Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cysteamine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1987

The effect of cysteamine on the somatostatin content of guinea-pig islets.

Cysteamine is known to deplete the immunoreactive somatostatin content in different organs from rat and mouse. The aim of the present work was to test if cysteamine also affects the somatostatin content in guinea-pig islets, since guinea-pigs have a carbohydrate metabolism different from that of other laboratory animals. Cysteamine was injected to guinea-pigs and the pancreatic islets were isolated four hours later. Cysteamine was also incubated in vitro with isolated pancreatic islets from untreated guinea-pigs. Cysteamine depleted the somatostatin content in the pancreatic islets in both the in vivo and in vitro studies.

Animals↗
PubMed1999

Exogenous cysteamine increases basal pancreatic exocrine secretion in the rat.

To determine whether exocrine pancreatic secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced by cysteamine. Rats were subcutaneously administered a single dose of cysteamine (30 mg/100 g body weight) 12 hr before experiment. Anesthetized rats were prepared with cannulation into bile duct, pancreatic duct, duodenum, and jugular vein and pancreatic juice was collected. For in vitro study, isolated pancreata of rats, pretreated with cysteamine, were perfused with an intraarterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 mL/min, and pancreatic juice was collected in 15-min samples. In vivo experiment of the rat, the mean basal pancreatic secretions, including volume, bicarbonate, and protein output were significantly increased from 18.4+/-0.5 microL/30 min, 0.58+/-0.05 microEq/30 min, and 214.0+/-26.1 microg/30 min to 51.6+/-3.7 microL/30 min, 1.52+/-0.11 microEq/30 min, and 569.8+/-128.9 microg/30 min, respectively (p<0.05). In the isolated perfused pancreas, cysteamine also resulted in a significant increase in basal pancreatic secretion (p<0.05). Simultaneous intraarterial infusion of octreotide (10 pmol/hr) to isolated pancreata partially reversed the effect of cysteamine on basal pancreatic secretion. These findings suggest that endogenous somatostatin play an important role on the regulation of basal pancreatic exocrine secretion.

Animals↗
PubMedDate not supplied

Evolution of ocular manifestations in nephropathic cystinosis: a long-term study of a population treated with cysteamine.

BACKGROUND: Nephropathic cystinosis is characterized by an accumulation of cystine crystals within most body tissues. Renal transplantation and oral cysteamine have improved the general prognosis of the disease, and ocular manifestations are now the most common complication. This long-term follow-up study describes the sequence of ocular manifestations in patients with nephropathic cystinosis treated with oral and topical cysteamine. METHODS: Data were recorded for all patients with cystinosis examined between 1980 and 2000. For each patient, photophobia and visual acuity were evaluated and slit-lamp and fundus examinations were performed. For some patients, an electroretinogram was also performed. RESULTS: Twenty-nine patients were observed during this period. They received oral and topical cysteamine. Photophobia and loss of visual acuity generally began by 10 years of age but were severe only after 15 years of age. Peripheral corneal epithelial infiltration appeared in the first few years of life. Infiltration evolved toward the depth and center of the cornea during the second decade of life. Retinopathy was present in 51.7% of the patients, with 3 cases of maculopathy and 3 cases of flattening on electroretinogram. CONCLUSIONS: Photophobia and corneal infiltration, although generally severe after 15 years of age, could be treated with topical cysteamine and corneal transplantation. Retinal infiltration, previously described as frequent and potentially blinding, is currently observed in only half of these patients, with mild visual impairment. This could be related to the treatment with oral cysteamine reaching the retinal vascularization.

Administration, Oral↗
PubMed1992

Somatostatin depleting potency of cysteamine-related thiols and amines in the rat: structure-activity relation.

Cysteamine, a potent duodenal ulcerogen, stimulates gastric acid and gastrin secretion and decreases immunoreactive somatostatin (IRS) from the gut and hypothalamus of the rat. To elucidate the structural requirements for this effect, we tested a series of cysteamine analogs for their IRS decreasing activity in comparison with their nucleophilic and reducing potencies. Adult female rats were sacrificed 4 hr after p.o. administration of the test chemicals given in molar equivalents to 30 mg/100 g of cysteamine-HCl. IRS decreasing activity in gastric mucosa, expressed as percentage of controls is listed in descending order: cystamine (55%), cysteamine (59%), 2-dimethylaminethanethiol (59%), ethylamine (66%), 1,3-propanedithiol (70%), propylamine (75%) and 3-aminothiophenol (79%). The following thiols and amines had no IRS decreasing effect (80% of controls): L-cysteine, ethanethiol, 1-propanethiol, penicillamine, dimercaprol, 1-4-dithiothreitol, ethanolamine, propionitrile, n-butyronitrile, o-, m- or p-aminophenol. The aryl 2-, 3- or 4-aminothiophenols, unlike most of their aminophenol analogs also decreased immunoreactive prolactin in the pituitary by 38 to 78%. IRS decreasing activity was independent of the reducing potency of cysteamine derivatives but was correlated significantly (r = 0.793, P < .01) with electron affinity of -SH, -NH2, -OH and -CN radicals in terminal alkyl chemicals. The structural requirement for decreasing activity is the presence of either -SH and -NH2 on a 2 to 3 carbon alkyl or aryl molecule. Both radicals when present together increase potency.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMed1991

[Intra-leukocyte cystine in cystinosis treated with cysteamine].

Data on cystine leukocyte content are analyzed in cystinotic patients receiving cysteamine as a depleting agent of cellular cystine. During 2 years, 63 measurements of cystine leucocyte content were performed in 15 cystinotic patients, aged 20 months to 22 years, taking daily 40 to 65 mg/kg of cysteamine. An original method was used to measure leukocyte cystine: a binding protein assay with a specific cystine-binding protein from E. coli. Results were taken individually because of various clinical situations in patients. In 8 patients taking cysteamine regularly, 6 hours after a dose, cystine leukocyte content was between 1 and 2 nmol 1/2 cystine/mg protein, about 10 times less than basal values without treatment and 5 to 10 times more than control subjects. In less compliant patients, cystine leukocyte content was close to basal values without treatment (3 to 25 nmol/mg). Some variability was observed between individuals receiving cysteamine: pharmacokinetic parameters may need further investigation. This sensitive and specific assay helped in controlling compliance and adjusting dosage regimen in each patient. The aim was to maintain a minimum effective dosage in order to avoid toxic side effects of cysteamine.

Adolescent↗
PubMed1990

Histamine, histamine formation capacity and gastrin in cysteamine-induced peptic ulcer.

We attempted to induce chronic peptic ulcer in the rat by injection of consecutive doses of cysteamine. We investigated the incidence of peptic ulceration and measured gastric mucosal histamine, histamine formation capacity (HFC), plasma gastrin and tissue (oesophagus, duodenum, liver and lung) histamine in rats 1, 7, 14, 21, and 28 days after injection of cysteamine-HCl (300 mg/kg s.c. and 100 mg/kg 8 h later). Saline injections were used in control rats. After 24 h all rats given cysteamine had duodenal ulcers and the ulcer incidences after 7 and 14 days were 60 and 40%, respectively. After Day 21 no ulcers were found. Microscopy revealed ulcer healing seen as epithelialized scars from Day 14 onwards. A rising incidence of gastric metaplasia of the duodenal mucosa was noted from Day 7 after cysteamine treatment, which may have pathophysiological significance. Gastric mucosal histamine was higher and plasma gastrin was lower after 24 h compared with controls and values obtained later in the study. Rats with duodenal ulceration had significantly higher gastric mucosal histamine than those without lesions and control rats. A direct relationship was found between plasma gastrin and HFC in rats given cysteamine. A small but significant increase in histamine content of the liver was also observed after 24 h. No significant changes were found in other tissue specimens. Thus, a rise in gastric histamine is associated with duodenal ulcers in this model.

Animals↗
PubMed1985

Involvement of histamine release in the mechanism of cysteamine-induced gastric acid hypersecretion.

To elucidate the mechanism of gastric hypersecretion induced by cysteamine, the effects of atropine, cimetidine, proglumide, cromolyn sodium and tranilast on the cysteamine response were studied in rats. Under urethane anesthesia, rat stomachs were perfused with 4 ml of physiological saline (pH 6.0) every 15 min. Acid secretion was progressively increased by cysteamine HCl (300 mg/kg, s.c.) for the duration of the experiment (6 hr). This effect was completely blocked by cimetidine and partially blocked by proglumide and atropine. Cromolyn sodium and tranilast, inhibitors of histamine release, also blocked cysteamine-induced acid hypersecretion. However, histamine-induced acid secretion was not affected by cromolyn sodium. It is concluded that the acid hypersecretion induced by cysteamine is mediated in part by histamine release.

Animals↗
PubMed1989

The role of gastric and duodenal pH in the cysteamine-induced duodenal ulcer in the rat.

Many secretory studies reported an increase in gastric acid secretion by the duodenal ulcerogen cysteamine. A detailed analysis of these experiments, especially the results from rats with chronic gastric fistula suggest that direct stimulation of gastric acid secretion may not be the primary mechanism of the duodenal ulcerogenic action of cysteamine. We used a different approach and measured the pH at the site of ulceration in the proximal duodenum. A duodenal ulcerogenic dose of cysteamine did not change the pH at the anterior or posterior wall of the duodenum during 4 hr. In the same dose and by the same route of administration, cysteamine nevertheless induced duodenal ulcers in 24 hr. These experiments demonstrate that in addition to the effect on gastric acid secretion, other factors are needed to the effect on gastric acid secretion, other factors are needed to explain the early duodenal ulcerogenic action of cysteamine.

Animals↗
PubMedDate not supplied

Detection and determination of cysteamine at the nanomole level.

Cysteamine determination is performed by using a coupled enzymatic system. The reaction product between cysteamine and bromopyruvate inhibits competitively and specifically D-amino acid oxidase activity. A reaction system allowing the quantitative assay of cysteamine at the nanomole level has been worked out. The standard curve is linear and the assay is useful in determining the cysteamine concentration in tissues and biological samples. The method is fast and of simple execution. The cysteamine concentration in several mammalian organs is also reported.

Amidohydrolases↗
PubMed1984

Diversion of bile and pancreatic secretion in the rat and its effect on cysteamine-induced duodenal and peptic ulcer development under maximal acid secretion.

In this investigation we assess whether diversion of bile and pancreatic secretion protects rats from ulceration under maximal acid secretion as it does in cysteamine-induced ulcers. The rats were divided into a cysteamine-group (Cy) comprising 16 rats and a secretagogue group (PC) with 18 white male rats. Half of the animals of each group were submitted to the diversion-operation (division of the duodenum distally from the pylorus, jejuno-duodenostomy and entero-y-anastomosis), Cy2 and PC2 respectively. The other animals were not operated (Cy1 and PC1). In the cysteamine group the rats were given twice cysteamine-HC1 injections subcutaneously and the PC group were given a 24 h infusion with pentagastrin and carbachol. All animals of the Cy1 group had duodenal ulcers, 3 perforated. However, only 2 rats had one ulcer each in the Cy2 group (p less than 0.01). The PC1 group totalled 30 duodenal ulcers in the 9 animals with 10 perforations, 13 ulcers in 6 animals with 3 perforations in PC2. Furthermore in PC1 group 34 gastric ulcers were found in 7 rats and only 4 ulcers in the PC2 group. It is therefore concluded, that the diversion operation provided protection against cysteamine-induced duodenal ulcers (p less than 0.01) and ulcer formation under maximal acid stimulation in the duodenum (p less than 0.02) as well as in the rat stomachs (p less than 0.05). In the PC group the restraint haltering of the animals promoted presumably a stress situation with bile reflux in the non-operated whereas in the operated animals (PC2) reflux did not occur.

Animals↗
PubMed1984

The role of bile salts in cysteamine-induced duodenal ulcer in the rat and the ulceroprotective property of lysolecithin.

UNLABELLED: Cysteamine induces duodenal ulcers in rats, but bile diversion inhibits ulcer formation. Since lysolecithin inhibits stress ulceration in rats, it is assessed now whether lysolecithin inhibits cysteamine-induced ulcers, too. Male rats were operated: division of the duodenum distally to the pylorus, duodenojejunostomy. Roux-en-Y duodenojejunostomy. 4 groups comprising 10 animals. Drinking solution for group 1, 3 and 4: Na taurocholate and glycocholic acid (5 mmol/l). For group 2 addition of 0.2 mmol/l lysolecithin. Cysteamine-HCl (10%) twice subcutaneously on the 19th day in group 1, 3 and 4, isotonic NaCl in group 2. In group four 1 ml lysolecithin per gastric tube 1 h before cysteamine. RESULTS: Group 1: 8 animals with 16 ulcers, group 2: 7 with 10 ulcers, group 3: no ulcers, group 4: 3 with 5 ulcers (p less than 0.05/p less than 0.02). CONCLUSION: Lysolecithin, a substance produced during fat digestion, exerted an ulceroprotective property (lyso-protection) under experimental conditions, as shown here for the first time, to the author's knowledge. The enhancement of cysteamine-induced duodenal ulcer development by bile salts is again documented.

Animals↗
PubMed1984

Effects of a gastric antisecretory-cytoprotectant 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (Sch 28 080) on cysteamine, reserpine and stress ulcers in rats.

Prostaglandin E2 and carbenoxolone, putative cytoprotective agents, were tested in cysteamine, reserpine and stress ulcers in rats. In cysteamine-induced duodenal ulcer, PGE2 was inactive at 0.1 and 0.5 mg/kg p.o.; carbenoxolone at 100 mg/kg p.o. decreased the incidence but not the severity of the ulcer. PGE2 at 5.0 mg/kg p.o. and carbenoxolone at 300 mg/kg p.o. showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion. PGE2 (0.1 and 0.3 mg/kg p.o.) was inactive and carbenoxolone (100 and 300 mg/kg p.o.) further aggravated the gastric ulceration caused by reserpine or cold-restraint stress. In contrast, atropine (3 and 10 mg/kg p.o.) and cimetidine (30, 100 and 300 mg/kg p.o.) were active in all three ulcer models. But the results with cimetidine in stress ulcer were somewhat variable. 2-methyl-8-(phenylmethoxy) imidazo [1,2-a] pyridine-3-acetonitrile (Sch 28 080), a novel structure with both cytoprotective and antisecretory activity, was highly efficacious in cysteamine, reserpine and stress ulcers (1-30 mg/kg p.o.), which was presumably adequately accounted for by its potent antisecretory activity. It is concluded that cysteamine, reserpine and stress ulcers may not be appropriate models for testing the potential antiulcer effect of primarily cytoprotective compounds.

Animals↗
PubMed1983

Epidermal growth factor inhibits cysteamine-induced duodenal ulcers.

The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300 mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also was studied. Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline. The effect was not due to inhibition of gastric acid secretion or stimulation of duodenal bicarbonate secretion since the dose of epidermal growth factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition of synthesis and secretion of endogenous epidermal growth factor may be a pathogenetic factor in cysteamine-induced duodenal ulcer.

Animals↗
PubMed1995

Thiazolidine prodrugs of cysteamine and cysteine as radioprotective agents.

The need for protection against the toxic effects of ionizing radiation comes from many different directions: occupational exposure, nuclear accidents, environmental sources and protection of normal tissue during the therapeutic irradiation of cancer. Sulfhydryl-containing compounds, including cysteamine and L-cysteine, have long been known to possess radioprotective properties, but their therapeutic utility is limited by their side effects at radioprotective doses. To avoid this drawback, thiazolidine prodrugs of cysteamine and L-cysteine were prepared by the condensation of each thioalmine with the aldose monosaccharides, D-ribose and D-glucose, producing RibCyst, GlcCyst, RibCys and GlcCys. The prodrugs were designed to liberate the parent thiolamine nonenzymatically, after ring opening and hydrolysis, which is then available to function as a radioprotective agent. Cysteamine's inherent toxicity, measured using Chinese hamster V79 cells growing in culture, was completely eliminated, even at concentrations as high as 25 mM, by providing the thiolamine in the form of a prodrug. Good protection against radiation-induced lethality was demonstrated by the cysteamine prodrugs using a clonogenic assay. Protection against radiation-induced DNA single-strand breaks, as measured by alkaline elution, was also shown by both RibCyst and GlcCyst; this activity was higher than that exhibited by either cysteamine or WR-1065. The L-cysteine prodrugs, RibCys and GlcCys, also possessed radioprotective abilities under most of the conditions studied. Protection against DNA damage was comparable between L-cysteine, WR-1065 and RibCys.

Animals↗
PubMed1993

The effects of hypoxia and cysteamine on X-ray mutagenesis in human cells. I. Dose response and Southern blot analysis of induced mutants.

The effects of cysteamine and hypoxia on X-ray-induced mutation in human lymphoblast cells have been investigated. Irradiation of these cells under these two sets of radioprotective conditions resulted in a fourfold lower mutant fraction at the hprt locus, compared to irradiation in the absence of any protection. Using Southern blot analysis, the molecular nature of mutants induced in these cells by X rays delivered under hypoxic conditions, or in the presence of 25 mM cysteamine, has been compared with that of mutants induced by an equally mutagenic treatment of X rays alone. Of 60 mutants from cultures treated with X rays alone, 16 exhibited no change in the restriction fragment pattern and were defined as point mutations, 27 were total gene deletions, and 17 were partial deletions or rearrangements. Of 46 mutants from cultures treated with X rays in the presence of 25 mM cysteamine, 22 were point mutations, 18 were total gene deletions, and only 6 were partial deletions or rearrangements. Of 45 mutants from cultures treated with X rays delivered under hypoxic conditions, 17 were point mutations, 14 were total gene deletions, and 14 were partial deletions or rearrangements. Both radioprotective conditions reduced the level of mutation in each mutational class, when compared to the maximum expected in the absence of protection. The spectrum of mutations induced by X rays in cysteamine was significantly different from X rays alone. However, the mutational spectrum of X rays under hypoxic conditions was not different from X rays alone or from X rays in cysteamine. The extents of the deletions induced at the hprt locus were also examined by hybridizing the Southern blots to X-chromosome markers that have been mapped to within 1200 kb of hprt. There were no significant differences among the three groups; however, many mutants were missing one or more of these markers, indicating that deletions of several hundred kilobases are not uncommon.

Base Sequence↗
PubMed1977

Pathogenesis of duodenal ulcer. Gastric hyperacidity caused by propionitrile and cysteamine in rats.

Cysteamine and propionitrile, experimental duodenal ulcerogens, stimulated gastric acid secretion in the rat. Gastric acid secretion was measured by two separate methods, the conventional pylorus ligation technique and a non-invasive technique based on the pH dependent liberation of azure A from azuresin in the stomach with subsequent excretion of the liberated dye in the urine. Volume, acid concentration and acid content of gastric fluids aspirated immediately before the pylrous ligation were markedly increased 1,4 and 7 hours after a single dose of either cysteamine or propionitrile. Both acid concentration and acid output of gastric contents collected 30 minutes after pylorus ligation were also significantly elevated 1.5 hours after propionitrile and 4.5 hours after cysteamine. Significant increases in gastric acid secretion after these chemicals were also measured by the non-invasive technique which demonstrated a 4 to 6 fold increase in 24 hour urinary azure A output in rats injected with either propionitrile or cysteamine. Enhanced gastric acid output may play an important role in the pathogenesis of duodenal ulcer produced by propionitrile and cysteamine.

Animals↗
PubMedDate not supplied

Growth hormone and somatostatin interaction in the ulcerogenic effect of cysteamine in female rats.

It is known that cysteamine's ulcerogenic effect depends, among others, on a depletion of somatostatin (SRIH). Since growth hormone (GH) affects the release of hypothalamic SRIH, we have studied the influence of GH and the GH-SRIH interaction on the severity of gastric mucosa lesions induced by cysteamine. Female rats of the Sprague-Dawley strain were pretreated with GH (1 mg/kg) and subjected to cysteamine-induced gastric lesions. We found that these animals showed an increased mortality and severity of gastric lesions. Pretreatment with SRIH (25 or 50 micrograms/kg) was followed by a decrease in mortality and of incidence and severity of gastric mucosa lesions as compared to those found in control animals pretreated with saline. The dose of 5 micrograms/kg was ineffective in this respect. The combined administration of GH and SRIH revealed that cysteamine ulcerogenic action remained unchanged. It is possible that high levels of plasma GH, as induced by exogenous GH administration, may decrease the release of gastro-intestinal SRIH and this in turn may potentiate the ulcerogenic activity of cysteamine.

Animals↗
PubMed1985

Pantethine, a cysteamine precursor, depletes immunoreactive somatostatin and prolactin in the rat.

Pantethine, a stable disulfide precursor of pantetheine, has been reported to increase intracellular concentration of cysteamine in cultured fibroblasts of patients with cystinosis. In order to determine whether pantethine acts like cysteamine in bringing about depletion of immunoreactive somatostatin (IRS) in rat neural and gastrointestinal tissues and depletion of immunoreactive PRL (IRPRL) in the anterior pituitary, groups of male rats were given pantethine by ip injection at a dose of 0.264 mM or 0.528 mM/100 g body weight or normal saline and killed 4 h later. The interval chosen corresponds to the time of maximum effect after oral cysteamine administration. In cerebral cortex, hypothalamus, duodenal and gastric mucosa, and pancreas, IRS was uniformly depressed by 50% or more as compared with control rats, the most striking changes occurring in the hypothalamus where there was a 64% depletion at the higher dose of drug. Both dosage levels depleted IRPRL in pituitary and serum. At the higher dose, IRPRL was reduced by approximately 85% in the pituitary and 75% in the serum. These findings support the hypothesis that pantethine administration leads to an accumulation of cysteamine within cells throughout the body and that the cysteamine so formed depletes IRS and IRPRL.

Animals↗