Role of leukotriene B4 (LTB4)-LTB4 receptor 1 signaling in post-incisional nociceptive sensitization and local inflammation in mice.

Leukotriene B4 (LTB4) is a potent lipid mediator involved in the recruitment and activation of neutrophils, which is an important feature of tissue injury and inflammation. The biological effects of LTB4 are primarily mediated through the high-affinity LTB4 receptor, BLT1. Postoperative incisional pain is characterized by persistent acute pain at the site of tissue injury and is associated with local inflammation. Here, we compared the role of LTB4-BLT1 signaling in postoperative incisional pain between BLT1-knockout (BLT1KO) and wild-type (BLT1WT) mice. A planter incision model was developed, and mechanical pain hypersensitivity was determined using the von Frey test before and after incision. Local infiltration of neutrophils and inflammatory monocytes was quantified by flow cytometry. Inflammatory cytokine levels in the incised tissue were also determined. Mechanical pain hypersensitivity was significantly reduced in BLT1KO mice compared to BLT1WT mice at 2, 3, and 4 days after incision. LTB4 levels in the tissue at the incision site peaked 3 hours after the incision. Infiltrated neutrophils peaked 1 day after the incision in both BLT1KO and BLT1WT mice. The accumulation of inflammatory monocytes increased 1-3 days after the incision and was significantly more reduced in BLT1KO mice than in BLT1WT mice. In BLT1KO mice, Interleukin-1ß and Tumor Necrosis Factor-α levels 1 day after the incision were significantly lower than those of BLT1WT mice. Our data suggest that LTB4 is produced and activates its receptor BLT1 in the very early phase of tissue injury, and that LTB4-BLT1 signaling exacerbates pain responses by promoting local infiltration of inflammatory monocytes and cytokine production. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.

Lysophosphatidic acid receptor1/3 antagonist inhibits the activation of satellite glial cells and reduces acute nociceptive responses.

Lysophosphatidic acid (LPA) exerts various biological activities through six characterized G protein-coupled receptors (LPA1-6 ). While LPA-LPA1  signaling contributes toward the demyelination and retraction of C-fiber and induces neuropathic pain, the effects of LPA-LPA1  signaling on acute nociceptive pain is uncertain. This study investigated the role of LPA-LPA1  signaling in acute nociceptive pain using the formalin test. The pharmacological inhibition of the LPA-LPA1 axis significantly attenuated formalin-induced nociceptive behavior. The LPA1  mRNA was expressed in satellite glial cells (SGCs) in dorsal root ganglion (DRG) and was particularly abundant in SGCs surrounding large DRG neurons, which express neurofilament 200. Treatment with LPA1/3 receptor (LPA1/3 ) antagonist inhibited the upregulation of glial markers and inflammatory cytokines in DRG following formalin injection. The LPA1/3 antagonist also attenuated phosphorylation of extracellular signal-regulated kinase, especially in SGCs and cyclic AMP response element-binding protein in the dorsal horn following formalin injection. LPA amounts after formalin injection to the footpad were quantified by liquid chromatography/tandem mass spectrometry, and LPA levels were found to be increased in the innervated DRGs. Our results indicate that LPA produced in the innervated DRGs promotes the activation of SGCs through LPA1 , increases the sensitivity of primary neurons, and modulates pain behavior. These results facilitate our understanding of the pathology of acute nociceptive pain and demonstrate the possibility of the LPA1 on SGCs as a novel target for acute pain control.

Inhibition of autotaxin activity ameliorates neuropathic pain derived from lumbar spinal canal stenosis.

Lumbar spinal canal stenosis (LSS) or mechanical compression of dorsal root ganglion (DRG) is one of the causes of low back pain and neuropathic pain (NP). Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator that is produced mainly from lysophosphatidylcholine (LPC) via autotaxin (ATX) and is known to induce NP via LPA1 receptor signaling in mice. Recently, we demonstrated that LPC and LPA were higher in cerebrospinal fluid (CSF) of patients with LSS. Based on the possible potential efficacy of the ATX inhibitor for NP treatment, we used an NP model with compression of DRG (CD model) and investigated LPA dynamics and whether ATX inhibition could ameliorate NP symptoms, using an orally available ATX inhibitor (ONO-8430506) at a dose of 30 mg/kg. In CD model, we observed increased LPC and LPA levels in CSF, and decreased threshold of the pain which were ameliorated by oral administration of the ATX inhibitor with decreased microglia and astrocyte populations at the site of the spinal dorsal horn projecting from injured DRG. These results suggested possible efficacy of ATX inhibitor for the treatment of NP caused by spinal nerve root compression and involvement of the ATX-LPA axis in the mechanism of NP induction.

Prospective evaluation of visual function in patients with ocular diseases after robot-assisted laparoscopic prostatectomy.

OBJECTIVES: To investigate intraocular pressure and visual function in patients with ocular diseases undergoing robot-assisted laparoscopic prostatectomy. METHODS: We carried out a prospective clinical study of patients undergoing robot-assisted laparoscopic prostatectomy for localized prostate cancer at The University of Tokyo Hospital from December 2015 to March 2017. An ophthalmologist measured intraocular pressure, and carried out visual field testing at 0-2 months before and 7 days after robot-assisted laparoscopic prostatectomy. During the surgery, an anesthesiologist measured intraocular pressure at specified time points. RESULTS: A total of 110 patients were enrolled and 98 eligible patients were analyzed; 37 were diagnosed with ocular diseases before robotic-assisted laparoscopic prostatectomy (17 with glaucoma, 20 with other ocular diseases). Intraocular pressure significantly increased during robot-assisted laparoscopic prostatectomy. Transient postoperative visual field defect was detected in 24 eyes of 17 patients, including six patients with ocular diseases at 7 days after surgery. At 3 months after surgery, one of 34 glaucomatous eyes and one of 40 eyes with non-glaucomatous ocular diseases continued to show visual field defect, although visual field defect in the remaining patients recovered to preoperative conditions within 3 months. CONCLUSIONS: Our findings suggest that robot-assisted laparoscopic prostatectomy can be safely carried out in patients with ocular diseases, even those with glaucoma, after precautionary consultation with an ophthalmologist.

Quantitative evaluation of stress in Japanese anesthesiology residents based on heart rate variability and psychological testing.

Clinical anesthesiologists, particularly residents, work in stressful environments. However, evidence-based physiological and psychological tests to evaluate stress are still lacking. In this single-center study of 33 residents, we investigated the relationship between heart rate variability (HRV), which had the potential to screen residents' stress levels using Holter electrocardiography (ECG) and psychological mood as assessed by the Profile of Mood States (POMS) questionnaire. HRV analysis revealed 2 findings. Firstly, standard deviation of the average of 5-min normal-to-normal R-R intervals (SDANN) was significant lower than that of same-aged healthy volunteers (69.3 ± 27.9 vs. 137.0 ± 43.0 ms, P < 0.05), which indicated suppression of autonomic nervous system activity throughout their work. Secondly, at induction of anesthesia, significant higher low frequency/high frequency ratio (LF/HF ratio: 1.326 vs. 0.846; P < 0.05) and lower HF (3326 vs. 5967 ms2; P < 0.05) and lower standard deviation of normal-to-normal R-R intervals (SDNN: 50.5 vs. 79.4 ms; nervous system was suppressed at the induction of anesthesia: expected to be the most stressful period of their work. On the other hand, deviation scores of POMS questionnaire elucidated that all the residents were within normal range of psychological mood, and without any significant diurnal changes with respect to total mood disturbance deviation (TMD) scores (48 vs. 47; P = 0.368). HRV elucidated physiological stress among anesthesiology residents quantitatively by evaluating autonomic nervous activities, especially at induction of anesthesia. These changes in HRV could be observed regardless of psychological mood.

Alteration of the lysophosphatidic acid and its precursor lysophosphatidylcholine levels in spinal cord stenosis: A study using a rat cauda equina compression model.

Cauda equina compression (CEC) is a major cause of neurogenic claudication and progresses to neuropathic pain (NP). A lipid mediator, lysophosphatidic acid (LPA), is known to induce NP via the LPA1 receptor. To know a possible mechanism of LPA production in neurogenic claudication, we determined the levels of LPA, lysophosphatidylcholine (LPC) and LPA-producing enzyme autotaxin (ATX), in the cerebrospinal fluid (CSF) and spinal cord (SC) using a CEC as a possible model of neurogenic claudication. Using silicon blocks within the lumbar epidural space, we developed a CEC model in rats with motor dysfunction. LPC and LPA levels in the CSF were significantly increased from day 1. Importantly, specific LPA species (16:0, 18:2, 20:4) were upregulated, which have been shown to produce by ATX detected in the CSF, without changes on its level. In SC, the LPC and LPA levels did not change, but mass spectrometry imaging analysis revealed that LPC was present in a region where the silicon blocks were inserted. These results propose a model for LPA production in SC and CSF upon neurogenic claudication that LPC produced locally by tissue damages is converted to LPA by ATX, which then leak out into the CSF.

Preoperative balloon pulmonary angioplasty enabled noncardiac surgery of a patient with chronic thromboembolic pulmonary hypertension (CTEPH): A case report.

RATIONALE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease with a poor prognosis, characterized by chronic thromboembolic obstruction of the pulmonary arteries and pulmonary hypertension. Balloon pulmonary angioplasty (BPA) is a newly emergent treatment for CTEPH, which may substitute pulmonary endarterectomy, the standard but more invasive treatment for CTEPH. Here, we report the case of a CTEPH patient who underwent 2 noncardiac surgeries without complications after preoperative intervention of BPA. PATIENT CONCERNS: A 79-year-old man presented with severe osteoarthritis of bilateral knees, with adaptation of total knee arthroplasty (TKA). Transthoracic echocardiogram revealed severe pulmonary hypertension with estimated right ventricular systolic pressure of 140 mm Hg. DIAGNOSIS: Pulmonary arteriography revealed total occlusion of the upper branch of the right pulmonary artery, and ventilation/perfusion scan showed multiple mismatched perfusion defects. His pulmonary artery pressure (PAP) was as high as 89/25 (46) mm Hg with normal range of pulmonary capillary wedge pressure. He was diagnosed with CTEPH. INTERVENTIONS: Four BPA sessions for 8 branches of the bilateral pulmonary arteries were done, until the mean PAP (mPAP) went under 30 mm Hg. For the TKA, we selected spinal anesthesia in order to minimize intraoperative hemodynamic changes. Cardiac surgeons were standby in case extracorporeal membrane oxygenation (ECMO) initiation was required. OUTCOMES: With appropriate pain management and use of intravenous vasopressors, intraoperative vital signs were stable. No symptoms of hemodynamic collapse were observed postoperatively. The patient was discharged on the 46th postoperative day following rehabilitation. Two years later, left-side unicompartment knee arthroplasty (UKA) was scheduled. Right heart catheterization study revealed the mPAP was 30 mm Hg, nearly the same value as the last study. The operation was performed under spinal anesthesia with continuous arterial pressure monitoring without need for intraoperative vasopressor. He was discharged without complications on the 24th postoperative day. LESSONS: BPA can be an effective preoperative intervention for CTEPH patients undergoing noncardiac surgery.

Recovery from Extreme Hemodilution (Hemoglobin Level of 0.6 g/dL) in Cadaveric Liver Transplantation.

Decompensated hepatic failure occurred in a patient with a rare blood type. The patient had extreme hemodilution due to massive bleeding during liver transplantation. A shortage of matched and universal donor blood prompted us to transfuse albumin and fresh frozen plasma for intravascular volume resuscitation. The lowest hemoglobin was 0.6 g/dL, accompanied by ST depression and a serum lactate of 100 mg/dL. The accuracy of the measured value of 0.6 g/dL was confirmed. However, the patient recovered from this critical situation after transfusion, and he was eventually discharged from the hospital without significant sequelae. Maintaining normovolemia, administering pure oxygen, ensuring appropriate anesthetic depth, and maintaining minimal inotropic support were essential for this patient's survival during massive bleeding.

The absence of the leukotriene B4 receptor BLT1 attenuates peripheral inflammation and spinal nociceptive processing following intraplantar formalin injury.

BACKGROUND: Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation, and its biological effects are mediated primarily through the high affinity LTB4 receptor BLT1. Although numerous studies have reported that LTB4-BLT1 signaling is involved in inflammatory diseases, the role of BLT1 signaling in pain remains undefined. To clarify the role of LTB4-BLT1 signaling in acute inflammatory pain induced by tissue injury, we performed pain behavioral analysis and assessment of local inflammation induced by peripheral formalin injections in BLT1 knockout mice. We examined the phosphorylation of cAMP response element-binding protein (CREB) in the spinal cord both in wild-type and BLT1 knockout mice because phosphorylation of CREB in spinal cord neurons is important for nociceptive sensitization following peripheral injury. We also examined the effect of a BLT1 antagonist on formalin-induced pain responses in mice. RESULTS: BLT1 knockout mice exhibited markedly attenuated nociceptive responses induced by intraplantar formalin injections. Edema formation and neutrophil infiltration in the paw were significantly decreased in BLT1 knockout mice compared with wild-type mice. Phosphorylation of CREB in the spinal cord after the intraplantar formalin injection was decreased in BLT1 knockout mice. In addition, mice pretreated with a BLT1 antagonist showed reduced nociception and attenuated CREB phosphorylation in the spinal cord after the formalin injection. CONCLUSIONS: Our data suggest that LTB4-BLT1 axis contributes not only to the peripheral inflammation but also to the neuronal activation in the spinal cord induced by intraplantar formalin injections. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.

Application of lobe-selective bronchial blockade against airway bleeding.

A 48-year-old man underwent resection of a right upper lobe necrotic tumor and part of his chest wall. Lobe-selective bronchial blockade of bleeding from the right upper lobe was achieved by combining a left-side double-lumen endotracheal tube with a bronchial blocker placed at the right intermediate bronchus. The bleeding right upper lobe was isolated, and the other lobes were protected from blood contamination during the lobectomy procedure.

[Anesthetic management of a patient with severe ovarian hyperstimulation syndrome].

We report anesthetic management of a patient with severe ovarian hyperstimulation syndrome (OHSS). A 33-year-old woman presented with severe abdominal acites and effusion after ovarian stimulation with HMG followed by ovulation induction with HCG. She was suspected of having intraabdominal hemorrhage because of ectopic pregnancy. Emergency laparotomy was performed under general anesthesia. Massive ascites and intraabdominal hemorrhage were observed and patient was treated by adequate fluid infusion and blood transfusion. Patient was treated with non-invasive positive pressure ventilation (NPPV) after operation and recovered. It is essential to maintain a correct balance of fluids, through appropriate intravenous infusion of crystalloids, albumin, blood transfusion and an adequate urine output. Further it is important to prevent thromboembolic event. Knowledge of the clinical features, complications and acute management of OHSS will permit the anesthesiologist to treat these patients in an optimal fashion.

[Identification of 23 mycobacterial species by Invader assay with targeting 16S rRNA gene and ITS-1 region--comparison with DDH method in clinical isolates].

PURPOSE AND METHOD: The Invader assay was developed to identify 23 mycobacterial species using probes derived from the species-specific region of the 16S rRNA gene and the 16S-23S rRNA internal transcribed spacer 1 (ITS-1) region, with minor modifications of our previous study. In the present study, we compared the identification capability between the Invader assay and DNA-DNA hybridization (DDH) method. DDH is commonly used to identify non-tuberculosis mycobacterium in Japan and 636 clinical mycobacterial strains cultured on Ogawa slants were tested. RESULTS: The Invader assay could identify 615 (96.7%) of the 636 strains. The results contained 14 M.lentiflavum, 3 M. parascrofulaceum and 1 M. intermedium, which were undetectable with DDH method. On the other hand, DDH method could identify 580 (91.2%) strains with duplicate assay. Of 628 strains except 8 strains identified as a few species by Invader assay, 551 (87.7%) strains were identified as the same species by two methods. Discordant results were mainly recognized for the identification of M. gordonae, M. avium, M. lentiflavum and M. intracellurare. The results of other methods targeting 16S rRNA indicated correctness of the Invader assay. CONCLUSION: These results indicate that Invader assay could identify more correctly than DDH method and could identify about 97% of clinically important mycobacterium.

Evaluation of the invader assay with the BACTEC MGIT 960 system for prompt isolation and identification of mycobacterial species from clinical specimens.

Rapid and accurate identification of mycobacterial species is essential for patient management. We describe the use of the Invader assay in conjunction with the BACTEC MGIT 960 system that together provide an efficient procedure for clinical use. This assay discriminates single-base differences (e.g., genotyping single-nucleotide polymorphisms) under homogeneous and isothermal conditions and can measure directly on genomic DNA without prior target DNA amplification. To identify a wide variety of mycobacterial species, 20 Invader probes were designed to target the 16S rRNA gene and the 16S-23S rRNA gene internal transcribed spacer 1 (ITS-1) region. To validate the Invader probes, we used 78 ATCC strains, and 607 clinical mycobacterial strains, which were identified by DNA sequencing of the 16S rRNA gene and ITS-1. The Invader assay could accurately identify and differentiate these strains according to target sequences. Moreover, it could detect and identify 116 (95.1%) of 122 positive liquid cultures from the BACTEC MGIT 960 system and did not react to 83 contaminated MGIT cultures. Species identification takes 6.5 h by the Invader assay: 2.0 h for DNA extraction, 0.5 h for handling, and up to 4 h for the Invader reaction. The Invader assay has the speed, ease of use, and accuracy to be an effective procedure for the bacteriological diagnosis of mycobacterial infections.

[Anesthetic management of a morbidly obese patient with mental retardation].

We report successful anesthetic management of a morbidly obese patient with mental retardation employing inhalation induction with sevoflurane in sitting position and epidural catheterization using ultrasound sonography. Inhalation induction with sevoflurane keeps spontaneous respiration and induction in sitting position may provide a greater margin of safety for airway control. Therefore, this method of induction is useful for morbidly obese patient. Regional anesthesia in an obese patient can be technically challenging because of difficulties in identifying the useful body landmarks. We successfully used ultrasound sonography to identify spinous process and could insert an epidural catheter at the right place.

Change in the concentration of neutrophil elastase in bronchoalveolar lavage fluid during anesthesia and its inhibition by cholesterol sulfate.

UNLABELLED: Cholesterol sulfate (CS) in the gastrointestinal tract exhibits a mucosal protective activity in mouse ulcer model. To clarify the possible role of CS for protection from the epithelial injury due to neutrophil elastase in the tracheobronchi, the authors determined the concentrations of CS and neutrophil elastase in bronchoalveolar lavage fluid (BALF) from patients under anesthesia, and they examined the inhibitory activity of CS toward neutrophil elastase. The concentrations of CS and neutrophil elastase were determined by thin-layer chromatography and enzyme-linked immunosorbent assaying, respectively, and the effect of CS on the activity of elastase was determined with a chromogenic substrate. CS was found to be present in human lung, tracheal mucosa, and BALF, and a high synthesis of it was detected in the tracheal mucosa, in which cellular cholesterol sulfotransferase was induced depending on the density of tracheal cells. Among lipids in the tracheal mucosa, only CS was demonstrated to exhibit inhibitory activity toward neutrophil elastase, a powerful erosive agent in inflammation. The secretion of elastase from neutrophils into BALF was stimulated during the course of general anesthesia. In contrast, the amount of CS in BALF gradually decreased during anesthesia. On immune-precipitation of neutrophil elastase in BALF, CS was detected in the immune precipitate, which indicates a possible association of CS with neutrophil elastase in BALF. CONCLUSION: CS, which is a major acidic lipid in the tracheobronchial epithelium, might function as an epithelial inhibitor toward neutrophil elastase secreted in response to several stimuli such as anesthesia.

[Outline and effectiveness of support system in the surgical center by supply, processing and distribution center (SPD)].

Supply, Processing and Distribution system had been introduced to surgical center (the University of Tokyo Hospital) since October of 2002. This system had reduced stock for medicine and materials and decreased medical cost dramatically. We designed some kits for therapeutic drugs related to anesthesia. They were prepared for general anesthesia, epidural and spinal anesthesia, and cardiovascular anesthesia, respectively. One kit had been used for one patient, and new kits were prepared in the anesthesia preparation room by pharmaceutical department staffs. Equipment, for general anesthesia as well as epidural and spinal anesthesia, and central catheter set were also designed and provided for each patient by SPD system. According to the questionnaire of anesthesia residents before and after introduction of SPD system, the time spent for anesthesia preparation had been reduced and 92.3% residents had answered that preparation for anesthesia on the previous day was getting easier. Most of the anesthesia residents had been less stressed after introduction of SPD system. Beside the dramatic economical effect, coordination with SPD system and pharmaceutical department reduced anesthesia preparation time and stress of the staff. Introduction of Support system of SPD to surgical center is important for safe and effective management of operating rooms.

Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission.

Bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals reducing pain threshold. We now show that the B2 kinin receptor is expressed in rat dorsal horn neurons and that bradykinin, a B2-specific agonist, augments AMPA- and NMDA-induced, and primary afferent-evoked EPSCs, and increases the frequency and amplitude of miniature EPSCs in superficial dorsal horn neurons in vitro. Administration of bradykinin to the spinal cord in vivo produces, moreover, an NMDA-dependent hyperalgesia. We also demonstrate that nociceptive inputs result in the production of bradykinin in the spinal cord and that an intrathecal B2-selective antagonist suppresses behavioral manifestations of central sensitization, an activity-dependent increase in glutamatergic synaptic efficacy. Primary afferent-evoked central sensitization is, in addition, reduced in B2 receptor knock-out mice. We conclude that bradykinin is released in the spinal cord in response to nociceptor inputs and acts as a synaptic neuromodulator, potentiating glutamatergic synaptic transmission to produce pain hypersensitivity.

Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord.

In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models the presynaptic inhibitory effect of the mu opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn neurons is substantially reduced, but only in those spinal cord segments innervated by injured primary afferents. The two nerve injury models also reduce the postsynaptic potassium channel opening action of DAMGO on lamina II spinal cord neurons, but again only in segments receiving injured afferent input. The inhibitory action of DAMGO on ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons is also reduced in affected segments following nerve injury. MOR expression decreases substantially in injured dorsal root ganglion neurons (DRG), while intact neighboring DRGs are unaffected. Decreased activation of MOR on injured primary afferent central terminals and the second order neurons they innervate may minimize any reduction by opioids of the spontaneous pain mediated by ectopic input from axotomized small diameter afferents. Retention of MOR expression and activity in nearby non-injured afferents will enable, however, an opioid-mediated reduction of stimulus-evoked and spontaneous pain carried by intact nociceptor afferents and we find that intrathecal DAMGO (1000 ng) reduces mechanical hypersensitivity in rats with SNL. Axotomy-induced changes in MOR may contribute to opioid- insensitive components of neuropathic pain while the absence of these changes in intact afferents may contribute to the opioid sensitive components.

SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C.

BACKGROUND: The T-helper (Th)1 immune reaction is essential for the eradication of hepatitis C virus (HCV) during interferon (IFN) therapy in patients with chronic hepatitis C. Osteopontin is a cytokine crucial for the initiation of the Th1 response. Recently, we identified four single-nucleotide polymorphisms (SNPs) in the promoter region of the osteopontin gene (OPN), at nucleotide (nt) -155, -443, -616, and -1748, and suggested that the SNP at nt -443 was a marker reflecting hepatitis activity in patients with HCV. Therefore, we examined the possibility that SNPs in OPN were also markers predicting the therapeutic efficacy of IFN in patients with chronic hepatitis C. METHODS: Blood was collected from 77 patients with chronic hepatitis C who had received either IFN monotherapy or IFN-ribavirin combination therapy (IFN-based therapies). SNPs in OPN, MxA, MBL, and LMP7 were analyzed by Invader assay. RESULTS: Promoter SNPs of OPN at nt -155, -616, and -1748 showed linkage disequilibrium at 100% to each other. Sustained virological response (SVR) was observed in 58% of all patients. The SVR rate was higher in patients with the G/G or G/A alleles in the OPN promoter SNP at nt -1748 than in those with A/A (85% vs 45%; P < 0.05). The SVR rate was also higher in patients with T/T at nt -443 than in those with C/C or C/T (86% vs 47%; P < 0.05). Such differences were particularly evident in patients with HCV genotype 1b who had a pretreatment viral load greater than 100 KIU/ml. All the patients who had G/G or G/A at nt -1748 and T/T at nt -443 obtained an SVR. On the other hand, there was no relationship between the efficacy of IFN-based therapies and SNPs in MxA, MBL, and LMP7, which had been shown to have association with the response to IFN monotherapies. CONCLUSIONS: SNPs in the promoter region of OPN may be useful as a marker to predict the efficacy of IFN-based therapies in patients with chronic hepatitis C, and further investigation regarding their real significance is warranted in a large series of patients.

Lipid compositions of human gastric fluid and epithelium: the role of sulfated lipids in gastric cytoprotection.

BACKGROUND: Gastric sulfatide, whose carbohydrate moiety resembles that of the anti-ulcer drug sucralfate, has been shown to play a role in mucosal protection in an experimental ulcer model. To elucidate the functional significance of gastric lipids, precise determination of the lipids in human gastric fluid and epithelium was performed, and the anti-ulcer effects of all lipids in the fluid were measured in mouse ulcer models. METHODS: The lipids in human gastric fluid and epithelium were analyzed by thin layer chromatography and immunostaining, and the anti-ulcer effects of gastric lipids were determined using mouse ulcer models. RESULTS: Human gastric epithelium contained both sulfatide and cholesterol sulfate (CS) as sulfolipids, which were also detected in gastric fluid, showing their stable natures in the gastric fluid. Hemorrhaging in HCl-induced gastric lesions was suppressed in a dose-dependent manner by the administration of sulfolipid-containing liposomes, but suppression of stress ulcers was only accomplished with CS-containing liposomes, ie, not with sulfatide-containing ones, due to the longer retainment of CS than sulfatide in the stomach. CONCLUSIONS: Among the lipids in human gastric fluid, CS was revealed to exhibit a gastroprotective activity, which was more effective than that of sulfatide.