Stethoscope discount 250 mg cipro bacteria are the simplest single cells that, thermometer or low level disinfectant Medical equipments Does not come in direct Examination table order genuine cipro on-line antibiotic used for kidney infection, computers Low level disinfectant contact with patient Hospital Waste Management Biomedical waste • A vast amount of waste is generated in the process of health care buy cipro 750 mg with mastercard antimicrobial chemotherapy 6th edition, research, testing, or related procedures on human beings or animals conducted in hospitals, clinics, labs. Category No 2 Animal waste (animal tissues, organs, body parts carcasses, bleeding parts, fuid, blood and experimental animals used in research, waste generated by veterinary hospitals/ colleges, discharge from hospitals, animal houses). Category No 3 Microbiology and biotechnology waste (wastes from laboratory cultures, stocks or specimens of micro-organisms live or attenuated vaccines, human and animal cell culture used in research and infectious agents from research and industrial laboratories, wastes from production of biological, toxins, dishes and devices used for transfer of cultures). Category No 5 Discarded medicines and cytotoxic drugs (wastes comprising of outdated contaminated and discarded medicines). Category No 6 Solid waste (items contaminated with blood and body fuids including cotton, dressings, soiled plaster casts, line beddings, other material contaminated with blood). Category No 7 Solid waste (disposable items other than the waste sharps such as tubing, catheters, intravenous sets etc. Category No 8 Liquid waste (waste generated from laboratory and washing, cleaning, house-keeping and disinfecting activities). Category No 10 Chemical waste (chemicals used in production of biological, chemicals, used in disinfection, as insecticides, etc). Presence of Corynebacterium indicates recent for incineration in appropriate bag contamination 39. Ans (a) (b) (Prions, Coxiella) Ref: Ananthnarayan 9th /p30 Holder’s method of Pasteurization(Heating at 63°C for 30 min) is ineffective for Coxiella burnettii, spores and prions. The dye changes colour to green after a defned period of time at a certain temperature. Typhi in a given time divided by the dilution of phenol which sterilizes the suspension in the same time. Lawn Culture • It provides uniform surface of growth of the bacterium on the solid medium. Pour-Plate Culture Stroke Culture Used to quantitate bacteria in urine cultures • This provides a pure growth of bacteria for carrying out diagnostic tests. I • For demonstration of oxygen requirement of the bacteria Stab Culture • Example where stab culture is used- mannitol motility medium, Triple sugar iron Stab culture is used for test. Liquid Culture • Used for blood culture and for sterility tests, where, the concentration of bacteria is small. The use of agar to use as solid media was suggested by Frau Hesse, the wife of one of the Robert Koch’ assistant. Lysogenic conversion: Bacteriophage when integrated with the bacterial chromosome, this stage is called as lysogenic conversion. So that after the conjugation is over- Both donor & recipient will have fertility plasmids • Along with the F factor, drug resistance genes may get transmitted-Responsible for the spread of multiple drug resistance among bacteria. Such donor mates with the recipient with high frequency and following which more chromosomal genes are transferred; however the F-factor doesn’t get transmitted. I • Don’t have self-replicative power (differs from plasmid) Transposon/ Jumping Gene- • They code for drug resistance enzymes, toxins or a variety of metabolic enzymes. About Other Options – Option a-Clinically, enzymatic drug inactivation is the most common mechanism for acquired microbial resist- ance by bacteria Koneman’s diagnostic Microbiology 6/e p945 – Most common mechanism of bacterial drug resistance- – Option c-Pneumococcal resistance:– Due to Alteration of target i. D alanyl-D alanine gets altered to D alanyl-D lactate which has less affnity for Vancomycin. The four Major Mechanisms of Antibacterial Resistance – Enzymatic inactivation of antimicrobial agents – like beta lactamases, aminoglycoside modifying enzymes etc. Herd Immunity • Overall immunity of a community to a pathogen • If Herd immunity is good- chance of epidemic is less • Eradication of a communicable disease- depends on good Herd immunity • Provided by mass vaccination by live vaccination to all individual at same time. Acute Phase Reactant Protein: Synthesized in liver at steady concentration, but synthesis either increases or decreases exponentially during acute infammatory conditions. Positive Acute Phase Reactant Protein: Levels of such proteins increase during acute infammation. Bailey and Scott’s 12/e p29 53 Review of Microbiology and Immunology Protective Characters of Skin and Skin Structures: (Bailey and Scott/P29, Box 3. Vaccines, toxoids, infection or antigen exposure can induce active immunity • Antitoxin and immunoglobulins are e. Rabies immunoglobulins • Passive immunity last for days to months • Immunoglobulins should be given immediately after the exposure but before the disease occurrence • Passive immunity can be transferred between individuals by Serum therapy (antibodies) • Passive immunity works immediately 11. Hapten antigenic Doesn’t have Immunogenicity – Hapten becomes immunogenic by combing with carrier molecule. By chromosome -14 Light chain kappa - Location of Immunoglobulin Chains By chromosome -2, • Heavy chains -chromosome -14 Light chain lambda - • Light chain kappa -chromosome -2, By chromosome -22 • Light chain lambda -chromosome -22 • After the synthesis, germ line recombination (rearrangement) of heavy and light chain occurs. Immunoglobulin Specifcity • Idiotypic specifcity: I – Based on antigenic determinant in paratope known as idiotopes Idiotypic specifcity- – Occurs due to change in variable region of the immunoglobulin. Based on antigenic • Isotypic specifcity: determinant in paratope known – Difference b/t Immunoglobulin of different classes and subclasses present in as idiotopes all individual in a given species – IgG /A/M/D/E – Occurs due to change in constant region of the heavy chain. Neutralization Test • Toxin antitoxin neutralization test- – Schick test- Diphtheria toxin – Naegler reaction – Streptolysin O neutralization test • Viral neutralization test • Bacteriophage neutralization test - By Plaque inhibition test. Opsonization • Enhanced phagocytosis by coating the microbial surfaces by opsonins. Due to antigen cross reactivity between them, antibody response against cow pox vaccine can protect against small pox. This antibody diversity is possible due to- – Presence of Multiple germ-line gene segments – Recombination of V-(D)-J Segments joining – Junctional fexibility – P-region nucleotide addition (P-addition) – N-region nucleotide addition (N-addition) – Somatic hypermutation – Combinatorial association of light and heavy chains 18. Immunoglobulin class IgG IgA IgM IgD IgE Heavy chain type Gamma chain Alfa chain Mu chain Delta chain Epsilon chain 21. Journal: Immunoglobulin genes and the origin of antibody diversity, Rev Fr Transfus Hemobiol. Kuby 6/e p131 Membrane-bound or secreted form of immunoglobulin: – Mature naive B cells produce only membrane-bound antibody (IgD or IgM), whereas differentiated plasma cells produce secreted antibodies (IgA). Epub 2007 Dec 17 – Peyer’s patches are composed of 30-40 lymphoid follicles present in intestinal sub mucosa – They are required for intestinal secretory immunoglobulin A responses which provides local or intestinal immunity or mucosal immunity. When antigen comes and binds to fab region of IgE, it in turn stimulates mast cell and mast cell degranulation occurs. Methods of diagnosis utilizing labeled antibodies – Labeled antibodies are used for- – Antibody detection- labeled anti human gamma globulin is used to detect human gamma globulin present in patient’s serum. Classical pathway: – Starts by Activation of C1 by antigen antibody complex – Activated C1 in turn activates C4 to C4a (anaphylotoxin) and C4b – C1 4b in turn activates C2 (in presence of Mg ion)to form C2a and C2b (kinin like, increases vascular permeability) – C14b2a is known as C3 convertase which activates C3 to C3a (chemotactic and anaphylotoxin) and C3b – C14b2a3b is known as C5 convertase which activates C5 to C5a (chemotactic and anaphylotoxin) and C5b – Late components add to C5b – to form C56789 (membrane attack complex) which forms pores on cell membrane causing cell lysis and also activates bystander cells to make them susceptible to lysis. I Lymph Node Lymph Node – T dependent area – • T dependent area – Paracortical area Paracortical area • B dependent area – Cortical follicle & Medulla. Class Switch Over of B Cells • Depending on the cytokine stimulus provided by the Tells, B cells undergo class switch over of B cells to produce different classes of immunoglobulin. Further differentiation seen 84 Structure of Immune System and Immune Response 17. Hence the progenitor T cells undergo positive selection followed by negative selection to delete the self reacting T cells.

The result is an imbalance in the I/G ratio and an accentuation of glucagon effects well above what would be seen in normal states of low insulin discount cipro amex infectonator 2 hacked, such as in fasting generic cipro 750 mg treatment for sinus infection home remedies. In addition to abnormal glucose metabolism discount 1000mg cipro fast delivery antibiotic resistance testing, disorders in the metabolism of lipid and protein intensify the seriousness of the disease. Superimposed on the disorders of carbohydrate, fat, and protein metabolism are diabetic-specific microvascular lesions in the retinas, renal glomeruli, and peripheral nerves. Diabetes, if untreated, leads to renal failure, erectile dysfunction, blindness, coronary arterial disease, and increased risk of cancer. In fact, adults with diabetes have heart disease death rates about two to four times higher than adults without diabetes. Also, stroke accounts for ~20% of diabetes-related deaths, and the risk for stroke is also two to four times higher among people with diabetes. The cause of diabetes continues to be a mystery, although both genetics and environmental factors such as obesity and lack of exercise appear to play significant roles. Data from the National Diabetes Statistical Report released in 2014 reported that there are 29. Diabetes has several clinical forms, each of which has a distinct etiology, clinical presentation, and course. Symptoms usually include frequent urination, increased thirst, increased food consumption, and weight loss. There are four main type of diabetes: (1) Type 1 diabetes (T1D) results from the body failure to produce insulin, (2) prediabetes results from insulin resistance, (3) Type 2 diabetes (T2D) results from insulin resistance and β-cell failure, and (4) gestational diabetes results from insulin resistance during pregnancy. Although most cases of T1D are a consequence of an inappropriate autoimmune destruction of the β cell, an autoimmune-independent subtype of T1D has recently been described, and recommendations have been put forth to divide T1D into type 1A (immune mediated) and type 1B (other forms of diabetes with severe insulin deficiency). Type 1B diabetes appears to be a rare form of T1D in which histologic examination of pancreatic sections demonstrates inflammation but no anti-islet autoantibodies. Whereas studies to gain deeper insight into type 1B diabetes are currently underway, it is known that type 1A diabetes results from a selective destruction of the β cells within the islets. A subtype of type 1A diabetes that has a latent onset in adults also exists, and recent findings suggest that its correct diagnosis and tailored insulin therapy may delay the progression and worsening of the disease (see Clinical Focus 34. The development of type 1A diabetes is usually divided into a series of stages, beginning with genetic susceptibility and ending with essentially complete β-cell destruction. Central to the pathology is insulitis β-cell injury, involving a lymphocytic attack on β cells. Consequently, amylin is normally cosecreted with insulin, and the plasma concentrations of the two hormones display a similar diurnal pattern of low fasting levels and rapid and robust increases in response to meals. As might be expected, because of the colocalization of both hormones within β cells, patients with T1D have an absolute deficiency of both insulin and amylin, whereas patients with T2D have a relative deficiency of both hormones, including a significantly impaired amylin and insulin response to meals. These findings have led to questions of whether amylin deficiency contributes to the metabolic derangements in diabetic patients and, if so, whether amylin replacement might convey clinical benefit when used in conjunction with insulin replacement. Extensive studies with amylin and amylin antagonists in rodents and with pramlintide (a synthetic analogue of the human amylin hormone) in diabetic patients have provided an understanding of the role of amylin in glucose homeostasis. Preclinical data indicate that amylin acts as a neuroendocrine hormone that complements the actions of insulin in postprandial glucose homeostasis via several mechanisms. These include a suppression of postprandial glucagon secretion and a slowing of the rate at which nutrients are delivered from the stomach to the small intestine for absorption. The net effect of these actions is to mitigate the influx of endogenous (liver-derived) and exogenous (meal-derived) glucose into the circulation and thus to better match the rate of insulin-mediated glucose clearance from the circulation. If one twin develops T1D, the odds that the second will develop the disease are much higher than for any random person in the population, even when the twins are raised apart under different socioeconomic conditions. In addition, people with certain cell-surface human leukocyte antigens bear a higher risk for the disease than others. Environmental factors are involved as well because the development of T1D in one twin predicts only a 50% or less chance that the second will develop the disease. The specific environmental factors have not been identified, although much evidence implicates viruses. Therefore, it appears that a combination of genetics and environment is a strong contributing factor to the development of T1D. Because the primary defect in T1D is the inability of β cells to secrete adequate amounts of insulin, these patients must be treated with injections of insulin. In an attempt to match insulin concentrations in the blood with the metabolic requirements of the person, various formulations of insulin with different durations of action have been developed. Patients inject an appropriate amount of these different insulin forms to match their dietary and lifestyle requirements. New technologies such as insulin pumps and continuous glucose monitors have not only aided treatment but also are paving the road to an artificial pancreas (see Chapter 30 Integrated Medical Sciences Box). The long-term control of T1D depends on maintaining a balance between several factors including insulin, diet, and exercise, as well as possibly including ancillary hormones such as amylin (see Clinical Focus 34. To strictly control their blood glucose, patients are advised to monitor their diet and level of physical activity, as well as their insulin dosage. Diabetic patients must take this into account and make appropriate adjustments in diet and/or insulin whenever general exercise levels change dramatically. This subtype was first revealed in the 1970s while testing a method to identify autoantibodies in the blood of people with T1D. Scientists found that T1D-related autoantibodies were virtually absent in the general population, but they showed up in about 10% of people diagnosed with T2D, which is not an autoimmune disease. This study also compared the use of insulin to that of sulfonylurea treatment (a common treatment for people with T2D that enhances β-cell insulin production) and found that, unlike those treated with insulin, patients treated with sulfonylurea lost β- cell function faster and progressed rapidly to insulin dependency. Thus, it is coming to light that a better treatment for this subtype of diabetes may be insulin, not sulfonylureas. Even more alarmingly, it is estimated that twice as many people have prediabetes, a condition that occurs when a person’s blood glucose levels are higher than normal but not high enough for the diagnosis of T2D. Recent research has shown that some long-term damage to the body, especially the heart and circulatory system, may already be occurring during prediabetes. Because red blood cells are constantly forming and dying, but typically they live for about 3 months, the A1C reflects the average of a person’s blood glucose levels over the past 3 months. The higher the A1C percentage, the higher a person’s blood glucose levels have been. Central to prediabetes and T2D is insulin resistance, a term that indicates the presence of an impaired biologic response to either exogenously administered or endogenously secreted insulin. Insulin resistance is manifested by decreased insulin-stimulated glucose transport and metabolism in adipose tissue and skeletal muscle and by impaired suppression of hepatic glucose output. It is clear that the molecular etiology of insulin resistance involves multiple genetic and nongenetic mechanisms contributing to the final phenotype. Furthermore, the resultant hyperglycemia of the syndrome and the compensatory rise in insulin in turn exacerbate insulin resistance, contributing significantly to the pathogenesis of the disease. New lessons learned from microbiology and immunology suggest an apparent role of intestinal microbiota in the etiology of obesity, insulin resistance, and T2D (see Integrated Medical Science Box). Although pinpointing the site of abnormality induced by these conditions is still an intensive area of current research, evidence strongly suggests that the defects induced by each occur at different loci in the insulin-signaling network. The affected patients demonstrate severe insulin resistance, including type A syndrome, Donohue syndrome, Rabson–Mendenhall syndrome, and lipoatrophic diabetes. In some cases, insulin resistance results from the secretion of counterregulatory hormones in a normal (e.

Efectiveness of standard epinephrine 1:1 effective cipro 750 mg antibiotic zyvox cost,000 (which is available in India) is the same as Laryngoscopy and/or bronchoscopy are indicated only in racemic epinephrine order cipro with amex antibiotics with sulfa, when given in dose of 0 buy discount cipro 1000mg on-line virus 20 orca. Patients can be discharged home if they demonstrate good color, adequate air entry, baseline consciousness, and no stridor at rest and have received a dose of A corticosteroids • Corticosteroids: they act through anti-infammatory action, whereby decreasing mucosal edema and also decreasing the need for nebulized epinephrine. In moderate to severe disease, it improves croup scores within 12–24 hours and decrease hospitalization rates. Using inhaled corticosteroids (budesonide) along with systemic steroid does not provide additional beneft – Usage of steroids has no signifcant adverse efects; however, it should be carefully evaluated for children with diabetes/immunocompromised state, recently diagnosed with varicella or tuberculosis. Poor ability to • Antibiotics are not needed, as etiology is viral infection maintain adequate oral intake plus increased insensible fuid • Heliox:Currently, the evidence is not sufcient to losses can lead to dehydration. The majority of patients are managed successfully as Complications in croup are rare. A secondary bacterial infection may rarely result in Spasmodic croup (laryngismus stridulus) may be a non- pneumonia or bacterial tracheitis, a life-threatening infection. Utility of bronchoscopy for recurrent night with the sudden onset of “croupy” cough and stridor. Comparison between single-dose oral prednisolone and oral patient becoming sensitized to viral antigens. Budesonide offers no advantage when added to oral dexamethasone symptoms when treated for refux. Correlating the clinical course of recurrent croup with endoscopic fndings: a retrospective observational study. Ann Otol ){It is a viral (parainfuenza) infection with subglottic airway Rhinol Laryngol. Steroid treatment of laryngotracheitis: a diferentiate it from supraglottic pathology meta-analysis of the evidence from randomized trials. Practical Pediatric Imaging: Diagnostic Radiology of Infants and Children, 3rd edition. Philadelphia, Pa: Lippincott-Raven; ){Assessment of severity is clinical, which decides treatment 1998. Controlled delivery of high vs low humidity vs mist therapy for croup in emergency 1. Red Book: 2003 Report of the Committee on Infectious Diseases, 26th randomised equivalence trial. Encephalopathy is a difuse disease afecting the brain that Encephalitis alters its structure or function and may be caused due to diverse Encephalitis means infammation of the brain. It is strictly a etiology like infective, metabolic, toxic, ischemic, nutritional pathological diagnosis; but surrogate clinical/imaging markers causes or trauma. Other early clinical fndings may include an increase implicated in the etiology; and the proportionate contribution in irritability, somnolence, or abnormal behavior greater than of each varies according to the geographical area. Even after a detailed diagnostic workup, one may not be according to the etiology. Encephalopathy generally results able to arrive at a defnitive diagnosis in many cases. Despite a Encephalopathy describes a clinical syndrome of altered wide array of pathophysiologic mechanisms, the clinical mental status, manifesting as reduced consciousness or altered manifestations tend to be very similar because of the common behavior, without any infammation of the brain. At the outset, (Lyme disease), Leptospira, Brucella, and Salmonella it is important to diferentiate infective from non­infective typhi causes, because infection mandates prompt antimicrobial {{ Rickettsial infections, fungal infections due to crypto­ therapy. There are no distinguishing clinical or radiological coccosis, histoplasmosis, coccidioidomycosis, and features to diferentiate the various causes of viral encephalitis. Cerebral ischemia is the single­most important of paramount importance as the children with impaired determinant that decides the outcome of such patients. These Once the airway and breathing have been addressed, children have loss of tone of the oropharyngeal muscles circulation must be evaluated. This involves assessment of causing the tongue to fall back and obstruct the airway, and the cardiac output. Symptoms of shock include tachycardia, pooling of secretions (leading to aspiration). Measures should cool extremities, delayed capillary refll time, mottled or pale be taken to secure the airway. Hypotension is a late fnding in airway obstruction, repositioning of the head with the chin lift shock. Vascular access is necessary for volume resuscitation maneuver may alleviate the obstruction. While establishing an is suspected, a jaw thrust maneuver is preferable and the neck intravenous access, samples should be drawn for various immobilized while securing the airway. If there is evidence of circulatory failure, fuid inserted if required and secretions cleared using a large­bore­ bolus (20 mL/kg of normal saline; maximum 60 mL/kg) suction cannula. If there is evidence of septic shock, Once the airway patency has been established, the larger volumes (60–80 mL/kg) may be needed to correct the adequacy of breathing should be evaluated. Once an intervention is performed, the clinician must the lung felds should assess for air entry, symmetry of breath reassess the patient. Pulse oximetry can be used to evaluate circulation through intravenous isotonic fuid administration oxygenation. Oxygen should be administered to all seriously­ and inotropes, if necessary, is essential to deliver oxygen ill children via non­rebreathing face mask. Adequacy of and metabolic substrates to the brain and remove toxic ventilation should be assessed by examination and arterial metabolites. Extreme hyperventilation has been associated and inappropriately treat with antiepileptic drugs. Hence, its absence must be identifed and treated appropriately, as unrecognized not be taken as a reassuring sign. Eforts should be It should not be administered round the clock and is unlikely taken to provide pain relief and sedation during painful to be efective after 48–72 hours. A neurosurgical benefts of relieving agitation outweigh the need for close consultation should be asked for. The use ){Identify and treat aggravating factors-seizures, noncon- of therapeutic hypothermia (32–34°C) may be appropriate vulsive status epilepticus, fever, pain, anxiety for children with out­of­hospital arrest and persistent coma ){Continuous monitoring of heart rate, respiratory rate, blood or those with ventricular fbrillation or pulseless ventricular pressure, temperature, oxygen saturations, electrocardiogram, tachycardia. T ereafter, the sugar levels should be monitored and the glucose infusion rates History (Table 3) modifed accordingly. Hyperglycemia resulting from stress is The patient’s history may hold the most important and a more common fnding in these conditions. Central nervous system benzodiazepine followed by phenytoin loading 20 mg/kg or infections, on the other hand, would present with complaints fosphenytoin) should be administered. The standard protocol evolving over a few days associated with a history of fever or 148 for the management of status epilepticus may be followed in recent illness. The presence of fever suggests an infective process (sepsis, The associated symptoms may indicate the focus of pneumonia, meningitis, encephalitis, or brain abscess); but infection. Symptoms such as headache, nausea and vomiting, may also indicate heat stroke or abnormality of hypothalamic irritability, seizures, focal defcits, rash, and joint pain temperature regulatory mechanisms. Other concurrent systemic result of fever, hypovolemic or septic shock, heart failure, or illnesses, e. Tachypnea with respiratory distress indicates lung pathology Nonaccidental trauma should always be considered in a (pneumonia, pneumothorax, empyema, or asthma).

During the second half of the spermatogenic cycle cipro 1000mg cranberry juice antibiotics for uti, they undergo considerable restructuring to form mature spermatozoa order cheap cipro bacteria found in water. Notable changes include alterations in the nucleus buy cipro master card antimicrobial properties, the formation of a tail, and a massive loss of cytoplasm. The nucleus becomes eccentric and decreases in size, and the chromatin becomes condensed. The acrosome, a lysosome-like structure unique to spermatozoa, buds from the Golgi apparatus, flattens, and covers most of the nucleus. The centrioles, located near the Golgi apparatus, migrate to the caudal pole and form a long axial filament made of nine peripheral doublet microtubules surrounding a central pair (called the “9 + 2 arrangement”). Throughout this reshaping process, the cytoplasmic content is redistributed and discarded. During spermiation, most of the remaining cytoplasm is shed in the form of residual bodies. The reasons for this lengthy and metabolically costly process become apparent when the unique functions of this cell are considered. Its only function is to reach, recognize, and fertilize an egg; hence, it must fulfill several prerequisites: it should possess an energy supply and means of locomotion, it should be able to withstand a foreign and even hostile environment, it should be able to recognize and penetrate an egg, and it must carry all the genetic information necessary to create a new person. The mature spermatozoon exhibits a remarkable degree of structural and functional specialization well adapted to carry out these functions. The cell is small, compact, and streamlined; it is about 1 to 2 μm wide and can exceed 50 μm in length in humans. It has a prominent nucleus, a flexible tail, numerous mitochondria, and an assortment of proteolytic enzymes. The spermatozoon consists of three main parts: a head, a middle piece, and a tail. The two major components in the head are the condensed chromatin and the acrosome. The haploid chromatin is transcriptionally inactive throughout the life of the sperm until fertilization, when the nucleus decondenses and becomes a pronucleus. The acrosome contains proteolytic enzymes, such as hyaluronidase, acrosin, neuraminidase, phospholipase A, and esterases. They are inactive until the acrosome reaction occurs on contact of the sperm head with the egg (see Chapter 38). Their proteolytic action enables the sperm to penetrate through the egg membranes. The middle piece contains spiral sheaths of mitochondria that supply energy for sperm metabolism and locomotion. The tail is composed of a 9 + 2 arrangement of microtubules, which is typical of cilia and flagella, and is surrounded by a fibrous sheath that provides some rigidity. Testosterone is the main hormone produced by steroidogenesis and is primarily secreted by the testes of males and the ovaries of females. In males, testosterone production is about 10 times greater than that in females and plays a key role in the development of the testes and prostate as well as promoting secondary sexual characteristics, such as increased hair growth, muscle, and bone mass. It is also essential for health and well-being as well as the prevention of osteoporosis. Testosterone is primarily synthesized in Leydig cells and is derived from cholesterol, involving many enzymatic steps. The adrenal cortex, ovaries, testes, and placenta produce steroid hormones from cholesterol. Cholesterol, a 27-carbon (C27) steroid, can be obtained from the diet or synthesized within the body from acetate. Cholesterol from lipoproteins is released in Leydig cells and transported from the outer mitochondrial membrane to the inner mitochondrial membrane, a process regulated by steroidogenic acute regulatory protein. Pregnenolone is a key intermediate for all steroid hormones in various steroidogenic organs (Fig. Pregnenolone can be converted to testosterone via two pathways, the δ5 pathway and the δ4 pathway. In the δ5 pathway, the double bond is in ring B; in the δ4 pathway, the double bond is in ring A (see Fig. Unlike all the earlier reactions, this is a reversible step but tends to favor testosterone. Although estrogens are only minor products of testicular steroidogenesis, they are normally found in low concentrations in men. Aromatization involves the removal of the methyl group in position 19 and the rearrangement of ring A into an unsaturated aromatic ring. The products of aromatization of testosterone and androstenedione are estradiol and estrone, respectively (see Fig. Excess receptors increase target cell sensitivity to low circulating hormones by increasing the probability that sufficient receptors will be occupied to induce a response. This response emphasizes the importance of compartmentalization for both enzymes and substrates in mediating hormonal action. Certain drugs can inhibit phosphodiesterase; gonadotropin hormone responses will increase dramatically in the presence of those drugs. One is the phosphorylation of cholesterol esterase, which releases cholesterol from its intracellular stores. Hyperprolactinemia in men with pituitary tumors, usually microadenomas, is associated with decreased testosterone levels. Testosterone diffuses into the blood immediately after being synthesized in Leydig cells. This amount slowly declines after age 50 and reaches about 4 mg/d in the seventh decade of life. Therefore, men do not undergo a sudden cessation of sex steroid production on aging as women do during their postmenopausal period when the ova are completely depleted. Testosterone circulates bound to plasma proteins, with only 2% to 3% present as the free hormone. It also prolongs the half-life of circulating testosterone because testosterone is cleared from the circulation much more slowly if bound to a protein. Skin, hair follicles, and most of the male reproductive tract contain an active 5α-reductase. Aromatization of some androgens to estrogens occurs in fat, liver, skin, and brain cells. Circulating levels of total estrogens (estradiol plus estrone) in men can approach those in women in their early follicular phase. Men are protected from feminization as long as production of and tissue responsiveness to androgens are normal. The treatment of hypogonadal male patients with high doses of aromatizable testosterone analogs (or testosterone), the use of anabolic steroids by athletes, abnormal reductions in testosterone secretion, estrogen-producing testicular tumors, and tissue insensitivity to androgens can lead to gynecomastia or breast enlargement. All of these conditions are characterized by a decrease in the testosterone/estradiol ratio. Androgens are metabolized in the liver to biologically inactive water-soluble derivatives suitable for excretion by the kidneys. The major products of testosterone metabolism are two 17-ketosteroids, androsterone and etiocholanolone.

Q. Kadok. Rocky Mountain College.