By T. Ashton. Sul Ross State University.

It induced micronuclei and/or chromosomal aberrations in the bone marrow of mice and rats order crestor 20 mg on line. Etoposide induced sister chromatid exchange in Chinese hamster lung cells and in human lymphocytes and other human cell lines in vitro discount crestor 5mg free shipping. Sister chromatid exchange induction has also been seen in mouse bone-marrow cells in vivo. Etoposide induced mutation and somatic recombination in Drosophila melanogaster in the wing spot test. It also induced a positive response in the Drosophila white–ivory assay, probably again through recombinogenic events. These mice can therefore be used to detect somatic intrachromo- somal recombination inversion events in vivo in various tissues. When these mice were given a single intraperitoneal injection of etoposide and spleen cells were exam- ined three days later, significant induction of inversion events was found by histo- chemical staining of tissue sections (Sykes et al. It induced primarily small colony mutants at the Tk locus in mouse lymphoma L5178Y cells. Small colony mutants in L5178Y cells are usually caused by chromosomal mutations (DeMarini et al. Whether cellular damage results in mutation or apoptosis depends on a number of factors (Ferguson & Baguley, 1994). Etoposide-induced apoptosis has been demon- strated in cultured retinoblastoma Y79 cells (Lauricella et al. In mice, etoposide caused apoptosis through a p53-dependent pathway in imma- ture thymocytes and also through a p53-independent pathway in a particular sub-popu- lation of these cells. The drug induced apoptosis at significantly lower levels and at later times in p53 null as compared with p53 wild-type mice (MacFarlane et al. Polyploidy was also demon- strated by cytogenetic techniques in Chinese hamster ovary cells. Etoposide inhibited accurate chromosomal segregation in both HeLa and PtK2 cells (Downes et al. It also retarded chromatid separation in vitro in a system derived from sperm nuclei in an extract of Xenopus laevis eggs. In general, events in mammalian cells in vitro occurred in the absence of exo- genous metabolic activation. Nevertheless, etoposide is metabolized by human liver microsomes (Kawashiro et al. Various metabolic species have been identified, but their mutagenic properties have not been studied. These effects are manifest as recessive mutations at specific loci and dominants at other loci. Deletion mutations occurred commonly, and these authors suggested that they had a recombinational origin. These authors suggested that etoposide caused a failure of reso- lution of recombined chromosome arms, probably associated with cell cycle arrest and triggering of the apoptotic pathway. Etoposide also induced aneuploidy, polyploidy and M-phase cycle arrest when introduced during the meiotic M phase. Additionally, many cells were arrested at late anaphase I, and the frequency of second divisions with a diploid chromosome number was significantly elevated. Cytogenetic changes were measured in pregnant mice given a single intraperitoneal injection of 1. Injection on day 7 increased the frequency of embryonic cells with structural aberrations, one-third of which were stable, consisting of chromosomes with metacentric or submeta- centric markers. Injection on day 6 or 8 increased the percentage of embryonic cells with numerical aberrations, most of which were hypoploidy (monosomy) (Sieber et al. It does not inhibit bacterial topoisomerases and may not mutate bacterial cells by the same mechanism as mammalian cells. It possesses readily oxidizable functions: Some of the etoposide-induced effects have been ascribed to the formation of free radicals by oxidation of its 4′-phenolic hydroxy group to a semiquinone free radical (Sakurai et al. The first is that etoposide itself causes the translocations, perhaps through a cytotoxic action. The second possibility for the role of etoposide in causing translocations is that it selects for cells that already have translocations. Chemotherapy has profound effects on the kinetics of the marrow: it causes cell death, forcing many marrow stem cells to divide, which might select for the rare stem cells with a translocation (Knudson, 1992). In the patients with Langerhans cell histiocytosis, a strongly increased risk for acute myeloid leukaemia of the promyelocytic type was found after treatment with etoposide alone; however, the possibility could not be ruled out that such patients have an inherently increased risk for acute promyelocytic leukaemia. In several cohort studies of germ-cell tumours in men, treatment with etoposide, cisplatin and bleomycin was associated with an increased risk for acute myeloid leukaemia. On the basis of the combined data from six studies, the relative risk for acute myeloid leukaemia was 40 times greater than that of the general population; substantially higher relative risks have been found with high cumulative doses of eto- poside. Although the other two agents (cisplatin and bleomycin) in etoposide-containing chemotherapy regimens for germ-cell tumours may have contributed to the positive association seen in the cohort studies, use of these agents in a similar regimen without etoposide has not been associated with acute myeloid leukaemia.

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Hallucinogenic or Psychotomimetic Drugs It has been common knowledge for centuries that many drugs may modify the behavior of man to the extent of producing psychotic behavior cheap crestor 10 mg without prescription. The interests of psychiatrists in these phenomena have stemmed largely from the supposed resemblance of these psychoses to schizophrenia generic crestor 5mg without prescription, because of the time-honored, though as yet unproven, hypotheses (11) that schizophrenia is due to a "toxin. Two psychotomimetic drugs are discussed briefly here as examples, from the viewpoint of their psychopharmacologic effects and their possible pertinence to interrogation procedures. Mescaline has also been studied as a potential diagnostic and therapeutic adjunct with psychiatric patients. Cattell (27) found mescaline to be a useful drug in investigating personality structure, -121- but of no value in the therapy of psychiatric patients. New psychodynamic material was gained from the first two groups, but relatively little from the last group. Cattell reasoned that the new material obtained in the mescaline state had been condensed and repressed in the drug-free state. Mescaline in general (63, 65, 66, 110) has been found to produce perceptual distortions and hallucinations, accentuation of affective experiences, and increased psychotic manifestations. In some patients contact and communication were increased and in others decreased. Hoch (63) noted that mescaline in "normals" produced more of an "organic reaction" with some schizophrenic features, as compared to its effect in schizophrenics and latent schizophrenics where mescaline produced more complete schizophrenic disorganization. Hoch also emphasized that mescaline produced a falling off in intellectual functioning. These articles are typical of the reports on the psychopharmacologic effects of mescaline. When interrogators extrapolate clinical psychiatric observations of this kind to the problems of interrogation, mescaline might serve their purposes in attempting to create an atmosphere of fear or terror in the informant and the illusion of magical overpowering omnipotence about himself. After such a transient state has been created, the susceptible informant might be induced subsequently to reveal information. The perceptual and cognitive disturbances produced by the drug make it unsuitable for obtaining undistorted information while the source is under its influence. From the viewpoint of the informant, the creation of a transient psychotic state by the ingestion of mescaline or lysergic acid might offer him some temporary protection against being successfully interrogated. An interrogator is not likely to consider an individual in a psychotic state a suitable candidate for providing reliable and useful information, at least until the drug effect wears off. They noted that the drug transiently increased the mental activity of their patients 30 to 60 rain after ingestion. The effect was a transitory toxic state in which repressed material came forth "sometimes with vivid realism" and emotional expression. Alterations were observed in thinking, speech, emotions, mood, sensation, time perception, ideation, and neurologic signs. The reaction was typical of an exogenous toxic state, simulating a schizophrenic reaction. The reaction was not specific and the extent to which it was dependent on the basic personality was not determined. An interesting, unexplained phenomenon was that only two out of the sixteen cases had the expected bizarre hallucinatory experiences. The conclusions reached on mescaline hold equally for the possible applications of this drug to -123- interrogation. Major Tranquilizers Recently a large number of new compounds with sedative and anxiety-relieving properties have been introduced, sufficiently different from the classical sedatives, such as paraldehyde, chloral hydrate, barbiturates and bromides, to warrant using new terms to describe them. The use of these drugs has revolutionized psychiatric therapeutic procedures, especially within the mental hospitals. A thorough review of their effects and mechanism of action in mental illness would be out of place here. Unfortunately, the usefulness of these tranquilizers in exploring psychologic processes and in facilitating communication has not been very extensively tested. Yet, for the sake of completeness, and to indicate the directions further research might take, the psychologic actions of these drugs deserve mention. Therefore, the psychopharmacologic actions of only this compound are discussed here. Delay and his associates (38) appear to have been the first to explore chlorpromazine in the treatment of mental illness. They found that the effects of chlorpromazine in patients with manic psychoses were somnolence, decreased responses to external and internal stimuli, pleasant indifference, and decreased spontaneity of speech. Subsequent reports (5, 20, 28, 32, 75, 81, 87, 88, 134) have been in agreement that chlorpromazine is effective in quieting or abolishing severe agitation and psychomotor excitement, whether of manic-depressive, schizophrenic, or toxic origin. Most of these reports agree that the basic disorder in these conditions is not -124- altered by the drug. In the psychoneuroses, chlorpromazine was reported (52, 80) to decrease anxiety and tension temporarily, but to have no specific ameliorative effects on conversion symptoms, obsession, piaobia, depression, or physical pain.

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Discuss the working of at least one electrode from each category along with its diagramatic description purchase crestor 20mg without prescription, working and advantages crestor 20mg free shipping. Do you think an ‘Automatic Titrator’ (Preset End-Point Titrator) is a technological advancement in potentiometric titration? Expatiate its efficacy and advantages in a busy ‘quality assurance laboratory’ with a neat-labelled diagram and its modus operandi. Hence, these measurements may be employed effectively to record the alteration in concentration of an ion in question in the course of a titration, and ultimately the end-point is established. This specific process is commonly referred to as amperometric method or amperometry. In this particular case, the total current flowing shall remain almost equal to the current carried by the ions that undergoes equal electrolytic migration together with the current caused on account of the diffusion of the ions. Thus, we have : I = Id + Im where I = Total current, Id = Diffusion current, and Im = Migration current. An awkward situation arises when dealing with a dilute solution where it has been observed that the depletion of the electrode layer ultimately leads to an enhancement of the resistance of the solution and thereby affecting subsequently an alteration in the Ohm’s Law potential drop (I × R) in the cell. This ulti- mately gives rise to a doubtful observed potential operative at the electrode. In order to overcome this serious anomaly, it is a normal practice to add an excess of an indifferent electrolyte to the system, such as : 0. Thus, we may have : Diffusion current = Limiting current – Residual current It follows from above that the diffusion current is directly proportional to the concentration of the electro-active substance present in the solution. Now, if a situation is created whereby a portion of the electro- active substance is eliminated by interaction with a specific reagent, the diffusion current shall decrease significantly. It represents the fundamental underlying principle of amperometric method or amperometry. Hence, at an appropriate applied voltage the apparent diffusion current is measured as a function of the volume of the titrating solution added. Now, if a graph is plotted between the ‘current’ against the ‘volume of reagent added’, the end-point will be represented by the point of intersection of two lines indicating the change of current both before and after the equivalence is achieved. In other words, only the substance under titration gives rise to a diffusion current ; whereby the electro-active substance is removed from the solution by means of precipitation with an inactive substance. An appreciably high potential is usually 4 2 4 applied to yield a diffusion current for lead. The small curvature just prior to the end-point (or equivalence point) shows the incompleteness of the analytical reaction in this particular region. However, the end-point may be achieved by extrapolation of the linear portions, as shown in the said figure. In other words, the reagent gives rise to a diffusion current, whereas the solute does not ; it means an electro-active precipitating reagent is being added to an inactive substance. In this particular instance, a diffusion current for 8-hydroxyquinoline is normally achieved at – 1. The end-point may be obtained by extrapolation of the lower-end of the V-shaped portion of the curve as depicted in the above Figure. Thus, the final end-point of the potentiometric titration is indicated by a zero-current as depicted in Figure 17. Since the resulting diffusion coefficient of the reagent is found to be slightly different from the corresponding substance under titration, therefore, the slope of the line just before the end-point actually differs very slightly from that after the end-point. However, in actual practice it is rather convenient to add the reagent unless and until the current attains a zero value. This correction is applied by multiplying the measured corresponding diffusion current (Id) by the following factor : V+v V where, V = Initial volume of the solution, and v = Volume of the titrating reagent added. The use of concentrated reagents have the following advantages, namely : (a) Relatively very small amount of dissolved O2 is incorporated into the system, which eliminates completely the prolonged bubbling of inert gas (e. If need be, an appropriate maximum suppressor can also be incorporated judiciously. The amperometric titration may normally be performed very quickly, because the equivalence point (or end-point) is determined graphically. A series of measurements at constant applied volt- age just prior and latter to the end-point are more than enough. The titrations can be carried out both satisfactorily and effectively in such situations where the solubility relations offer erroneous and unsatisfactory results given by visual indicator and potentiometric methods. It is quite evident that the readings in the vicinity of end-point offer practically no specific value and importance in amperometric titrations. Because the readings are mostly taken in particular zones where there exists either an excess of reagent or of titrant, and which specific points the hydrolysis or solubility is entirely suppressed by the effect of Mass Action. The point of intersection of these lines ultimately gives rise to the desired end-point. A good number of amperometric titrations may be performed on considerably dilute solutions (say, 10–4 M) at which neither potentiometric nor visual indicator methods ever can give precise and accurate results, and 4. In order to eliminate the migration current (Im) completely either the ‘foreign salts’ already present cause little interference or invariably added so as to serve as the ‘supporting electrolyte’. It is duly controlled and monitored by the potential divider (R) and is conveniently measured with the help of a digital voltmeter (V).

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