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At least 415 records · Page 23Linked to original sources
PubMed2000

The relative toxicity of compounds in mainstream cigarette smoke condensate.

Many different in vivo and in vitro tests are currently used to assess the toxicity of chemicals and complex mixtures such as cigarette smoke condensate. In vivo tests include assays in rodents to determine carcinogenicity, tumorigenicity and reproductive effects In vitro tests of mutagenicity are conducted with both bacterial and mammalian cell systems. A first step towards lowering the toxicity of cigarette smoke condensate is the identification of the relevant compound However, changing the concentration of a given smoke component may not linearly alter the biological activity of the complex mixture due to interactive effects. The "effective toxicity" of a chemical constituent is a function of the concentration, the metabolic fate, the potency in in vivo and in vitro assays, and the ability to reach the target tissues. The logarithm of the octanol-water partition coefficient (log P) is an important parameter since it affects metabolism, biological transport properties and intrinsic toxicity. Using concentration data from the International Agency for Cancer Research (IARC), biological activity data from the Registry of Toxic Effects of Chemical Substances (RTECS) database and measured and calculated log P values, we have rank ordered some of the important compounds in cigarette smoke condensate by their measured or potential toxicity. Condensates from different cigarette brands, tar categories and styles vary in their concentrations of these compounds. Chemicals of greater commercial or scientific interest may be toxicity tested more extensively, thereby increasing the probability of positive test results and highlighting the need for consideration of structure-activity relationships.

Acetaldehyde↗
PubMedDate not supplied

Citric acid cycle: a mainstream metabolic pathway influencing life span in Drosophila melanogaster?

The role of the citric acid cycle enzyme NADP-dependent isocitrate dehydrogenase (IDH-NADP) and its allele product variants in resisting the oxidative agent paraquat, was analyzed among descendants of reciprocal crosses between fast developmental time short-lived individuals (F-) and slow developmental time long-lived ones (S+), in Drosophila melanogaster. Taking preadult developmental time into account, the data suggested that IDH-NADP differences in enzymatic activity between electrophoretically fast and slow allele product variants could play an important role in paraquat resistance and longevity, because individuals with slow developmental time bearing the fast electrophoretic variant of IDH-NADP ("fast" allele) were the most resistant. The fast electrophoretic variant of this enzyme is known to be the most active one and its activity is related to increased reduction of NADP to NADPH. This process could be very important for an effective balance between several pathways that use NADPH as precursor molecules and the oxidative stress defense system that uses it as an oxygen free radical reductor. We also reported a strong maternal effect on these traits, because survivors of a paraquat bioassay carrying cytoplasm inherited from slow developmental long-lived females (S+ cytoplasm) showed the highest frequency of the fast electrophoretical variant of IDH-NADP.

Alleles↗
PubMed2001

Vacuolar H(+) pyrophosphatases: from the evolutionary backwaters into the mainstream.

Vacuolar-type H(+)-translocating inorganic pyrophosphatases have long been considered to be restricted to plants and to a few species of phototrophic bacteria. However, in recent investigations, these pyrophosphatases have been found in organisms as disparate as thermophilic Archaea and parasitic protists, and have resulted in the definition of a novel subclass in plants themselves. Among the many evolutionary and practical implications of these findings is the possibility that this research will spawn new approaches to the treatment of several prolific and debilitating parasite-mediated infections.

Amino Acid Sequence↗
PubMed1999

Reduction in Ames Salmonella mutagenicity of mainstream cigarette smoke condensate by tobacco protein removal.

The mutagenic activity of cigarette smoke condensates (CSC) made from tobacco before and after removal of protein was assessed by the Ames Salmonella assay in bacterial strains TA98 and TA100. Removal of protein and peptides from flue-cured tobacco via water extraction followed by protease digestion reduced the mutagenicity of the resultant CSC by 80% in the TA98 strain and 50% in the TA100 strain. Similarly, reductions of 81% in TA98 and 54% in TA100 were seen following water extraction and protease digestion of burley tobacco. The significant reductions in Ames mutagenicity following protein removal suggest that protein pyrolysis products are a principal contributor to the genotoxicity of CSC as measured in this assay.

Endopeptidases↗
PubMed2003

How to move pain and symptom research from the margin to the mainstream.

Pain, dyspnea, nausea, and other physical symptoms receive rather little study despite their major public health impact and the similar neural circuitry that makes these symptoms tractable therapeutic targets. Pain accounts for more than 20% of medical visits and 10% of prescription drug sales but only 0.6% of National Institutes of Health research funds. Clinical pain research remains clustered in the few clinical specialties of the founders of the field--neurology, anesthesia, cancer, and dentistry. Remarkable recent advances in basic science have not been widely applied by cardiologists, gastroenterologists, urologists, and gynecologists. Research funding in dyspnea and nausea is an order of magnitude smaller than funding in pain, despite mechanisms that may be common to all three. Political pressure from an aging population may soon influence funding agencies to train additional researchers in these areas. Academic health centers that develop the cross-disciplinary infrastructure to conduct this research will win major shares of this influx of funding and improve the diagnosis and management of many diseases.

Drug Industry↗
PubMed2006

Involvement of semiquinone radicals in the in vitro cytotoxicity of cigarette mainstream smoke.

Free radicals in cigarette smoke have attracted a great deal of attention because they are hypothesized to be responsible in part for several of the pathologies related to smoking. Hydroquinone, catechol, and their methyl-substituted derivatives are abundant in the particulate phase of cigarette smoke, and they are known precursors of semiquinone radicals. In this study, the in vitro cytotoxicity of these dihydroxybenzenes was determined using the neutral red uptake (NRU) assay, and their radical-forming capacity was determined by electron paramagnetic resonance (EPR). All of the dihydroxybenzenes studied were found to generate appreciable amounts of semiquinone radicals when dissolved in the cell culture medium employed in the NRU assay. Hydroquinone exhibited by far the highest capacity to form semiquinone radicals at physiological pH, even though it is not the most cytotoxic dihydroxybenzene. Methyl-substituted dihydroxybenzenes were found to be more cytotoxic than either hydroquinone or catechol. The formation of semiquinone radicals via auto-oxidation of the dihydroxybenzenes was found to be dependent on the reduction potential of the corresponding quinone/semiquinone radical redox couple. The capacity to generate semiquinone radicals was found to be insufficient to explain the variance in the cytotoxicity among the dihydroxybenzenes in our study; consequently, other mechanisms of toxicity must also be involved. The observed interactions between 2,6-dimethylhydroquinone and hydroquinone in the cytotoxicity assay and EPR analysis suggest that care needs to be taken when the bioactivity of cigarette smoke constituents is evaluated, i.e., the effect of the cigarette smoke complex matrix on the activity of the single constituent studied must be taken into consideration.

Animals↗
PubMed2000

Cultural determinants in the treatment of Arab Americans: a primer for mainstream therapists.

As the population of Arab Americans grows, so does their presence among mental health clientele, creating a need among clinicians for information about these clients. The broad lines of Arab culture are delineated: its roots, language, religion, and political history; patterns of immigration to the United States; and the salient differences between Arab culture and the dominant U.S. culture. The effects of negative stereotyping and discrimination against Arab Americans are examined, as are specific clinical issues in treating them. Recommendations for more culturally sensitive treatment are enumerated.

Arabs↗