Video-based e-learning program for schoolteachers to support children of parents with mental illness: a cluster randomized trial.

BACKGROUND: Some children of parents with mental illness need support. This study aimed to develop and test the effectiveness of an e-learning program for training elementary schoolteachers to support children of parents with mental illness. METHODS: The program, which included a 30-min video-based e-learning program, aimed to help schoolteachers gain basic knowledge about mental illness and children of parents with mental illness, recognize children in need of support, and gain confidence in supporting them. A school-based cluster randomized controlled trial was conducted, and the schools were randomly divided into intervention and control groups. The teachers at these schools signed up for the program and participated individually. The outcome measures for the schoolteachers were evaluated at three time points: baseline (T1), post (T2), and one month later (T3). Along with the Sense of Coping Difficulty subscale (primary outcome measure), the following self-developed outcome measures were used: actual behaviors and attitude toward supporting children, knowledge, and self-assessment of program goals achievement. The Sense of Coping Difficulty subscale results at T3 were compared between the groups. Effectiveness over time was assessed for all the outcome measures. The interaction between baseline and intervention effects on the Sense of Coping Difficulty subscale was analyzed. As a part of the process evaluation, open-ended text responses were analyzed qualitatively. RESULTS: Baseline responses were collected from 87 participants in the intervention group and 84 in the control group. The total score of the Sense of Coping Difficulty subscale at T3 was significantly lower in the intervention group than in the control group (p = 0.007). Over time, a significant effect was observed on the Sense of Coping Difficulty subscale, actual behavior, knowledge of onset timing and probability of onset, and achievement of all program goals. Exploratory analysis was particularly effective for those who encountered a high level of difficulty in supporting children. The participants' text responses indicated that they planned to look carefully at children's backgrounds and stay close to them in the future. CONCLUSIONS: The program was effective for schoolteachers in supporting children of parents with mental illness. TRIAL REGISTRATION: UMIN000045483; 14/09/2021.

Histological finding of maternal antibody-associated congenital heart block accompanied by large atrial septal defect and severe cardiac dysfunction.

Cardiac dysfunction commonly occurs in congenital heart block associated with maternal anti-SSA antibodies, especially after pacemaker implantation. We report the case of a 4-year-old girl with antibody-associated congenital heart block and a large secundum atrial septal defect who presented with significant cardiac dysfunction 4 years after pacemaker implantation. Histological findings were useful for determining the course of treatment and perioperative risk of intracardiac repair.

Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study.

BACKGROUND: Genetic factors such as single-nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. METHODS: Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. RESULTS: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). CONCLUSIONS: We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. TRIAL REGISTRATION: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903 , date of registration: June 27, 2016, retrospectively registered.

Effects of posture and lower limb muscle strength on the results of the Star Excursion Balance Test.

[Purpose] This study aimed to clarify the relationship between the distance measurements in the Star Excursion Balance Test and participants' posture and lower limb muscle strength. [Participants and Methods] Nine healthy male college students participated in this study. Star Excursion Balance Test distance was measured in both lower limbs by performing anterior, posterolateral, and posteromedial trials; measuring the maximum reach; and performing three-dimensional motion analysis to determine the posture at maximum reach. Isokinetic muscle strength for knee flexion/extension, hip flexion/extension, and hip adduction/abduction were measured using an isokinetic machine. [Results] The hip extension strength, reach side ankle dorsiflexion angles, stance side knee flexion, reach side knee flexion, and knee flexion strength were selected as significant explanatory variables in the anterior direction. For the posteromedial direction, hip adduction and hip extension strength, reach side hip flexion angle, and stance side hip flexion angle were selected. For the posterolateral direction, reach side knee flexion angle and stance side ankle dorsiflexion, knee flexion strength and reach side hip flexion angle were selected. [Conclusion] The related factors differed between the dominant and non-dominant legs even in the same reach direction.

The relationship between the deep squat movement and the hip, knee and ankle range of motion and muscle strength.

[Purpose] We examined and clarified the relationship between the maximum squat depth and the range of motion of the ankle, knee, and hip joints, and the knee and hip muscle strength. [Participants and Methods] Nine healthy males participated in this study and performed a deep squat with the upper extremities raised; the movement was analyzed by two-dimensional motion analysis. We measured the ankle dorsiflexion, hip flexion, and knee flexion ranges of motion, as well as the knee extension and hip flexion muscle strengths and analyzed the relationship between the squatting motion, the range of motion, and the muscle strength of each joint. [Results] The right ankle dorsiflexion range of motion was a significant predictor of the ankle dorsiflexion angle on both sides. The right knee flexion range of motion was a significant predictor of the knee flexion angle, and the left knee flexion range of motion was a significant predictor of the trunk anterior tilt angle on both sides. The right ankle dorsiflexion range of motion was a significant predictor of the right hip flexion angle and vice versa. [Conclusion] This study reveals that movement on one side affects contralateral movement, which is important when evaluating the deep squat motion as a functional test.

Analysis of lower extremity side-reaching motion in junior high school baseball players.

[Purpose] The aim of this study was to clarify the movement pattern of the pelvis and trunk of junior high school baseball players based on the lateral reach motion of the lower limb, which is related to poor pitching movement. [Participants and Methods] Twenty-five male students belonging to a baseball club participated in this study. Each participant performed the lower limb side reach movement in the standing position, during which the movements of the knee joint, hip joint, pelvis, and trunk were analyzed. [Results] A significant correlation was found between reach distance and reach leg hip abduction, supporting leg hip abduction, trunk side bending, and trunk tilt. We found a significant correlation between reach leg hip abduction and pelvic tilt and trunk side bending and between supporting leg hip abduction and pelvic tilt, knee valgus, and trunk side bending. Furthermore, we found a significant correlation between knee valgus and lower leg tilt and trunk tilt and between trunk side bending and pelvic tilt. [Conclusion] This study suggests that in the standing position movement at this age, the hip and trunk movements are related to and affect performance.

Three-dimensional kinematic analysis of glenohumeral, scapular, and thoracic angles at maximum shoulder external rotation associated with baseball shadow pitching: comparison with normal pitching.

[Purpose] The glenohumeral, scapular, and thoracic angles at maximum shoulder external rotation during shadow pitching were evaluated and compared with those observed during normal pitching. [Participants and Methods] Our study included 13 healthy males with experience in pitcher activity. All participants performed both, shadow pitching using a towel and normal pitching using a ball. The external rotation of the glenohumeral joint, scapular posterior tilting, and thoracic extension angles in the cocking phase were measured using a 3-dimensional motion analysis system. The ratios of the glenohumeral external rotation angle to the scapular posterior tilting and/or thoracic extension angle were calculated to evaluate the contribution of the scapulothoracic joint at maximum external rotation during throwing/pitching activity. [Results] The glenohumeral external rotation angle at maximum shoulder external rotation was significantly smaller during shadow pitching than during normal pitching. The ratio of the glenohumeral external rotation angle to the scapular posterior tilting and/or thoracic extension angle showed no statistically significant difference. [Conclusion] We conclude that shadow pitching can reduce the external rotation motion of the glenohumeral joint compared to that during normal pitching and might be a useful pre-throwing program beneficial in the rehabilitation of those presenting with throwing injuries.

Impact of Pain on Incident Risk of Disability in Elderly Japanese: Cause-specific Analysis.

BACKGROUND: Although several cross-sectional studies have reported that pain is associated with functional disability in the elderly, data regarding a longitudinal association between pain and disability are inconsistent. This study aimed to investigate the association of pain severity with subsequent functional disability due to all causes as well as stroke, dementia, and joint disease/fracture. METHODS: The authors conducted a prospective cohort study of 13,702 Japanese individuals aged 65 yr or older. Information regarding pain severity during the previous 4 weeks and other lifestyle factors was collected via questionnaire in 2006. Data on the incidence of functional disability were retrieved from the Long-term Care Insurance database. Cox proportional hazards regression analysis was used to estimate the multivariate-adjusted hazard ratios for incident functional disability. RESULTS: The authors documented 2,686 (19.6%) cases of incident functional disability. The multivariate hazard ratio of functional disability was 1.15 (95% CI, 1.02 to 1.31) among respondents with moderate pain and 1.31 (95% CI, 1.12 to 1.54) among respondents with severe pain in comparison with those without pain (P trend < 0.001). These positive associations were particularly remarkable for disability due to joint disease/fracture: the multivariate hazard ratio was 1.88 (95% CI, 1.37 to 2.58) for moderate pain and 2.76 (95% CI, 1.93 to 3.95) for severe pain (P trend < 0.001). There was a negative association between pain severity and disability due to dementia (P trend = 0.041) and no significant association between pain severity and disability due to stroke. CONCLUSIONS: Among elderly Japanese individuals, the authors found a significant positive association between pain severity and future incident functional disability.

Effects of pitavastatin on walking capacity and CD34+/133+ cell number in patients with peripheral artery disease.

This multi-center prospective non-randomized comparative study investigated the effects of pitavastatin in patients with peripheral artery disease (PAD) in terms of exercise tolerance capacities and peripheral CD34+/133+ cell numbers. At baseline, a peripheral blood test was administered to 75 patients with PAD, along with a treadmill exercise test using the Skinner-Gardner protocol to measure asymptomatic walking distance (AWD) and maximum walking distance (MWD). Each patient was assigned to a 6-month pitavastatin treatment group (n = 53) or a control group (n = 22), according to the patient's preference. The tests were repeated in both groups at 3 and 6 months. Baseline AWD and MWD correlated positively with the ankle-brachial pressure index (r = 0.342, p = 0.0032 and r = 0.324, p = 0.0054, respectively). Both AWD and MWD values improved at 3 and 6 months compared with baseline, and the degrees of their improvement were higher in the pitavastatin treatment group. CD34+/133+ cell numbers did not change over time or between groups. Eighty-seven percent of patients in the treatment group attained low-density lipoprotein cholesterol levels below 100 mg/dL after 3 months. The study shows that pitavastatin may be effective in increasing exercise tolerance capacity in patients with PAD.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

AIM: Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. METHODS: Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. RESULTS: The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. CONCLUSIONS: This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF.

Chlorpromazine-induced changes in membrane micro-architecture inhibit thrombopoiesis in rat megakaryocytes.

Chlorpromazine often causes severe and persistent thrombocytopenia. Several clinical studies have suggested the presence of an as-yet-unknown mechanism in this drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. As we previously demonstrated in rat peritoneal mast cells or adipocytes, chlorpromazine is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane. Therefore, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of chlorpromazine on the membrane capacitance and Kv1.3-channel currents in rat megakaryocytes. By electron microscopic imaging of the cellular surface, we also examined the effects of chlorpromazine on the membrane micro-architecture of megakaryocytes. Chlorpromazine markedly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging techniques. As shown by electron microscopy, chlorpromazine actually changed the membrane micro-architecture of megakaryocytes, and was likely to halt the process of pro-platelet formation in the cells. This drug persistently decreased the membrane capacitance and almost totally and irreversibly inhibited the Kv1.3-channel currents in megakaryocytes. This study demonstrated for the first time that chlorpromazine is likely to inhibit the process of thrombopoiesis persistently in megakaryocytes, as detected by the long-lasting decrease in the membrane capacitance and the irreversible suppression of the Kv1.3-channel currents. Chlorpromazine-induced changes in the membrane micro-architecture are thought to be responsible for its persistent effects.

Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties.

BACKGROUND: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm), the absence of such changes by these drugs indicates their mast cell-stabilizing properties. METHODS: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. RESULTS: Relatively lower concentrations of tranilast (100, 250 µM) and ketotifen (1, 10 µM) did not significantly affect the GTP-x03B3;-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM) and ketotifen (50, 100 µM) almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. CONCLUSIONS: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells.

BACKGROUND: Macrolides, such as clarithromycin, have antiallergic properties. Since exocytosis in mast cells is detected electrophysiologically via changes in membrane capacitance (Cm), the absence of such changes due to the drug indicates its mast cell-stabilizing effect. METHODS: Employing the whole-cell patch clamp technique in rat peritoneal mast cells, we examined the effects of clarithromycin on Cm during exocytosis. Using a water-soluble fluorescent dye, we also examined its effect on deformation of the plasma membrane. RESULTS: Clarithromycin (10 and 100 µM) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-x03B3;-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells. CONCLUSIONS: This study provides for the first time electrophysiological evidence that clarithromycin dose-dependently inhibits the process of exocytosis. The mast cell-stabilizing action of clarithromycin may be attributable to its counteractive effect on plasma membrane deformation induced by exocytosis.

Electromyographic analysis of the infraspinatus and scapular stabilizing muscles during isometric shoulder external rotation at various shoulder elevation angles.

[Purpose] This study aimed to clarify activation of the infraspinatus and scapular stabilizing muscles during shoulder external rotation at various shoulder elevation angles. [Subjects] Twenty subjects participated in this study and all measurements were performed on the right shoulder. [Methods] Isometric shoulder external rotation strength and surface electromyographic data were measured with the shoulder at 0°, 45°, 90°, and 135° elevation in the scapular plane. The electromyographic data were collected from the infraspinatus, upper trapezius, middle trapezius, lower trapezius, and serratus anterior muscles. These measurements were compared across the various shoulder elevation angles. [Results] The strength measurements did not differ significantly by angulation. The infraspinatus activity was 92%, 75%, 68%, and 57% of the maximum voluntary contraction, which significantly decreased as shoulder elevation increased. The serratus anterior activity was 24%, 48%, 53%, and 62% of the maximum voluntary contraction, which significantly increased as shoulder elevation increased. [Conclusion] Shoulder external rotation torque was maintained regardless of shoulder elevation angle. The shoulder approximated to the zero position as the shoulder elevation increased so that infraspinatus activity decreased and the scapular posterior tilting by the serratus anterior might generate shoulder external rotation torque.

Effect of 12-month rehabilitation with low loading program on chronic respiratory disease.

[Purpose] The purpose of this study was to examine the effect of 12-month rehabilitation with low loading program on chronic respiratory disease. [Subjects and Methods] Twelve patients with chronic respiratory disease participated in this study, in which the effect of long-term rehabilitation for 12 months was assessed. Nine patients had chronic obstructive pulmonary disease, two had asthma, and one had interstitial pneumonia. In all patients, symptoms, lower-extremity strength, walking distance, activities of daily living, and quality of life were investigated to examine the effect of respiratory rehabilitation. [Results] After 12 months, the isometric knee extension strength and weight-bearing index both showed a significant increase. [Conclusion] The findings of this study suggested that improvement in lower-limb muscle strength can be achieved through long-term intervention, and indicated the validity of repetitive standing and walking exercises.

Ezetimibe enhances macrophage reverse cholesterol transport in hamsters: contribution of hepato-biliary pathway.

Reverse cholesterol transport (RCT) is pivotal in the return of excess cholesterol from peripheral tissues to the liver for excretion in bile and eventually feces. RCT from macrophages is a critical anti-atherogenicity mechanism of HDL. As the cholesterol absorption inhibitor ezetimibe promoted RCT in mice, which lack cholesterol ester transfer protein (CETP), we investigated its effects in hamsters, which have CETP. A high-cholesterol diet (HC) increased cholesterol levels throughout lipoprotein fractions and ezetimibe markedly reduced VLDL/LDL cholesterol levels under both normal chow (NC) and HC. However, ezetimibe did not affect and reduced HDL-cholesterol levels under NC and HC, respectively. Intraperitoneal injection of (3)H-cholesterol pre-labeled macrophages in an in vivo RCT assay increased tracer accumulation in the liver but reduced it in bile under HC, and these changes were completely cancelled by ezetimibe. Under both NC and HC, ezetimibe reduced tracer levels in the liver but increased them in feces, indicating promotion of RCT in vivo. We performed a RCT assay using hamsters subjected to bile duct ligation (BDL) to clarify whether a transintestinal cholesterol efflux (TICE) pathway contributes to ezetimibe's enhancement of RCT. BDL markedly inhibited macrophage-derived (3)H-cholesterol excretion to feces and cancelled ezetimibe's stimulatory effect on RCT, suggesting that biliary cholesterol excretion is a major contributor in RCT promotion by ezetimibe but the contribution of the TICE pathway is minimal. In conclusions, ezetimibe exerts an additive anti-atherogenic property by enhancing RCT in hamsters. Our findings suggest that this property is independent of the TICE pathway.

Salicylate inhibits thrombopoiesis in rat megakaryocytes by changing the membrane micro-architecture.

BACKGROUND/AIMS: Salicylate causes drug-induced immune thrombocytopenia. However, some clinical studies indicate the presence of additional mechanisms in the drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. Since salicylate is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. METHODS: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate on the membrane capacitance in rat megakaryocytes. Taking electron microscopic imaging of the cellular surface, we also examined the effects of salicylate on the membrane micro-architecture of megakaryocytes. RESULTS: Salicylate significantly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging technique. As shown by electron microscopy, salicylate actually halted the process of pro-platelet formation in megakaryocytes. CONCLUSION: This study demonstrated for the first time that salicylate inhibits the process of thrombopoiesis in megakaryocytes, as detected by the decrease in the membrane capacitance. Salicylate-induced changes in the membrane micro-architecture are thought to be responsible for its effects.

Mast cell involvement in the progression of peritoneal fibrosis in rats with chronic renal failure.

AIM: Peritoneal fibrosis is a serious complication in patients with end stage renal disease (ESRD), especially those undergoing long-term peritoneal dialysis therapy. Since the peritoneum is a major site of mast cell accumulation, and since mast cells are known to facilitate the progression of organ fibrosis, they would also contribute to the pathogenesis of peritoneal fibrosis. The aim of this study was to reveal the involvement of mast cells in the progression of peritoneal fibrosis in chronic renal failure. METHODS: Using a rat model with chronic renal failure (CRF) resulting from 5/6 nephrectomy, we examined the histopathological features of the rat peritoneum and compared them to those of age-matched sham-operated rat peritoneum. By treating the CRF rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of peritoneal fibrosis. RESULTS: The CRF rat peritoneum was characterized by the wide staining of collagen III and an increased number of myofibroblasts, indicating the progression of fibrosis. Compared to sham-operated rat peritoneum, the number of toluidine blue-stained mast cells was significantly higher in the fibrotic peritoneum of CRF rats. The mRNA expression of fibroblast-activating factors and stem cell factor was significantly higher in peritoneal mast cells obtained from CRF rats than in those obtained from sham-operated rats. Treatment with tranilast significantly suppressed the progression of peritoneal fibrosis in CRF rats. CONCLUSIONS: This study demonstrated for the first time that the number of mast cells was significantly increased in the fibrotic peritoneum of CRF rats. The proliferation of mast cells and their increased activity in the peritoneum were thought to be responsible for the progression of peritoneal fibrosis.

[A Case of Cesarean Section Preceded by Coil Embolization for Subarachnoid Hemorrhage under General Anesthesia].

We report a case of subarachnoid hemorrhage due to rupture of a cerebral aneurysm in a 29-year-old woman in the 34th week of pregnancy. The aneurysm at the anterior communicating artery was up to 10 mm in diameter on magnetic resonance imaging and scheduled for emergent coil embolization. Simultaneously, obstetricians determined that cesarean section should be performed. Maintaining anesthesia by propofol and remifentanil, coil embolization was first performed to avoid aneurism re-rupture, and the patient was then transferred from an angiography room to an operating room where a cesarean section was performed. After delivery, fentanyl 600 µg was intravenously administered, and the patient was extubated immediately after the operation without any complaints. The neonate (weighing 1,882 g, Apgar score 4 at 1 min and 5 at 5 min) also recovered with no complications after 24 hr artificial ventilation. In conclusion, intravenous anesthesia mainly with remifentanil is adequate for a pregnant patient receiving cesarean section preceded by neurosurgery.

Glucocorticoid mediates the transcription of OAT-PG, a kidney-specific prostaglandin transporter.

OAT-PG is a kidney-specific prostaglandin transporter and exclusively expressed at the basolateral membrane of proximal tubules in rodent kidneys. We previously reported that OAT-PG was dominantly expressed in the male kidney similar to the other SLC22 family proteins as organic anion transporter (OAT) 1 and OAT3. Recently, Wegner et al. revealed that a transcription factor, B-cell CLL/lymphoma 6 (BCL6), is associated with the male-dominant expressions of OAT1 and OAT3 in the rat kidney. Here, we performed the luciferase assay to investigate whether OAT-PG is also transcriptionally regulated by BCL6. However, the promoter activity of OAT-PG was not directly affected by BCL6 overexpression nor the testosterone treatment, suggesting that different regulatory mechanisms underlie the male-dominant transcriptional regulation of OAT-PG compared to those of OAT1 and OAT3. We newly found that adrenalectomy (Adx) of male rat caused a significant reduction of OAT-PG expression without any significant changes in the OAT1 and OAT3 expressions, and it was recovered by the dexamethasone administration. Furthermore, the renocortical PGE2 concentration was markedly increased in Adx male rat, concomitant with the downregulation of OAT-PG, and it was reduced to the basal level by dexamethasone treatment. In the luciferase assay, dexamethasone stimulated OAT-PG promoter activity but not OAT1. The luciferase activity responsiveness to dexamethasone was significantly reduced by the deletion of glucocorticoid response elements in the OAT-PG promoter region. These results suggest that glucocorticoid plays an important role in the regulation of the renocortical PGE2 concentration by the transcriptional regulation of OAT-PG in the rat kidney.