Pathophysiological effects

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

Pharmacokinetics The study of physiological and pathophysiological effects on drug handling in the body. 

Although it appears that severe IL-4-regulated enteropathy is not required for immune expulsion of T. spiralis, it is still possible that Th2 cytokines can act in a direct fashion to create an environment unfavourable for intestinal parasites. It remains to be shown directly whether these effects are sufficient to expel parasites. Indeed, there is considerable evidence to support a variety of pathophysiological effects of IL-4 and/or TNF on the gut. These effects may be mediated by factors including cytokines and mast-cell products (e.g. leukotrienes and 5-hydroxytryptamine). 7. spiralis infections result in increased fluid and mucus secretion into the lumen as well as increased intestinal propulsive activity and more rapid intestinal transit (Castro et al, 1979 Russell, 1986 Vermillion and Collins, 1988 Vermillion et al., 1991 Weisbrodt et al, 1994 Barbara et al, 1997). The increased contractility of radial and longitudinal muscle is greater in high-... 

McCloy RF, Arnold R, Bardhan KD, Cattan D, Klinkenberg-Knol E, Maton PN, et al Pathophysiological effects of long-term acid suppression in man. Dig Dis Sci 1995 40 96S-120S. 

Inhibition of cytokine activity in vivo by administration of monoclonal antibodies (and, more recently, by gene knockout studies) continues to elucidate the physiological and pathophysiological effect of various cytokines. 

A number of stimuli are known to act as inducers of TNF production (Table 9.6). Bacterial LPS represents the most important inducer, and TNF mediates the pathophysiological effects of this molecule. TNF biosynthesis is regulated by both transcriptional and post-transcriptional mechanisms. Macrophages appear to express TNF-a mRNA constitutively, which is translated only... 

Jacobs, B. C., O Hanlon, G. M., Bullens, R. W. M., Veitch, J., Plomp, J. J. and Wilhson, H. J. Immunoglobulins inhibit pathophysiological effects of anti-CQlb-positive sera at motor nerve terminals through inhibition of antibody binding. Brain 126 2220-2234,2003. 

Kiorpes, A.L., R.B. Winter, D.S. Hodgson, S.J. Galitzer, and M.C. Savides. 1982. Pathophysiological effects of paraquat intoxication in domestic ruminants low dose studies. Vet. Human Toxicol. 24 81-85. 

The increasingly accepted hypothesis that acetaldehyde may be the causative agent in initiating the multitude of acute pharmacological and chronic pathophysiological effects of alcohol prompted Nagasawa et al. to seek methods to reduce its blood levels. One possibility would be the administration of (S)-penicillamine (4), a compound related to cysteine. The condensation of this amino acid with acetaldehyde produced 2,5,5-trimethylthiazolidine-4-carboxylic acid 242). The chirality of this compound was deducted by NMR analysis to be 72% 2S, 4S and 28% 2R, 4S. Thus, this result is consistent with the configuration found previously for the thiazolidines formed from (R)-cysteine and aldehydes 241 ... 

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