Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-D-aspartate receptor in spinal cord dorsal horn.

The N-methyl-d-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is one of the mechanisms involved in central sensitization during chronic pain. Previously, this laboratory created a spatio-temporal knockout (KO) of the N-methyl-d-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO completely blocks NR1 gene and subsequent NMDA receptor expression and function in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at 24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective effects of KO were transient and were not seen at 48 h after CFA. These observations suggest the presence of NMDA-independent pathways that contribute to CFA-induced pain. CFA induces the activation of several signaling cascades in the SCDH, including protein kinase C (PKC)gamma and extracellular signal-regulated kinases (ERK1/2). The phosphorylation of PKCgamma and ERK1/2 was inhibited in the SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory reactions are responsible for the recurrence of pain after NR1 KO in the SCDH.

[Mechanism-based pharmacotherapy for cancer pain].

Cancer pain is usually treated by 1) pharmacotherapy, 2) nerve block, 3) radiation therapy, 4) cognitive therapy and 5) alternative medicine. Among these methods, pharmacotherapy is the simplest way to relieve cancer pain without special equipment or special settings. WHO cancer treatment guideline shows morphine is effective to most cancer pain. However, 10-20% of the patients' pain is refractory to morphine. A majority of such refractory pain is due to nerve injury caused by cancer itself or by treatment. Recently, many biological processes involved in the mechanism of neuropathic pain have been elucidated. Pharmacological treatment aimed at blocking such processes should produce specific effects on the pain. Such mechanism-based pharmacotherapy is the most effective way to treat difficult pain.

Speciation of selenium compounds with ion-pair reversed-phase liquid chromatography using inductively coupled plasma mass spectrometry as element-specific detection.

For selenium speciation analysis, the hyphenation of chromatographic separation with element-specific detection has proved a useful technique. A powerful separation system, which is capable of resolving several biologically and environmentally important selenium compounds in a single column, is greatly needed. However, that has been difficult to achieve. In this paper eight selenium compounds, namely, selenite [Se(IV)], selenate [Se(VI)], selenocystine (SeCys), selenourea (SeUr), selenomethionine (SeMet), selenoethionine (SeEt), selenocystamine (SeCM) and trimethylselenonium ion (TMSe+), were separated by using mixed ion-pair reagents containing 2.5 mM sodium 1-butanesulfonate and 8 mM tetramethylammonium hydroxide as a mobile phase. The separation of these anionic, cationic and neutral organic selenium compounds on a LiChrosorb RP18 reversed-phase column took only 18 min at a flow-rate of 1.0 ml/min with isocratic elution, and baseline separation among the six organic Se compounds was achieved. Inductively coupled plasma mass spectrometry (ICP-MS) was employed as element-specific detection. A comparison of ICP-MS signal intensity obtained with a Barbington-type nebulizer and with an ultrasonic nebulizer (USN) was made. Different signal enhancement factors were observed for the various selenium compounds when a USN was used. The speciation technique was successfully applied to the study on chemical forms of selenium in a selenium nutritional supplement. Selenomethionine was found to be the predominant constituent of selenium in the supplement.

Autologous blood transfusion in patients with hepatocellular carcinoma undergoing hepatectomy.

BACKGROUND: Homologous blood transfusion (HBT) has the risk of an immunosuppressive effect and may adversely affect the prognosis of patients with carcinomas. Autologous blood transfusion (ABT) has not yet become a standard procedure in gastroenteric cancer surgery. We investigated the usefulness and problems of ABT combined with the use of recombinant human erythropoietin (rh-EPO). METHODS: An evaluation of autologous blood transfusion (ABT) combined with recombinant human erythropoietin (rh-EPO) treatment was conducted in 46 patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative autologous blood donation (ABD) was accomplished for 25 of the 46 patients. The preoperative changes in hemoglobin and hematocrit in relation to route of administration of erythropoietin were studied. In addition, intraoperative blood requirements and the postoperative complications for patients who predonated were compared with those of patients who underwent surgery without autologous predonation. RESULTS: The proportion of patients not requiring additional homologous blood transfusions (HBT) during operation was significantly higher in the ABD group than in the non-ABD group (88% versus 38%). The incidence of postoperative complications was significantly higher in patients receiving HBT than in nontransfused patients and in those receiving ABT. CONCLUSIONS: Preoperative autologous blood donation in combination with rh-EPO therapy markedly reduced the requirement for homologous blood transfusion during surgery in patients with hepatocellular carcinoma having hepatectomy.

Isotope dilution analysis of Se in human blood serum by using high-power nitrogen microwave-induced plasma mass spectrometry coupled with a hydride generation technique.

To establish a method for sensitive, accurate, and precise determination of Se in real samples, isotope dilution analysis using high-power nitrogen microwave-induced plasma mass spectrometry (N2 MIP-IDMS) was conducted. In this study, freeze-dried human blood serum (Standard Reference Material, NIES No. 4) provided by NIES (National Institute for Environmental Studies) was used as a real sample. The measured isotopes of Se were 78Se and 80Se which are the major isotopes of Se. The appropriate amount of a Se spike solution was theoretically calculated by using an error multiplication factor (F) and was confirmed experimentally for the isotope dilution analysis. The mass discrimination effect was corrected for by using a standard Se solution for the measurement of Se isotope ratios in the spiked sample. However, the sensitivity for the detection of Se was not so good and the precision of the determination was not improved (2-3%) by N2 MIP-IDMS with use of the conventional nebulizer. Therefore, a hydride generation system was connected to N2 MIP-IDMS as a sample introduction system (HG-N2 MIP-IDMS) in order to establish a more sensitive detection and a more precise determination of Se. A detection limit (3 sigma) of 10 pg mL-1 could be achieved, and the RSD was less than 1% at the concentration level of 5.0-10.0 ng mL-1 by HG-N2 MIP-IDMS. The analytical results were found to be in a good agreement with those obtained by the standard addition method using conventional Ar ICPMS.

[A case of multiple colon cancer appeared after thymectomy for thymoma with myasthenia gravis].

A 62-year-old woman was admitted to our hospital because of diarrhea and melena. Thymectomy for thymoma with myasthenia gravis was carried out on this patient four years ago. Barium enema revealed four tumor shadows in the ascending and transverse colon. Multiple colon cancer was diagnosed and extended right hemicolectomy was carried out. The postoperative course was uneventful and she has been free from any symptom. In this paper, we discussed the relationship between thymoma and the incidence of nonthymic malignancy.

Control of parathyroid hormone hydrolysis by the kidney.

In order to assess the role of the kidney in controlling the degradation, fate, half-life, and consequently the functional level of the parathyroid hormone in vivo, highly purified bovine parathyroid hormone (bPTH 1-84) and synthetic N-terminal peptide of the bovine parathyroid hormone (bPTH 1-34) were iodinated and their hydrolysis by the kidney and liver tissue of rats were measured under various levels of parathyroid function and calcium metabolism. While the hydrolysis of bPTH 1-84 did not change significantly in response to acute change of serum parathyroid hormone in response to injections of EDTA, phosphate, and calcium or after parathyroidectomy, less bPTH 1-34 was hydrolyzed 60 min after injection of EDTA or phosphate along with the rise of serum PTH than in the controls. No significant change was found in the hydrolysis of bPTH 1-34 after calcium infusion or parathyroidectomy with a consequent fall of serum parathyroid hormone. Increase of calcium ions in the incubation medium in vitro resulted in a more pronounced increase of bPTH 1-34 hydrolysis than that of bPTH 1-84. Hydrolysis of the N-terminal portion of parathyroid hormone probably plays a more important role in the acute control of the functional level of the parathyroid hormone than the hydrolysis of the whole molecule.