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Receptor Agonists A group of halogenated aromatic hydrocarbons (Ah) that affect the male reproductive tract can activate the Ah receptor medications kidney damage order lincocin 500 mg otc. Observed effects include decreased anogenital distance medicine yeast infection best purchase for lincocin, delayed testis descent, impaired spermatogenic function, decreased accessory sex gland weights, and feminization of male sexual behavior. The effect may be mild or severe, and the duration may vary from transient dysfunction to permanent gonadal damage. This can occur either by a direct chemical action of the agent or indirectly via the metabolic products formed during the reaction process. Any disruption of these events by toxicants may lead to hypogonadism, infertility, and/or decreased libido/sexual function (Table 13. Endocrine disrupters are widespread in the environment, have an ability to bioaccumulate, and resist biodegradation. Many agricultural products (phytoestrogens), industrial chemicals, and heavy metals have significant environmental consequences as a result of their multiple routes of exposure. Methyl chloride is used in the production of organosilicates and gasoline antiknock additives. Such organic solvents have been reported to induce changes in semen quality, testicular size, and serum gonadotropins. Morphological sperm abnormalities due to secretory dysfunction of the Leydig and Sertoli cells may impair the sperm-fertilizing capacity. Heavy Metals Heavy metals, mainly lead, cadmium, cobalt, mercury, boron, aluminum, chromium, arsenic, and lithium, exert adverse reproductive effects in human and experimental animals. Testicular biopsies revealed peritubular fibrosis, and vacuolation, suggesting a direct testicular effect. In animal studies, cadmium has been shown to cause strain-dependent severe testicular necrosis in mice. It can also induce the expression of heat shock proteins, oxidative stress response genes, and heme oxygenase induction mechanisms. This is likely to affect pre- and postimplantation loss or contribute to congenital abnormalities in offspring. Anabolic Steroids Abuse of anabolic steroids to build stamina and muscle mass is very common among athletes and has resulted in severe oligozoospermia and decreased libido. Radiation Therapy Radiotherapy (X-rays, neutrons, and radioactive materials) is routinely used for the treatment of seminomatous germ cell tumors and lymphomas. Testicular damage due to radiation exposure is generally more severe and difficult to repair than that induced by chemotherapy. The time taken for damage and recovery not only depends upon dose but also on duration and developmental stage of the germ cells in the testes. Other Pharmacological Drugs Numerous pharmacological agents and many clinically approved drugs have gonadotoxic effects, especially at higher doses. This approach has been utilized for the development of potential male contraceptive agents. Ketoconazole, an antifungal agent, inhibits testosterone biosynthesis primarily by inhibiting the activities of steroidogenic enzymes in Leydig cells without any direct effect at the pituitary level. Hyperthermia Progressive germ cell damage occurs in the cryptorchid testis secondary to the increased temperature of the extrascrotal location. Elevated testicular temperature is also considered to be responsible for testicular dysfunction in men with varicocele. Hyperthermia results in impaired Leydig cell function, a gradual loss in size of seminiferous tubules, and peritubular hyalinization with fibrosis of the testis, which is accompanied by characteristic structural changes, notably the retention of cytoplasmic droplets in the ejaculated sample. Chronic Infection/Inflammation An infection/inflammation of the genitourinary tract in an infertile man is suspected when the semen analysis shows an increased number of leukocytes (>1 to 2 million white blood cells/ml semen).

Each mean positive control value must exhibit at least a twofold increase over the respective mean vehicle control value for each tester strain treatment zona order lincocin 500mg on line. A dose level is considered toxic if it causes a >50% reduction in the mean number of revertants per plate relative to the mean solvent control value (this reduction must be accompanied by an abrupt dose-dependent drop in the revertant count) or a reduction in the background lawn symptoms of high blood pressure buy generic lincocin. In the event that fewer than three nontoxic dose levels are achieved, the affected portion of the assay is repeated with an appropriate change in dose levels. All conclusions are based on sound scientific judgment; however, as a guide to interpretation of the data, the following criteria may be considered. Although there is no evidence supporting a specific requirement for a two- or threefold increase over background, this arbitrary rule is the most common method used in the evaluation of data. For a test article to be evaluated positive, it must cause a dose-related increase in the mean revertants per plate of at least one tester strain over a minimum of two increasing concentrations of test article. Ideally, the most appropriate determinant of a positive (mutagenic) response is a reproducible, statistically significant dose-related increase in revertant colonies. Several statistical procedures have been published; however, a recommended choice has yet to be established. The protocols for the two assays differ somewhat but follow the same basic principles. Treatment with the test article in the presence and absence of an exogenous metabolic activation system (Aroclor 1254-induced rat liver S9 plus enzyme cofactors); 4. A selection period during which cells are cloned in the presence of a selective agent; 6. Data collection, calculations to determine mutant frequency, cytotoxicity and cloning efficiency and assessment of the response to the test article. The two assays differ procedurally in certain areas, such as the way cells are cultured and cloned and the time for the expression and selection periods. However, the major difference in the two assays is in the specific target gene for mutation. The major difference in the protocols for the two assays involves the way the cells are cultured. Both assays detect point mutations involving base substitutions, deletions, frameshifts, and rearrangements within the locus and, thus, can be used interchangeably for detection of these types of lesions. The precise distribution of large and small mutant colonies appears to be the characteristic mutagenic "fingerprint" of carcinogens in this system. For either assay, maintenance of an acceptable background mutant frequency is essential. An acceptable background mutant frequency range must be established in any laboratory conducting these assays. Once a historical database has been established for a particular solvent, the untreated control can be dropped. Two positive controls, one directly acting and one requiring metabolic activation, are also included with each assay. Doses that produce more than 90% reduction in surviving cells as compared with the negative controls are not used to determine mutagenic effects of the treatment material, since that degree of toxicity alone is known to induce mutations in these systems. Currently, achievement of 70 to 90% reduction in surviving cells is considered optimal for detecting mutagenic activity from a cytotoxic test agent. For test compounds that do not induce toxicity, demonstration by chemical analysis that appropriate doses were used becomes more critical. The % Suspension Growth is determined by comparing the growth of treated cells vs. The % Cloning Growth is determined by comparing the number of colonies generated by treated cells vs. In general, test compounds are tested up to a concentration of 5 mg/ml or up to or in slight excess of the limits of solubility or up to doses that produce 90% reduction in surviving cells as compared with the negative controls. In addition, control of pH and osmolality is critical since excesses of either will induce false-positive results.

This recovery is best explained by the presence of which of the following structures between the bleached cell and its fluorescent neighbors Genes of laterality symptoms 5 weeks pregnant buy lincocin 500 mg on line, such as iv or inv symptoms 6 weeks pregnant order discount lincocin line, determine the right-left axis ("sidedness"). A mutation in a laterality gene is the most logical explanation for a child who was born with which of the following abnormalities Bifid heart Dextrocardia Double-outlet right ventricle Persistent truncus arteriosus Transposition of the great vessels A 31-year-old man with a history of epilepsy has a major motor (grand mal) seizure. During an operation, a cystic mass is found attached to the umbilicus and to the apex of the bladder. A 76-year-old man with a history of prostatic hypertrophy has the recent onset of increased difficulty urinating. Symptoms began shortly after he started taking a nasal decongestant orally for cold symptoms. Which of the following types of receptors is most likely to be involved in these adverse effects A 49-year-old man is taken to the emergency department because of neck pain that began after the car he was driving was hit in the rear by a pick-up truck. Several hours later he begins to have headaches and numbness in the scalp over the left occipital region. The most likely cause is compression of which of the following structures on the left The graph shows urine/plasma osmolarity versus urinary flow rate in a healthy human subject. Four drugs produce the same therapeutic effect by the same mechanism, but each has a unique toxicity. When used at a maximally effective therapeutic dose, the drug with which of the following sets of characteristics is most likely to have the highest incidence of toxicity Ultrasonography shows a marked increase in the amount of amniotic fluid; the fetus is normal in size for gestational age. An early diastolic sound followed by a low-pitched rumbling decrescendo diastolic murmur is present 4 cm left of the sternal border in the fourth intercostal space and is heard best with the patient in the left lateral decubitus position. Serum and urine calcium concentrations are abnormally increased, and urinalysis shows excessive protein (4+) and proteinaceous casts. Bone marrow examination is most likely to show uncontrolled proliferation of which of the following cells He is most likely to be taking a drug with which of the following mechanisms of action A previously healthy, tall, and slender 19-yearold woman has the sudden onset of right-sided chest pain followed by progressive dyspnea. Ten hours later, an x-ray of the chest shows a collapsed right lung and air in the right pleural space. A 52-year-old man with recently diagnosed type 2 diabetes mellitus comes to the physician for a follow-up examination. Laboratory studies show an increased hemoglobin A1c despite patient compliance with diet and exercise recommendations. The virulence of this organism is related to a bacterial constituent that interferes with which of the following host phagocyte functions A 46-year-old man has a 4-week history of epigastric pain; test of stool is positive for occult blood. Examination of tissue obtained on biopsy of the gastric antrum shows curved bacterial rods. She begs her husband to stay with her at the hospital because she is afraid to be left alone. A 51-year-old woman with cancer is being treated with a hematopoietic growth factor. Leukocyte differentials before and after treatment are shown: Before Treatment 1000/mm3 1% 90% 9% After Treatment 10,000/mm3 1% 9% 90% Leukocyte count Eosinophils Lymphocytes Neutrophils the growth factor is most likely to be which of the following Ampicillin resistance is stable in strain X when it is grown for multiple generations in the absence of the antibiotic.

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