Mesalazine for ulcerative colitis complicated with diabetic nephropathy.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
H Ishihara
Publications and source records attributed to H Ishihara.
SH2-containing inositol phosphatase 2 negatively regulates insulin-induced glycogen synthesis in L6 myotubes.
AIMS/HYPOTHESIS: PI(3,4,5)P3 produced by PI3-kinase seems to be a key mediator for insulin's metabolic actions. We have recently cloned rat SHIP2 cDNA which is abundantly expressed in target tissues of insulin. Here, we clarify the role of SHIP2 possessing 5'-phosphatase activity toward PI(3,4,5)P3 in insulin signalling in the skeletal muscle. METHODS: The role of SHIP2 in insulin-induced glycogen synthesis was studied by expressing wild-type (WT)-SHIP2 and a 5'-phosphatase defective (Delta IP)-SHIP2 into L6 myotubes by means of adenovirus mediated gene transfer. RESULTS: The early events of insulin signalling including tyrosine phosphorylation of the insulin receptor and IRS-1, IRS-1 association with the p85 subunit, and PI3-kinase activity were not affected by expression of WT- and Delta IP-SHIP2. Although PI(3,4,5)P3 and PI(3,4)P2 are known to possibly activate a downstream molecule of PI3-kinase Akt in vitro, overexpression of WT-SHIP2 inhibited insulin-induced phosphorylation and activation of Akt. Conversely, Akt activity was increased by expression of Delta IP-SHIP2. GSK3 beta located downstream of Akt is an important molecule to further transmit insulin signal for glycogen synthesis in skeletal muscles. In accordance with the results of Akt, insulin-induced phosphorylation and inactivation of GSK3 beta, subsequent activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2, whereas these events were increased by expression of Delta IP-SHIP2. CONCLUSION/INTERPRETATION: Our results indicate that SHIP2 plays a negative regulatory role via the 5'-phosphatase activity in insulin signalling, and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced Akt activation leading to glycogen synthesis in L6 myotubes.
Adenoviridae↗
Ketamine and midazolam kinetics during continuous hemodiafiltration in patients with multiple organ dysfunction syndrome.
OBJECTIVE: To assess the effect of continuous hemodiafiltration (CHDF) on ketamine and midazolam kinetics in multiple organ dysfunction syndrome (MODS). DESIGN AND SETTING: Consecutive clinical study in a general intensive care unit of a university hospital. PATIENTS: Twelve adult patients with MODS requiring CHDF. MEASUREMENTS AND RESULTS: A total of 68 samples were collected during CHDF for ketamine, norketamine, and midazolam assays. The clearance values for ketamine and norketamine were 10.8 +/- 6.6 and 10.9 +/- 11.5 ml/min and their daily extractions were 21.4 +/- 7.1 and 10.2 +/- 11.5 mg/day, respectively. Midazolam was not eliminated through the filter during CHDF. There were no changes in Ramsay Sedation Score or Glasgow Coma Scale during CHDF. CONCLUSIONS: Small fractions of ketamine and norketamine were eliminated during CHDF in MODS. Midazolam was not eliminated during CHDF. CHDF did not affect the sedation using ketamine and midazolam even in MODS patients.
Analgesics↗
Clinical features and skewed X-chromosome inactivation in female carriers of X-linked recessive spinal and bulbar muscular atrophy.
In X-linked recessive disorders, a few female gene carriers become symptomatic. Recent evidence implicates skewed X-chromosome inactivation in such female carriers. We studied the clinical features of eight female gene carriers of X-linked recessive spinal and bulbar muscular atrophy (SBMA), and evaluated the relationship between phenotype and genotype from the viewpoint of X-chromosome inactivation. Seven of eight cases were symptomatic, showing mild muscle weakness, frequent muscle cramps, slight elevation of the serum creatinine kinase level, or neurogenic changes on the electromyogram. Only one carrier was asymptomatic clinically. For the estimation of X-chromosome inactivation, the methylation status of the androgen receptor (AR) gene was determined by polymerase chain reaction-based assay. Highly skewed inactivation of the affected AR gene was found in the asymptomatic carrier, while symptomatic carriers had a random or lower inactivation pattern of the affected AR gene. These findings suggest that most female carriers of SBMA show some clinical abnormalities, and highly skewed inactivation of the affected X-chromosome seems to closely relate with escape of the manifestation in female carriers of SBMA.
Adult↗
Prediction of neurologic outcome in patients with spinal cord injury by using hyperbaric oxygen therapy.
The effectiveness of hyperbaric oxygen therapy (HBO) in predicting neurological recovery in patients with spinal cord injury was evaluated. HBO has been used to treat spinal cord injury, but HBO does not appear to greatly alter the neurological outcome. This is the first report of the use of HBO as a diagnostic tool to evaluate neurological recovery after spinal cord injury. The study group consisted of 22 patients, aged 21-73 years, with spinal cord injuries. The effect of HBO was evaluated on admission and categorized as one of four grades (excellent, good, fair, or poor). The neurological status was evaluated on admission and at the time of follow-up, according to Frankel grade and the American Spinal Injury Association (ASIA) motor score. Correlations between the HBO effect and Frankel grade recovery and correlations between the HBO effect and recovery rate of the ASIA motor score were evaluated. The recovery in Frankel grade from admission to the final follow-up became better as the effectiveness of HBO increased (r = 0.445; P = 0.0414). The Frankel grade (r = 0.036; P = 0.871) and ASIA motor score (r = 0.029; P = 0.893) on admission did not correlate with the recovery in Frankel grade. There was a significant correlation between the HBO effect and the recovery rate of the ASIA motor score (r = 0.586; P = 0.0072), but this correlation was weaker than that for the ASIA motor score on admission (r = 0.752; P = 0.0006). We conclude that HBO can be employed to assess the status of spinal cord function recovery after spinal cord injury.
Adult↗
Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells.
Vascular smooth muscle cells play a key role in the development of atherosclerosis. Culture of vascular smooth muscle A10 cells with high glucose for 4 weeks enhanced platelet-derived growth factor (PDGF)-induced BrdU incorporation. Since a long period of high glucose incubation was required for the effect, and it was inhibited by co-incubation with azaserine, the role of hexosamine biosynthesis in the development of atherosclerosis in diabetes was studied in A10 cells. Addition of glucosamine to the culture media enhanced PDGF-stimulated BrdU incorporation, and PDGF-induced tyrosine phosphorylation of the PDGF beta-receptor was increased by glucosamine treatment. Of the subsequent intracellular signaling pathways, PDGF-induced PDGF beta-receptor association with PLC gamma was not affected, whereas tyrosine phosphorylation of Shc, subsequent association of Shc with Grb2, and MAP kinase activation were relatively decreased. In contrast, PDGF-induced PDGF beta-receptor association with the p85 regulatory subunit of PI3-kinase and PI3-kinase activation were increased by 20% (P<0.01) and 36% (P<0.01), respectively. The intracellular signaling molecules responsible for the glucosamine effect were further examined using pharmacological inhibitors. Pretreatment with PLC inhibitor (U73122) had negligible effects, and MEK1 inhibitor (PD98059) showed only a slight inhibitory effect on the PDGF-induced BrdU incorporation. In contrast, pretreatment with PI3-kinase inhibitor (LY294002) significantly inhibited glucosamine enhancement of PDGF-induced BrdU incorporation. These findings suggest that glucosamine is involved in the development of atherosclerosis by enhancing PDGF-induced mitogenesis specifically via the PI3-kinase pathway.
Adaptor Proteins, Signal Transducing↗
Molecular and cellular permeability control at the blood-brain barrier.
The blood-brain barrier (BBB) is formed by brain capillary endothelial cells. These cells have at least three properties which distinguish them from their peripheral counterparts: (1) tight junctions (TJs) of extremely low permeability; (2) low rates of fluid-phase endocytosis; (3) specific transport and carrier molecules. In combination, these features restrict the nonspecific flux of ions, proteins, and other substances into the central nervous system (CNS) environment. The restriction protects neurons from harmful compositional fluctuations occurring in the blood and allows uptake of essential molecules. Breakdown of the BBB is associated with a variety of CNS disorders and results in aggravation of the condition. Restoration of the BBB is thus one strategy during therapy of CNS diseases. Its success depends on a precise knowledge of the structural and functional principles underlying BBB functionality. In this review we have tried to summarise the current knowledge of TJs, including information gained from non-neuronal systems, and describe selected mechanisms involved in permeability regulation.
Animals↗
Immunohistochemical localization of aromatase and apoptosis-associated proteins in ovarian serous cystadenocarcinoma arising from ovarian endometriosis.
An immunohistochemical study was made of a case of serous cystadenocarcinoma that had been shown to have arisen from ovarian endometriosis. Aromatase cytochrome P450 (P450arom), an enzyme responsible for estrogen biosynthesis, was localized in the epithelial linings of the endometriosis and faintly in the transitional part, whereas it was not expressed in the carcinoma tissue. In contrast, estrogen receptors, progesterone receptors, and apoptosis-associated proteins, Fas, Fas ligand, and Bax were expressed in both endometriosis and carcinoma tissues of the tumor, whereas Bcl-2 was not expressed in either tissue of the tumor. It was suggested that the undifferentiated shift of the histologic grade might result in the loss of P450arom and that the malignant transformation was not caused by an altered balance of apoptosis-associated proteins. Accumulation of these studies may lead to a better understanding of the nature of malignant transformation of ovarian endometriosis.
Adult↗
Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.
BACKGROUND: Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension. METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines. RESULTS: 5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v.. CONCLUSION: In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.
Animals↗
Use of olprinone, a phosphodiesterase III inhibitor, in an asthmatic patient.
Phosphodiesterase (PDE) III exists in airway smooth muscles. In addition, PDEIII inhibitors have been suggested to relax airway smooth muscle by increasing intracellular cAMP concentrations. We report a successful use of olprinone, a PDEIII inhibitor, for treatment of an asthmatic attack. A 15-year-old male patient treated with oral theophylline 400 mg x d(-1) was anesthetized with propofol, fentanyl and ketamine for knee joint surgery. Immediately after tracheal intubation, an asthma attack occurred with peak airway pressure (Paw)>40 cmH2O. Thus, propofol 20 mg was additionally given to increase anesthetic depth, and Paw gradually decreased to 30 cmH2O. In addition, we started monitoring bronchial cross-sectional area using a superfine fiberoptic bronchoscopic method previously reported. However, as Paw did not further decrease for 30 min, olprinone was intravenously infused (10 microg x kg(-1) x 10 min(-1) + 0.3 microg x kg(-1) x min(-1), total 5 mg). Olprinone infusion rapidly decreased peak Paw from 30 cmH2O to 24 cmH2O and increased bronchial cross-sectional area by 50%. These findings suggest that olprinone produced bronchodilation.
3',5'-Cyclic-AMP Phosphodiesterases↗
Plasma cytokine response to surgical stress in schizophrenic patients.
Schizophrenic patients are reported to have immunological dysfunction, however, the immune response to surgery in schizophrenic patients remains unclear. We measured plasma interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) before, during and after colectomy, hemicolectomy and sigmoidectomy in 25 chronic schizophrenic patients (Group S) and 25 control patients (Group C) using ELISA assays. We could find no significant difference in the baseline plasma concentrations of IL-6, IL-8 and TNF-alpha between Group S and Group C. Plasma IL-6 concentrations (32.1 (30.3) and 15.8 (9.6) pg/ml) in Group S at the end of the operation and 24 h after surgery were significantly lower than 76.9 (37.1) and 35.1 (21.5) pg/ml of Group C. Plasma IL-8 concentration (6.1 (2.8)) in Group S at the end of the operation was significantly lower than 8.7 (4.2) pg/ml of Group C. There were no significant changes in plasma TNF-alpha concentration throughout the study period in either group. Plasma cortisol concentrations of schizophrenic patients during surgery were significantly lower than those of control patients. The plasma IL-6 concentrations correlated with plasma cortisol concentrations in either group. We conclude that proinflammatory cytokine response to abdominal surgery is inhibited in schizophrenic patients.
Adult↗
Down-regulation of occludin expression in astrocytes by tumour necrosis factor (TNF) is mediated via TNF type-1 receptor and nuclear factor-kappaB activation.
Tight junctions form the diffusion barrier of brain microcapillary endothelial cells and support cell polarity. Also astrocytes express tight junction components such as occludin, claudin-1, ZO-1 and ZO-2, but do not establish a permeability barrier. However, little is known about the function and regulation of these molecules in astrocytes. We studied the impact of tumour necrosis factor (TNF) on occludin and ZO-1 expression in astrocytes. TNF decreased occludin, but not ZO-1 expression. In brain microcapillary endothelial cells, as well as in epithelial cells, occludin expression was not influenced by TNF. Removal of TNF from astrocytes restored the basal level of occludin. Down-regulation was inhibited by caffeic acid phenethyl ester, a specific inhibitor of nuclear factor-kappaB (NF-kappaB) activation. Exposure of astrocytes isolated from mice deficient in either TNF type-1 receptor (TNFR1), TNF type-2 receptor (TNFR2), or both, respectively, revealed that down-regulation was mediated entirely by TNFR1. ZO-1, which can interact with occludin, was found to co-precipitate connexin43, but not occludin. These findings demonstrate that TNF selectively down-regulates occludin in astrocytes, but not in cells forming established tight junctions, through TNFR1 and suggest that NF-kappaB is involved as a negative regulator.
Animals↗
Oestrogen receptor-alpha gene polymorphism is associated with endometriosis, adenomyosis and leiomyomata.
Endometriosis, adenomyosis and leiomyomata develop in women of reproductive age and regress after menopause or ovariectomy, suggesting that they grow in an oestrogen-dependent fashion. We investigated whether polymorphism in the oestrogen receptor-alpha (ERalpha) gene is related to oestrogen-dependent benign uterine disease. A total of 203 women with regular menstrual cycles underwent laparotomy or laparoscopy and were diagnosed histologically with endometriosis, adenomyosis and/or leiomyomata. Patients with cervical carcinoma in situ, tubal occlusion or adhesion but no other gynaecological disease were considered to be disease-free. A total of 179 women undergoing annual health examination were grouped as reference population. The distribution of PVUII genotypes (PP, Pp, and pp) of the ERalpha gene was different between each pair of the four groups of endometriosis, adenomyosis/leiomyomata, disease-free, and reference population (P = 0.022-0.0005), except between the former two groups. The PP genotype was less frequent in the groups of endometriosis (P = 0.0002) and adenomyosis/leiomyomata (P = 0.002) as compared to that in the disease-free group. In the endometriosis group, there was no difference in the distribution of PVUII genotypes due to complicating diseases (adenomyosis and/or leiomyomata) or severity of the clinical stages. These results suggest that the PVUII polymorphism of the ERalpha gene is associated with the risk for endometriosis, adenomyosis, and leiomyomata.
Adult↗
Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium.
Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Leptin is involved in the stimulation of reproductive functions, and local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta might play a role in early development. The mRNA and protein of the long form leptin receptor (OB-R(L)) but not of leptin are expressed in the human endometrium and the abundance of OB-R mRNA expression varies during the menstrual cycle with a peak in the early secretory phase. We examined the steroidal regulation of OB-R(L) mRNA expression. Northern blot analyses showed that in organ-cultured proliferative endometrial specimens, oestradiol (10(-9) and 10(-8) mol/l) had no acute effect on the OB-R(L) mRNA expression, whereas oestradiol plus progesterone (10(-8), 10(-7) and 10(-6) mol/l) or medroxyprogesterone acetate (10(-8) and 10(-7) mol/l) suppressed the expression by approximately 50%. This progestin-induced suppression was blocked by a concomitant addition of mifepristone. Additionally, incubation of endometrial specimens in the presence of leptin resulted in the phosphorylation of its intracellular target, STAT3 (signal transducer and activator of transcription 3). These results indicate that, in the human endometrium, progestins act via the progesterone receptors to suppress functional OB-R(L) mRNA expression, and may thereby alter the sensitivity of the endometrium to leptin.
Adult↗
Can initial distribution volume of glucose predict hypovolemic hypotension after radical surgery for esophageal cancer?
UNLABELLED: We recently reported that the initial distribution volume of glucose (IDVG) reliably measures the central extracellular fluid volume in the presence or absence of fluid gain or loss. We examined which variables, including IDVG, can predict subsequent hypovolemic hypotension produced by the continuous shift of the extracellular fluid from the central to the peripheral compartment early after radical surgery for esophageal cancer. IDVG and plasma volume were calculated after measuring cardiac index (CI), central venous pressure, and pulmonary artery wedge pressure immediately after admission to the intensive care unit. Intraoperative fluid balance and urine volume were also recorded. Postoperative hypovolemic hypotension was clinically defined as systolic blood pressure < 80 mm Hg responsive to IV fluid administration. Either IDVG < 105 mL/kg or CI < 3.4 L. min(-1). m(-2) was associated with subsequent hypovolemic hypotension (P = 0.002 for the former and P = 0.00 03 for the latter), while remaining variables were not. IDVG and CI were well correlated (r = 0.8 7, n = 25, P = 0.0001). Our results suggest that IDVG can help predict the subsequent hypovolemic hypotension early after radical surgery for esophageal cancer. IMPLICATIONS: Routine cardiovascular variables immediately after major surgery cannot predict the subsequent hypovolemic hypotension produced by the shift of the extracellular fluid. Glucose dilution using glucose 5 g and a one-compartment model can predict it simply and rapidly.
Adult↗
A comparison of the relaxant effects of olprinone and aminophylline on methacholine-induced bronchoconstriction in dogs.
UNLABELLED: IV aminophylline, a nonselective phosphodiesterase (PDE) inhibitor, is often used to treat an asthma attack during anesthesia. However, in some instances, aminophylline-resistant attacks are observed. Selective PDE3 inhibitors are now clinically available and have been reported to produce bronchodilation. Thus, we compared the relaxant effects of olprinone, a novel PDE3 inhibitor, and aminophylline on methacholine-induced bronchoconstriction. Dogs were anesthetized with pentobarbital. Bronchoconstriction was elicited with methacholine (0.5 microg/kg + 5.0 microg. kg(-1). min(-1)) and assessed as percentage of changes in the bronchial cross-sectional area (BCA; basal = 100%) monitored by bronchoscope. Initially, the relaxant effects of olprinone (n = 8; 0-1000 microg/kg) and aminophylline (n = 8; 0-50 mg/kg) were compared. The bronchial cross-sectional areas were assessed before and 30 min after methacholine infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg) and aminophylline (50 mg/kg). Olprinone and aminophylline dose-dependently antagonized bronchoconstriction by 56.2% +/- 21.3% (SD) and 68.0% +/- 30.3% with -log 50% effective dose (mean) of 4.80 +/- 0.38 (15.8) microg/kg and 1.96 +/- 0.42 (10.9) mg/kg, respectively. Aminophylline 50 mg/kg significantly increased plasma epinephrine, whereas olprinone did not. In addition, propranolol significantly reduced aminophylline-induced relaxation, but not olprinone-induced relaxation. Therefore, the relaxant effects of olprinone are independent of plasma epinephrine, whereas aminophylline effects may partially result from increased circulating concentrations of epinephrine. IMPLICATIONS: We compared the relaxant effects of olprinone and aminophylline on methacholine-induced bronchoconstriction in dogs. The relaxant effects of olprinone are independent of plasma epinephrine, whereas the aminophylline effects may be partly caused by an increase in plasma epinephrine.
Aminophylline↗
The relationship between pneumatic tourniquet time and the amount of pulmonary emboli in patients undergoing knee arthroscopic surgeries.
Near-fatal pulmonary embolism can occur immediately after tourniquet release after orthopedic surgeries. In this study, we determined the relationship between tourniquet time and the occurrence of pulmonary emboli in 30 patients undergoing arthroscopic knee surgeries, by using transesophageal echocardiography. The right atrium (RA) was continuously monitored by transesophageal echocardiography, and the number of emboli present was assessed with the following formula: Amount of emboli = 100 x [(total embolic area in the RA after tourniquet release) - (total area of emboli or artifact in the RA before tourniquet release)]/(RA area). The area was assessed 0-300 s after tourniquet release by using image-analysis software. The peak amount of emboli appeared approximately 50 s after tourniquet release. In addition, there was a significant correlation between amount of emboli (Ae [%]) and tourniquet time (Ttq [min]): (Ae = 0.1 x Ttq - 1.0, r = 0.795, P < 0.01). This study suggests that acute pulmonary embolism may occur within 1 min of tourniquet release and that the number of emboli is dependent on Ttq.
Adult↗
Density detection in dependent left lung region using transesophageal echocardiography.
BACKGROUND: Densities in dependent lung regions worsen oxygenation in patients with acute respiratory distress syndrome. Identification of these densities requires examination using computed tomography (CT). In this study, the authors evaluated the use of transesophageal echocardiography (TEE) to estimate densities in the dependent lung. METHODS: Forty consecutive patients with acute lung injury or acute respiratory distress syndrome who underwent CT and TEE examination were included in this study. Densities in the lower left lung area were detected through the descending aorta by TEE. Density areas observed by TEE were compared with those obtained by CT. The effect of positive end-expiratory pressure (PEEP) application on density area was also evaluated. RESULTS: Density areas in the dependent lung region measured by TEE were 12.0+/-6.1 cm2 (mean +/- SD) at mid esophageal position. Density areas evaluated using TEE in the left lung correlated significantly with those estimated with CT in the left and right lungs (P < 0.01 in both lungs). In addition, the authors observed a significant correlation between PaO2/FIO2 and density areas estimated using TEE (P < 0.05). During positive end-expiratory pressure application, the area of density estimated with TEE decreased and PaO2 improved. CONCLUSIONS: The authors clearly demonstrated that it is possible to estimate the density area of the dependent left lung regions in patients with acute lung injury or acute respiratory distress syndrome using TEE. It is also possible to observe the changes of density areas during application of positive end-expiratory pressure.
Adult↗