Fatal Fournier's gangrene caused by Clostridium ramosum in a patient with central diabetes insipidus and insulin-dependent diabetes mellitus: a case report.

BACKGROUND: Clostridium ramosum is a generally non-pathogenic enteric anaerobe, and Fournier's gangrene is a rare necrotizing soft tissue infection with male predisposition affecting the perineum and the genital area. We report, to our knowledge, the first case of Fournier's gangrene caused by C. ramosum in a female patient with multiple underlying conditions. CASE PRESENTATION: A 44-year-old woman with a 6-year history of insulin-dependent diabetes mellitus after total pancreatectomy and an 11-year history of central diabetes insipidus developed a pain in the genital area after a month of urinary catheter use. The lower abdominal pain worsened gradually over 2 weeks, and the pain, general fatigue, and loss of appetite prompted the patient's hospital admission. As she had severe edema in her pelvic and bilateral femoral areas, ceftriaxone was started empirically after collecting two sets of blood cultures. On hospital day 2, CT examination revealed the presence of necrotizing faciitis in the genital and pelvic areas, and the antibiotics were changed to a combination of meropenem, vancomycin, and clindamycin. Gram-positive cocci and gram-positive rods were isolated from blood cultures, which were finally identified as Streptococcus constellatus and C. ramosum using superoxide dismutase and 16S rDNA sequencing. An emergent surgery was performed on hospital day 2 to remove the affected tissue. Despite undergoing debridement and receiving combined antimicrobial chemotherapies, the patient's clinical improvement remained limited. The patient's condition continued to deteriorate, and she eventually died on hospital day 8. In the present case, the underlying diabetes mellitus, urinary incontinence due to central diabetes insipidus, undernutrition, and edema served as the predisposing conditions. CONCLUSIONS: C. ramosum is a potentially opportunistic pathogen among immunosuppressed persons and a rare cause of necrotizing fasciitis.

The rationale and design of reduction of uncontrolled hypertension by Remote Monitoring and Telemedicine (REMOTE) study.

PURPOSE: Although self-measurement of home blood pressure (HBP) is common in Japan and HBP telemonitoring via the Internet is possible, whether telemonitoring improves HBP control better than conventional practice remains unclear. Furthermore, hypertension care with online communication using telemonitored HBP is feasible, whereas the efficacy and safety of such telemedicine have not been established. We aim to compare traditional care, care with office visits using HBP telemonitoring, and antihypertensive telemedicine based on HBP telemonitoring. METHODS AND DESIGN: In total, 444 patients with uncontrolled hypertension will be recruited and randomly assigned to three groups: (1) control: usual care with office visits and HBP self-report, (2) telemonitoring: weekly assessment of transmitted HBP by physicians and treatment adjustment upon office visits, or (3) telemedicine: online communication instead of office visits to adjust medication using telemonitored HBP. Primary outcome is the time to control of HBP, and secondary outcomes include achieved HBP levels, adherence, treatment intensity, adverse events, patient satisfaction and cost-effectiveness. DISCUSSION: Hypertension care with telemonitoring and telemedicine are expected to require shorter time to achieve HBP control compared to usual care. Combining HBP telemonitoring with telemedicine may lower the hurdles for starting and persisting to hypertension treatment and eventually reduce cardiovascular events.

Evaluation of insulin sensitivity and secretion in primary aldosteronism.

In primary aldosteronism (PA), insulin response to glucose is not fully understood. Insulin action was elucidated using indices in 32 PA and 21 essential hypertension (EH) patients. These patients were evaluated using homeostasis model assessment (HOMA) indices, quantitative insulin sensitivity check index (QUICKI), and insulinogenic index (IGI), which were expressed for insulin sensitivity/secretion and the early phase of insulin secretion. Insulin sensitivity and early phase of insulin secretion were decreased in PA, and there was a negative correlation between serum potassium concentration and insulin sensitivity indices. These findings suggest that glucose intolerance in PA may be caused by hypokalemia-induced insulin resistance and hypokalemia-independent impairment of early-phase insulin secretion.

Effects of renal Na+/Ca2+ exchanger 1 inhibitor (SEA0400) treatment on electrolytes, renal function and hemodynamics in rats.

BACKGROUND: Na(+)/Ca(2+) exchanger 1 (NCX1) controls intracellular Ca(2+) concentration in various cell types. In the kidney, NCX1 is expressed mainly in the distal tubular basolateral membrane as well as in vascular smooth muscle. Tubular NCX1 is involved in Ca(2+) reabsorption, and NCX1 in renal arterioles may control intraglomerular pressure. However, the functions of renal NCX1 have not been studied in vivo. Therefore, this study examined the effects of renal NCX1 blockade on water and solute metabolism, renal function and blood pressure in rats. METHODS: Wistar-Kyoto rats were uninephrectomized, and an osmotic mini pump was implanted to infuse the remnant kidney cortex with a specific NCX1 inhibitor, SEA0400 (SEA), or vehicle for 7 days. RESULTS: Serum Ca(2+) concentration and urinary Ca(2+) excretion were similar between the vehicle- and SEA-treated groups. However, serum phosphate was significantly decreased by 8 % in the SEA group, with similar urinary phosphate excretion between the two groups. Systolic blood pressure was higher in the SEA group (117 ± 3 vs. 126 ± 1 mmHg, n = 9-11), with a 1.6-fold increase in plasma aldosterone concentration. However, SEA significantly reduced urinary protein excretion and the glomerular sectional area by 16 and 8 %, respectively. Similar experiment in spontaneously hypertensive rats produced different results. CONCLUSION: Renal SEA treatment reduced serum phosphate concentration, urinary protein and glomerular size with higher systemic blood pressure compared to control Wistar-Kyoto rats. Further study on renal NCX1 may be beneficial in delineating the pathophysiology of glomerular pressure control and calcium/phosphate regulations.

Effects of a high-sodium diet on renal tubule Ca2+ transporter and claudin expression in Wistar-Kyoto rats.

BACKGROUND: Urinary Ca2+ excretion increases with dietary NaCl. NaCl-induced calciuria may be associated with hypertension, urinary stone formation and osteoporosis, but its mechanism and long-term effects are not fully understood. This study examined alterations in the expressions of renal Ca2+ transporters, channels and claudins upon salt loading to better understand the mechanism of salt-induced urinary Ca2+ loss. METHODS: Eight-week old Wistar-Kyoto rats were fed either 0.3% or 8% NaCl diet for 8 weeks. Renal cortical expressions of Na+/Ca2+ exchanger 1 (NCX1), Ca2+ pump (PCMA1b), Ca2+ channel (TRPV5), calbindin-D28k, and claudins (CLDN-2, -7, -8, -16 and -19) were analyzed by quantitative PCR, western blot and/or immunohistochemistry. RESULTS: Fractional excretion of Ca2+ increased 6.0 fold with high-salt diet. Renal cortical claudin-2 protein decreased by approximately 20% with decreased immunological staining on tissue sections. Claudin-16 and -19 expressions were not altered. Renal cortical TRPV5, calbindin-D28k and NCX1 expressions increased 1.6, 1.5 and 1.2 fold, respectively. CONCLUSIONS: Chronic high-salt diet decreased claudin-2 protein and increased renal TRPV5, calbindin-D28k, and NCX1. Salt loading is known to reduce the proximal tubular reabsorption of both Na+ and Ca2+. The reduction in claudin-2 protein expression may be partly responsible for the reduced Ca2+ reabsorption in this segment. The concerted upregulation of more distal Ca2+-transporting molecules may be a physiological response to curtail the loss of Ca2+, although the magnitude of compensation does not seem adequate to bring the urinary Ca2+ excretion down to that of the normal-diet group.

The current state and future of internet technology-based hypertension management in Japan.

Internet-based information and communication technology is altering our lives. Although medicine is traditionally conservative, it can benefit in many ways from adopting new technology and styles of care. Hypertension is a prime condition for the practical application of digital health management because it is prevalent and undercontrolled, and its primary index, home blood pressure, can be effectively telemonitored. Compared to other conditions that require laboratory measures or the use of drugs with frequent side effects, hypertension can be managed without actual office visits with sufficiently low risk. In this review of hypertension in Japan, we discuss the current and somewhat fragmented state of internet technology and the components and processes necessary for smooth, integrated, and multidisciplinary care in the future. Although further clinical trials are required to show the safety and efficacy of information and communication technology-based care for hypertension, the deployment of telemonitoring and telemedicine in daily practice should be expedited to solve the hypertension paradox. Challenges remain relating to cost, data integration, the redesigning of team-based care, and the improvement of user experience, but information and communication technology-based hypertension management is sure to become pivotal in improving public health.

Efficacy of Telemedicine in Hypertension Care Through Home Blood Pressure Monitoring and Videoconferencing: Randomized Controlled Trial.

BACKGROUND: The burden of time is often the primary reason why patients discontinue their treatment. Telemedicine may help patients adhere to treatment by offering convenience. OBJECTIVE: This study examined the efficacy and safety of telemedicine for the management of hypertension in Japan. METHODS: Patients with uncomplicated hypertension were recruited through web advertising between November 2015 and February 2017. They were then screened, stratified by office systolic blood pressure (SBP), and randomized into two groups: usual care (UC) and telemedicine. The telemedicine group used a 3G network-attached home blood pressure (BP) monitoring device, consulted hypertension specialists from an academic hospital through web-based video visits, and received prescription medication by mail for 1 year. The UC group used the same BP monitoring device but was managed using self-recorded BP readings, which included their diary entries and office BP taken in a community practice setting. RESULTS: Initial screening was completed by 99 patients, 54% of whom had untreated hypertension. Baseline BP was similar between the groups, but the weekly average SBP at the end of the 1-year study period was significantly lower in the telemedicine group (125, SD 9 mmHg vs 131, SD 12 mmHg, respectively; P=.02). SBP in the telemedicine group was 3.4 mmHg lower in the morning and 5.8 mmHg lower in the evening. The rate of SBP control (135 mmHg) was better in the telemedicine group (85.3% vs 70.0%; P=.01), and significant adverse events were not observed. CONCLUSIONS: We present evidence suggesting that antihypertensive therapy via home BP telemonitoring and web-based video visits achieve better BP control than conventional care and is a safe treatment alternative that warrants further investigation. TRIAL REGISTRATION: UMIN-CTR UMIN000025372; https://tinyurl.com/47ejkn4b.

High Deep Femoral Artery Bifurcation Can Disturb Safe Femoral Venous Access: CT Assessment in Patients Who Underwent Femoral Venous Access Under Doppler Ultrasound Guidance.

Purpose: To retrospectively evaluate the variations of deep femoral artery (DFA) bifurcation on computed tomography (CT) and technical success in femoral venous access. Materials and Methods: CT images of 353 patients who underwent adrenal venous sampling were evaluated. Height with relation to the inferior border of the femoral head and direction of DFA bifurcations were classified as follows: type L, low bifurcation; type H1, high lateral bifurcation; type H2, high posterior to posterolateral bifurcation; type H3, high posteromedial bifurcation; and type H4, high medial bifurcation crossing in front of the femoral vein. Technical success and complications during femoral venous access were also evaluated. Results: The frequencies of types L, H1, H2, H3, and H4 were 82.7%, 9.1%, 6.9%, 0.4%, and 0.9%, respectively. In 92.2% of type H1 and 69.4% of type H2, the superior femoral artery displaced medially by the high DFA partially overlapped the femoral vein. Upon the inclusions of H3 and H4, in 14.4% of cases, the high DFAs could obstruct the access route to the femoral vein. Using Doppler ultrasound guidance, no significant differences were observed in the rates of success for puncture in the first attempt (84.5% vs. 75.4%, p = 0.122) and accidental arterial puncture (1.0% vs. 0%, p = 1.00) between low and high DFA bifurcations, respectively. Conclusions: High DFA bifurcation is observed in 17.3% of patients and could obstruct the access route to the femoral vein. This can be evaluated using Doppler ultrasound guidance to avoid accidental arterial puncture during femoral venous access.

Clinical factors affecting spot urine fractionated metanephrines in patients suspected pheochromocytoma/paraganglioma.

Urinary measurement of fractionated metanephrines is one of the best available biochemical tests for the diagnosis of pheochromocytoma and paraganglioma; however, false-positive results remain an issue. In addition, despite their convenience, there is no evidence to suggest that spot urine samples should replace the standard 24-h urine collection method. The objective of this study is to elucidate clinical variables that may influence the levels of spot urine fractionated metanephrines and to examine their instability. The study is a retrospective review of prospectively collected data from 949 patients whose spot urine fractionated metanephrines were measured under suspicion of pheochromocytoma or paraganglioma at our institution from January 2011 to June 2017. The effects of clinical factors such as age, sex, renal function, and medications on the level of spot urine fractionated metanephrines were evaluated. Urinary fractionated metanephrines were significantly higher in female subjects. They correlated with age but not with estimated glomerular filtration rate (eGFR). A multivariate regression model for urinary fractionated metanephrine levels revealed that age, female sex, eGFR, and the presence of α1-blocker medication were significantly positively correlated with urinary metanephrine (M) levels. Age, female sex, eGFR, and presence of α1-blockers and antidepressant and antipsychotic medications positively correlated with urinary normetanephrine (NM). In addition, age, female sex, eGFR, and presence of α1-blockers and antidepressant and antipsychotic medications were positively correlated with urinary M + NM. In conclusion, sex, age, eGFR, and treatment with α1-blockers, antidepressants, and antipsychotics may affect the levels of urinary fractionated metanephrines. When assessing urinary fractionated metanephrines in patients with suspected PPGLs, we must consider these factors.

Soluble (pro)renin receptor increased by hypoxia maintains oxidative metabolism in trophoblasts.

Elevated soluble (pro)renin receptor (s(P)RR) concentration in maternal blood is associated with gestational hypertension and preeclampsia. Placenta has abundant expression of (P)RR, and the binding of (P)RR with pyruvate dehydrogenase E1 beta subunit (PDHB) is reported to maintain oxidative metabolism. Thus, we hypothesized that placental hypoxia may increase (P)RR, and the increased (P)RR may preserve PDHB expression. Expression and functional analyses were performed using human placental trophoblast cells, mainly JAR cells. (P)RR co-immunoprecipitated and showed co-immunofluorescence with PDHB mainly in the mitochondria. Hypoxia treatment significantly increased intracellular s(P)RR protein expression, but secreted s(P)RR in the culture medium was decreased by hypoxia. Hypoxia treatment did not alter PDHB expression or activity in the basal condition, but when (P)RR was knocked down by siRNA, PDHB protein and activity were reduced by hypoxia. Acetyl-CoA, the product of PDH activity, was significantly reduced by hypoxia treatment with (P)RR siRNA. S(P)RR is generated from full-length PRR when cleaved by specific proteases. Protease inhibitor experiments suggested furin and site 1 protease as the enzymes generating s(P)RR in JAR cells, and only when treated by site 1 protease inhibitor, PF429242, PDHB protein showed a significant trend to decrease with hypoxia. In JAR cells, hypoxia increased intracellular s(P)RR, and (P)RR preserved the expression and function of PDHB during hypoxia. (P)RR may help maintain oxidative metabolism and efficient energy production during placental ischemia in hypertensive disorders of pregnancy.

Cosyntropin stimulation in adrenal vein sampling improves the judgment of successful adrenal vein catheterization and outcome prediction for primary aldosteronism.

The importance of cosyntropin stimulation during adrenal vein sampling (AVS) is not fully established, partly due to insufficient AVS data relating the presence and absence of cosyntropin stimulation with postoperative outcome. Therefore, we investigated differences in AVS indices before and after cosyntropin stimulation, and determined whether unstimulated or stimulated AVS indices better correlated with treatment outcome. A retrospective study was conducted in two parts: one with 185 patients who underwent AVS and the other with 81 patients who underwent unilateral adrenalectomy for unilateral aldosterone oversecretion. The selectivity index (SI), lateralized ratio (LR), and contralateral ratio (CR) before and after cosyntropin stimulations were determined, along with blood pressure outcome 1 year after surgery. Primary aldosteronism was diagnosed according to the Japanese Endocrine Society 2009 guidelines. The percentage of AVS patients with successful catheterization, defined as unstimulated SI > 2 before and stimulated SI > 5, increased after cosyntropin stimulation from 52% to 93% and from 74% to 98% for the right and left adrenal veins, respectively. LR decreased after cosyntropin stimulation (P < 0.001). In the postoperative patients, complete and partial clinical success was achieved in 49 and 27%, respectively. Low CR (<1) and high LR (≥2.6) after cosyntropin stimulation better correlated with postoperative blood pressure outcome than those before stimulation (CR < 1 and LR ≥ 2). These data suggest that cosyntropin stimulation facilitated the judgment of catheter insertion and postcosyntropin AVS indices may be more useful for predicting treatment outcome after unilateral adrenalectomy. Further study should examine the usefulness of cosyntropin stimulation in AVS performed in other settings.

Comparison of the shortened and standard saline infusion tests for primary aldosteronism diagnostics.

The saline infusion test (SIT) is widely used to confirm PA, but some patients may not tolerate the standard loading volume of 2 L saline over 4 h. The shortened SIT, loading only 1 L saline over 2 h, is suggested to be useful and would be more acceptable if the diagnostic utility of the shortened SIT is comparable to that of the standard SIT. We compared the diagnostic values of the plasma aldosterone concentration after 2 h of 1 L saline loading (2 h PAC) and that after 4 h of 2 L saline loading (4 h PAC) for the prediction of unilateral aldosterone hypersecretion and postoperative outcome. This retrospective, single-center study involved 555 PA-suspected patients who underwent SIT, 153 patients with adrenal vein sampling (AVS) results, and 37 patients with a 1-year postoperative evaluation. To detect the Japanese cutoff of 4 h PAC > 60 pg/mL, a 2-h PAC Youden Index at 66 pg/mL showed 91% sensitivity and 75% specificity. For unilateral aldosterone hypersecretion, the sensitivity and specificity of 2 h PAC were not inferior to those of 4 h PAC by Markov chain Monte Carlo (MCMC) methods. The sensitivity and specificity of 2 h PAC for postoperative reduction of anti-hypertensive drugs were also not inferior to those of 4 h PAC. Although using the 2 h PAC > 66 pg/mL cutoff may increase false positives for PA diagnosis, the shortened SIT, possibly using a cutoff value higher than 66 pg/mL, may be as useful as the standard SIT for selecting PA patients for AVS and to predict postoperative outcomes with reduced burden on patients.

Safety and feasibility of unilateral double femoral venous access including double sheath insertion via a single-hole method for adrenal venous sampling.

PURPOSE: To assess the safety and feasibility of unilateral double femoral venous access including double sheath insertion via a single-hole method (two-in-one method) for adrenal venous sampling (AVS). MATERIALS AND METHODS: Two 5-Fr sheaths were percutaneously inserted into a single femoral vein for AVS in 324 patients. Two needles were inserted sequentially in tandem under ultrasound guidance; furthermore, two sheaths were individually inserted (two-in-two method) if both punctures were successfully achieved. In the presence of a single puncture, two sheaths were inserted through two guidewires and a temporarily inserted sheath (two-in-one method). This protocol was repeated until two sheaths were successfully inserted. Thus, two sheaths were inserted with the two-in-one method in 56 patients (17.3%) and two-in-two method in 268 patients (82.7%). RESULTS: No significant differences in the technical success rates of AVS were observed (p = 0.067-0.647). Minor groin hematoma was observed more frequently in the two-in-one than in the two-in-two method (8.9% vs. 2.6%, p = 0.039). No major groin hematoma, deep venous thrombosis, or pulmonary embolization was observed. The mean number of needle puncture was 2.5 ± 1.3 and duration of inserting two sheaths 5.1 ± 3.9 min. CONCLUSION: Unilateral double femoral venous access including the two-in-one method is safe and feasible for AVS.

The (pro)renin receptor in health and disease.

The (pro)renin receptor ((P)RR) was first identified as a single-transmembrane receptor in human kidneys and initially attracted attention owing to its potential role as a regulator of the tissue renin-angiotensin system (RAS). Subsequent studies found that the (P)RR is widely distributed in organs throughout the body, including the kidneys, heart, brain, eyes, placenta and the immune system, and has multifaceted functions in vivo. The (P)RR has roles in various physiological processes, such as the cell cycle, autophagy, acid-base balance, energy metabolism, embryonic development, T cell homeostasis, water balance, blood pressure regulation, cardiac remodelling and maintenance of podocyte structure. These roles of the (P)RR are mediated by its effects on important biological systems and pathways including the tissue RAS, vacuolar H+-ATPase, Wnt, partitioning defective homologue (Par) and tyrosine phosphorylation. In addition, the (P)RR has been reported to contribute to the pathogenesis of diseases such as fibrosis, hypertension, pre-eclampsia, diabetic microangiopathy, acute kidney injury, cardiovascular disease, cancer and obesity. Current evidence suggests that the (P)RR has key roles in the normal development and maintenance of vital organs and that dysfunction of the (P)RR is associated with diseases that are characterized by a disruption of the homeostasis of physiological functions.

Primary aldosteronism in Klinefelter's syndrome: two cases.

SUMMARY: Primary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter's syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter's syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter's syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter's syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter's syndrome should be carefully considered. LEARNING POINTS: The pathogenesis of primary aldosteronism is still unclear. Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma. Serum luteinizing hormone, which is increased in patients with Klinefelter's syndrome, might contribute to the development of primary aldosteronism.

ACTH-Dependent Cyclic Cushing Syndrome Triggered by Glucocorticoid Excess Through a Positive-Feedback Mechanism.

CONTEXT: Cyclic Cushing syndrome is a rare variant of Cushing syndrome that demonstrates periodic cortisol excess. It has been thought that inhibition of a glucocorticoid positive-feedback loop is associated with remission of hypercortisolism in ACTH-dependent cyclic Cushing syndrome. However, the underlying mechanism that triggers the development of the hypercortisolism is still unknown. We observed a case of ACTH-dependent cyclic Cushing syndrome that was developed by exogenous glucocorticoids, possibly through a glucocorticoid positive-feedback loop. CASE DESCRIPTION: A 75-year-old woman had experienced cyclic ACTH and cortisol elevations six times in the previous 4 years. Her diagnosis was cyclic Cushing syndrome. During the hypercortisolemic phase, neither low-dose nor high-dose dexamethasone suppressed her plasma ACTH and cortisol levels. Daily metyrapone therapy decreased her plasma cortisol and ACTH levels during every hypercortisolemic phase. After the sixth remission of a hypercortisolemic phase, she took 25 mg of hydrocortisone for 4 weeks and developed ACTH-dependent hypercortisolemia. Treatment with 1 mg of dexamethasone gradually increased both plasma ACTH and cortisol levels over 2 weeks, resulting in the eighth hypercortisolemic phase. Treatment using a combination of dexamethasone and metyrapone did not increase plasma ACTH or cortisol level and successfully prevented development of ACTH-dependent hypercortisolism. CONCLUSION: We present an interesting case of cyclic Cushing syndrome in which ACTH-dependent hypercortisolemic phases relapsed during exogenous glucocorticoid treatment. A glucocorticoid positive-feedback loop and endogenous glucocorticoid synthesis may play key roles in the periodicity of hypercortisolism in cyclic Cushing syndrome.

Buffering roles of (pro)renin receptor in starvation-induced autophagy of skeletal muscles.

Autophagy is an intracellular catabolic process contributing to the regulation of nutrient homeostasis and cellular remodeling. Studies revealed that the nuclear translocation of transcription factor EB (TFEB) plays a key role in lysosomal biogenesis and autophagic pathways. The (pro)renin receptor [(P)RR] is a multifunctional protein playing a pivotal role in regulation of the tissue renin-angiotensin system and is known as an essential constituent of vacuolar H+ -ATPase, considered to be necessary for the autophagy-lysosome pathway. On the basis of these findings, we postulated that (P)RR may also contribute to the regulation of starvation-induced autophagy. In this study, starvation increased the expression of (P)RR and autophagy-related genes, especially, in the skeletal muscles of mice. In C2C12 mouse myoblast cells, starvation increased (P)RR expression and TFEB translocation, leading to the expression of autophagy-related genes. Knockdown of (P)RR enhanced both the TFEB translocation to the nucleus and the expression of autophagy-related genes during starvation. These results suggest that (P)RR plays a buffering role in starvation-induced autophagy by affecting the nuclear translocation of TFEB. Thus, (P)RR, which increases during starvation, is one of the important factors that control autophagy in the skeletal muscles. (P)RR may act as a buffer to reduce excessive TFEB-dependent autophagy flux.

Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency.

CONTEXT: Growth hormone deficiency (GHD) leads to obesity and may induce tissue hypoxia. As (pro)renin receptor [(P)RR] is reported to contribute to the aerobic metabolism by stabilizing pyruvate dehydrogenase (PDH), it may play a substantial role in GHD. OBJECTIVE: We aimed to investigate serum soluble (P)RR [s(P)RR] concentration, the origin of s(P)RR, and significance of (P)RR in GHD. DESIGN SETTING AND PARTICIPANTS: Serum s(P)RR concentration was examined in 72 patients with pituitary diseases, including 32 patients with severe GHD (SGHD) and after GH replacement in 16 SGHD patients. Leptin-deficient ob/ob obese mice were treated with pegvisomant, a GH receptor antagonist, to explore the source of elevated serum s(P)RR in GHD. Adipocytes were cultured with 5% O2 to examine the effects of hypoxia. RESULTS: Serum s(P)RR concentration was higher in patients with SGHD than in those without SGHD. Obesity was the important determinant of s(P)RR concentration. Serum s(P)RR concentration significantly decreased after GH replacement in SGHD patients. (P)RR mRNA expression was increased specifically in the adipose tissue (AT) of pegvisomant-treated obese mice compared with that of control obese mice. Hypoxia in cultured adipocytes increased (P)RR expression without affecting the PDH E1 ß subunit (PDHB) expression; however, with (P)RR knockdown by small interfering RNA, hypoxia significantly decreased the expression of PDHB. CONCLUSION: GHD patients showed increased serum s(P)RR concentration, possibly caused by obesity and hypoxia. (P)RR expression in AT of GHD patients may be elevated to help maintain aerobic metabolism under hypoxia. Thus, the elevated serum s(P)RR level may reflect hypoxia in ATs.

Image Fusion Guidance with Pre-procedural CT with Real-Time Fluoroscopy for Adrenal Venous Sampling.

PURPOSE: To assess the effectiveness of image fusion guidance (IF) with pre-procedural computed tomography (CT) with intraprocedural fluoroscopy for adrenal venous sampling (AVS). MATERIALS AND METHODS: AVS before and after ACTH stimulation including bilateral segmental sampling of effluent tributaries was performed in 62 patients with IF. A 3D volume rendering image, including adrenal glands and veins extracted from previously obtained contrast-enhanced CT images, was manually registered to the real-time X-ray fluoroscopy. The technical success rates, procedure time, radiation exposure, and volume of contrast medium used were compared with 49 patients who underwent AVS without IF. RESULTS: No significant differences in the technical success rates with and without IF were observed (98.4 vs. 91.8% for the right adrenal veins, p = 0.168, and 98.4 vs. 100% for the left adrenal veins, p = 1.000). The procedure time with IF was significantly shorter than that without IF (95.6 ± 18.8 vs. 108.4 ± 20.0 min, p = 0.001). The total dose-area product with IF was significantly lower than that without IF (43.1 ± 30.7 vs. 72.2 ± 45.3 Gy cm2, p < 0.001). The contrast medium volume used with IF was significantly lower than that without IF (54.6 ± 21.9 vs. 65.7 ± 27.6 mL, p = 0.020). CONCLUSIONS: Although the contribution to improving the technical success rates was small in our study, IF can effectively reduce procedure time, radiation exposure, and volume of contrast medium during AVS.