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An Israeli team working with the Negev Arab Bedouin community: "a well-targeted approach in terms of the identification of families at risk for devastating genetic diseases asthma bracelet purchase salmeterol with american express, coupled with appropriate genetic education and counseling asthma questions generic salmeterol 25mcg without prescription, can make good use of the available genetic technology asthma and allergy specialists salmeterol 25 mcg with visa. Noting that "Israel is engaged in cloning, mapping, sequencing, and evaluating several human genes, primarily of pathological implications and with Jewish orientation," Yossi Segal of the Israeli Academy of Sciences and Humanities is cautious in predicting future use of the four potential areas for the application of genetic engineering designed to insert a gene into a human: somatic cell therapy, germline gene therapy, enhancement genetic engineering, and eugenic genetic engineering. Whether or not the human species should be more alert to the qualitative, and not only to the quantitative consequences of its reproductive policies, whether the impact of modern techniques of genetic manipulations should also be examined by their effects on the gene pool, are important issues towards the twenty-first century. Professor of medicine and specialist on Jewish medical ethics Fred Rosner of the Mount School of Medicine: "It is prohibited in Jewish law to marry a woman from a family of epileptics or lepers (Yeba1 2 Carmi, et al. According to Rashi (Yebamot 64b), any hereditary disease is included in this category. Zohar, a professor of philosophy at Bar-Ilan University in Israel, responds to rabbi Max Reichlers 1910 essay "Jewish Eugenics. To work out a Judaic response to the sort of new eugenics now looming on our horizon it will be necessary to evaluate the various specific means that might serve a modern individualized eugenics. I hope that some of the groundwork for that has been laid in this examination of traditional Judaic voices. Rabbi Moshe Tendler of Yeshiva College complains that many Jewish newspapers have accepted advertisements seeking Ashkenazi families to study the biological basis for bipolar disorder and schizophrenia, fearing that such materials will reawaken the idea that "Jews carry genes that are polluting the world. If you have a [disease] gene, dont you owe it to society not to propagate that gene? The,neoconservative Jewish magazine Commentary publishes an anti-eugenics article by clergyman (originally Lutheran, later Roman Catholic) Richard John Neuhaus (1936-2009), who warns that eugenics is back "with a vengeance. A Micro-Chronology of Jewish Eugenics 325 with practices that have no relation to reproduction, such as prolonging the lives of the irreversibly comatose. Anti-eugenics activist Jeremy Rifkin: "the new eugenics bears little resemblance to the shrill cries of racial purity that culminated in the Holocaust. The old eugenics was motivated by fear and hate; the new eugenics is spurred by market forces and consumer desire. Genetic engineering is coming to us not as a sinister plot, but rather as a social and economic boon. When the Jewish-American anti-eugenics activist Barry Mehler accuses psychologist Raymond B. Cattell (1905-1998) of "fascism," "racism," and "eugenics," the American Psychology Association postpones granting Cattell a lifetime achievement award. Professor Zeev Herzog, Department of Archaeology and Ancient Near Eastern Studies at Tel Aviv University, writing in Haaretz: "Following 70 years of intensive excavations in the Land of Israel, archaeologists have found out: the patriarchs acts are legendary stories, we did not sojourn in Egypt or make an exodus, we did not conquer the land. Those who take an interest have known these facts for years, but Israel is a stubborn people and doesnt want to hear about it. Similarly, scientists should not be allowed to publish statements and conclusions not supported by the data simply because they appear,politically correct at the moment or do not generate an outcry. The correct statement from their own data is that some Jews (Sephardim) are more similar to Palestinians than either group is to other Jews (Ashkenazim or Ethiopian Jews). Tim Cole, former Paul Resnick Resident Scholar at the Center for Advanced Holocaust Studies at the United States Holocaust Memorial Museum: "At the end of the twentieth century the,Holocaust is being bought and sold. Millions of dollars more have financed memorial projects throughout the United States, ranging from the installation of holocaust memorials to the establishing of University chairs in Holocaust Studies. Steven Spielbergs 1993 movie Schindlers List netted over $221 million at foreign box offices and seven Academy Awards. Tudor Parfitt of the European Association for Jewish Studies and Yulia Egorova studying under him at the School of African Studies, University of London, comment that such assertions "may represent attempts by some Jewish groups to traverse barriers that can appear insurmountable when dealing with more closely situated black communities at home in New York, Washington, and elsewhere. For these groups, then, the genetic studies on the Lemba may be presumed to have great ideological value, as they may be used to prove that Zionism or Judaism are not, as 4. Therefore, any assault on pre-human,mud people or demonic Jews is not only desirable but divine. Minorities, who are depicted as responsible for crime and other social ills, are seen as the tool of the Jew-devils in their war against the white Aryans. Students with muscular, athletic bodies as well as the bowed and infirm will register their outrage. Protestants, Catholics and Jews (in the season of the New Year when the Jewish people pray for their names to be written down in the Book of Life) will join hands to express their fury at the presence of a professor on their campus whose intellectual coldness and academic credentials have led him to a prestigious chair as tenured professor.

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The microsomal P450 system is most highly concentrated in the liver asthma respiratory alkalosis salmeterol 25mcg without prescription, but it is also present in many extrahepatic tissues including the lung asthma symptoms 3 months order salmeterol 25 mcg line, kidney asthma prevalence definition discount salmeterol 25mcg, placenta, small intestine, skin, adrenal, testis, ovary, eye, pancreas, mammary gland, aorta wall, brain, nasal epithelial membrane, colon, salivary gland, prostate, heart, lymph node, spleen, thymus, and thyroid. A second P450 monooxygenase system, localized to mitochondria of steroid-metabolizing tissues (adrenal, ovary, and testis), is primarily involved in the oxidative biosynthesis of endogenous steroids such as cholecalciferol, cortisone, and deoxycorticosterone. Alcohol and Aldehyde Dehydrogenases An extremely important metabolic pathway for alcohols and aldehydes is oxidation to aldehydes and ketones and to carboxylic acids, respectively. Alcohol dehydrogenases are widely distributed in mammalian tissues, with the highest concentrations occurring in the liver. However, the in vivo reduction of aldehydes by this enzyme is not normally a quantitatively important reaction because aldehydes are rapidly oxidized to their corresponding carboxylic acid derivatives by aldehyde dehydrogenase. Aldehyde dehydrogenases are also widely distributed in mammalian tissues, with the highest concentration in the liver. This enzyme system catalyzes the oxidative deamination of a wide variety of xenobiotic and endobiotic. There are two major types of monoamine oxidase (A and B), whose relative concentration varies in tissues of the same species. In general, the A form of the enzyme is more active with endogenous neurotransmitter amines (serotonin, norepinephrine, and epinephrine), whereas the B form is more active toward xenobiotic amines such as 2-phenethylamine. H2O2-Dependent Peroxidases Easily oxidized phenols and arylamines are excellent substrates for peroxidase-catalyzed one-electron oxidation reactions. These reactions are very important in toxicology because of the reactivity and toxicity of the free radicals (molecules with a highly reactive unpaired electron) formed. A well-studied example of this type is the cooxidation of xenobiotics catalyzed by the hydroperoxidase activity of prostaglandin H synthase. Prostaglandin H synthase activity is high in several extrahepatic sites that are targets for chemicalmediated toxicity but which contain very low amounts of P450 monooxygenase activity. Other peroxidases are also involved in bioactivation of easily oxidized compounds. Oxyhemoglobin in erythrocytes can oxidize arylamines to products that cause methemoglobinemia; chloroperoxidase and myeloperoxidase of activated polymorphonuclear leukocytes and macrophages bioactivate certain drugs including various sulfonamides by N-oxidation to reactive nitroso products that contribute to adverse drug reactions; and diethylstilbestrol, a transplacental carcinogen, is oxidized by estrogeninducible peroxidases in the reproductive tract. These few examples emphasize that H2O2-dependent peroxidases can activate aromatic alcohols (phenols) and aromatic amines to reactive free radicals, which are often very toxic. Those reactions that go to completion in vivo are either reductions of carbonyl groups or are catalyzed by the intestinal microflora. Reduction that occurs anaerobically is of much less toxicological concern due to the decreased formation of toxic oxygen-free radicals. In addition to being oxidatively metabolized, many polyhalogenated alkanes are converted by a P450dependent, one-electron reduction pathway to a free radical intermediate and inorganic halide. Several other classes of xenobiotics are also efficiently reduced by the P450 monooxygenase system Reduction Reactions Several functional groups, including nitro, azo, tertiary amine N-oxide, aldehyde, ketone, sulfoxide, and alkyl polyhalide, are reduced by mammals in vivo. Although some of these reactions, or more accurately the initial sequence of the reactions, occur under aerobic conditions in vitro, Biotransformation 305 under anaerobic conditions. These include tertiary amine N-oxides (converted to tertiary amines), hydroxylamines (primary amines), and hydrazo derivatives (primary amines). In general, aldehyde reductases reduce only aldehydes, whereas carbonyl reductases reduce both aldehydes and ketones. In the presence of oxygen these radicals are rapidly reoxidized to the parent aromatic nitro or azo compound, concomitant with the generation of the superoxide anion radical. This futile cycling explains the toxicity of compounds, such as paraquat (Figure 6) or nitrofurantoin, which generate toxic superoxide under conditions in which little or no metabolism of the compound is detected. Compounds that are more difficult to reduce, such as carbon tetrachloride, require the intact P450 monooxygenase system as a source of electrons for reduction. Hydrolysis Reactions When certain xenobiotics, including esters and amides, are administered to animals they are hydrolyzed. Hydrolysis reactions are important for the sequential metabolism of chemicals converted to epoxides by the P450 system. These reactions are classified as phase I because they free up functional groups.

Occupational asthma - drugs and enzymes

Rats exposed to asthma lesson plans order salmeterol 25 mcg visa aniline in the diet developed sarcomas of the spleen and other body organs asthmatic bronchitis 6 month purchase 25 mcg salmeterol with amex. In addition asthma treatment emergency discount salmeterol 25mcg online, transgenic mice developed skin tumors and leukemia following dermal exposure to benzene. A causal relationship between benzene exposure and leukemia has been reported in numerous epidemiological studies. The two most frequently cited side effects are salt and water retention and hyperglycemia. Chronic Toxicity (or Exposure) Human Uses Diazoxide is administered intravenously for the treatment of hypertension and administered orally for the treatment of hypoglycemia. Exposure Routes and Pathways Diazoxide is therapeutically administered either intravenously or orally. Diazoxide exhibits the ability to relax smooth muscle and therefore may be contraindicated in late pregnancy. Commonly observed side effects include decreased urination, swelling of feet or lower legs, and rapid weight gain. Occasionally, increased tachycardia may be observed and on rare occasions fever, skin rash, stiffness of arms or legs, trembling and shaking of hands and fingers, unusual bleeding or bruising, may be observed. Exposure Standards and Guidelines Toxicokinetics Diazoxide is well absorbed orally. It is distributed to the plasma where it is highly bound (490%) to the plasma proteins. Diazoxide is regulated in the state of California as a Proposition 65 reproductive toxin. Further Reading Silvani P, Camporesi A, Mandelli A, Wolfler A, and Salvo I (2004) A case of severe diazoxide toxicity. Mechanism of Toxicity Diazoxide acts as an antihypertensive by relaxing the arteriole smooth muscle. Epoxidation of the 3,4-dihydrodiol may lead to the formation of a diol-epoxide, the purported metabolite responsible for its carcinogenicity. Dibenz[a,h]anthracene has not been isolated in the fat tissues, reflecting the effectiveness of the metabolizing enzyme system. Dibenz[a,h]anthracene is a by-product of incomplete combustion and therefore is a fairly ubiquitous compound, generally strongly bound to the sediment. Acute and Short-Term Toxicity (or Exposure) Animal Exposure Routes and Pathways the primary route of exposure to dibenz[a,h]anthracene is via the skin, from petroleum-based products. An additional significant route of exposure is through inhalation of cigarette smoke. While ingestion is a route of exposure, the significance of such exposure is debatable. Dibenz[a,h]anthracene is found in many food items (cereals, fruits, and vegetables) in the low parts per billion (ppb) level. It is found in petroleum products such as coal tar, mineral oil, and petroleum waxes. Human Toxicokinetics Dibenz[a,h]anthracene has an octanol to water partition coefficient (log Kow) of 6. Dibenzo[a,h]anthracene is poorly absorbed via the gastrointestinal track, being excreted primarily unchanged with the feces. The majority of absorbed portion will distribute to the kidney and liver where it is oxidized to the Like many organic compounds, excessive acute exposure to dibenz[a,h]anthracene can lead to dizziness, nausea, and general central nervous system disturbances that resemble intoxication. Chronic Toxicity (or Exposure) Animal Dibenz[a,h]anthracene is a confirmed animal carcinogen. Lung Dibenzofuran 791 tumors have been induced in rats receiving intratracheal administration of dibenz[a,h]anthracene.

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