The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor-naïve patients with chronic HCV genotype 1b infection in a real-world cohort.

It is unclear whether multiple nonstructural (NS) 5A resistance-associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor-naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor-naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy.

Development of non-invasive method for assessment of hepatic steatosis.

Steatosis is a critical feature of liver disease and is considered to play a pivotal role in the progression of nonalcoholic fatty liver disease, as well as being a surrogate marker of metabolic syndrome. The purpose of this study was to develop a non-invasive diagnostic method for assessment of liver steatosis. It is well known that ultrasonic velocity depends on materials and temperature. For example, the ultrasonic velocity in water is 1530m/s at 37°C and 1534m/s at 39°C, while that in fat is 1412m/s at 37°C and 1402m/s at 39°C. On this basis, we thought that the percentage of fat in hepatic steatosis could be assessed by detecting changes of ultrasonic in the liver, caused by warming. In order to confirm the effectiveness of this method, we obtained the ultrasonic velocity changes of tissue phantom including lard oil and the liver of living rabbit by ultrasonic warming, and then succeeded in 2-D imaging of ultrasonic velocity changes of the phantom and the liver of living rabbit. We named this the ultrasonic velocity-change method. The experimental results show the possibility that hepatic steatosis could be characterized using our novel, non-invasive method.

L-type Ca²âº channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory.

Drug addiction is driven, in part, by powerful and enduring memories of sensory cues associated with drug intake. As such, relapse to drug use during abstinence is frequently triggered by an encounter with drug-associated cues, including the drug itself. L-type Ca(2+) channels (LTCCs) are known to regulate different forms of synaptic plasticity, the major neural substrate for learning and memory, in various brain areas. Long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA) may contribute to the increased motivational valence of drug-associated cues triggering relapse. In this study, using rat brain slices, we found that isradipine, a general LTCC antagonist used as antihypertensive medication, not only blocks the induction of NMDAR LTP but also promotes the reversal of previously induced LTP in the VTA. In behaving rats, isradipine injected into the VTA suppressed the acquisition of cocaine-paired contextual cue memory assessed using a conditioned place preference (CPP) paradigm. Furthermore, administration of isradipine or a CaV1.3 subtype-selective LTCC antagonist (systemic or intra-VTA) before a single extinction or reinstatement session, while having no immediate effect at the time of administration, abolished previously acquired cocaine and alcohol (ethanol) CPP on subsequent days. Notably, CPP thus extinguished cannot be reinstated by drug re-exposure, even after 2 weeks of withdrawal. These results suggest that LTCC blockade during exposure to drug-associated cues may cause unlearning of the increased valence of those cues, presumably via reversal of glutamatergic synaptic plasticity in the VTA.

Establishment of educational program for multiorgan procurement from deceased donors.

INTRODUCTION: Multiorgan procurement is not an easy procedure and requires special technique and training. Since sufficient donors are not available for on-site training in Japan, establishment of the educational program for multiorgan procurement is mandatory. MATERIALS AND METHODS: Development of e-learning and simulation using pigs are our main goals. E-learning contains three dimensional computer graphic (3DCG) animations of the multiorgan procurement, explanation of both donor criteria and procurement procedure, and self-assessment examination. To clarify the donor criteria, the risk factors to 3-month survival of the recipients were analyzed in 138 adult cases of liver transplantation. The 3DCG animation for liver procurement was developed, which was used in the lecture prior to the simulation on August 10, 2013. The results of the examination after this lecture (exam 2013) were compared with the results after the lecture without using animation in 2012 (exam 2012). The simulation was performed by 97 trainees divided into 9 teams, and the surveys were conducted. RESULTS: The risk factors for early outcome of the recipients were cold ischemia time (≥ 10 hours), Model for End-stage Liver Disease score (≥ 20), and donor age (≥ 55 years). Results of examination showed that overall percentage of the correct answers was significantly higher in exam 2013 than in exam 2012 (48.3% vs 32.7%; P = .0001). The survey after the simulation of multiorgan procurement revealed that most trainees thought that the simulation was useful and should be continued. CONCLUSION: The novel educational program could allow young surgeons to make precise assessments and perform the exact procedure in the multiorgan procurement.

Induction of elastin expression in vascular endothelial cells relates to hepatoportal sclerosis in idiopathic portal hypertension: possible link to serum anti-endothelial cell antibodies.

Hepatoportal sclerosis accompanied by dense elastic fibre deposition is generally regarded as the primary lesion in the development of idiopathic portal hypertension (IPH). This study was performed to clarify the mechanism of elastic fibre deposition in the peripheral portal tracts of IPH liver in relation to serum anti-endothelial cell antibodies (AECA). In-vitro experiments were performed using human dermal microvascular endothelial cells (HMVEC) and patients' sera. The presence of serum AECA was assayed by a cell-based enzyme-linked immunosorbent assay (ELISA) using HMVEC. Immunohistochemical analysis of elastin was performed using liver tissue sections of IPH patients. IPH sera contained one or more AECA that could bind to the vascular endothelial cells of the peripheral portal tracts of the liver. When the value of AECA greater than the mean ± 2 standard deviations of healthy controls was regarded as positive, the positive detection rate of either immunoglobulin (Ig)G, IgA or IgM AECA in IPH sera was 30% (10 of 33 cases). IPH sera induced the expression of elastin in HMVEC, which appeared to be associated with the presence of AECA. Apoptosis was also induced in HMVEC by the stimulation with IPH sera. In vivo, elastin expression was observed in the endothelial cells of the peripheral portal tracts of IPH livers in a proportion of cases. The disease pathogenesis of IPH seems to be heterogeneous, and this study elucidated a possible contribution of the induction of elastin expression in the portal vessels to hepatoportal sclerosis of IPH, which might be linked to serum AECA as a causative factor.

Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms.

Although the roles of dopaminergic signaling in learning and behavior are well established, it is not fully understood how the activity of dopaminergic neurons is dynamically regulated under different conditions in a constantly changing environment. Dopamine neurons must integrate sensory, motor, and cognitive information online to inform the organism to pursue outcomes with the highest reward probability. In this article, we provide an overview of recent advances on the intrinsic, extrinsic (i.e., synaptic), and plasticity mechanisms controlling dopamine neuron activity, mostly focusing on mechanistic studies conducted using ex vivo brain slice preparations. We also hope to highlight some unresolved questions regarding information processing that takes place at dopamine neurons, thereby stimulating further investigations at different levels of analysis.

Comparison of extracellular-type-Kyoto solution and Perfadex as a preservation solution in a pig ex vivo lung perfusion model: impact of potassium level.

BACKGROUND: The ex vivo lung perfusion (EVLP) system has been used successfully to assess donor lungs. Perfadex (PX) is usually the flush and preservation solution in EVLP systems. We have used the extracellular-type-Kyoto (ET-K) solution containing 44 mEq/L potassium for clinical lung transplantation, investigating whether it rather than PX affects the EVLP system. METHODS: We used domestic slaughterhouse pigs to analyze the EVLP system. After 20-minute warm ischemia and 6-hour cold ischemia, EVLP was performed for 2 hours. Pig heart-lung blocks were divided into the PX (n = 5) and ET-K (n = 5) groups depending on the flush/cold preservation solution. At the beginning, we discarded the first 100 mL of effluent in the PX group and the first 200 mL in the ET-K group. We measured pulmonary physiological data and potassium levels. RESULTS: In both groups, perfusion for 2 hours showed no differences between the 2 groups with respect to the final flow, pulmonary arterial pressure, pulmonary vascular resistance, PaO(2)/FiO(2), and shunt fraction. The potassium level in the perfusate was 4.4 mEq/L for the PX and 5.4 mEq/L for the ET-K group. CONCLUSION: The pig EVLP system was not affected when ET-K was used instead of PX as the flush/preservation solution. The initial 200 mL of effluent should be discarded when using the ET-K to ensure that the potassium level does not increase.

Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice.

Previous studies showed that mice with genetic predisposition for high alcohol consumption as well as human alcoholics show changes in brain expression of genes related to immune signaling. In addition, mutant mice lacking genes related to immune function show decreased alcohol consumption (Blednov et al., 2011), suggesting that immune signaling promotes alcohol consumption. To test the possibility that activation of immune signaling will increase alcohol consumption, we treated mice with lipopolysaccaride (LPS; 1mg/kg, i.p.) and tested alcohol consumption in the continuous two-bottle choice test. To take advantage of the long-lasting activation of brain immune signaling by LPS, we measured drinking beginning one week or one month after LPS treatment and continued the studies for several months. LPS produced persistent increases in alcohol consumption in C57BL/6J (B6) inbred mice, FVBxB6F1 and B6xNZBF1 hybrid mice, but not in FVB inbred mice. To determine if this effect of LPS is mediated through binding to TLR4, we tested mice lacking CD14, a key component of TLR4 signaling. These null mutants showed no increase of alcohol intake after treatment with LPS. LPS treatment decreased ethanol-conditioned taste aversion but did not alter ethanol-conditioned place preference (B6xNZBF1 mice). Electrophysiological studies of dopamine neurons in the ventral tegmental area showed that pretreatment of mice with LPS decreased the neuronal firing rate. These results suggest that activation of immune signaling promotes alcohol consumption and alters certain aspects of alcohol reward/aversion.

The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as ß-carotene, lutein and lycopene.

GABAergic transmission modulates ethanol excitation of ventral tegmental area dopamine neurons.

Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. We previously demonstrated that ethanol enhances GABA release onto VTA-DA neurons via activation of 5-HT2C receptors and subsequent release of calcium from intracellular stores. Here we demonstrate that excitation of VTA-DA neurons by ethanol is limited by an ethanol-enhancement in GABA release. In this study, we performed whole-cell voltage clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs) and cell-attached recordings of action potential firing from VTA-DA neurons in midbrain slices from young Long Evans rats. Acute exposure to ethanol (75 mM) transiently enhanced the firing rate of VTA-DA neurons as well as the frequency of mIPSCs. Simultaneous blockade of both GABA(A) and GABA(B) receptors (Picrotoxin (75 µM) and SCH50911 (20 µM)) disinhibited VTA-DA firing rate whereas a GABA(A) agonist (muscimol, 1 µM) strongly inhibited firing rate. In the presence of picrotoxin, ethanol enhanced VTA-DA firing rate more than in the absence of picrotoxin. Additionally, a sub-maximal concentration of muscimol together with ethanol inhibited VTA-DA firing rate more than muscimol alone. DAMGO (3 µM) inhibited mIPSC frequency but did not block the ethanol-enhancement in mIPSC frequency. DAMGO (1 and 3 µM) had no effect on VTA-DA firing rate. Naltrexone (60 µM) had no effect on basal or ethanol-enhancement of mIPSC frequency. Additionally, naltrexone (20 and 60 µM) did not block the ethanol-enhancement in VTA-DA firing rate. Overall, the present results indicate that the ethanol enhancement in GABA release onto VTA-DA neurons limits the stimulatory effect of ethanol on VTA-DA neuron activity and may have implications for the rewarding properties of ethanol.

Establishment of an ex vivo lung perfusion model using non-heart-beating large pigs.

BACKGROUND: Functional evaluation of potentially damaged lungs donated after cardiac death is crucial for widespread clinical transplantation. To date, the mean weight of animals used in studies of ex vivo lung perfusion (EVLP) has been 60 kg; however, in the clinical setting, donor weight may be greater. OBJECTIVE: To investigate EVLP using lungs from large pigs (mean weight, 115 kg) to simulate human adult lungs donated after cardiac death. MATERIALS AND METHODS: Five heart-lung blocks were obtained at 20 minutes after death at the slaughterhouse. The lungs were flushed and preserved on ice for 6 hours before being connected to an ex vivo lung circuit, and were perfused for at least 2 hours. RESULTS: In all cases, perfusion was sustained for at least 2 hours. Mean (SEM) final flow rate was 4.9 (0.1) L/min, pulmonary artery pressure was 14.8 (1.7) mm Hg, and oxygen tension/fraction of inspired oxygen was 518.0 (18.0) mm Hg. The shunt fraction was 20.5% (4.0%). Histologic analysis demonstrated no significant pulmonary edema at the end of perfusion. CONCLUSION: We successfully completed EVLP using lungs from large pigs.

Add-on combination therapy with adefovir dipivoxil induces renal impairment in patients with lamivudine-refractory hepatitis B virus.

Combination therapy with adefovir dipivoxil (ADV) and lamivudine (LAM) is recommended for patients infected with LAM-refractory hepatitis B virus (HBV). However, the effects of such therapy on renal function and serum phosphorus levels have not been fully evaluated. Combination therapy with ADV and LAM was given to 37 patients infected with LAM-refractory HBV, including 17 with hepatic cirrhosis. Serum HBV DNA levels decreased to below 2.6 log(10) copies/mL in 23 (62%) of 37 patients at 12 months, 25 (78%) of 32 patients at 24 months, and 16 (84%) of 19 patients at 36 months. Except for one cirrhotic patient, serum alanine aminotransferase levels were below 50 IU/L in all patients during combination therapy. Serum creatinine levels increased in 14 (38%) of 37 patients, and serum phosphate levels decreased to below 2.5 mg/mL in 6 (16%) of 37 patients during combination therapy. Patients who received combination therapy for 36 months or longer had a significantly incidence of elevated serum creatinine levels. Fanconi syndrome occurred in a 57-year-old woman with cirrhosis after ADV was added to LAM. Combination therapy with ADV and LAM can maintain biochemical remission in patients with LAM-refractory HBV. However, the dosing interval of ADV should be adjusted according to renal function and serum phosphate levels in patients receiving long-term treatment.

Favorable acute and long-term outcomes after the resection of pulmonary aspergillomas.

OBJECTIVE: This retrospective study was designed to examine the acute and long-term outcomes after surgical treatment of patients with pulmonary aspergillomas. PATIENTS AND METHODS: From 1992 to 2006, 24 patients (21 men, mean age 58.4 years) with pulmonary aspergillomas underwent pulmonary resection. Operative indications were massive or repetitive hemoptysis in 6 patients, medically unmanageable localized infection in 14 patients, and undetermined mass in 4 patients. Eighteen patients (75.0 %) had background pulmonary diseases and four patients (16.7 %) were mildly immunocompromised. Eight patients had simple aspergillomas, while sixteen patients had complex aspergillomas. Two patients with pleural empyema had their pleural spaces sterilized before pulmonary resections. Fungus balls and pulmonary cavities along with the surrounding lung were removed in all patients. RESULTS: Surgical procedures consisted of 13 lobectomies, 5 pneumonectomies including one completion pneumonectomy, 2 segmentectomies and 4 wedge resections. Postoperative complication occurred in 10 patients (41.6 %) and one patient died from aortic bleeding due to postoperative empyema. Other major complications were prolonged air leaks, bleeding, and chylothorax. In the follow-up period, all but one patient were free from aspergillosis. Hemoptysis was not seen in any patient. Overall survival rates at 2, 5, and 10 years were 86.6 %, 79.4 % and 79.4 %, respectively. Disease-free survival rates from aspergillosis were 86.6 %, 72.6 % and 72.6 % at 2, 5, and 10 years, respectively. CONCLUSION: Pulmonary resection for aspergilloma showed favorable acute and long-term outcomes when surgical treatment was applied in selected patients.

Characterization of salt tolerance in ectoine-transformed tobacco plants (Nicotiana tabaccum): photosynthesis, osmotic adjustment, and nitrogen partitioning.

Ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) biosynthetic genes (ect. ABC) from Halomonas elongata were introduced to tobacco plants using an Agrobacterium-mediated gene delivery system. The genes for ectoine biosynthesis were integrated in a stable manner into the tobacco genome and the corresponding transcripts were expressed. The concentration of ectoine under salt-stress conditions was higher in the roots than in leaves. A close relationship was found between stomatal conductance and the amount of transported nitrogen, suggesting that water transport through the xylem in the stem and transpiration may be involved in nitrogen transport to leaves. The data indicate that the turgor values of the ectoine transgenic lines increased with increasing salt concentration. The data revealed two ways in which ectoine enhanced salinity tolerance of tobacco plants. First, ectoine improved the maintenance of root function so that water is taken up consistently and supplied to shoots under saline conditions. Second, ectoine enhanced the nitrogen supply to leaves by increasing transpiration and by protecting Rubisco proteins from deleterious effects of salt, thereby improving the rate of photosynthesis.

Use of real-time magnetic resonance image guidance in endoscopic sinus surgery.

We evaluated the effectiveness of magnetic resonance image (MRI) guidance using an optical tracking system (MRI-guided therapy: MRT) in performing endoscopic sinus surgery (ESS). The profiles of the fourteen patients in the present study were as follows: eleven with mucocele in the paranasal sinus, one with recurrent chronic sinusitis, one with maxillary cancer, and one with Graves' ophthalmopathy. Preparation of the MRT system required an additional 54 min in cases involving general anesthesia, and an additional 17 min in cases involving local anesthesia, in comparison with corresponding control groups undergoing ESS in a traditional operating room. We developed nonmetal probes that were visualized in a real-time mode and assistive devices for the optical tracking system that were equipped to avoid obstruction caused by surgical instruments as well as by the hands of surgeons. Using these unique devices, anatomic landmarks were visualized using the present MRT system. The prognosis of patients was favorable, and in particular, no patients with sinus mucocele showed a recurrence of their lesions. We concluded that the MRT system used here for performing ESS was beneficial, especially in terms of the intranasal marsupialization of sinus mucoceles and for the verification of orbital contents.

Overexpression of a DEAD box/RNA helicase protein, rck/p54, in human hepatocytes from patients with hepatitis C virus-related chronic hepatitis and its implication in hepatocellular carcinogenesis.

Hepatitis C virus (HCV) infection is the most common cause of chronic hepatitis, which frequently progresses to hepatocellular carcinoma. The pathogenesis of its persistent infection and tumour progression has not been fully characterized yet. The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8. The RCK protein, rck/p54, which is a 54-kDa cytoplasmic protein belonging to the DEAD box/RNA helicase family, is considered to facilitate the translation of mRNA(s) of genes for cell proliferation and malignant transformation not only in B-cell lymphomas having the t(11;14) translocation but also in other solid tumours. The aim of this work was to examine the involvement of rck/p54 in carcinogenesis of hepatocellular carcinoma from HCV-related chronic hepatitis. We examined the expression of rck/p54 in 29 cases of HCV-related chronic hepatitis and eight cases of hepatocellular carcinoma by immunohistochemistry and Western blot analysis. Twenty-six of 29 cases with HCV-related chronic hepatitis and all cases with hepatocellular carcinoma tested overexpressed rck/p54 protein. The expression of rck/p54 was lowered by treatment with IFN-alpha in two cases who showed the decrease in HCV RNA levels. These findings suggest that rck/p54 protein is possibly involved in the replication of HCV genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas.

A case of dermatomyositis complicated with pneumomediastinum successfully treated with cyclosporin A.

We describe a rare case of a 46-year-old Japanese man with dermatomyositis (DM) and interstitial lung disease who developed spontaneous pneumomediastinum and subcutaneous emphysema. Relatively mild myositis, mild elevation of CK values and the absence of anti-Jo-1 antibody were observed and the case was similar to amyopathic DM. Treatment of this patient with oral prednisolone and cyclosporin A (CsA) was effective for the myositis and interstitial lung disease. The administration of CsA enabled rapid tapering of the dose of prednisolone without aggravating the disease. Pneumomediastinum and subcutaneous emphysema disappeared 5 months later without recurrence. The serum levels of KL-6 were monitored every 2 weeks to help determine whether this may have contributed to the recurrence of interstitial pneumonitis. This is a rare case of pneumomediastinum in a patient with DM.

Co-overexpression of DEAD box protein rck/p54 and c-myc protein in human colorectal adenomas and the relevance of their expression in cultured cell lines.

The RCK gene was cloned through a study of the breakpoint of the t(11;14)(q23;q32) chromosomal translocation observed in a human B-cell lymphoma and overexpression of the protein (rck/p54) due to the translocation was shown to be associated with malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. It is considered that rck/p54 protein may have significant effects on the mRNA structure of genes associated with cell proliferation, facilitating protein synthesis. Expression of rck/p54 in colorectal adenomas, which are a premalignant lesion of colorectal cancer, was examined by Western blot analysis and immunohistochemistry. The rck/p54 protein was found to be overexpressed in tumor tissues resected from 17 of 26 cases (65.4%) of colorectal adenomas and 13 of 14 c-myc-positive cases (92.8%) also co-overexpressed rck/p54 protein. Thus, a significant correlation between rck/p54 and c-myc co-overexpression was found (Spearman's rank correlation, P = 0.0018). We demonstrate that overexpression of rck/p54 in two different cell lines, COS 7 and human colorectal cancer cell line SW480, caused an increase in c-myc protein levels by enhancement of its translation efficiency and/or stabilization of its mRNA. These results suggest that rck/p54 of the DEAD box protein/RNA helicase family may contribute to cell proliferation and carcinogenesis in the development of human colorectal tumors at the translational level by increasing synthesis of c-myc protein.

Intestinal motility in an in vivo rat model of intestinal ischemia-reperfusion with special reference to the effects of nitric oxide on the motility changes.

BACKGROUND: To clarify the relation between intestinal ischemia-reperfusion (IR) and dysmotility, the authors investigated changes in the motility pattern in the duodenum and jejunum in an in vivo rat model of IR when artery- (and vein-) fed jejunum was clamped transiently. The authors also studied the effect of nitric oxide on the motility changes in this model by means of the administration of L-NAME (N(G)-nitro-L-arginine methyl ester) or S-methylisothiourea sulfate (SMT). MATERIALS AND METHODS: A force transducer was sutured onto the serosal side of the duodenum or jejunum. After a 3-to 4-day recovery period, contractions were recorded during periods of preischemia, ischemia (60 minutes), and reperfusion (90 minutes). An intestinal IR was produced by clamping and releasing the mesenteric artery and vein with artery forceps. RESULTS: In the jejunum, there was a prolongation in the duration of contraction and there were decreases in the number of contractions (NC) during the IR. When treated with L-NAME, no decrease in the NC was observed during the 45 to 90 minutes after reperfusion. S-methylisothiourea sulfate did not affect the IR-induced motility changes significantly. In the duodenum, there was a prolongation in the duration of contraction and a decrease in the NC and AC only during the reperfusion. L-NAME or S-methylisothiourea sulfate inhibited the decreases in the NC during the reperfusion. CONCLUSIONS: Intestinal IR causes motility changes in the ischemic site during the IR and in the nonischemic site during the reperfusion. The IR-induced motility changes partly depend on nitric oxide production.