Excess intracellular ATP causes neuropathic pain following spinal cord injury.

Intractable neuropathic pain following spinal cord injury (NP-SCI) reduces a patient's quality of life. Excessive release of ATP into the extracellular space evokes neuroinflammation via purinergic receptor. Neuroinflammation plays an important role in the initiation and maintenance of NP. However, little is known about whether or not extracellular ATP cause NP-SCI. We found in the present study that excess of intracellular ATP at the lesion site evokes at-level NP-SCI. No significant differences in the body weight, locomotor function, or motor behaviors were found in groups that were negative and positive for at-level allodynia. The intracellular ATP level at the lesion site was significantly higher in the allodynia-positive mice than in the allodynia-negative mice. A metabolome analysis revealed that there were no significant differences in the ATP production or degradation between allodynia-negative and allodynia-positive mice. Dorsal horn neurons in allodynia mice were found to be inactivated in the resting state, suggesting that decreased ATP consumption due to neural inactivity leads to a build-up of intracellular ATP. In contrast to the findings in the resting state, mechanical stimulation increased the neural activity of dorsal horn and extracellular ATP release at lesion site. The forced production of intracellular ATP at the lesion site in non-allodynia mice induced allodynia. The inhibition of P2X4 receptors in allodynia mice reduced allodynia. These results suggest that an excess buildup of intracellular ATP in the resting state causes at-level NP-SCI as a result of the extracellular release of ATP with mechanical stimulation.

Long-term outcomes of patients with cirrhosis presenting with bleeding gastric varices.

AIM: To establish a therapeutic strategy for cirrhosis patients with gastric variceal bleeding. METHODS: The outcomes of 137 patients with bleeding gastric varices were evaluated. RESULTS: The bleeding source was gastroesophageal varices (GOV) in 86 patients, and gastric fundal varices (FV) in 51 patients. The Child-Turcotte-Pugh classes were A, B, and C in 26, 79, and 32 patients, respectively; 34 patients (24.8%) had hepatocellular carcinoma (HCC), of which 11 also had complicating portal venous tumor thrombosis (PVTT). Patients with GOV were treated by endoscopic variceal ligation or endoscopic injection sclerotherapy (EIS) with ethanolamine oleate, while those with FV were treated by EIS with cyanoacrylate; 29 patients with FV also underwent additional balloon-occluded retrograde transvenous obliteration (BRTO). Hemostasis was successfully achieved in 136 patients (99.3%), and the cumulative 1-year, 3-year, and 5-year rebleeding rates were 18.1%, 30.8%, and 30.8%, respectively, in the patients with GOV, and 2.2%, 12.5% and 12.5%, respectively, in the patients with FV. The overall 1-year, 3-year, and 5-year survival rates were 79.7%, 71.5% and 64.4%, respectively, in the patients with GOV, and 91.0%, 76.9% and 59.5%, respectively, in the patients with FV. Multivariable analysis identified PVTT and alcoholic cirrhosis as a significant risk factor associated with rebleeding, model for end-stage liver disease (MELD) score and PVTT as significant factors associated with survival. CONCLUSIONS: Endoscopic therapies with or without BRTO appeared to be useful therapeutic strategies to prevent rebleeding in patients with gastric variceal bleeding, and favorable outcomes were obtained, except in patients with underlying HCC associated with PVTT and/or severe liver damage.

Effects of dietary sialic acid in n-3 fatty acid-deficient dams during pregnancy and lactation on the learning abilities of their pups after weaning.

The effects of dietary sialic acid in dams on the learning abilities of their pups after weaning were investigated using rats deficient in n-3 fatty acids. Nine-week-old female Wistar rats were fed an n-3 fatty acid-deficient diet for 3 wk and were mated at 12 wk of age. During pregnancy and lactation, the female rats were fed the n-3 fatty acid-deficient diet, and were given water or water containing 1% N-acetylneuraminic acid (NANA) ad libitum. After weaning, the learning abilities of the pups were evaluated using a novel object recognition test. The recognition index of pups nursed by dams fed on water containing 1% NANA (NANA-intake dams) was significantly higher than that of pups nursed by dams fed only on water (NANA non-intake dams). There were no significant differences in the total sialic acid or docosahexaenoic acid contents in the cerebral cortex or hippocampus of pups nursed by dams fed on either type of water. The total dimethylacetal (DMA, from plasmalogen) level in the cerebral cortex of pups nursed by NANA-intake dams was significantly higher than that of pups nursed by NANA non-intake dams. These results suggest that dietary sialic acid in dams during pregnancy and lactation might be beneficial for the learning abilities of pups after weaning, which may be related to the plasmalogen level in the brain of pups.

[A patient with peritoneal metastasis from gastric cancer who responded to weekly chemotherapy with paclitaxel on the third line and could take meal].

We report a patient with peritoneal metastasis from gastric cancer who responded to weekly chemotherapy with paclitaxel (TXL) as the third line treatment and could take meals for half a year. The patient was a 64-year-old man who underwent total gastrectomy for advanced gastric cancer with peritoneal metastasis. He was first treated with TS-1 as an outpatient treatment; however, tumor markers rose. He could not take meals and had to be hospitalized. CPT-11 was infused on the second line, but due to disease progress, the patient was administered weekly TXL. TXL (70 mg/m2) was infused over 1 hour after short premedication. Administration was continued for 3 weeks followed by 1 week rest. The tumor markers decreased, and he could take meals and was discharged from hospital. The toxic events were leukopenia (grade 2), alopecia (grade 2) and pneumonia (grade 3).

Does radical resection improve the survival in patients with carcinoma of the gallbladder who are 75 years old and older?

Radical resections have been reported to improve the surgical outcome for patients with carcinoma of the gallbladder. In recent years surgeons have had more opportunities to operate on elderly patients. We investigated whether the survival rate of aged patients who had radical resections were better than rates for those who had simple cholecystectomy. Of the 300 patients treated for carcinoma of the gallbladder between 1971 and 1999, 206 resected cases (except pancreaticoduodenectomy and hepatectomy) were divided into two groups: age 75 years or older, 54 patients (the older group), and age less than 75 years, 152 patients (the younger group). Clinical features and progression of the carcinomas did not differ between the two groups. In the older group, 22 patients (40.7%) had simple cholecystectomy, 32 (59.3%) had radical resections; in the younger group, 65 patients (42.8%) had simple cholecystectomy, and 87 (57.3%) had radical resection. None of the older patients who had radical resection died postoperatively. Postoperative survival was not different between the two groups. In the older group the 5-year survival rate for patients who had radical resections was better (60.9%) than the rate for those who had simple cholecystectomy (14.1%) (p = 0.0098). Radical resection is effective for the aged patients with the carcinoma of gallbladder.