Disease relevance of Mercaptamine

• Of the 27 children who never received cysteamine, 16 were followed at the National Institutes of Health until renal failure occurred; their mean (+/- SD) creatinine clearance was 8.0 +/- 4.8 ml per minute per 1.73 m2 of body-surface area at a mean age of 8.3 +/- 1.9 years [1].
• Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline [2].
• Adult EGF(-/-) mice displayed more severe lesions in response to cysteamine treatment compared with wild-type counterparts, although triple null mice were not more susceptible to dextran sulfate sodium-induced colitis, suggesting a differential role for these ligands in the injury response [3].
• Treatment with cysteamine, which reduces the concentration of intracellular cystine, delays disease progression but has undesirable side effects [4].
• Concomitant treatment with bromocriptine at 0.5 but not at 0.25 mg/kg body weight significantly attenuated the inhibitory effect of cysteamine on gastric carcinogenesis [5].

Psychiatry related information on Mercaptamine

• Cooperative behavior in the thiol oxidation of rabbit muscle glycogen phosphorylase in cysteamine/cystamine redox buffers [6].
• Huntington's disease: effect of cysteamine, a somatostatin-depleting agent [7].
• Thus, the cysteamine-related memory deficits are of long duration and are not due to any acute neuroactive properties of the drug itself [8].
• The results showed that, with respect to CSF, the mice injected with cysteamine learned the bar pressing task faster whereas no evidence of changes in locomotor activity was provided [9].
• In the operant conditioning studies, biweekly injections (Monday and Wednesday) of cysteamine administered one hour before testing produced no statistically significant changes in acquisition or performance of either the delayed spatial alternation or the signaled discrimination task [10].

High impact information on Mercaptamine

• Improved renal function in children with cystinosis treated with cysteamine [1].
• At the end of the study, creatinine clearance was higher in the cysteamine group than in the control group (38.5 vs. 29.7 ml per minute per 1.73 m2; 95 percent confidence limits on the difference, 1.8 and 15.8), even though the cysteamine group was on average 1.4 years older than the control group [11].
• After an in vitro study of cystinotic corneal stromal cells showed cystine depletion by cysteamine and after topical cysteamine was determined to be nontoxic in rabbits, we performed a controlled double-blind clinical trial of 10 mM cysteamine eyedrops in young patients with cystinosis, using one eye for treatment and the other as the control [12].
• Therapy with cysteamine caused a consistent, dose-related decline in levels of cystine in leukocytes and in extracellular fluid, caused no improvement so far in renal tubular function or growth velocity, and improved creatinine clearance in some patients [13].
• Cysteamine rapidly reduces the concentration of prolactin in pituitary tissue in vivo and in vitro [14].

Chemical compound and disease context of Mercaptamine

• With this limitation in mind, we conclude that oral cysteamine, by depleting cells of cystine, helps maintain renal glomerular function, improves growth, and constitutes the current treatment of choice for nephropathic cystinosis [11].
• Pantethine is an experimental hypolipemic agent and has been suggested as a source of cysteamine in the treatment of nephropathic cystinosis [15].
• METHODS: This mutein peptide (bFGF-CS23) was administered orally in comparison with cimetidine to rats with chronic duodenal ulcers previously induced by cysteamine [16].
• Comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice: WR-2721, cysteamine, diethyldithiocarbamate, and N-acetylcysteine [17].
• The mechanism by which cysteamine reduces the PRL content of pituitary cells was studied in primary cultures of estradiol-induced pituitary tumors in Fischer 344 rats [18].

Biological context of Mercaptamine

• Cysteamine-induced ulceration in EGF(-/-) mice was used to examine its role in mucosal cytoprotection [3].
• We find that the 5,5'-dithobis(2-nitrobenzoic acid)-coupled assay method for cysteamine S-phosphate hydrolysis is not suitable for serum, and we were unable to confirm the existence of this isoenzyme in serum by this assay method [19].
• The data suggest that oxidative stress by cysteamine can be synergistic with the conditioning heat treatment at 44 degrees C which induces thermotolerance [20].
• The kinetics of thermotolerance induction and the time to reach the maximum of thermotolerance expression after combined cysteamine treatment at 44 degrees C for 15 min was found to be comparable to the effects of 44 degrees C treatment alone for 30 min [20].
• Studies with synchronized Chinese hamster cells heated at 43 degrees for 1 hr in the presence of 16 mM cysteamine demonstrated that the potentiation of heat killing occurred in all phases of the cell cycle [21].

Anatomical context of Mercaptamine

• Thus, cysteamine (formed intracellularly in these experiments) undergoes thiol-disulfide exchange with cystine in the lysosomes, producing cysteamine-cysteine mixed disulfide and free cysteine, which enter the cytoplasm [22].
• Effects of cysteamine and antibody to somatostatin on islet cell function in vitro. Evidence that intracellular somatostatin deficiency augments insulin and glucagon secretion [23].
• Cysteamine is thus probably without effect on the HCO3- secretory process itself but impairs the ability of the duodenal mucosa to respond to acid [24].
• Bromocriptine and lergotrile greatly reduced gastric-acid output in cysteamine-treated rats [25].
• In vitro studies demonstrated that circularly or longitudinally cut muscle strips taken from different regions of the stomach and duodenum responded to cysteamine with increased contractility [26].

Associations of Mercaptamine with other chemical compounds

• From isoelectric focusing experiments in conjunction with cysteamine treatment (a method that measures cysteine content in apo E), the E2 isoform of this subject was determined to have only one cysteine residue, in contrast to all previously studied E2 apoproteins, which had two cysteines [27].
• Ethanol-induced damage to mucosal capillaries of rat stomach. Ultrastructural features and effects of prostaglandin F2 beta and cysteamine [28].
• To determine the role of gastrin in the ulcerogenic mechanism, cysteamine and propionitrile were administered to fasted rats and their effect on fasting and food-stimulated serum gastrin levels was studied [29].
• Similarly, indomethacin inhibited mucin secretion by cysteamine but did not significantly influence cytoprotection [30].
• The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine [31].

Gene context of Mercaptamine

• A preliminary therapeutic trial using an oral administration of cysteamine was carried out and demonstrated the efficiency of this treatment for cystine clearance in Ctns(-/-) mice [4].
• These findings suggest that cysteamine alters PRL secretion in humans [32].
• The TSH response to TRH stimulation was not blunted during long term cysteamine therapy [32].
• Cysteamine also caused large reductions in label incorporation into SRIF-14, SRIF-28, and OXT 1 and 4 h after drug injection [33].
• Effects of cysteamine administration on the in vivo incorporation of [35S]cysteine into somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin in rat hypothalamus [33].

Analytical, diagnostic and therapeutic context of Mercaptamine

• Cysteamine also improved growth; those in the cysteamine group between two and three years of age grew at 93 percent of the normal velocity, as compared with 54 percent in the control group [11].
• His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg----Ser) than apo E2 (158 Arg----Cys), as determined by cysteamine treatment and peptide mapping [34].
• The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist [35].
• Addition of 10 mM cysteamine during gastric inhibitory polypeptide perfusion caused a 300% increase in immunoreactive gastrin [36].
• Manometrically recorded contractions at the stomach corpus, midantrum, and antropyloric region as well as in the proximal duodenum of the conscious rat showed decreased contractions at the corpus and midantrum and an increase at the pyloric and duodenal sites during an intravenous infusion of cysteamine [26].

References