Effects of N-(2-ethylhexyl)-3-hydroxybutyramide hydrogen succinate on the metabolisms of monoamines in the rat brain

N-(2-Ethylhexyl)-3-hydroxybutyramide hydrogen succinate (M-2H) has been reported to increase REM sleep. The effects of M-2H on the metabolisms of monoamines which have been implicated in the regulation of the sleep-wakefulness cycle were studied in rats. M-2H (500 mg/kg p.o.) increased the levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in various regions of the rat brain. However, no appreciable changes occurred in levels of serotonin (5-HT), norepinephrine, dopamine, or 3,4-dihydroxyphenylacetic acid. The effect of M-2H (500 mg/kg p.o.) on 5-HT metabolism was investigated with intraventricularly-injected [14C]-5-HT. Although [14C]-5-HT level was not significantly changed, [14C]-5-HIAA level was above control level in four brain regions such as the hypothalamus, hippocampus, midbrain and pons-medulla at 3 h after the administration of M-2H. M-2H retarded the efflux of intraventricularly-injected [14C]-5-HIAA in all brain regions except the cortex. These results suggest that M-2H preferentially impaired the transport system for acid metabolites of monoamines, resulting in increase of monoamine metabolite levels in the brain.     

Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation.

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.     

Capsaicin-like effect of (6)-shogaol on substance P-containing primary afferents of rats: a possible mechanism of its analgesic action.

The effects of (6)-shogaol, a pungent component of dried ginger with a capsaicin-like chemical structure, on the release of immunoreactive substance P from the spinal dorsal horn were examined by in vitro superfusion of the dorsal-half slices of the spinal cord of the rat. (6)-Shogaol (30 microM to 1 mM) increased dose-dependently the release of immunoreactive substance P. The maximum effect of (6)-shogaol was observed at a concentration of 100 microM and less than a half of the effect of 10 microM capsaicin. The effect of (6)-shogaol (100 microM) was attenuated in slices from rats with dorsal rhizotomy and abolished by elimination of calcium ions from the perfusion medium. Pretreatment with (6)-shogaol in vitro inhibited the capsaicin-evoked release of immunoreactive substance P. On the other hand, systemic administration of (6)-shogaol (160 mg/kg) produced antinociception in rats, with a peak effect between 15 and 30 min and a smaller dose of 80 mg/kg was without effect. Treatment of rats with (6)-shogaol, at a dose of 160 mg/kg but not at 80 mg/kg, for 20 min significantly decreased release of immunoreactive substance P, evoked by capsaicin (10 microM), from the slices of cord. These data suggest that (6)-shogaol shares the sites of action with capsaicin, on the terminals of substance P-containing primary afferents, to release of the neuropeptide and inhibit the release of substance P, by subsequent stimulation of the primary afferents. The latter action of (6)-shogaol might be relevant to its analgesic effect.     

The investigation of isoflurane therapy for status asthmaticus patients]

Status asthmaticus is defined as an attack of bronchial asthma that resists conventional treatment and continues for more than 24 hours. We report here about patients with status asthmaticus who were successfully treated with isoflurane inhalation. Of the 19 patients who were transferred to the intensive care unit (ICU) and underwent mechanical ventilation from January 1996 to May 2001, eleven patients who were first treated by isoflurane inhalation were targeted in this study. Their improvement was assessed 6 and 24 hours after anesthesia compared with their condition before anesthesia. The tidal volume, pH, and PaCO2 improved within 6 hours after anesthesia. For the next step, among the patients who were transferred to the critical care center soon after an attack of bronchial asthma and underwent mechanical ventilation, 8 patients who were treated by isoflurane inhalation anesthesia (Group I) and another 4 patients who were not treated by isoflurane (Group NI) were compared to assess the usefulness of isoflurane inhalation therapy. The patients in Group I stayed in the ICU and underwent mechanical ventilation for a shorter period. These patients had hypotension and liver dysfunction after the inhalation anesthesia, but these symptoms were improved by decreasing the concentration of isoflurane. Isoflurane inhalation therapy seemed useful for intractable status asthmaticus, and earlier introduction of this therapy is expected to achieve a greater therapeutic effect.     

Dietary Olive Oil Intake Improves Running Endurance with Intramuscular Triacylglycerol Accumulation in Mice

Olive oil is a functional food shown to have a variety of bioactive effects. Therefore, we expect it to be a novel functional food with an exercise-mimetic effect on skeletal muscles. This study aimed to investigate the effect of olive oil on the endurance capacity and muscle metabolism in mice. Mice fed a 7% (w/w) olive oil diet for eight weeks showed improved treadmill running endurance and increased intramuscular triacylglycerol (IMTG) accumulation in the gastrocnemius muscle compared to soybean oil diet-fed controls. The increase in running endurance with olive oil intake was independent of the muscle fiber type. To elucidate underlying the mechanism of elevated IMTG levels, we examined the expression levels of the genes related to lipid metabolism. We found that the expression of diacylglycerol O-acyltransferase1 (DGAT1) was significantly upregulated in the muscle of olive oil diet-fed mice. In addition, the olive oil diet-fed mice showed no metabolic impairment or differences in growth profiles compared to the controls. These results suggest that dietary olive oil intake affects muscle metabolism and muscle endurance by increasing energy accumulation.     

Effectiveness of steroid therapy for pancreatic cysts complicating autoimmune pancreatitis and management strategy for cyst-related complications

Abstract

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications.

Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications.

Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10?mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size.

Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.     

Intraductal papillary adenoma: Usefulness of magnetic resonance cholangiopancreatography in the diagnosis of cystic branch-duct dilatation of the pancreas

A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice.     

Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene

We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c-kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val-->Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c-kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease.