Alterations in methionine to homocysteine ratio in individuals with first-episode psychosis and those with at-risk mental state.

BACKGROUND: Disturbance of the methionine (Met) cycle, which produces Met from homocysteine (Hcy), is suggested to be involved in several diseases, including psychiatric disorders. This study was aimed to investigate both levels of Met and Hcy in serum from individuals with first-episode psychosis (FEP) and individuals with at-risk mental state (ARMS). METHOD: We measured serum Met and Hcy levels in individuals with FEP (n = 13) and ARMS (n = 30) using HPLC with fluorescence detection and LC-ESI-MS/MS. Met and Hcy levels in healthy controls (n = 41) were also measured. Differences between the 3 groups were analyzed by one-way analysis of variance (ANOVA) with Bonferroni correction. RESULTS: Serum Met levels were decreased (p = 0.038) and Hcy levels were increased (p = 0.017) in the FEP group. Hcy levels were also significantly increased compared to the ARMS group (p = 0.016), while Met levels were not significantly different between the FEP and ARMS groups. A significant decrease in the Met to Hcy ratio (Met/Hcy) was observed in the FEP group compared to both the control (p = 4.58 × 10-4) and ARMS (p = 8.07 × 10-3) groups. Furthermore, Met/Hcy ratio was correlated with Positive and Negative Syndrome Scale, especially positive scores (p = 5.90 × 10-5). CONCLUSION: Taken together, these data indicate that a decrease in the serum Met/Hcy ratio may be a risk factor for developing psychosis during the transition from ARMS to FEP, and may prove to be a useful marker of the phase between ARMS and FEP.

Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.

Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic beta cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic beta cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.

Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice.

BACKGROUND: Peritoneal fibrosis is a major complication leading to the loss of peritoneal function in patients undergoing peritoneal dialysis. However, the effect of catalase depletion on peritoneal fibrosis has not yet been investigated. METHODS: The impact of catalase deficiency on progressive peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 14 days. RESULTS: The CG injections resulted in a thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of interstitial type I collagen, peritoneal deposition of lipid peroxidation products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of 8-hydroxy-2'-deoxyguanosine in peritoneal fluid in both mouse groups on day 14. The extent of these changes, however, was significantly higher in acatalasemic mice than in wild-type mice. The level of catalase activity remained low in the acatalasemic peritoneum without the compensatory upregulation of glutathione peroxidase, but with an insufficient upregulation of superoxide dismutase activity in CG-injected mice. CONCLUSIONS: Acatalasemia, therefore, exacerbates oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis which is the most important complication of peritoneal dialysis. This study suggests that catalase plays a crucial role in the defense against oxidant-mediated peritoneal injury in a mouse peritoneal fibrosis model.

Downregulation of the beta1,3- galactosyltransferase gene in tonsillar B lymphocytes and aberrant lectin bindings to tonsillar IgA as a pathogenesis of IgA nephropathy.

IgA is a glycoprotein with multiple O-glycans. Under-O-glycosylation of the hinge in IgA in patients with IgA nephropathy (IgAN) is reported. The development of IgAN is frequently preceded by episodes of upper respiratory tract infections such as tonsillitis. Therefore, the tonsils may be related to the pathogenesis of IgAN. However, the mechanism of underglycosylation in tonsillar IgA has not yet been fully elucidated. Since O-glycans in IgA are produced by glycosyltransferases, we hypothesized that dysregulation of the enzymes is associated with underglycosylation.