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By T. Asam. Converse College.

Capsular polysaccharide is a constituent of the pro- tective coating around a number of bacteria such as the Prion (Figure 24 purchase suhagra master card erectile dysfunction young adults treatment. The three human diseases in which prions have been implicated include kuru 100mg suhagra sale erectile dysfunction va disability compensation, Creutzfeldt- Capsid Jakob disease, and Gerstmann-Straussler syndrome. They have also been implicated in the following animal diseases: sheep and goat scrapie, bovine spongiform encephalopathy, chronic wasting of elk and mule deer, and transmissible mink encephalopathy. They resist formalin, heat, Capsomere ultraviolet radiation, and other agents that normally inacti- vate viruses. They possess a 28-kDa, hydrophobic, glyco- protein particle that polymerizes, forming an amyloid-like fbrillar structure. In addition to the pneu- possibly attributable to genes that encode substances which mococcus, other microorganisms such as Streptococci and dampen antiviral immune responsiveness. The variability among infectious B lymphocytes and is used in the laboratory for this purpose disease agents is of critical signifcance in the development to develop long-term B lymphocyte cultures. The classifcation of infuenza A viruses into these few surviving viruses, bacteria, or animal parasites, a subtypes is based on their hemagglutinin (H) and neuramini- new population of infectious agents is produced. Three hemagglutinin (H1, H2, and H3) may be repeated, thereby obfuscating the protective effects of the immune response. Besides the 0 50 sanctuary viruses enjoy once they have entered host cells, nm these disease agents have additional means to escape host immune mechanisms. This process may be repeated M2 many times leading to the production of numerous strains of a particular virus that are antigenically and, therefore, sero- logically distinct. The more extensive and two neuraminidase (N1 and N2) subtypes are the princi- antigenic shift may be a consequence of dual infection with pal infuenza A virus antigenic subtypes that produce disease a human and an animal infuenza A virus. Due to antigenic change (antigenic drift), infection or vaccination by one strain provides little or no protection Release against subsequent infection by a distantly related strain of E-B virus into the same subtype. Infuenza B viruses undergo less frequent particles oropharynx antigenic variation. This is the reason for B cell pool T T cell pool with B T with vaccination against epidemic strains with killed virus. Immunity against Microorganisms 755 to the development of a novel pandemic strain for which Rickettsia immunity: the immune response in rickettsial humans have no preexisting antibody. It is necessary for the effector lymphocyte to that act as opsonins render microorganisms susceptible to come into direct contact with the virus-infected target cell. Antibody-dependent cel- dation in infuenza penumonia and have a signifcant role lular cytotoxicity has also been demonstrated. Chlamydia immunity: Chlamydiae infect many animal Infuenza hemagglutinin is an infuenza virus coat glyco- species and various anatomical sites. No single pattern of protein that binds selected carbohydrates on human cells, the host response can be described, but there may be similarities initial event in viral infection. In vitro studies and geni- tal respiratory and ocular animal models have provided most A v-myb oncogene is a genetic component of an acute trans- of the information about both protective and pathologic host forming retrovirus that leads to avian myeloblastosis. Acute infammation is the initial response with resents a truncated genetic form of c-myb. Chlamydial infection produces both humoral and cell-medi- Acyclovir 9 (2-hydroxyethoxy-methylguanine) is an anti- ated immune responses. Cell-mediated immunity has been viral nucleoside analog that blocks herpes simplex virus-2 found important in both mouse and guinea pig models. Immunity to Q fever is an acute disease caused by the rickettsia Coxiella chlamydial infections is short lived. Cattle, sheep, goats, and several small marsupials effective vaccine for chlamydia infections in humans, but a serve as reservoirs. It is rare in the also induce atypical pneumonia, rapidly progressive pneu- United States but endemic in Africa, Asia, and South monia, or be a coincidental fnding to a systemic illness. Clinically, patients develop papulo ulcers that heal disease has a relatively low mortality. Solid immunity that follows infection pro- include complement fxation, with a titer of greater than 1:32, tects against reinfection. Also, the Frei test, which consists viduals may be too late to prevent central nervous system of the intracutaneous inoculation of a crude antigen into the or liver invasion. For example, Rift Valley fever virus may forearm, is used and can be read after 72 h. They produce multiple clinical syndromes in the dominant antigen is nucleocapsid protein in complement humans, including respiratory, genitourinary, gastroin- fxation assays. Little is known concerning the role of cell- testinal, and conjunctival infections. An oral vaccine has been erinary vaccines against Rift Valley fever and Nairobi sheep very successful in preventing acute respiratory disease disease are available. Humans develop serotype-specifc neutralizing antibodies to the structural proteins, thereby B-type virus (Aspergillus macaques) is an Old World preventing reinfection with the same serotype. Clinical fea- nonstructural proteins produce signifcant immunologic tures include intermittent shedding and reactivation in the effects. There is no virus enve- tend these monkeys may become infected with fatal conse- lope. The inter- Calcivirus immunity: Human calciviruses have been nal structural proteins are not believed to be involved in shown to cause gastric distress. IgA antibody responses appear more spe- a nuclear staining pattern with early antigen and a nuclear cifc. Therefore, people body shows no cross-reactivity with other herpesviruses or who recover often become susceptible again on rechallenge. High titers attained after several infections are protective in some studies although this has not been confrmed. The immune response to the acute infection either kills antibodies are directed mainly against the protein S antigen. Among cor- the virus infection but may mediate pathological changes onavirus antigens, there is high antigenic variability of the S1 of choriomeningitis when injected intracerebrally. This subunit induces neutralizing antibodies infection induces interferon γ and tumor necrosis factor α that bind to discontinuous epitopes. The S1 sub- cell proliferation that eliminates pathogen-infected cells and unit of the molecule contains the most immunogenic sites of selected tumors. No vaccines for humans are pres- induces neutralizing S-protein-specifc antibodies. Flavivirus immunity: Yellow fever, dengue, Japanese Coxsackie A viruses have 23 virotypes, and Coxsackie B encephalitis, and tickborne encephalitis are the most impor- viruses have six types. The E protein plays a criti- Coxsackie viruses include herpangina, epidemic pleuro- cal role in infection and immunity since it possesses cellular dynia, aseptic meningitis, summer grippe, and acute nonspe- receptor-binding determinants, a membrane fusion activity, cifc pericarditis and myocarditis. Macrophages clear the viremia, yet antiviral function may be affected by their Cytopathic effect (of viruses) refers to injurious effects of state of activation and levels of virus-specifc antibodies. Selected viruses produce disease even sion on virus-infected cells, which could represent an immune though they have little cytopathic effect because the immune escape mechanism. Virus-specifc antibodies provide protec- system recognizes and destroys the virus-infected cells.

The other tissues that accumulate iodide are salivary Iodide that is actively transported into the colloids of thy­ gland proven suhagra 100mg impotence natural treatment clary sage, placenta purchase suhagra online impotence natural treatment, choroid plexus, mammary gland, gas­ roid follicles is immediately converted to iodine by means tric mucosa, and ciliary body; however, they do not – of oxidation. Mutation of pendrin gene leads to Pendred syndrome, which is characterized by defective organification of iodine, goiter and sensorineural deafness. Thyroglobulin Synthesis Thyroglobulin is the glycoprotein with two subunits and the molecular weight of 660,000. It is synthesized in the endoplasmic reticulum of thyroid cells, packaged in Golgi apparatus and then, secreted into the colloid by exocytosis. The thyroid hormones are synthesized in the thyroglobulin molecule and remain bound with the thyroglobulin till they are secreted. Note, thyroxine contains four iodine atoms, at 3, 5, 3´ and 5´ positions, and triiodothyronine con- Once reactive iodine is formed (by oxidation of iodide to tains three iodine atoms at 3, 5 and 3´ positions of the thyronine iodine), it binds immediately with the tyrosine molecule, ring structures. They actively accumulate iodide from blood for syn­ Intramolecular Coupling thesis of thyroid hormones. For the positions of iodine atoms in thyroid hormones, thyroxine and triiodo­ Secretion of Thyroid Hormones thyronine are abbreviated as T and T respectively. The lysosomal enzymes digest the peptide bonds Metabolism of Thyroid Hormones between iodinated residues and thyroglobulin. In circu­ nated by the microsomal enzyme iodotyrosine deiodi- lation, most of the thyroid hormones bind with the plasma nase. As physiological effects of thyroid hormones depend on their free-form level in plasma, and the free hormone component influences feedback control of hypothalamo- pituitary-thyroid axis, in thyroid dysfunctions, mainly the free hormone concentrations are measured. However, it is ideal to measure both total and free level of hormones in blood for diagnosing thyroid dysfunctions. The opposite phenomenon occurs when level of Protein Binding plasma binding protein decreases in plasma. Thus, initial change observed in thyroid hormones due teins: to change in plasma proteins is a temporary effect. Therefore, the half­lives of circulat­ site on it for a molecule of thyroid hormone. Normally, about 35% of secreted T4 is converted to (cancer chemotherapeutic drug). Salicylates, pheny­ T3 in the circulation by the enzyme 5´-deiodinase toin (anticonvulsant), mitotane (cancer chemothera­ peutic drug) and 5­fluorouracil inhibit binding of T (Flowchart 57. As 5´­deiodinase is present in high concentration in 4 pituitary and cerebral cortex, the ratio of T3/T4 is very Albumin high in these structures. Effect of Diet the concentration of free T3 and T4 depends on the concentration of plasma proteins that bind these hor­ Fasting decreases conversion of T4 to T3. Regulation of Secretion Secretion of thyroid hormones is regulated by a feedback control mechanism. The secretion the selenium in the amino acid is essential for their is less during the day. D3 is present in brain and repro­ by influencing almost all the steps involved in it. D1 and D2 are 5´-deiodinase that convert T4 to T3 and sis of T and T (coupling reaction), secretion of thy­ 3 4 maintain the intracellular T3 in their target tissues. Therefore, mild to moderate hyperthyroidism is observed in tumors of placental origin like choriocarcinoma. With few exceptions like adult brain and gonads, receptors for thyroid hormones are pre­ sent in all tissues and organs. Though the developing neu­ rons in infants and children are highly sensitive to thyroid Fig. Note, the mechanism hormones, it is not clear why the adult neurons are not so of thyroxine action is similar to steroid hormones. T3 and T4 enter the cells of the target organs by carrier mediated (energy dependant) transport. Chapter 57: Thyroid Gland 489 General Effects on Basal Metabolism of endogenous protein and fat. Thus, significant weight loss occurs promptly in increased thyroid activity, without the metabolism of a cell depends on the rate of its oxy­ adequate nutrient supplementation. T3 also stimulates the transcription of genes for both + + in last six months of fetal life and first six months of post­ α and b subunits of Na ­K pump. During this period, thyroid hormones initiate strongly perceived that increased oxygen consumption + + and facilitate the process of differentiation and matura- stimulated by thyroid hormones is mediated by Na ­K tion of brain cells. Thyroid hormones are required for following neural Target tissues: the increased consumption of oxygen functions: by thyroid hormone is observed in all tissues of the body, 1. Growth of cerebral and cerebellar cortices, and basal which is prominent especially in skeletal muscle, liver, ganglia. Receptors for thyroid hormones roid hormones induce formation of enzymes essential are almost absent in adult brain. Basal metabolic rate: In the resting stage, oxygen for neurotransmitter synthesis. Increase in number of receptors on different brain tis­ roid state, it increases to about 400 mL/min. Synthesis of proteins and various enzymes like succinic Mitochondrial mechanism: Metabolism is increased dehydrogenase that are required for energy genera­ by thyroid hormones not only by increased oxygen con­ tion in neurons. General alertness and responsiveness to various stim­ cytochrome oxidase activity. This is why thyroid deficiency in newborn oxidation of nutrients and heat production. Thyroid hormones enter the brain in adults Effects Secondary to Metabolic or and found in gray matter of various parts of the brain. After thyroid­ 4 3 Increased body metabolism increases nitrogen excre- ectomy, D2 type 2 deiodinase activity in brain increases tion. Therefore, increased food intake should be associ­ enormously, which is reversed in 3 to 4 hours following ated with hypermetabolic states to prevent catabolism injection of T3. Therefore, mental retardation is an of the heart and also increase the sensitivity of b important feature of a thyroid deficiency in infancy and early childhood receptors to catecholamines. Myocardial contractility: Myocardial contractility incre­ (ankle jerk) is diagnostic in hypothyroidism. They stimulate linear growth of bones, and endochon- of the sarcoplasmic reticulum in cardiac muscle, dral ossification and maturation of epiphyseal bone which facilitates sequestration of calcium. They enhance the activity of chondrocytes in carti­ that in turn increase stroke volume. However, in myocytes, thyroid proteins hormones inhibit phospholamban, adenylyl cyclase, T3 In hypothyroid children, bone growth is slowed and + + nuclear receptor and Na ­Ca exchanger, in addition to epiphyseal closure is delayed. Systolic pressure: Increased heart rate and stroke vol­ teristics of mucopolysaccharides in the subcutaneous tis­ ume result in increase in cardiac output (Flowchart sue. Thus, systolic blood pressure increases signifi­ glycosaminoglycans (mucopolysaccharides). Diastolic pressure: Via its calorigenic action, thyroid hor­ Cardiovascular Effects mones increase body temperature that causes thermo- Thyroid hormones increase heart rate and myocardial con­ genic cutaneous vasodilation and decreases peripheral tractility. Pulse pressure and circulation time: the net effect On Protein Metabolism on blood pressure is increased pulse pressure.

This markedly (c) increased the potency and the specifcity of these compounds for 2 purchase generic suhagra line erectile dysfunction doctors northern virginia. However order suhagra 100mg overnight delivery erectile dysfunction protocol, there does appear to be signifcant diferences in the efect of tiaga- Figure 6. Tus, increase in tonic current that was apparent afer a couple of minutes (*) the thalamus seems to be less sensitive to the efects of tiagabine and increased gradually throughout the experiment. This and the failure Reproduced with permission from The American Physiological Society. This results in vary and increase during seizures, such tonic inhibition would be an efect on the current that is similar to benzodiazepines or barbi- expected to demonstrate similar increases during seizure activi- turates, although mechanistically diferent. Tree action potentials triggered in the interneuron elicit three inhibitory postsynaptic currents in the pyramidal cell. A train of action potentials (100 Hz) from the interneuron elicits an outward current in the pyramidal cell. The overall efect are permeable to sodium ions, and are responsible for fast excit- on the network is thus difcult to predict. Tiagabine potentiates these depolarizing re- the GluR2 component are also permeable to calcium ions. Rela- sponses [78], and thus the concern is that, through this mechanism, tively large concentrations of glutamate result in channel opening tiagabine could in some circumstances enhance seizure activity. Glutamate is present in abundance in receptors [86]; whether this is responsible for its antiepileptic efect brain tissue, and is the major excitatory transmitter in the central or dose-related side-efects is unknown. Tese tribute to seizure generation, and thus drugs that modulate gluta- presynaptic receptors can increase or decrease neurotransmitter mate uptake may have an antiepileptic efect. In addition, axonal kain- in the brain in large concentrations (10 mmol), but this is predom- ate receptors can afect axonal excitability, leading to ectopic action inantly intracellular glutamate [80]. It is thus difcult to predict whether the efect of ka- maintained at concentrations 5000 times lower than this (approx- inate receptor activation would be pro- or anti-ictogenic [90]. How- imately 2 µmol) by high-afnity glutamate uptake into predomi- ever, the agonist kainaic acid is a powerful convulsant, and kainate nantly glia. Tese receptor subtype from that expressed on principal cells, raising the possibil- subtypes have very diferent properties (Table 6. Indeed, there has been a report of a GluR5-specif- ic antagonist with antiepileptic efects in pilocarpine-induced sei- Table 6. Voltage-gated potassium channels are thus depolarization, then the resultant depolarization will result in re- critical for determining neuronal excitability. The α-subunits vary in size; the secondary consequences, afecting the phosphorylation of proteins largest have six transmembrane segments (similar to a single do- that can produce long-term synaptic potentiation, modulation of main of the sodium and calcium channels). Tese sites modulate receptor function by afecting but are open at the resting potential (inward rectifying channels); rates of desensitization, afnity for glutamate and channel opening. Tus, felbamate, a drug that acts at the glycine blocked by internal ions at depolarized potentials. Remacemide and its des-glycine metabolite may have a variety are opened by activation of G-protein-linked receptors (e. Tere are other potassium channels that other factors, such as pH, redox state and phosphorylation, which are similar in structure to the voltage-gated potassium channel, but may provide additional drug targets. Tere are also specifc potassium channels that Metabotropic glutamate receptors are inactivated by acetylcholine – termed M-type channels. Metabotropic glutamate receptors are G-protein-linked receptors Although modulation of potassium channels would seem to that can be classifed into three groups. Group I receptors are mainly be an ideal target for antiepileptic drugs, most drugs have no or expressed postsynaptically, where they enhance postsynaptic poorly characterized efects on potassium channels. Phenytoin and calcium entry, calcium release from internal stores and depolari- levetiracetam may selectively block delayed rectifer potassium zation through inhibition of potassium currents. Group I receptors channels [102,103]; this inhibition could prolong the action poten- may thus play a part in neurodegeneration. Group I antagonists tial duration, thereby prolonging the ‘refractory period’, resulting have neuroprotective and antiepileptic potential [97]. The aferhyperpolarization induced by (pilocarpine model, kainate model), whereas an up-regulation has calcium-dependent potassium channels also reduces neuronal ex- been considered as a compensatory antiepileptic efect (e. In absence seizures Retigabine, a putative antiepileptic drug, has as perhaps its main and the related thalamocortical loop, region-specifc changes in mode of action potentiation of potassium channels. Indeed, H-currents are enhanced by is non-inactivating, hyperpolarizes neurons, so decreasing neuronal acetazolamide, gabapentin and lamotrigine [110,111,112]. Increasing the H-current may have two po- may also be afected by retigabine, potentially leading to vasodilata- tentially antiepileptic efects. The use of retigabine in epilepsy has diminished substantially excitatory transmission to the soma and decrease excitability, so since the occurrence of skin and retinal changes associated with the perhaps contributing to the efcacy of acetazolamide, gabapentin drug; the mechanisms underlying these changes are unknown. In the thalamus, it would depo- The extent to which other antiepileptic drugs afect potassium larize thalamocortical neurons and so inhibit or terminate spike– channels remains unknown, but it is likely that modulation of po- wave discharges, possibly explaining the efcacy of acetazolamide, tassium channels will be a future target for antiepileptic drug de- and lamotrigine against absence seizures. H-currents contribute to the resting membrane potential, and to the integration of synaptic and somatic integration by partially set- Monoamines ting the neuronal input resistance. The latter determines the neu- It has been well established that monoamines have an integral role ron’s sensitivity to incoming signals, as the H-current shunts the in epileptic phenomena. In the thalamus, H-currents serve as the classi- tic brain tissue have shown alterations in both catecholaminergic cal ‘pacemaker’ currents and generate, together with T-type calcium and indoleaminergic activity when compared with non-epileptic currents, physiological oscillations [30]. In addition, monoamine content has been shown to difer in 86 Chapter 6 the cerebrospinal fuid of epileptic patients compared with non-ep- (a) ileptic patients [122]. Indeed, experimentally induced attenuation 8 of monoamine content has been directly implicated in the onset 2 and propagation of many seizure disorders [123,124] whereas ex- r = 0. As yet, it remains unclear how these pathways interact to control seizures or whether or not anatomical subpopulations of striatal ef- 5 ferents have the propensity to control specifc types of seizure. Furthermore, dopaminergic terminals have been found to exist in close proximity to the dendrites of inhibitory 7 8 7 6 interneurons. Tus, it appears that dopamine has the potential to 4 provide a regulatory control over the degree of excitatory input into 3 the cortex [128]. This efect appears to be biphasic in that at supratherapeutic the α-hydroxylation of dopamine and is considered to be primar- levels carbamazepine and zonisamide reduced brain monoamine ily an inhibitory neurotransmitter. Such has been proposed to modify excitatory responses within this intracellular pathways may provide a powerful means of altering region. However, identifying the relevance of intra- Serotonergic neurotransmission has been shown to infuence the cellular drug targets is complex because of the intricate relation- generation of certain types of seizure disorder in various experi- ships between diferent intracellular processes and the consequent mental models, including hippocampal kindling [139] and system- difculty in distinguishing direct from indirect efects. One report comparing the efects on intracellular mechanisms may be important for monoamines and their metabolites in brain tissue from epileptic the action of antiepileptic drugs in other conditions, especial- patients undergoing temporal lobe resections for seizure control ly psychiatric disorders, and as neuroprotectants [156]. More recently, seizure-related reductions in may be efective against generalized tonic seizures [142].

The scrotum becomes more rugose and Testosterone directly binds with testosterone receptors pigmented purchase generic suhagra pills erectile dysfunction normal age. Changes in internal genitalia: Seminal vesicles mainly regulates gonadotropin secretion buy suhagra without prescription impotence of organic origin meaning, causes muscle increase in size and start secreting fructose. Prostate development, controls spermatogenesis, and influences gland enlarges and secretion increases from prostate male sex drive and libido. Growth and distribution of body hairs: Hair growth is Physiological Actions classified into three groups depending on their sensi- Testosterone is an anabolic hormone. Chapter 67: Male Reproductive System 601 Ambisexual hairs are the hairs in the axilla, and sexual 1. Androgen stimulates growth of all types of tains it throughout adulthood and also in old age. It promotes hair growth in axilla, on the chest and pubic triangle, and around the anus. In the In male fetus, between 8th and 18th week testosterone face, hairs grow in the form of moustache and beard. The development of Wolffian duct into epididymis, a triangle of which the apex is upward). The hair line vas deferens and seminal vesicles depends directly on on the scalp recedes in males. Secre- tal tubercle into penis, scrotum and testis is mediated tion of sebaceous gland increases and becomes thick. Voice change: Enlargement of larynx and thickening of and water retention from kidney. Body configuration: General increase in body height Effects on Brain and girth occurs (growth spurt). Especially, Broaden- ing of the shoulder occurs with general increase in size Many areas in the brain have androgen receptors. These changes impart masculine ever, the receptors are densely located in limbic areas, phenotypic expression. In these areas, testosterone is aromatized to estrogen Testosterone causes closure of epiphysis of long bone, (Flowchart 67. Sexual dimorphism of neurons in the brain with It causes muscle hypertrophy, increases muscle pro- respect to their distribution, size, number and activity tein synthesis and increases muscle mass. Effects on Spermatogenesis Other Effects Testosterone stimulates spermatogenesis, the exact Testosterone, by its negative feedback effects, inhibits mechanism of which is not known. Follistatin influences developing spermatogenic cells duced in testis by aromatization of androgen in Sertoli cells. Testicular androgens are testos- the major function of testes is to secrete testicular hor- terone (see above), androstenedione and dihydrotestos- mones, especially testosterone that controls gametogenesis, terone. Among them, testosterone is the major androgen sexual development and anabolic effects. Types and Structure Pituitary Control There are two types of inhibins: inhibin A and inhibin B. Anterior pituitary controls testicular functions by secreting Inhibins are made up of two subunits: α and β. The inhibin A is made up of bin that maintains the gametogenic functions of the testis. Activins and inhibins are Testosterone provides negative feedback signal to hypo- found in the gonads, brain, and many other tissues. Activin results from various combinations of βA and βB subunits of inhibin that forms βAβB, βBβB, and βAβA. Follistatin Follistatin is a single chain protein having molecular weight of about 40,000. The failure of migration of testis from abdominal cavity into the scrotum during fetal development is called unde- Hypergonadotropic Hypogonadism scended testis or cryptorchidism. The usual site of unde- If this occurs due to testicular dysfunctions, plasma level scended testis is inguinal rings. From posterior wall of the abdomen testis first descends into the inguinal region and then from there Hypogonadotropic Hypogonadism into the scrotum. The descent from inguinal region to scrotum depends sex characteristics regress slowly as androgenic main- on testosterone and other factors. Treatment − Enuchoids are usually tall, with narrow shoulders Treatment with gonadotropin hormones facilitates the and less muscular development. Complications Androgen Secreting Tumors Undescended testis decreases sperm production, as temperature is high in the abdomen. The incidence of Hypersecretion of testis is usually due to a tumor in the malignant tumors is significantly more in undescended testis. Gametes (sperms) are produced in millions every day, and the process continues throughout life starting from puberty, though the rate of production decreases in old age. Sertoli cells provide support to the germ cells in the process of spermatogenesis. The tight junctions between Sertoli cells from the blood-testis barrier that provides protection to developing sperms from harmful blood born toxins. Leydig cells secrete testosterone that provides hormonal stimulation for spermatogenesis. In examination, ‘Describe the steps of spermatogenesis and factors controlling spermatogenesis, may be asked as a Long Question. Spermatogenesis, Factors controlling spermatogenesis, Functions of Sertoli cells, Leydig cells, Blood-testis barrier, Spermiogenesis, Semen analysis, Physiological actions of testosterone, Testicular abnormalities, are usual Short Questions in exam. Correlate the functional organization of female reproductive tract with their functions. The important event in female reproductive functions is the cyclical release of gamete during the reproductive cycles. The ovarian changes are mainly growth, matura- tion and release of ovum and secretion of hormones, and uterine changes are mainly endometrial alterations to nourish the implanted fertilized gamete, or shedding of endometrium associated with uterine bleeding in the absence of fertilization. The follicular development during each cycle is a detailed and organized process controlled by hypothalamo-pituitary-ovarian endocrine axis. The ovarian follicles are named after him as Graafian follicles in recognition Female external genitalia include labia majora, labia of his outstanding contribution in the field of Regnier de Graaf minora, clitoris, vestibule of vagina and vestibular glands reproductive physiology. Chapter 68: Female Reproductive System: Functional Anatomy, Oogenesis and Follicular Development 605 Fig. The length of vagina in adult is about 8 cm, but it is highly stretchable as its wall is folded normally. These elongate to about double of its length during sexual are two major skin folds that form the outer lips of vaginal act.

Longitudinal ultrasound image of the distal interphalangeal joint showing severe joint damage secondary to psoriatic arthritis buy suhagra australia erectile dysfunction treatment options injections. Longitudinal ultrasound image order genuine suhagra online does erectile dysfunction cause low libido, palmar aspect, demonstrating the double cortical sign in the proximal 565 interphalangeal joint in a patient with poorly controlled gout. Longitudinal ultrasound image demonstrating significant destruction of the right proximal interphalangeal joint from psoriatic arthritis. Color Doppler can help quantify the extent of active inflammation and neovascularization (Figs. The flexor tendon anatomy of the fingers is unique in that the superficial and deep tendons lie on top of one another. Distinguishing the deep from the superficial tendons is best done in the transverse plane. The flexor digitorum profundus tendon lies deepest and functions to provide flexion of the distal interphalangeal joint (Fig. The flexor digitorum superficialis tendon functions to provide flexion of the proximal interphalangeal joint and lies on top of the flexor digitorum profundus tendon. When the flexor digitorum superficialis tendon reaches the proximal phalanx, the tendon divides in half with each half wrapping around flexor digitorum profundus tendon to insert into the base of the middle phalanx (Fig. The palmar (volar) plates, which help reinforce and stabilize the interphalangeal joint and limit joint hyperextension, are then evaluated for laxity (Figs. A careful search for giant cell tumors of the tendon and tendon sheath is then undertaken gives the high incidence of occurrence in this anatomic region (Figs. The tissues surrounding the joint is then evaluated for soft tissue mass, ganglion cyst, and if the history suggests, for foreign body (Figs. Longitudinal color Doppler view demonstrating active synovitis of the distal interphalangeal joint in a patient with rheumatoid arthritis. A: Transverse view of the flexor tendons of the finger demonstrates the flexor digitorum profundus and the flexor digitorum superficialis. These tendons are immediately adjacent to each other and can sometimes be difficult to distinguish. B: Longitudinal view shows the flexor tendons overlying the metacarpophalangeal joint. The superficial and deep tendons are difficult to distinguish on longitudinal views. Transverse ultrasound image of the flexor digitorum superficialis tendons at the point that the superficial tendon begins to split. One of the checkrein ligaments (thin arrow) is seen proximally, lying superficial to the ventral joint recess (curved arrow). On each side, it receives fibers from the aCl, whereas its proximal end is U-shaped due to the presence of the checkrein ligaments (3). A: Lateral plain film reveals a small fleck of bone (arrowhead) avulsed from the base of the middle phalanx. C: Lateral sagittal ultrasound image demonstrates concomitant injury of the accessory collateral ligament that appears swollen and hypoechoic (arrows). A: Longitudinal gray-scale image of a left second flexor tendon demonstrates multiple irregular hypoechoic masses (white arrows) along the tendon (T) in a patient with history of rheumatoid arthritis. Synovial fluid separates superficial flexor tendon (st) from deep flexor tendon (dt). Ultrasound images of two common rock climbers’ tendon injuries (two different cases). A: Longitudinal ultrasound image over the middle phalanx in a climber affected by combined A2 and A3 pulley tear and persistent finger pain demonstrates a swollen flexor digitorum profundus tendon (arrowheads) reflecting tendinitis. Note the thin slip (arrow) of the flexor digitorum superficialis inserting onto the phalanx. B: Coronal ultrasound image over the radial aspect of the proximal interphalangeal joint of the index finger reveals an injured collateral ligament (arrows) that appears diffusely swollen and hypoechoic. Transverse view of the flexor tendons (T) of the fifth finger in a patient demonstrates a soft tissue mass (m) surrounding the medial, lateral, and deep aspect of the tendon. In both of these cases, large giant cell tumors have partially encased the tendons. A: Longitudinal gray-scale image of a distal interphalangeal joint of the index finger demonstrates a hypoechoic nodule (white arrows) in the volar aspect of the tendon (T). B: Longitudinal power Doppler image showing prominent vascularity (arrows) in the periphery of the nodule. A: Transverse view of the proximal fifth finger demonstrates a minimally echogenic splinter (cursors) surrounded by hypoechoic inflammatory tissue. B: Similar view with the transducer reoriented so that the splinter is perpendicular to the sound displays the splinter as a more highly echogenic structure that is easier to detect and recognize sonographically). A: Longitudinal gray-scale image of the dorsum of the finger demonstrates a subcutaneous hypoechoic mass (black arrows), corresponding to a hard painful lump. B: Longitudinal power Doppler image demonstrates prominent vascular flow suggestive of hyperemia. As with the metacarpophalangeal joints, the clinician should recognize that each imaging modality has its advantages and disadvantages and each should be viewed as complementary rather than mutually exclusive. Positron emission tomography shows promise in identifying subclinical abnormalities of the interphalangeal joints in selected patients. Ultrasound features of nonstructural lesions of the proximal and distal interphalangeal joints of the hands in patients with finger osteoarthritis. Technique for intra-articular injection of the interphalangeal joint of the fingers. Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis. The common digital nerves pass along the metacarpal bones and divide as they reach the distal palm (Fig. The volar digital nerves supply the majority of sensory innervation to the fingers and run along the ventrolateral aspect of the finger beside the digital vein and artery. The smaller dorsal digital nerves contain fibers from the ulnar and radial nerves and supply the dorsum of the fingers as far as the proximal joints (Fig. A: the common palmar digital nerves arise from fibers of the median and ulnar nerves. The thumb 572 also has contributions from superficial branches of the radial nerve. B: the smaller dorsal digital nerves contain fibers from the ulnar and radial nerves and supply the dorsum of the fingers as far as the proximal joints. The proper palmar digital arteries lie just below their corresponding digital nerves, with each artery lying just dorsal to its respective digital nerve. The proper palmar digital arteries interconnect and anastamose with the smaller arteries which supply the interphalangeal joints and pulp of the fingertips (Fig. The proper palmar digital arteries also give off dorsal branches which anastomose with the larger dorsal digital arteries to provide blood supply to the dorsal second and third phalanges as well as the matrix of the respective fingernail (Fig.

Overall order suhagra australia erectile dysfunction treatment natural remedies, 43 patients 5% for placebo) and falls (2% buy generic suhagra 100mg on line erectile dysfunction rap, 5% and 10% for 4, 8 and 12 mg/day, (15%) remained seizure-free for the preceding 3 months. Adverse events reported in 75% of patients continuing in the perampanel doses ranged from 4 to 14 mg/day (mean 8. Comparing the last 3 months of observation with baseline, 34 day, versus 9% for placebo), somnolence (9%, 16% and 18% for 4, 8 patients (46%) were responders, with 10 (14%) being seizure-free. Weight In a multicentre, double-blind trial, patients > 12 years with pri- increase >7% was observed in 14. Perampanel 553 Adverse events in the long-term extension study reported in history of psychiatric illness. Of the 12 patients who developed ag- >10% included dizziness, somnolence, headache, fatigue, irrita- gression, seven withdrew from the study, one responded to dosage bility and weight gain [26]. No clinically relevant changes in vital signs, electrocardio- In the core phase 3 perampanel studies, 143 adolescents gram or laboratory parameters were reported. Al- (8%) in the perampanel group versus none randomized to placebo most 4000 patients had been recruited, 2627 of whom were rand- [34]. No serious adverse events with term efect of adjunctive perampanel (2–12 mg/day) versus placebo perampanel were reported throughout these trials. Of 15 identi- on cognition in adolescents (12–17 years of age) with inadequate- fed adverse events, dizziness, ataxia, somnolence, irritability and ly controlled focal seizures was evaluated in a randomized dou- weight increase were found to be signifcantly associated with per- ble-blind study (6 weeks titration, 13 weeks maintenance). Tose most relevant were somno- serious in two perampanel patients (one each on 8 and 12 mg/day). The (n = 13, 18%), followed by ataxia, irritability falls, cognitive slowing situation is made more complicated by the high prevalence of and depression in single cases [28]. This was identifed based on review of the full clinical studies patients with a history of serious anger management issues and/ safety database. Anger, aggression and hostile behaviour have been or hostile or aggressive behaviour. In all other patients, the pos- reported in patients taking adjunctive perampanel, particularly at sibility of irritability, impulsivity anger and aggression should be higher dosage. Most of the events were either mild or moderate sensitively discussed with the patient and their close family when and some patients recovered either spontaneously or with dosage prescription of perampanel is being considered. However, thoughts of harming others, physical assault not themselves notice the change in their behaviour and so family or threatening behaviour were observed in around 1% of patients input is essential. Suicidal ideation has also been the perampanel dose is titrated to the optimum amount for each reported with perampanel during post-marketing use [32,33]. Documentation of any personal or family his- In a pooled analysis of the three phase 3 studies of adjunctive tory of psychiatric disorders will alert the prescriber to consider perampanel in patients with focal seizures (n = 1480; safety anal- slower introduction of the drug. The most common problem was are particularly susceptible to developing behavioural side-ef- aggression (n = 3; perampanel 12 mg/day in two patients, peram- fects with perampanel and hence its introduction should be panel 2 mg/day in the third). Tere are no good data to suggest quency of 5%, 12% and 20% with perampanel 4, 8, and 12 mg/day, that behavioural problems with perampanel are likely to be any versus 6% for placebo. Aggres- were irritability (4 mg/day, 4%; 8 mg/day, 7%; 12 mg/day, 12%; ver- sion and hostility have the potential for serious medico-legal im- sus 3% for placebo) and aggression (4 mg/day, 1%; 8 mg/day, 2%; plications and so accurate documentation in the case notes and 12 mg/day 3%; versus 1% for placebo). Tese symptoms can be managed data for over 850 patients and 100-week data for over 350 patients. Serious psychiatric adverse events cide whether or not to discontinue the drug should a behavioural were reported by 47 patients (3. Efcacy and safety of adjunctive ary generalization, in adults and children over 12 years of age. Perampanel, a selective, noncom- experience and are becoming more confdent in using the drug for petitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antag- patients with less severe epilepsies. Perampanel study 207: long-term open-label Approaches to control side-efects, particularly irritability and ag- evaluation in patients with epilepsy. Long-term safety of perampanel References and seizure outcomes in refractory partial-onset seizures and secondary generalised 1. New avenues for anti-epileptic es with perampanel in real life in Germany and Austria. First clinical experience with perampanel: the structure, regulation and function. Perampanel as adjunctive therapy in patients with partial-onset sei- ampanel: a review of clinical trial data. Novel treatment options for double-blind, placebo-controlled phase 3 (core) studies in patients with refractory epilepsy: focus on perampanel. Acta European Congress on Epileptology, 29 June to 3 July 2014, Stockholm, Sweden. Review of psychiatric and behavioural adjunctive perampanel for refractory partial-onset seizures. Inefective useful for the treatment of status in absences N epilepticus and neonatal seizures. H C2H5 Inefective in absences O Usual preparations Tablets: 15, 30, 50, 60 and 100 mg Tablets: 250 mg Elixir: 15 mg/5 mL Suspension: 50 mg/mL Injection: 200 mg/mL Usual dosage Oral Adults and children >9 years Initial: 30 or 50 mg/day in adults Initial: 62. Serum phenobarbital phenobarbital also apply to levels are increased by co- primidone. Enzyme-inducing administration of valproic acid and drugs increase the phenobarbital– some other drugs primidone ratio in serum. Isoniazid and nicotinamide increase serum primidone levels The Treatment of Epilepsy. A conductance possible contribution of phenylethylmalonamide to clinical efects has not been ascertained Bioavailability >95% >90% Time to peak levels 0. Initially believed to have only sedative properties, barbitu- 3 2 rates have been recognized as antiepileptic agents since 1912, when 5 4 3N H H O N Hauptmann discovered serendipitously a dramatic reduction of sei- C2H5 H O H zure frequency in patients with bromide-resistant epilepsy treated with phenobarbital (phenobarbitone) [1]. Its frst century in clinical (b) (d) O O use was recently celebrated with a special symposium [2,3]. Because C4 3 2C C4 3 2C O N O O N O of its broad spectrum, recognized efcacy, low cost and ease of use H H with once daily dosing, it is recommended by the World Health Or- ganization as a frst-line agent for focal and tonic–clonic seizures in Figure 42. Over the years, attempts have been made to modify the molecular clonic seizures and electrically kindled seizures [8]. It also appears structure of phenobarbital in order to identify agents with greater to prevent seizures induced by a variety of chemicals (such as efcacy and lesser toxicity. Primidone was introduced into clinical strychnine, thiosemicarbazide and bicuculline) and photic seizures practice in 1952 and is still relatively widely used. In contrast, phenobarbital worsens spike–wave can be attributed largely to metabolically derived phenobarbital. This pattern of activity in various anticonvulsant ileptic properties and were introduced into therapeutics in 1932 and tests, and particularly its ability to limit the spread of seizure activity 1948, respectively; however, neither drug achieved widespread use. This is borne out in keted with the aim of decreasing the sedation associated with phe- clinical practice, and phenobarbital has proven value in controlling nobarbital. The clinical success of phenobarbital also infuenced the generalized tonic–clonic seizures, other generalized seizure types development of subsequent distinct molecules (i.

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