Immediate elimination of labile HbA1c with allosteric effectors of hemoglobin

Our aim was to find a simple method of removing labile glycosylated hemoglobin (HbA1c) from blood samples before it is measured by cation-exchange chromatography. Labile HbA1c is formed by the binding of glucose to the NH2-terminal valine of the beta-chain of HbA. We sought a more competitive binder for the same site to dissociate labile HbA1c to glucose and HbA. Inorganic phosphates were found to have a strong allosteric effect and a great ability to eliminate labile HbA1c. We developed our method with 4 mM tetrapolyphosphate in the hemolyzing solution to eliminate labile HbA1c during the automatic processing (at pH 6 and heated for 2 min at 45 degrees C) of blood samples for HbA1c estimation. This may be useful when estimating HbA1c by the manual method.     

Proton NMR studies on ischemic rat brain tissue.

The spin-lattice relaxation time (T1) of water protons and the cross-relaxation time (TIS) between irradiated protein protons and observed water protons were measured in order to study water-macromolecular interactions in ischemic rat brain tissues. Tissues were obtained by bilateral common carotid artery occlusion from stroke-prone spontaneously hypertensive rats. Water, Na, and K contents were measured in ischemic brain tissue at the same time. Water and Na content increased while the TIS value and K content decreased following ischemic insults. The T1 value did not change until 180 min after ischemia had been induced. Changes in the TIS value occurred earlier than changes observed for the T1 value, water, and electrolyte contents. Results indicate that the value of TIS may be useful for detecting cerebral ischemia and that the physical structure of water-macromolecular interaction may be altered soon after ischemic onset in brain tissue.     

Nutritional condition and absorptive capacity of 14 infants with short bowel syndrome

We examined the absorptive capacity and the nutritional condition of 14 infants with short bowel syndrome, whose residual small intestine was 90 cm or less. Their age ranged from 1 year to 18 years. Examined items were body weight, height, serum albumin, total cholesterol, triglyceride, fat soluble vitamins, trace elements and rapid turn over protein as markers of the nutritional condition. Fecal fat, fecal bile acid, d-xylose absorption test, sugar-, amino acid-evoked potential difference in the small intestine and disaccharidase activity of the mucosa were examined as markers of the absorptive capacity. Our results showed that the body weight was below the normal range in the patients with small intestine of less than 50 cm. Most nutritional markers were within normal range, however, cholesterol and vitamin D were low in the patients with fat malabsorption, especially in patients with less than 50 cm of small intestine. Fecal bile acid was higher than the normal range in all the patients. Potential difference was in normal range or slightly lower than normal in all the patients. We concluded that infants with less than 50 cm of small intestine had malabsorption of sugar, protein and fat. Therefore, prolonged nutrient support, especially fat, is necessary.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Clinical study on intracranial arachnoid cyst: with reference to the middle cranial fossa

Thirty-two cases of congenital arachnoid cyst (AC), 26 cases of supratentorial, and 6 cases of infratentorial cyst are reported. They were encountered over a period of 9 years. The 26 supratentorial cysts consisted of 21 cases located in the middle fossa, 2 in the frontal, and 3 in the suprasellar. Patients' ages ranged from 7 months to 67 years (mean: 19.3 years), with a male to female ratio of 23:9. The most common symptoms were headache, epileptic seizure, and cranial enlargement. Based on observations between neuroradiological examinations including analysis of the cyst content, and operation, typical AC might be defined as "duplicated arachnoid and its splitting", and it may be said that "there is continuous existence of cerebral structure such as cortex and white matter lying adjacent to AC on MRI". Out of 32 cases, 15 received surgical treatment because of mass effect of AC itself, abnormal dynamics of the AC fluid, and/or increasing sign of ICP. 13 cases had resection of AC outer membrane with craniotomy, and the remaining two had cystoperitoneal shunt. One of the shunting cases complicated subdural hematoma. Surgical treatment was discussed and radical craniotomy rather than a shunt procedure was preferred. Prognosis of all cases was favorable and uneventful.     

The free radical scavenger edaravone suppresses experimental dextran sulfate sodium-induced colitis in rats

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental dextran sulfate sodium (DSS)-induced colitis in rats. The rats were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. The edaravone and vehicle saline were injected subcutaneously twice a day. After the experimental period, the wet colonic weight, macroscopic mucosal damaged area, histological damage score, mucosal myeloperoxidase (MPO) activity, mucosal tissue lipid peroxidate and serum interleukin-6 (IL-6) levels were measured. In the DSS-induced colitis model, edaravone treatment (1-20 mg/kg day) significantly reduced the wet colonic weight, macroscopic damaged area, and the histological damage score. Edaravone treatment also reduced mucosal MPO activity, mucosal tissue lipid peroxidate level and serum IL-6 level. In particular, edaravone at a dose of 20 mg/kg day significantly reduced mucosal MPO activity and serum IL-6 level. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone against IBD patients is strongly expected.     

Real-time imaging of Rab3a and Rab5a reveals differential roles in presynaptic function

We investigated the roles of two Rab-family proteins, Rab3a and Rab5a, in hippocampal synaptic transmission using real-time fluorescence imaging. During synaptic activity, Rab3a dissociated from synaptic vesicles and dispersed into neighbouring axonal regions. Dispersion required calcium-dependent exocytosis and was complete before the entire vesicle pool turned over. In contrast, even prolonged synaptic activity produced limited dispersion of Rab5a. A GTPase-deficient mutant, Rab3a (Q81L), dispersed more slowly than wild-type Rab3a, and decreased the rate of exocytosis and the size of the recycling pool of vesicles. While overexpression of Rab3a did not affect vesicle recycling, overexpression of Rab5a reduced the recycling pool size by 50%. We propose that while Rab3a preferentially associates with recycling synaptic vesicles and modulates their trafficking, Rab5a is largely excluded from recycling vesicles.     

Lack of association between DNA base excision repair gene XRCC1 Gln399Arg polymorphism and risk of malignant lymphoma in Japan

Growing evidence suggests that the polymorphism of DNA base excision repair gene XRCC1 Arg399Gln is associated with altered DNA repair proficiency and subsequent cancer susceptibility; however, no evidence is available for malignant lymphoma. We therefore conducted a case-control study (372 cases, 500 controls) to evaluate links with malignant lymphoma risk in Japan. The risk was evaluated in terms of odds ratio (OR) and 95% confidence interval (CI) adjusted for age and sex in an unconditional logistic regression model. There was no statistical risk change with the Arg/Gln (adjusted OR 0.89; 0.65-1.23, P = 0.492) or the Gln/Gln (0.57; 0.27-1.17, P = 0.127) compared with the Arg/Arg of the XRCC1 Arg399Gln polymorphism. The results were unchanged in analyses according to histological subtype (diffuse large lymphoma, follicular lymphoma, low-grade lymphoma of mucosa-associated lymphoid tissue, and others). These data suggest that XRCC1 Gln399Arg polymorphism plays a limited role in lymphomagenesis. Further study on the interaction between the polymorphism and environmental exposure is required.     

Elevated binding activity of CD8+ cells with phytohaemagglutinin by asbestos fibre in vitro.

Asbestos fibres are known to depress the mitogenic stimuli of phytohaemagglutinin (PHA) to lymphocytes. We examined effects of asbestos (chrysotile) fibre on the proliferation of PHA-stimulated lymphocytes and the PHA binding activity of lymphocytes in vitro. The incorporation of 3H-thymidine and the expression of interleukin-2 receptor were depressed when the cells were exposed to 50 micrograms/ml of chrysotile fibre. The PHA binding activity of lymphocytes was significantly enhanced after chrysotile fibre exposure, as compared with non-exposed group. These results indicate that the depression of PHA stimuli with chrysotile fibre was not due to blocking of PHA binding to lymphocytes. The enhancement of PHA binding activity by chrysotile fibre was observed on CD8+ but not on CD4+ cells. It is possible, therefore, that treatment of peripheral blood mononuclear cells with chrysotile fibre induces increased reactivity of CD8+ cells with PHA, and that intensely activated CD8+ cells suppress proliferation of lymphocytes.