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Strychnine convulsions have no predictive value since they arise through antagonism of spinal (glycine-mediated) rather than cortical inhibition purchase malegra dxt 130 mg with visa erectile dysfunction foods to avoid. The most commonly used agent is pentylenetetrazol (PTZ) purchase 130 mg malegra dxt otc psychogenic erectile dysfunction icd-9, also called leptazol. Anti- convulsant activity is again assessed as the dose required to protect 50% of animals, usually mice, against the clonic seizures induced by a dose of PTZ that would otherwise produce them in almost every mouse injected, the so-called CD97 (convulsive dose in 328 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION 97% of animals). The anticonvulsant activity of a drug may also be evaluated by measuring its ability to raise the convulsive threshold, i. Comparison of the efficacy of drugs in the threshold and maximal seizure tests may distinguish between their abilities to raise seizure threshold or reduce seizure spread and development. MODELS OF PARTIAL SEIZURES (3) Focal Partial seizure activity can be induced by the localised application of chemicals such as cobalt or alumina to the cortex or the injection of chemicals such as PTZ or kainic acid directly into particular brain areas like the hippocampus. A similar effect can be obtained by the repeated localised injection of subconvulsive doses of some convulsants. The ability of a drug to reduce the kindled seizure itself may be indicative of value in partial seizure but if it slows the actual development of kindling that may indicate some ability to retard epileptogenesis. SPONTANEOUSLY EPILEPTIC (GENETIC) ANIMALS Various animals show spontaneous epilepsy or seizures that can be readily induced by sensory stimulation (see Jobe et al. Tottering mice display seizures that resemble absence attacks behaviourally, in their EEG pattern and response to drugs. DBA/2 mice show reflex seizures to audiogenic stimuli while photically-induced seizures can be obtained in the Senegalese baboon, Papiopapio, which are similar to generalised tonic± clonic epilepsy. PREDICTIVE VALUE It has become clear that drugs which are effective in protecting mice against PTZ are effective in absence seizures while those able to control the tonic response to maximal electroshock are effective in tonic±clonic seizure. Some drugs are effective in only one test and clinical condition whilst a few are active in both (Table 16. It could be argued that an antiepileptic drug should really stop the development of epilepsy, i. If the development of kindling reflects the process of epilepto- genesis then drugs effective against its progression should stop the development of THE EPILEPSIES 329 Table 16. Clinical comparisons are not related to recommended doses but simply indicate whether a drug is effective (‡) or not (7). Generally, drugs that are to be used clinically to control tonic± clonic seizures control electroshock but not pentylenetetrazol-induced convulsions in rats and mice, whilst the converse applies to drugs effective in absence seizures. Na valproate is effective in both experimental models and is used in both clinical conditions, although in all cases higher doses have to be used than for any other drug. Phenytoin and carbamazepine do not stop the development of kindling, although acutely they reduce the fully kindled seizure, and in studies of post- traumatic epilepsy following brain damage in humans (car accidents) these drugs stop the appearance of seizures in the first week or so but do not control epileptogenesis, since seizures can develop subsequently in those patients after therapy has stopped. Generally drugs that increase GABA function or block NMDA receptors retard kindling. CAUSE AND PATHOLOGY With such a diversity of seizures it would be surprising if a common cause of epilepsy had been found or even existed, although it is conceivable that a focus might arise in the same way wherever it was found. The actual symptoms would then be determined simply by the location of the focus and their extent, partial or general, by how easily or widely the influence of the focal neurons spread. Other factors might then control that spread and could vary from one region to another depending on local neuronal circuitry and NTutilisation. The fact that different drugs with different mechanisms of action are effective in different epilepsies may support that view. Epilepsy may be secondary to focal lesions such as congenital malformations, infarcts, tumours, cysts or inflections but fortunately many patients with these problems do not develop epilepsy. Brain damage such as neuronal loss and glial proliferation may in fact be seen in epileptics but these changes may be secondary to, rather than the cause of, epilepsy. They probably reflect the consequences of intense neuronal activation since in patients dying in status epilepticus they appear to be of recent origin and can be induced in animals by systemic or locally administered convulsant (see Meldrum and Corsellis 1984). Everyone is capable of having a convulsion, indeed their induction has been a common treatment for depression.

Why would endurance exercise training likely increase this large amounts of sweat malegra dxt 130 mg low price erectile dysfunction quiz test, and losing correspondingly large individual’s exercise capacity? Ventilatory limitation is evidenced by severe dyspnea as a next morning without correcting the salt deficit buy malegra dxt 130 mg visa erectile dysfunction pump as seen on tv, he is likely primary symptom in exercise, falling arterial blood oxy- to have further difficulties in the heat. Even if the medical genation, and exercise termination at relatively low heart officer has guessed incorrectly about the patient’s salt bal- rate. Arterial blood oxygen saturation fell during exercise be- fluid intake should be able to excrete any excess salt result- cause increased cardiac output (increased pulmonary blood ing from the treatment. Hyponatremia can produce symptoms similar to the pa- tent (a result of increased skeletal muscle oxygen extrac- tient’s symptoms. However, the medical officer was able to tion) increase demands for oxygenation in lungs with inade- exclude hyponatremia (although not necessarily some de- quate diffusing capacity. Exhaustion occurred before a maximal heart rate was Giving a hyponatremic patient large volumes of fluid with- reached because lung disease creates severe dyspnea even out an equivalent of salt (which would have been a reason- in mild exercise. The pulse pressure rose during exercise because sympa- thetic stimulation and enhanced venous return increase the would worsen the hyponatremia, perhaps to a dangerous stroke volume at constant arterial compliance. Endurance exercise training would have little effect on any Reference aspect of lung function. Clinical complications of body fluid and elec- adaptations within exercising muscle that would increase trolyte balance. Body Fluid Bal- muscle oxidative capacity and reduce lactic acid production. Boca Raton, FL: CRC Press, By reducing the ventilatory demands of exercise, these 1996;297–317. PART IX Endocrine Physiology CHAPTER Endocrine Control Mechanisms Daniel E. Hormones are chemical substances, involved in cell-to-cell transported in the bloodstream bound to carrier proteins, communication, that promote the maintenance of home- whereas most peptide and protein hormones are soluble in ostasis. Steroid hormones and thyroid hormones are generally docrine abnormalities. The word “hormone” is derived gan systems by a group of specialized chemical substances from the Greek hormaein, which means to “excite” or to “stir called hormones. Certain endocrine disease nate a variety of different physiological processes. The states, such as diabetes mellitus, thyroid disorders, and re- processes that hormones regulate fall into four areas: (1) the productive disorders, are fairly common in the general pop- digestion, utilization, and storage of nutrients; (2) growth ulation; therefore, it is likely that they will be encountered and development; (3) ion and water balance; and (4) repro- repeatedly in the practice of medicine. In addition, because hormones either directly or indi- rectly affect virtually every cell or tissue in the body, a num- ber of other prominent diseases not primarily classified as Hormones Regulate and endocrine diseases may have an important endocrine com- Coordinate Many Functions ponent. Atherosclerosis, certain forms of cancer, and even certain psychiatric disorders are examples of conditions in It is difficult to describe hormones in absolute terms. As a which an endocrine disturbance may contribute to the pro- working definition, however, it can be said that hormones gression or severity of disease. They Feedback Regulation Is an Important are highly potent, specialized, organic molecules produced Part of Endocrine Function by endocrine cells in response to specific stimuli and exert The endocrine system, like many other physiological sys- their actions on specific target cells. The mecha- equipped with receptors that bind hormones with high nism is usually negative feedback, although a few positive affinity and specificity; when bound, they initiate charac- feedback mechanisms are known. Both types of feedback teristic biological responses by the target cells. Although many hormones travel by just its rate of hormone secretion to produce the desired this mechanism, we now realize that there are many hor- level of effect, ensuring the maintenance of homeostasis. Since negative feedback is their target cells by diffusion through the interstitial fluid. First-order feedback regulation Hormone Receptors Determine Whether a is the simplest type and forms the basis for more complex Cell Will Respond to a Hormone modes of regulation. In this example, an endocrine cell se- In the endocrine system, a hormone molecule secreted cretes a hormone that produces a specific biological effect into the blood is free to circulate and contact almost any in its target tissue. As the biological response in- that possess specific receptors for the hormone, will re- creases, the amount of hormone secreted by the endocrine spond to that hormone.

It is known generic 130 mg malegra dxt with mastercard thyroid causes erectile dysfunction, for example malegra dxt 130mg free shipping erectile dysfunction treatment without side effects, that the X the second meiotic division, each of the two secondary spermato- chromosome of the germ cells is inactive during meiosis. One pri- this chromosome contains the genes needed to produce many es- mary spermatocyte therefore produces four spermatids. The epithelial wall of the tubule, called the germinal epithelium, is indeed composed of Structure of Spermatozoa germ cells in different stages of spermatogenesis. It consists of an oval head and an At the end of the second meiotic division, the four sper- elongated flagellum. Although the head of a spermatozoon lacks matids produced by the meiosis of two secondary spermatocytes mitochondria, it does contain a nucleus with 23 chromosomes. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 Chapter 20 Male Reproductive System 705 FIGURE 20. In the first meiotic division, the homologous chromosomes of a diploid parent cell are separated into two haploid daughter cells. In the second meiotic division, these chromatids are distributed to two new haploid daughter cells. The body of the flagellum contains numerous mitochondria spiraled around a Knowledge Check filamentous core. What are the functions of the seminiferous tubules, germi- ing movement. The maximum unassisted rate of spermatozoa move- nal epithelial cells, and interstitial cells? Discuss the effect of testosterone on the production of sperm Recent findings indicate that ejaculated spermatozoa (plural of cells and the development of secondary sex characteristics. Diagram a spermatozoon and its adjacent sustentacular cell of these sperm cells are defective, however, and are of no value. It is and explain the functions of sustentacular cells in the sem- not uncommon for them to have enlarged heads, dwarfed and mis- iniferous tubules. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 706 Unit 7 Reproduction and Development Spermatogonia (46 chromosomes) Wall of seminiferous Primary tubule spermatocytes (46 chromosomes) Secondary spermatocytes (23 chromosomes) Spermatids (23 chromosomes) Sustentacular cell Lumen of seminiferous tubule Spermatozoa (23 chromosomes) (a) (b) Acrosome of head Head Body of flagellum Flagellum FIGURE 20. Spermatogonia undergo mitotic division to replace themselves and produce a daughter cell that will undergo meiotic division. Upon completion of the first meiotic division, the daughter cells are called secondary spermatocytes. No- tice that the four spermatids produced by the meiosis of a primary (c) spermatocyte are interconnected. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 Chapter 20 Male Reproductive System 707 Pseudostratified ciliated columnar epithelium Smooth muscle Sperm in lumen of duct Connective tissue FIGURE 20. The tail is continuous with the beginning por- tion of the ductus deferens; both store spermatozoa to be discharged during ejaculation. The time required to produce ma- SPERMATIC DUCTS, ACCESSORY ture spermatozoa—from meiosis in the seminiferous tubules to storage in the ductus deferens—is approximately 2 months. From here, it penetrates the in- Objective 10 Describe the location and structure of each segment of the male duct system. The histological structure of the ductus deferens includes a Objective 12 Describe the location, structure, and functions layer of pseudostratified ciliated columnar epithelium in contact of the ejaculatory ducts, seminal vesicles, prostate, and with the tubular lumen and surrounded by three layers of tightly bulbourethral glands. Stimulation through these nerves causes peristaltic contractions of the muscular layer, Spermatic Ducts which propel the stored spermatozoa toward the ejaculatory duct. The spermatic ducts store spermatozoa and transport them from Much of the ductus deferens is located within a structure the testes to the urethra. The accessory reproductive glands pro- known as the spermatic cord (see figs. Male Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 708 Unit 7 Reproduction and Development Seminal crypt Smooth muscle FIGURE 20. Glandular epithelium plexus, nerves, the cremaster muscle, lymph vessels, and connec- tive tissue. The portion of the spermatic cord that passes anterior to the pubic bone can be easily palpated. This layer partitions the lumen pierces the capsule of the prostate on its posterior surface and into numerous intercommunicating spaces that are lined by pseu- continues through this gland (see fig. Both ejaculatory dostratified columnar and cuboidal secretory epithelia (referred ducts receive secretions from the seminal vesicles and then eject to as glandular epithelium).