PURPOSE: To investigate the pathways of radiation induced apoptosis and the effect of cysteamine (beta-mercaptoethylamine), as a radioprotector, on it. MATERIALS AND METHODS: HL-60 cells were assigned to control, irradiated, and cysteamine (1 mM, 10mM) pretreated groups, Irradiation was given in a single fraction of 10 Gy (6 MV x-ray) and cysteamine was administered 1 hour before irradiation. The activities of caspase-8 were measured in control and irradiated group to evaluate its relation to the radiation induced apoptosis. To evaluate the role of cysteamine in radiation induced apoptosis, the number of viable cells, the expression and activity of caspase-3, and the expression of poly (ADP-ribose) polymerase (PARP) were measured and compared after irradiation the HL-60 cells with cysteamine pretreatment or not. RESULTS: The intracellular caspase-8 activity, known to be related to the death receptor induced apoptosis, was not affected by irradiation (p>0.05). The number of viable cells began to decrease from 6 hours after irradiation (p>0.05), but the number of viable cells in 1 mM cysteamine pretreated group was not decreased afger irradiation and was similar to those in the control group. In caspase-3 analyses, known as apoptosis executioner, its expression was not different but its activity was increased by irradiation (p>0.05). However, this increase of activity was suppressed by the pretreatment of 1mM crysteamine. The cleavage of PARP, thought to be resulted from caspase-3 activation, occurred after irradiation, which was attenuated by the pretreatment of 1mM cysteamine. CONCLUSION: these results show that radiation induced apoptotic process is somewhat different from death receptor induced one and the pretreatment of 1 mM cysteamine has a tendency to decrease the radiation-induced apoptosis in HL-60 cells.
Apoptosis* ; Caspase 3 ; Caspase 8 ; Cysteamine* ; HL-60 Cells ; Humans

Ghrelin, a novel gastrointestinal peptide with 28 amino acids, is secreted from the A-like cells of the gastric fundus. This peptide hormone does not only promote the release of growth hormone, but also stimulates food intake, gastric motility and cardiac output. Increased plasma ghrelin level has been reported in patients with upper gastrointestinal (GI) disease or in their disease animal model, suggesting its important role in the pathogenesis of upper GI disease.
Appetite/*physiology ; Cysteamine/metabolism ; Dyspepsia/etiology ; *Eating ; Gastrointestinal Diseases/*etiology ; Ghrelin/*physiology ; Humans ; Peptic Ulcer/etiology

Animal Feed ; Animals ; Cysteamine ; Female ; Goats ; Mammary Glands, Animal ; growth & development ; physiology

AIMTo know the effect of cysteamine on the pancreatic secretion and enzyme activity in geese.

METHODSEight adult geese fitted chronic pancreatic and duodenal cannulas were used to evaluate the effect of cysteamine (CS) on the pancreatic secretion and enzyme activity. The experiment was consist of control and treated phase. CS was added in the diet at the dosage of 100 mg/kg bw on the first day of treated phase. The birds were free fed at daytime (8:00-20:00) and fasted at nighttime (20:00-8:00). The pancreatic juice samples were collected continuously for three days in each phase.

RESULTSCS increased the average rate of pancreatic secretion by 240.16% (P < 0.01), in which that of daytime was elevated by 234.45% (P < 0.01), while that of nighttime elevated by 253.70% (P < 0.01). The secretion volume at daytime was more than that of night. CS increased trypsin activity by 49.05% (P < 0.01), whereas lipase and amylase activity was reduced by 25.44% (P < 0.01) and 21.95% (P < 0.01) separately. The one hour total activity of trypsin, lipase and amylase were elevated by 406.88% (P < 0.01), 153.58% (P < 0.01) and 166.59% (P < 0.01) respectively. Ratios of pancreatic secretion were different between day and night.

CONCLUSIONThese results indicate that CS can affect the pancreatic juice secretion and pancreatic enzyme activity by depleting the somatostatin, so that benefits to improve the digestive foundation and supply more nutrition for quickly growing in geese.

Animals ; Cysteamine ; pharmacology ; Geese ; physiology ; Pancreas ; drug effects ; enzymology ; secretion ; Pancreatic Juice ; secretion ; Pancreatin ; metabolism

AIMTo investigate the effects of cysteamine compound (Lactonin) on milk production of late-lactating cows during hot summer when the temperature humidity index (THI) was higher than 76 and cows were suffered from heat stress.

METHODSIn this experiment 96 black and white dairy cows, based on milk yield (M) prior to the experiment, were assigned into 4 groups (G): G1 (M < 24 kg/d), G2 (24 < M< 28 kg/d), G3 (28 < M < 32 kg/d) and G4 (M > 32 kg/d). Each group (n = 24) was further divided into subgroups of Lactonin (3000 U/d) treatment (LT, n = 49) and control (n = 47).

RESULTSIn G1 of LT, the rectal temperature decreased (P < 0.05), milk yield, fat-corrected milk, milk fat and feed conversion rate (FCR) increased (P < 0.05). These were companied with trendy of higher milk protein and lower somatic cell count. With whole LT cows (n = 49), the mean milk fat (%) increased (P < 0.05), mean milk protein tended to increase, and the mean milk yield and FCM tended to be enhanced. Plasma T3, T4 tended to decline whereas insulin enhanced (P < 0.01) significantly in LT herd (n = 49).

CONCLUSIONLactonin helps heat-stressed cow to maintain a more normal metabolism in hot summer. This positive effect of Lactonin on cow performance is associated with Lactonin-dependent alteration of plasma insulin, T3 and T4.

Animals ; Cattle ; Cysteamine ; pharmacology ; Female ; Hot Temperature ; Lactation ; Milk ; secretion ; Seasons

AIMTo know the effect of cysteamine (CS) on the plasma levels of somatostatin (SS) and some metabolic hormones in adult geese.

METHODSFourteen adult crossbred geese (Chuan white x Tai lake) fitted with chronic wing vein cannulas were used in this study to evaluate the effect of CS on SS, TSH, T3 and T4 levels. The experiment was consisted of control and treated phase. The diet was added CS at dosage of 100 mg/kg bw on the first day of the treated phase. The blood samples were collected from the cannulas and analyzed by radioimmunoassay.

RESULTSThe plasma SS concentration was (1.87 +/- 0.10) microg/L in control phase. Whereas SS concentrations on day 1, 3, 5, 7 of treated phase were decreased markedly (P < 0.05 or P < 0.01). Thereafter it was rose on the seventh day, however it was still lower than that of control. The thyroid stimulating hormone (TSH) content (2.45 +/- 0.31 mIU/L) was significantly decreased by 21.63% (P < 0.01) on day 1, and 18.37% (P > 0.05) on day 3 and day 5. Comparing with control phase (5.41 +/- 0.98 microg/L), T4 contents were elevated by 60.26% (P < 0.01), 43.25% (P < 0.01), 37.15% (P < 0.01) and 16. 82% (P < 0.01) respectively on day 1, 3, 5, 7. T3 level was (1.05 +/- 0.06) microg/L in control phase, whereas the levels was significantly increased by 36.19% (P < 0.01) on day 3. Also, the insulin concentration was higher than that of control (4.43 +/- 0.41 mU/ L) by 18.28% (P < 0.05) on the day 5.

CONCLUSIONThese results indicate that CS can decrease the plasma SS and TSH levels, whereas increase the levels of T4, T3 and insulin, therefore change metabolism, improve the nutrition transform and accelerate the growth in geese.

Animals ; Cysteamine ; pharmacology ; Diet ; Geese ; Insulin ; blood ; Somatostatin ; blood ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

Cystinosis, an autosomal recessively inherited lysosomal storage disease, results from impaired transport of the amino acid cystine out of cellular lysosomes. The consequent accumulation and crystallization of cystine destroys tissues, causing growth retardation, Fanconi syndrome, renal failure, eye problems, and endocrinopathies. The gene for cystinosis, CTNS, was mapped to chromosome 17p13. The diagnosis of cystinosis was made by measuring the leukocyte cystine content. The presence of typical corneal crystals on slit-lamp examination is also diagnostic. Since treatment with cysteamine has proved extremely effective, early diagnosis and treatment are critical aspects. We experienced a typical case of cystinosis in a 12-year-old boy with growth retardation.
Child ; Crystallization ; Cysteamine ; Cystine ; Cystinosis* ; Diagnosis ; Early Diagnosis ; Fanconi Syndrome ; Humans ; Leukocytes ; Lysosomal Storage Diseases ; Lysosomes ; Male

PURPOSE: Inhibition of the intimal hyperplasia after vascular surgery is an important issue. The purpose of this study is to define whether perivascular application of rapamycin, imatinib mesylate or cysteamine can reduce intimal hyperplasia in a carotid balloon injury model. METHODS: Each drug was mixed with 40% pluronic gel solution and was topically applied over the injured carotid artery evenly. Two or four weeks after injury, the arteries were harvested and morphometric analysis was done. RESULTS: The medial areas were not significantly different in each group and a thinning of the media as a toxic drug effect was not observed in any treatment group. The intimal area and intima-to-media (I/M) ratio were significantly reduced in rapamycin-treated group and imatinib-treated group (P < 0.05). But cysteamine-treated group showed a trend of decrease in I/M ratio in 2 weeks, but no difference in 4 weeks. CONCLUSION: Perivascular delivery of imatinib or rapamycin with pluronic gel attenuated the development of intimal hyperplasia. But cysteamine did not. Further studies are needed to refine the optimal drug dosages in large animal models.
Arteries ; Benzamides ; Carotid Arteries ; Carotid Artery Injuries ; Cysteamine ; Hyperplasia* ; Imatinib Mesylate ; Mesylates* ; Models, Animal ; Piperazines ; Pyrimidines ; Sirolimus*

PURPOSE: To investigate the effect of cysteamine on mixed peripheral blood mononuclear cells (PBMCs)-chemically injured keratocytes reaction (mixed lymphocyte-keratocyte reaction; MLKR). METHODS: PBMC stimulation assay was performed after keratocytes were chemically injured with 0.05 N NaOH for 60 seconds. MLKR was treated with various concentrations of cysteamine (0-10 mM). Intracellular reactive oxygen species (ROS) formation was measured using the oxidation-sensitive fluorescent probe, 2'7'-dichlorofluorescein diacetate (DCF-DA). Proliferation rate of PBMCs stimulated by NaOH-treated keratocytes and secretion profiles of matrix metalloprotease-9 (MMP-9), transforming growth factor-beta1 (TGF-beta1), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF) were determined using the bromodeoxyuridine proliferation assay and enzyme-linked immunosorbent assay, respectively. RESULTS: Proliferation rate of PMBCs was suppressed by cysteamine in a dose-dependent manner (p = 0.019). Fluorescence of DCF-DA decreased depending on cysteamine concentration (p < 0.001). MMP-9, IL-6 and TGF-beta1 levels were suppressed by cysteamine in a dose-dependent manner (p < 0.05), whereas MIF levels increased with cysteamine concentration of 0.5-10 mM (p = 0.008). CONCLUSIONS: These study results indicate that cysteamine induced the ROS-mediated inhibition of inflammatory cytokine release and proliferation of PBMCs stimulated by chemically injured keratocytes. Thus, cysteamine can be used in the treatment of chemical corneal burns.
Bromodeoxyuridine ; Burns ; Cysteamine* ; Enzyme-Linked Immunosorbent Assay ; Fluorescence ; Humans* ; Interleukin-6 ; Macrophages ; Reactive Oxygen Species ; Transforming Growth Factor beta1

A role of endogenous somatostatin in pancreatic exocrine secretion induced by intrapancreatic cholinergic activation was studied in the isolated rat pancreas perfused with modified Krebs-Henseleit solution. Intrapancreatic neurons were activated by electrical field stimulation (EFS: 15 V, 2 msec and 8 Hz). Pancreatic exocrine secretion, including volume flow and amylase output, and release of somatostatin from the pancreas were respectively determined. Somatostatin cells in the islet were stained with an immunoperoxidase method. EFS significantly increased pancreatic volume flow and amylase output, which were reduced by atropine by 59% and 78%, respectively. Intraarterial infusion of either pertussis toxin or a somatostatin antagonist resulted in a further increase in the EFS-evoked pancreatic secretion. EFS also further elevated exocrine secretion in the pancreas treated with cysteamine, which was completely restored by intraarterial infusion of somatostatin. EFS significantly increased not only the number of immunoreactive somatostatin cells in the islet but also the concentration of immunoreactive somatostatin in portal effluent. It is concluded from the above results that intrapancreatic cholinergic activation elevates pancreatic exocrine secretion as well as release of endogenous somatostatin. Endogenous somatostatin exerts an inhibitory influence on exocrine secretion induced by intrapancreatic cholinergic activation via the islet-acinar portal system in the isolated pancreas of the rat.
Amylases ; Animals ; Atropine ; Cysteamine ; Infusions, Intra-Arterial ; Neurons ; Pancreas ; Pertussis Toxin ; Portal System ; Rats ; Somatostatin* ; Somatostatin-Secreting Cells