganglion—to regulate the overall function of an organ. For example, the heart receives two inputs such as these; one increases heart rate, and the other decreases it. The terminal ganglia that receive input from cranial nerves are found in the head and neck, as well as the thoracic and upper abdominal cavities, whereas the terminal ganglia that receive sacral input are in the lower abdominal and pelvic cavities. Terminal ganglia below the head and neck are often incorporated into the wall of the target organ as a plexus. This can apply to nervous tissue (as in this instance) or structures containing blood vessels (such as a choroid plexus). For example, the enteric plexus is the extensive network of axons and neurons in the wall of the small and large intestines. The enteric plexus is actually part of the enteric nervous system, along with the gastric plexuses and the esophageal plexus. They have connective tissues invested in their structure, as well as blood vessels supplying the tissues with nourishment. The outer surface of a nerve is a surrounding layer of fibrous connective tissue called the epineurium. Within the nerve, axons are further bundled into fascicles, which are each surrounded by their own layer of fibrous connective tissue called perineurium. Finally, individual axons are surrounded by loose connective tissue called the endoneurium (Figure 13. With what structures in a skeletal muscle are the endoneurium, perineurium, and epineurium comparable? Cranial Nerves The nerves attached to the brain are the cranial nerves, which are primarily responsible for the sensory and motor functions of the head and neck (one of these nerves targets organs in the thoracic and abdominal cavities as part of the parasympathetic nervous system). They can be classified as sensory nerves, motor nerves, or a combination of both, meaning that the axons in these nerves originate out of sensory ganglia external to the cranium or motor nuclei within the brain stem. Three of the nerves are solely composed of sensory fibers; five are strictly motor; and the remaining four are mixed nerves. Learning the cranial nerves is a tradition in anatomy courses, and students have always used mnemonic devices to remember the nerve names. A traditional mnemonic is the rhyming couplet, “On Old Olympus’ Towering Tops/A Finn And German Viewed Some Hops,” in which the initial letter of each word corresponds to the initial letter in the name of each nerve. The names of the nerves have changed over the years to reflect current usage and more accurate naming. An exercise to help learn this sort of information is to generate a mnemonic using words that have personal significance. It is also responsible for lifting the upper eyelid when the eyes point up, and for pupillary constriction. The trochlear nerve and the abducens nerve are both responsible for eye movement, but do so by controlling different extraocular muscles. The trigeminal nerve is responsible for cutaneous sensations of the face and controlling the muscles of mastication. The facial nerve is responsible for the muscles involved in facial expressions, as well as part of the sense of taste and the production of saliva. The glossopharyngeal nerve is responsible for controlling muscles in the oral cavity and upper throat, as well as part of the sense of taste and the production of saliva. The vagus nerve is responsible for contributing to homeostatic control of the organs of the thoracic and upper abdominal cavities. The spinal accessory nerve is responsible for controlling the muscles of the neck, along with cervical spinal nerves. Three of the cranial nerves also contain autonomic fibers, and a fourth is almost purely a component of the autonomic system.

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Its effect on intracranial pressure remains controversial in practice levitra extra dosage 60mg on-line, but controlled studies in which ventilation was controlled showed no effect on intracranial pressure purchase 60 mg levitra extra dosage amex. Concordant treatment with a benzodiazepine has been shown to prevent the development of unpleasant emergence phenomena. It has a direct negative inotropic effect on the myocardium, and a direct vasodilatory action on vascular smooth muscle. This is generally overwhelmed by central sympathetic stimulation that occurs, however, leading to increases in heart rate, systemic arterial pressure, and possibly systemic vascular resistance. The cardiovascular effects of ketamine are attenuated by alpha and beta blocking agents, verapamil, benzodiazepines, and high epidural blockade. Respiratory effects Ketamine is a mild respiratory depressant, and there is a dose related increase in respiratory depression with incremental doses of ketamine. Ketamine generally preserves airway patency, and protective airway reflexes are not repressed. Transient stridor or laryngospasm are rarely reported, and are associated with coincident respiratory infection. Ketamine increases oral secretions, and this may be more clinically important in those children with upper respiratory infections. Laryngospasm and the potential for emesis/aspiration are more pronounced in infants and patients with a full stomach, hence these patients should be considered at risk for airway compromise. The mechanisms of this response is considered to be a combination of drug induced increase in circulating catecholamine, direct smooth muscle dilatation, and inhibition of vagal tone. Neuromuscular Effects Ketamine increases skeletal muscle tone, and there are frequently random movements of the head or extremities. Ketamine also appears to potentiate the effects of neuromuscular blocking agents, both depolarizing and non-depolarizing. Dosage Recommendations In the intensive care unit all anesthetic/analgesic/sedative agents should be titrated to effect, with the unique physiology of each patient kept in mind. These children may be compromised from a pulmonary, hemodynamic, or neurologic perspective, and judicial use of any agent is warranted. Ketamine, for example, while supporting hemodynamics in the majority of patients, can cause hypotension if the patient’s myocardial reserve is limited. Co-administration of benzodiazepines reduces the incidence of emergence phenomena in older children, but will prolong the duration of sedation. This is not generally problematic in the intensive care setting, but should be considered. Propofol Propofol (2,6 diisopropyl phenol, “Diprivan”) has low aqueous solubility, and the commercial preparation is a 1% (i. It has a rapid onset and short duration of action, and produces respiratory and cardiac depression that is dose related. It is most useful for short procedures or “short” continuous infusions (see below). Propofol’s unique pharmacokinetics are its most attractive feature-rapid onset of hypnosis and rapid resolution of effects after discontinuation of the drug. The distribution of propofol is describes by an open three-compartment model: rapid initial distribution from blood to highly perfused tissues (brain, heart, lung, liver)-t/12 1. Propofol has a large central volume of distribution, is highly protein bound, and has an apparent high volume of distribution at equilibrium. Propofol is extensively metabolized in the liver and possibly other sites to inactive glucuronide and sulfate conjugates which are excreted in the urine. In adults with renal or hepatic disease, propofol pharmacokinetic parameters are not significantly altered. Clinical effects are realized within 40 seconds of administration, and emergence occurs within 10 to 30 minutes, depending partially on the length of administration. Propofol may be an effective anti-convulsant for status epilepticus unresponsive to other drugs. Cardiovascular Propofol may produce hypotension by a direct vasodilatory effect on both arterial and venous beds and by reducing sympathetic tone. Propofol is thus more likely to induce hypotension in patients with hypovolemia, compromised myocardial function, or vasomotor instability. Respiratory - 93 - Propofol acts as a moderate respiratory depressant, and blunts both hypoxic and hypercapnic ventilatory drive. Propofol is a mild bronchodilator and pulmonary dilator, but does not affect hypoxic vasoconstriction. Metabolic Propofol significantly decreased Vo2 and Vco2 in excess of its sedative effects, possibly due to a decrease in cellular metabolism.

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This secondary response is the basis of immunological memory buy levitra extra dosage 40mg without prescription, which protects us from getting diseases repeatedly from the same pathogen purchase levitra extra dosage 40 mg otc. By this mechanism, an individual’s exposure to pathogens early in life spares the person from these diseases later in life. Self Recognition A third important feature of the adaptive immune response is its ability to distinguish between self-antigens, those that are normally present in the body, and foreign antigens, those that might be on a potential pathogen. As T and B cells mature, there are mechanisms in place that prevent them from recognizing self-antigen, preventing a damaging immune response against the body. These mechanisms are not 100 percent effective, however, and their breakdown leads to autoimmune diseases, which will be discussed later in this chapter. T Cell-Mediated Immune Responses The primary cells that control the adaptive immune response are the lymphocytes, the T and B cells. T cells are particularly important, as they not only control a multitude of immune responses directly, but also control B cell immune responses in many cases as well. Thus, many of the decisions about how to attack a pathogen are made at the T cell level, and knowledge This OpenStax book is available for free at http://cnx. The variable region domain is furthest away from the T cell membrane and is so named because its amino acid sequence varies between receptors. The differences in the amino acid sequences of the variable domains are the molecular basis of the diversity of antigens the receptor can recognize. Thus, the antigen-binding site of the receptor consists of the terminal ends of both receptor chains, and the amino acid sequences of those two areas combine to determine its antigenic specificity. Antigens Antigens on pathogens are usually large and complex, and consist of many antigenic determinants. An antigenic determinant (epitope) is one of the small regions within an antigen to which a receptor can bind, and antigenic determinants are limited by the size of the receptor itself. They usually consist of six or fewer amino acid residues in a protein, or one or two sugar moieties in a carbohydrate antigen. Protein antigens are complex because of the variety of three-dimensional shapes that proteins can assume, and are especially important for the immune responses to viruses and worm parasites. It is the interaction of the shape of the antigen and the complementary shape of the amino acids of the antigen-binding site that accounts for the chemical basis of specificity (Figure 21. T cells do not recognize free-floating or cell-bound antigens as they appear on the surface of the pathogen. They bring processed antigen to the surface of the cell via a transport vesicle and present the antigen to the T cell and its receptor. Antigens are processed by digestion, are brought into the endomembrane system of the cell, and then are expressed on the surface of the antigen-presenting cell for antigen recognition by a T cell. Intracellular antigens are typical of viruses, which replicate inside the cell, and certain other intracellular parasites and bacteria. Extracellular antigens, characteristic of many bacteria, parasites, and fungi that do not replicate inside the cell’s cytoplasm, are brought into the endomembrane system of the cell by receptor-mediated endocytosis. Professional Antigen-presenting Cells Many cell types express class I molecules for the presentation of intracellular antigens. This is especially important when it comes to the most common class of intracellular pathogens, the virus. The three types of professional antigen presenters are macrophages, dendritic cells, and B cells (Table 21. Dendritic cells also kill pathogens by 1000 Chapter 21 | The Lymphatic and Immune System phagocytosis (see Figure 21. The lymph nodes are the locations in which most T cell responses against pathogens of the interstitial tissues are mounted. Macrophages are found in the skin and in the lining of mucosal surfaces, such as the nasopharynx, stomach, lungs, and intestines. B cells may also present antigens to T cells, which are necessary for certain types of antibody responses, to be covered later in this chapter. In fact, only two percent of the thymocytes that enter the thymus leave it as mature, functional T cells. In negative selection, self-antigens are brought into the thymus from other parts of the body by professional antigen-presenting cells. Tolerance can be broken, however, by the development of an autoimmune response, to be discussed later in this chapter. The discussion that follows explains the functions of these molecules and how they can be used to differentiate between the different T cell functional 1002 Chapter 21 | The Lymphatic and Immune System types. This proliferation of T cells is called clonal expansion and is necessary to make the immune response strong enough to effectively control a pathogen. Again, the specificity of a T cell is based on the amino acid sequence and the three- dimensional shape of the antigen-binding site formed by the variable regions of the two chains of the T cell receptor (Figure 21. Clonal selection is the process of antigen binding only to those T cells that have receptors specific to that antigen.

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