bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-B06-5: MITOCHONDRIAL CALPAIN-1 ACTIVATES NLRP3 INFLAMMASOME VIA CLEAVING ATP5A1 AND INDUCING MITOCHONDRIAL ROS IN CVB3-INDUCED MYOCARDITIS
Authors: Liu Xiaoxiao , Chen Zhiwei , Yu Yong , Shi Hui , Li Minghui , Yu Ying , Wang Yucheng , Chen Ruizhen , Ge Junbo
Published: January 2023

Therapeutic options on myocarditis are currently limited. Inhibition of Calpains have been shown to prevent CVB3-induced cardiac injuries, but the underlying mechanism has not been identified. Here, we examined whether NLRP3 inflammasome participates in CVB3-induced myocarditis and investigated the effects of Calpain-1 on CVB3-induced cardiac injury. NLRP3 inflammasome was activated in CVB3-infected hearts, evidenced by elevated protein levels of NLRP3, N-terminal domain of Gasdermin D, cleaved caspase-1, and increased colocalization of NLRP3 and ASC. Selectively inhibiting the activation of NLRP3 inflammasome by treating mice with MCC950 intraperitoneally decreased serum levels of CK-MB, LDH, IL-18, IL-1beta, prevented infiltration of inflammatory cells, and improved cardiac function in the setting of CVB3 infection. Meanwhile, transgenic mice overexpressing the endogenous Calpain inhibitor, Calpastatin (Tg-CAST) not only showed decreased apoptosis, inflammation, fibrosis, and enhanced cardiac function, but also exhibited inhibition of NLRP3 inflammasome and pyroptosis. Also, in vitro selectively inhibiting Calpain-1 with PD151746 protected cardiomyocytes from CVB3 infection with downregulated NLRP3 inflammasome and preserved cell viability. Mechanistically, we showed that mitochondrial dysfunction preceded inflammatory response after CVB3 treatment, and eliminating mitochondrial ROS over-produced by CVB3 with mito-TEMPO recapitalized phenotype observed in Tg-CAST mice. More directly, Tg-CAST mice presented alleviated mitochondrial dysfunction, and upregulation or inhibition of Calpain-1 activation in vitro regulated the mitochondrial respiration chain. Mito-TEMPO reversed the promoting effect of Calpain-1 on cell viability and NLRP3 inflammation. We also found that it was the mitochondrial Calpain-1, which was increased after CVB3 stimulation that activated NLRP3 inflammasome and resulted in cell death. Furthermore, ATP synthase-alpha (ATP5A1) was revealed to be the cleaving target of Calpain-1 after CVB3 treatment. Downregulating ATP5A1 with siATP5A1 impaired mitochondrial function, decreased cell viability and induced NLRP3 inflammasome. Taken together, these findings indicate that CVB3 infection induced Calpain-1 accumulation in mitochondria, resulted in ATP5A1 cleavage, mitochondrial ROS overproduction, eventually leading to NLRP3 inflammasome activation and pyroptosis, confirming the roles of Calpain in viral myocarditis and suggesting novel mechanisms. As a result, targeting Calpain appears a promising approach for the treatment of patients with viral myocarditis.
PS-B06-6: LOSS OF SKELETAL MUSCLE MASS INFLUENCES IMMUNE HOMEOSTASIS AND ACCELERATES THE RENAL-RELATED RISK OF HYPERTENSION
Authors: Mogi Masaki , Liu Shuang , Kiyoi Takeshi
Published: January 2023

Objective:

Patients with systemic lupus erythematosus (SLE) are predisposed to developing sarcopenia associated with their underlying proinflammatory condition and a decrease in motility. Also, SLE related autoimmune renal diseases are in part imputed to classical vascular risk factors such as hypertension. The relationship between circulating autoantibodies and hypertension has been recognized. How sarcopenia hastens immune dysfunction in SLE and autoimmunity per se is an underlying cause of hypertension remains uncertain. The present study elucidated the relationship between skeletal muscle loss and systemic immune status with regards to how sarcopenia-mediated immune dysfunction contributes as a critical risk factor in hypertension.

Design and Methods:

A denervation-induced skeletal muscle loss model was established, and the function of the immune system was evaluated. Systemic immune cell proportions and serum cytokine levels were profiled. Calcium influx and mitochondrial function were also assessed in the T cells. Finally, MRL/lpr mice were used to assess the influence of denervation-induced sarcopenia on SLE-related lupus nephritis progression and circulating autoantibodies, along with the cytokines that contributes to the development of hypertension, such as TNF-α and MCP-1, were evaluated.

Results:

The results of immune status profiling and functional assessment demonstrated that the loss of skeletal muscle shifts the immune balance in favor of the Th1/Th17 axis. Along with the peak Ca2+ influx, denervation-induced amyotrophy also impaired the spare respiratory capacity in mitochondrial of T cells, as well as the basal respiration and adenosine triphosphate production. The results of proteinuria tracing, serum blood urea nitrogen level, and C3 and IgE deposition in mesangium and capsular adhesion suggests that the sarcopenia promoted nephritis progression. A significant increase of the level in TNF-α, which promotes renal vasoconstriction, a pro-hypertensive effect, was also observed in sarcopenic mice.

Conclusion:

Consequently, sarcopenia might promote the progression of lupus nephritis because of the enhancement of systemic Th1/Th17 functions and accelerate the deposition of the vascular damage factors. The data herein suggested that the protection from developing hypertension in SLE patient may afforded by preventing skeletal muscle losing. A multidisciplinary approach is required to minimize the overall adverse impact of sarcopenia in the management of SLE-related hypertension.
PS-B06-7: ENDOTHELIAL DYSFUNCTION EXACERBATES KIDNEY DYSFUNCTION IN AGEING KIDNEY VIA ACTIVATION OF INFLAMMASOME
Authors: Wada Yoshihisa , Nagasu Hajime , Kadoya Hiroyuki , Kashihara Naoki
Published: January 2023

Background:

Ageing affects the function of the immune system and leads to immunosenescence, which is characterized by defective immune responses and increased systemic inflammation (also termed inflammageing). Inflammageing is maladaptive and results from multiple mechanisms, including aberrant inflammasome activation. The ASC is an essential component of inflammasomes that activates caspase 1. Endothelial dysfunction is also a common pathophysiologic mechanism of age-related organ damage. Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is an important mediator in the maintenance of vascular homeostasis. We have reported that the eNOS-NO pathway attenuates the progression of kidney injury via suppression of inflammasomes. However, the relationship between the eNOS-NO pathway and inflammageing in the kidney remains unclear. To determine if the eNOS-NO pathway attenuates kidney damage via the regulation of inflammasome activation in ageing kidneys, we used eNOS-deficient mice (eNOSKO) and eNOS-ASC double-knockout mice (eNOS-ASC-DKO).

Methods:

Wild-type mice (WT) and eNOSKO were used to determine the role of the eNOS-NO pathway in ageing kidneys. WT and eNOSKO were sacrificed at 18 months of age to harvest kidney tissue. The localization of inflammasome activation in the kidney was evaluated with immunohistochemical analyses. To determine the role of inflammasomes in ageing kidneys, we generated eNOS-ASC-DKO. The mRNA expression of inflammasome components were determined in isolated glomeruli.

Results:

The glomerular injury was more exacerbated in eNOSKO-18 M than in WT-18 M. In the immunohistochemical analyses, the expression of ASC coexisted with the macrophages detected by F4/80 staining in eNOSKO-18 M. These data suggested that the inflammasome activation was located in the macrophages. In the isolated glomeruli, the mRNA of the inflammasome components was higher in eNOSKO-18 M than in WT-18 M. The glomerular damage and tubulointerstitial damage were ameliorated in eNOS-ASC-DKO-18 M compared to eNOSKO-18 M. In summary, in eNOS-deficient mice, inflammasomes were activated in macrophages, and interstitial fibrosis was exacerbated. However, in eNOS-ASC-DKO-18 M mice, the tubulointerstitial damage was attenuated.

Conclusion:

Endothelial NOS/NO signaling ameliorates kidney damage in the aging process via the modulation of inflammageing associated with inflammasome-activation.
PS-B07-8: LEAFY VEGETABLE CONSUMPTION AND RISK OF METABOLIC SYNDROME AND ITS SYMPTOMS: A SYSTEMATIC REVIEW OF COHORT AND RANDOMISED CONTROL TRIALS
Authors: Muriuki Esther Njeri , Celik Begum , Kuhnle Gunter G C , Mills Charlotte E
Published: January 2023

Objective:

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including dyslipidemia, hypertension, hyperglycemia, and obesity. It increases the risk of type 2 diabetes, cardiovascular disease, and all cause mortality and exerts an enormous global burden on health systems. A better understanding of dietary approaches that can reduce the risk of MetS or its symptoms is crucial. Leafy vegetables contain bioactive compounds such as nitrates, dietary fibre and flavonoids that are protective against illnesses. However, investigations of whether leafy vegetable consumption can reduce MetS and its symptoms are unclear. This systematic review investigates the effect of leafy vegetable consumption on the risk of MetS and its symptoms.

Design and method:

Randomised control trials (RCT), and observational studies were searched in the Web of Science, Scopus, and MEDLINE databases until October 2020. Inclusion criteria were: studies in adults aged ≧ 18 years without MetS symptoms, the intervention of leafy vegetables, the outcome of a change in or incidence of MetS or any of its symptoms. The Cochrane tool and Newcastle Ottawa Scale were used to assess the risk of bias in RCTs and cohort studies, respectively.

Results:

A total of eight studies (six RCTs and two cohort studies) were included in the qualitative analysis. There were no trials assessing obesity or MetS. The results are shown in Table 1.

Conclusion:

Few studies evaluated the impact of leafy vegetable consumption on MetS and its symptoms. Beneficial effects of leafy vegetables are reported for blood glucose and blood pressure regulation, but the evidence is limited. More studies are needed to build a robust body of evidence.
PS-B07-11: EFFECT OF TRF INTERVENTION ON DIET INDUCED OBESITY: A NON-PHARMACOLOGICAL THERAPEUTIC STRATEGY
Authors: Fatima Nazmin , Sonkar Gyanendra Kumar , Mahdi Abbas Ali
Published: January 2023

Objectives:

Time-restricted feeding (TRF) regulates the circadian rhythm of food intake that protects against metabolic disorders. The aim of our study are 12 hours time restricted feeding effects on diet induces obesity in rats model.

Material & Method:

Total 21 Wistar rats were included i.e. control, TRF and High Fat diet (HFD) group. HFD group was fed with fatty diet at ad lib for two months and shifted to TRF (12 hours feeding i.e 8:00pm - 8:00am) for three months, after which they were again put back on ad lib. TRF group fed chow diet during 8:00pm to 8:00am for three months and then these rats shifted to ad lib for three months. Control group fed chow diet at ad lib. Body weight was calculated and blood samples were collected to measure blood glucose, insulin, lipid profile and gene expression.

Results:

The body weight of HFD group were significantly increased and TRF with chow diet were significantly decreased as compared to control rats (p = 0.0263) and (p = 0.0054) respectively. The level of HDL was reduced in rats fed with HFD whereas total cholesterol, TG and LDL were increased. TRF intervention with HFD diet reduced body weight, blood glucose level, TG and LDL and elevated the level of insulin, total cholesterol and HDL. Per1 and Bmal1 gene were up regulated in HFD group and after TRF intervention had reduced mRNA expression. TRF intervention with HFD and chow diet showed its legacy effect when put on ad lib.

Conclusion:

TRF intervention is easily adaptable lifestyle modification and non-pharmacological strategy can reduces the risk factor of obesity and its associated metabolic disorders.
PS-B08-5: EFFECT OF HIGH SALT INTAKE ON THE SODIUM CONTENT OF EACH BONE IN RATS
Authors: Munesada Mahiro , Kitada Kento , Kidoguchi Satoshi , Nakano Daisuke , Nishiyama Akira
Published: January 2023

Objective:

It has been reported that salt intake affects sodium content at the tissue level. Salt intake alters bone sodium content, which shifts the balance of osteoblasts and osteoclasts population and thereby affects bone density. However, it remains to be clarified whether there are site-specific changes in bone sodium content. In the present study, we examined the effect of high salt intake on the sodium content of each bone in normal rats.

Design and method:

Male Sprague Dawley rats (9 weeks old) were fed with a 0.2% normal salt diet with tap water to drink or a 4% high salt diet with 0.9% NaCl water to drink for 3 weeks. Each bone sodium content was measured by the ashing-flame photometer method.

Results:

High salt intake significantly increased total bone sodium content. Compared with normal salt group, high salt group exhibited a significant increase in the bone sodium content of skulls, ribs, or tailbones. On the other hand, high salt intake did not alter bone sodium content in the scapula, pelvis, vertebrae, and limb bones.

Conclusions:

There is a site-specificity of bone sodium accumulation with high salt intake. These findings suggest that each bone has local sodium regulation independently of whole bones and that bones could be separated into whether or not to store sodium. It may be necessary to evaluate the sodium content of each bone in various pathological models, rather than a simple measurement of the total bone sodium content.
PS-B09-8: N-METHYL-D-ASPARTATE (NMDA) RECEPTORS INDUCE RENAL VASODILATION AND REGULATES BLOOD PRESSURE.
Authors: Romero Cesar A , Wang Hong , Ren Yilin , Wall Susan M
Published: January 2023

Introduction:

N-methyl-D-aspartate receptors (NMDAr) are glutamate/glycine receptors expressed in the kidney. NMDAr induce renal vasodilation through an unknown mechanism. Connecting tubule-glomerular feedback (CNTGF) is a vasodilator feedback mechanism, initiated by ENaC in the connecting tubule producing afferent arteriole (AffA) vasodilatation and promoting sodium excretion. We hypothesized that NMDAr activation stimulate CNTGF and that the inhibition of NMDAr decrease CNTGF vasodilation inducing hypertension.

Methods:

We explore the presence of NMDAr receptors in mouse by transcriptome analysis of microdisseted tubules segments, total kidney western blot and immunofluorescence. We used mpkCCD cells (mouse principal cells) to explore the interaction between NMDAr and ENaC in PC using trasnwell current analysis and split-open tubule using patch clamp method. To determine the effect of NMDAr on CNTGF, we measured CNTGF-mediated AffA dilation in the presence or absence of NMDAr agonists glutamate and glycine with and without NMDAr antagonist (MK801), using a double-microperfusion method in rabbits, and in-vivo by micropunture technique in rats. To evaluate the effect of NMDAr on blood pressure (BP), we measure BP in NMDA 2C global knock out mice. BP was measure using tail cuff methods. To confirm the effect of NMDAr on BP we infused subcutaneously NMDAr inhibitor MK801 for 7 days in a gain of function β ENaC mutated allele mice on129/Sv background on normal salt diet.

Results:

NMDAr was found to be expressed in connecting tubule and co-localized with AQP2 and ENaC. In mpkCCD cells and open split tubules, NMDAr activation increase ENaC activity, while NMDAr inhibition decrease ENaC activity (p < 00.1). In-vitro, tubular microperfusion of NMDAr agonist increased AffA dilation (p < 0.001). NMDAr agonist-induced dilation was blunted with MK-801 (NMDAr blocker) and totally blocked with benzamil (CNTGF inhibitor). In vivo, NMDAr agonist increase CNTGF mediated vasodilation (P < 0.01). NMDAr 2C knock out mice showed high BP in comparison with wildtype (SBP 114.6 ± 7.3 vs 100.4 ± 2.2 mmHg, respectively, p = 0.01). In β ENaC mutated mice, the infusion of NMDAr inhibitor (Mk-801) induces hypertension (SBP 146 ± 8 mmHg) while the vehicle infused mice remained normotensives (110.7 ± 7.7 mmHg; p < 0.01).

Conclusions:

NMDAr in the connecting tubule increase renal vasodilation by activating CNTGF. The genetic ablation of NMDAr 2C or the pharmacological inhibition of NMDAr increase blood pressure. Future studies need to confirm the role of NMDAr in the pathogenesis of hypertension.
PS-B09-9: ENOS-NO PATHWAY REGULATES INFLAMMASOME ACTIVATION IN DIABETIC MICE VIA MODULATION OF CEBP TRANSLOCATION
Authors: Nagasu Hajime , Umeno Reiko , Kadoya Hiroyuki , Kashihara Naoki
Published: January 2023

Background:

Diabetic kidney disease (DKD) is one of the most common vascular complications of diabetes mellitus (DM). Endothelial dysfunction is also a common pathophysiologic mechanism of diabetic vascular complications. Nitric oxide (NO) produced in the endothelial cells by endothelial nitric oxide synthase (eNOS) is an important mediator for the maintenance of vascular homeostasis. In persons with diabetes, eNOS produces superoxide anion rather than nitric oxide, referred to as eNOS uncoupling which may contribute to endothelial dysfunction, albuminuria, and diabetic nephropathy. eNOS uncoupling can then lead to dysfunction of the eNOS-NO-pathway in diabetic glomeruli. To determine the mechanism of regulation of inflammasome activation by eNOS-NO pathway in DKD, we used eNOS deficient mice and eNOS-ASC double knockout mice.

Methods:

We used wild-type (WT) and eNOS-deficient mice (eNOSKO) to determine the role of the eNOS-NO pathway. Diabetes was induced by a single intraperitoneal injection of streptozocin. We then divided the mice into four groups: WT, WT/STZ, eNOSKO, and eNOS/STZ. Four weeks after the induction of DM, the mice were sacrificed, and their kidney tissues were harvested. Urinary albumin excretion was checked before the sacrifice, and glomerular damage was assessed by periodic acid-Schiff (PAS) staining. To determine the role of inflammasome on the development of glomerulopathy, we generated eNOS-ASC double knockout mice (eNOS-ASC-DKO). Also, to investigate inflammasome activation in glomeruli, the glomeruli were isolated from the kidney tissue by using Dynabeads.

Results:

Urinary albumin excretion was increased in WT/STZ compared with WT. These urinary albumin excretions were increased much more in eNOS/STZ than in WT/STZ, while the glomeruli were more damaged in eNOSKO/STZ than in WT/STZ. Urinary albumin excretion was lower in eNOS-ASC-DKO/STZ compared with eNOSKO/STZ, and the glomerular damage also was ameliorated in eNOS-ASC-DKO after treatment with STZ. S-Nitroso glutathione (GSNO) attenuated NLRP3 inflammasome activation after treatment with LPS-ATP. These results indicate that NO directly inhibits NLRP3-inflammasome activation. In addition, GSNO decreased the expression of inflammasome-related genes. To investigate the detailed the mechanism (epigenetic regulation), we performed Assay for Transposase-Accessible Chromatin-Sequencing (ATAC-seq) analysis. The binding region of the transcription factor CCAAT/ enhancer binding protein (C/EBP) β; was closed in the LPS+GSNO group significantly, compared with the LPS group.

Conclusion:

In eNOS-deficient mice, inflammasomes were activated, and glomerular injuries were exacerbated. However in eNOS-ASC-STZ mice, the glomerular damage were attenuated. Our data suggested that eNOS/NO signaling attenuates inflammasome activation via regulation of CEBP β;, leading to the suppressed development of DKD.
PS-C17-8: PREVALENCE OF PREDIABETES IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Pandey Naveen Kumar , Karki Biplave , Karki Prahlad
Published: January 2023

Objective:

Prediabetes is defined as an intermediate metabolic state between normoglycaemia and diabetes and includes those with impaired glucose tolerance and impaired fasting glucose. Diabetes mellitus is a well recognised risk factor for cardiovascular disease and acute coronary syndrome. However, evidence is limited regarding the prognostic value of ‘prediabetes’ on the clinical outcome of ACS. The objective of this study was to know the prevalence of prediabetes in ACS.

Design and methods:

This was a single center descriptive cross-sectional study to know the prevalence of prediabetes in 115 patients consisting of 71 males and 44 females, admitted with ACS in the Department of Cardiology between August 2020 to July 2021

Results:

Based on the definition of the American Diabetes Association, 35 (30.4%) patients were newly diagnosed diabetic, 46 (40%) patients were prediabetic and 34(29.6%) were non-diabetic. Based on HbA1c alone, 26.1% patients were classified as newly diagnosed diabetic patients, 38.3% patients were classified as prediabetic and 35.7% as non-diabetic. Compared with patients without diabetes, patients with prediabetes tended to have a longer hospital stay (p = 0.04), higher creatinine level (p = 0.01) and higher incidence of heart failure (p = 0.046).

Conclusion:

Prediabetes is common in patients presenting with ACS who are not previously known to have diabetes. Further multi-center studies with long term clinical follow-up are needed to draw a firm conclusion regarding the impact of prediabetes on clinical outcome.
PS-C18-1: SLEEP SCORE AMONG HEALTH-RELATED QUALITY OF LIFE SUBSCALES PREDICTS TECHNIQUE SURVIVAL IN PATIENTS WITH PERITONEAL DIALYSIS
Authors: Nagasaka Tomoki , Uchiyama Kiyotaka , Hama Eriko Yoshida , Kusahana Ei , Nakayama Takashin , Yasuda Itaru , Morimoto Kohkichi , Washida Naoki , Itoh Hiroshi
Published: January 2023

Purpose:

There is sufficient evidence that peritoneal dialysis (PD) is superior to hemodialysis in terms of health-related quality of life (HRQOL), and higher HRQOL scores are associated with better clinical outcomes in patients with PD, however, the specific HRQOL subscales that predict prognosis remain uncertain.

Design and method:

In addition to various PD-related parameters and exercise capacity, HRQOL of outpatients with PD were assessed using Kidney Disease Quality of Life-Short Form Japanese version 1.3 from March 2017 to March 2018, and the association of HRQOL items with technique survival was prospectively analyzed until June 2021.

Result:

Among the 50 recruited PD outpatients, age and PD vintage were 63.8 ± 9.6 and 3.8 ± 2.8 years, respectively, and 21 patients discontinued PD and transferred to hemodialysis during the study period. In a univariate Cox proportional hazards model, higher scores (per 10) for symptoms, sleep, and vitality among HRQOL subscales were significantly associated with lower technique failure rate (Hazard Ratio(HR) 0.66, P = 0.002; HR 0.70, P = 0.006; and HR 0.80, P = 0.04, respectively). In multivariate analysis adjusted for Charlson comorbidity index, incremental shuttle walk test distance, and baseline PD vintage, only higher sleep score was significantly associated with lower technique failure rate (HR 0.68 per 10, P = 0.003). Among PD-related parameters, serum potassium level was significantly inversely correlated with sleep score (r = -0.34, P = 0.01).

Discussion and Conclusion:

Our results suggest that sleep score among HRQOL subscales is particularly useful as a predictor of technique survival in patients with PD. Improvement in sleep quality may improve technique survival in prevalent PD patients.
PS-C19-3: HYDROCHLOROTHIAZIDE WAS NOT ASSOCIATED WITH PHOTOSENSITIVE OR PHOTOTOXIC REACTIONS AND DNA-DAMAGE IN VIVO AND IN VITRO (THE HCTOX-STUDY)
Authors: Goetzinger Felix , Hohl Mathias , Millenaar Dominic Norman , Lauder Lucas Douglass , Reichrath Joerg , Meyer Markus Robert , Boehm Michael , Ukena Christian , Mahfoud Felix
Published: January 2023

Objective:

Pharmacoepidemiologic studies associated the use of HCT with an increased risk of skin cancer, resulting in a decrease of HCT prescriptions, in turn leading to worsening of blood pressure therapy in a significant proportion of patients. However, whether HCT causes skin cancer remains elusive. Hence, we aimed to examine the photosensitive and phototoxic potential of HCT in vivo in a randomized, placebo-controlled trial. To further enlighten the pathophysiologic mechanisms of carcinogenesis and phototoxicity caused by HCT in vitro, we conducted a series of laboratory experiments.

Design and method:

A randomized, double-blind, placebo-controlled clinical trial to assess the phototoxic properties of HCT was conducted, assigning 30 healthy normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg daily or placebo once daily for 15 days. The skin photosensitivity by phototesting, office blood pressure, serum 25-hydroxyvitamin D (25(OH)D) status and urinary excretion of thymidine-dimers, i.e. cyclobutan-dimers by ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) following whole-body irradiation were assessed.

To further assess the pathophysiologic mechanisms of possibly HCT induced photosensitivity, human keratinocytes (HaCaT) were incubated with HCT and then irradiated with UV-B radiation (311 nm one burst of 100 J/cm2). rt-PCR-testing and western blots were performed to analyze reactive oxygen species, inflammation, and carcinogenesis.

Results:

All 30 participants were adherent to the protocol, which was confirmed by UHPLC-HRMS analysis of serum and plasma. Skin photosensitivity to exposure of UV-A and UV-B radiation did not change in both groups (HCT vs. placebo: MED-UVB change 0.0 J/cm2 vs. 0.2 J/cm2; p = 0.06). No thymidine-dimers were detectable in either group. Systolic blood pressure decreased in both groups (-5.2 mmHg vs. 5.4 mmHg; p = 0.94), as did diastolic blood pressure (-4.3 mmHg vs. -1.9 mmHg; p = 0.34). Serum 25(OH)D increased in both groups (3.1 ng/ml vs. 1.2 ng/ml; p = 0.52).

HCT in combination with a single high-intensity bursts of UV-B radiation was not associated with increased expression of inflammatory proteins, chronic inflammation and reactive oxygen species.

Conclusions:

HCT was not associated with increased photosensitivity for UV-A or UV-B radiation in healthy volunteers. Moreover, no relevant DNA-damages as measured by UHPLC-HRMS were detectable in either group. The combination of HCT treatment and a single burst of UV-B did not increase inflammatory markers. HCT appeared to be safe in healthy volunteers and was not associated with photosensitivity or DNA-damages in vivo.
PS-C19-4: NOCTURNAL HYPERTENSION AMONG TREATED HYPERTENSIVE PATIENTS
Authors: Sukhbaatar Pagmadulam , Badrakh Burmaa , Sodovsuren Naranchimeg , Unurjargal Tsolmon
Published: January 2023

Nocturnal hypertension among treated hypertensive patients Pagmadulam sukhbaatar t, Burmaa Badrakh 2, Naranchimeg Sodovsuren, 2Tsolmon Unurjargal2 t Mongolia-Japan University Hospital of MNUMS 2 Mongolian National University of Medical Sciences

Objectives of this study were to determine the prevalence of nocturnal hypertension in treated hypertensive patients and factors associated with its presence.

Methods:

This hospital based cross-sectional study included 160 hypertensive patients, who underwent 24-h ambulatory blood pressure monitoring. According to the national guideline for hypertension nocturnal hypertension was defined as mean night-time systolic blood pressur ≧ 120 mm Hg or mean night-time diastolic blood pressure ≧ 70 mm Hg. Cardiovascular risk factors (smoking, alcohol use, obesity, diabetes, lack of physical activity) were compared in hypertensive patients with and without nocturnal hypertension.

Results:

The mean age of the participants was 62.4 years and 42.5% were men. Approximately 15% and 16.2% of all patients were current smokers and alcohol over users. 61.2% and 75% had obesity and physical activity lacking and 11.2% had diabetes. All patients were on blood pressure lowering medications, but 43.7% of patients were taken only one medication for high blood pressure.

Mean night-time systolic blood pressure and diastolic blood pressure were in men and women 140.6 ± 20.2 mm Hg and 86.5 ± 11.2 mm Hg and 145.6 ± 17.1 mm Hg and 79.8 ± 7.3 mm Hg respectively. The nocturnal hypertension was detected in 61.6% of patients (64% in male, 60% in female). Our study revealed that nocturnal hypertension was significantly higher in patients with diabetes and obesity than in patients without diabetes and obesity.

Conclusion:

The prevalence of nocturnal hypertension was high. Nocturnal hypertension among treated patients was associated with diabetes, obesity and mono therapy.
PS-C20-1: NIGHT-TIME BLOOD PRESSURE-LOWERING DRUG TREATMENT FOR THE PREVENTION OF CARDIOVASCULAR DISEASE IN DIABETES: A PROPOSED RANDOMISED CONTROLLED TRIAL
Authors: Ho Chau , Nelson Mark , Doust Jenny , Chowdhury Enayet Karim , Schlaich Markus , Xu Dan , Reid Christopher
Published: January 2023

Rationale:

An increase of 20 mmHg in night-time blood pressure (BP) and a pattern of a higher BP at night than during the day was independently associated with an increased risk of 21% and 48% cardiovascular disease respectively. This association was more likely to present in type 2 diabetes mellitus (DM) patients.

Objectives:

This proposed study aims to examine the effect of taking night-time BP lowering drug treatment targeting night-time BP profile as compared to the conventional once-daily morning dose on the prevention of cardiovascular disease event in diabetes.

Design:

A Prospective Randomized Open-label with Blinding of Endpoint assessment.

Methods:

Men and women diagnosed with type 2 DM patients who are 60 years or over in Australia will be included in the trial. As per the current Australia guideline, these individuals meet the criteria to initiate BP lowering drug treatment for CVD prevention. The trial will be conducted as a “digital clinical trial” for participant recruitment, retention and data collection through an interactive web page platform. Participants will be referred by their health practitioners. Eligible participants will be randomised to either night-time or morning dosing treatments with a 1:1 ratio: a) Taking all of their usual once-daily dose of BP-lowering medications at bedtime (between 20:00 and midnight) or b) Taking a once-daily dose of BP-lowering medications upon awakening (between 06:00 and 10:00). The primary endpoint is the occurrence of any first major CVD events after randomisation. We expect to complete the participant recruitment over the first two years and finalise the analysis after an average follow-up of 5 years.

Results:

We are finalising the project protocol and have applied the proposed project to relevant research grants. An ethics application has also been prepared. We plan to run a one -year pilot trial and then transfer to the full study.

Conclusion:

The outcomes of this study will contribute to Level 1 evidence on the effect of night-time BP-lowering drug treatment in the prevention of cardiovascular disease in diabetes. Due to the nature of pragmatic design, our research outcomes are straightforward and could be adopted in current practice without any further cost. Changing the ingestion time of BP-lowering drug treatment from morning to night-time is very cost-effective and promises to reduce the financial and clinical burden of CVD and DM on the healthcare system.
PS-C20-6: SINGLE-PILL COMBINATION ENABLES FAST TARGET BP ACHIEVEMENT
Authors: Brguljan Jana , Chazova Irina E , Gaciong Zbigniew , Simic Dragan , Vajer Peter , Zelveian Parounak Harutyun , Jelakovic Bojan
Published: January 2023

Objective:

To assess the treatment response and time to reaching the target clinical blood pressure (BP) with the single-pill combinations (SPCs) of perindopril/amlodipine (P/A) and perindopril/amlodipine/indapamide (P/A/I) in naïve and uncontrolled hypertensive patients.

Design and method:

440 adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial PRECIOUS. Office BP was measured with a validated automated BP-measuring device by qualified health professionals following guidelines protocol. At inclusion, naïve or patients uncontrolled on previous mono or dual therapy other than perindopril and amlodipine were assigned to dual SPC arm with initial dose of 4/5 mg P/A. Those uncontrolled on previous dual or triple therapy were assigned to triple SPC arm with initial dose of 4/5/1.25 mg P/A/I. If not reaching office BP control, initial dose was up titrated in 4-week intervals to 8/5 mg, 8/10 mg P/A or 8/10/2.5 mg P/A/I in dual SPC arm and to 8/5/2.5 mg or 8/10/2.5 mg P/A/I in triple SPC arm.

Results:

In the first 4-week interval, 43.6% of the FAS population reached the target BP with a significant decrease by -16.1/-10.1 mmHg from the mean baseline office BP of 157.0/98.1 mmHg (p < 0.001). The proportion of patients reaching BP control increased after each up-titration interval to 63.9%,78.0% and 79.8% after 8, 12 and 16 weeks, respectively. The mean BP values decreased further till the end of the trial, reaching the mean BP value of 128.1/81.1 mmHg after 16 weeks. Interestingly, in subgroup of patients who did not need up-titration (n = 154), a decrease of -24.2/-16.2 mmHg (-15.4%/-16.3%) was already achieved in the first 4 weeks and grew moderately to -28.2/-17.7 mmHg (-18.1%/-17.9%) till the end of the trial. On the other hand, in the first 4 weeks, in subgroup of patients who needed up-titration (n = 274) the decrease was a moderate -11.8/-6.9 mmHg (-7.1%/-6.6%), but grew with every up-titration step at the same pace to reach a decrease of -28.4/-16.7 mmHg (-17.6%/-16.4%) at the end of the trial.

Conclusions:

In only 4 weeks 43.6% of patients who responded to the initially prescribed therapy achieved target BP, exhibiting more than 2x bigger BP decrease than non-responders who needed further intensification of therapy. BP decrease from the baseline was similar in both groups, however following a different pattern. At the end of the trial, almost 80% of patients reached BP control with the SPC treatment strategy.
PS-C21-4: EPIGENETIC ALTERATION OF 11B;-HYDROXYSTEROID DEHYDROGENASE 1 IN THE ADIPOSE TISSUE OF PATIENTS WITH ENDOCRINE HYPERTENSION
Authors: Takeda Yoshiyu , Takeda Yoshimichi , Demura Masashi , Kometani Mitsuhiro , Karashima Shigehiro , Aono Daisuke , Konishi Seigo , Yoneda Takashi
Published: January 2023

Objective:

11Beta-hydroxysteroid dehydrogenase 1 (11β;-HSD1) is a key enzyme involved in metabolic syndrome. The epigenetic control of 11β;-HSD1 is unclear. We examined the 11β;-HSD1 mRNA level and methylation status of the promoter region of the 11β;-HSD1 gene in the adipose tissue of patients with endocrine hypertension.

Methods:

We evaluated 8 adipose tissue specimens from patients with subclinical Cushing syndrome (SCS) due to cortisol-producing adenomas, 10 tissue specimens from patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). SCS and primary aldosteronism were diagnosed according to the guideline of the Japanese Endocrine Society. The mRNA level of 11β;-HSD1 was quantified using a real-time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific for the human 11β;-HSD1 promoter region.

Results:

The glycohemoglobin level was significantly higher in patients with SCS or APA compared with those with NFA (p < 0.05). Blood pressure was significantly elevated in patients with APA compared with those with SCS or NFA (p < 0.01). The 11β;-HSD1 mRNA level was significantly increased in the adipose tissues of SCS and APA compared with NFA patients (p < 0.05). The methylation ratio was significantly lower in SCS compared with APA or NFA patients (p < 0.05).

Conclusion:

11β;-HSD1 gene expression is partly controlled by an epigenetic mechanism in human tissues. The pathophysiological roles of epigenetic control of 11β;-HSD1 gene expression in adipose tissue requires further study.
PS-C22-7: RENAL FUNCTION AND URINARY PROTEIN 1 YEAR AFTER INITIATION OF ESAXERENONE
Authors: Aoyama Kazuki , Nakajima Yuya , Meguro Shu , Itoh Hiroshi
Published: January 2023

Objective:

It has been two years since the prescription of esaxerenone was started in Japan, but there are currently limited reports on clinical data after administration. The purpose of this study is to examine the real-world clinical data on renal function, urinary protein, and other clinical data on the esaxerenone-treated group compared to the non-administration group.

Design and method:

In this study, research subjects were selected from the patient population attending the Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine, Japan between March 1, 2021 and January 31, 2022. 354 patients treated with esaxerenone and 14,480 patients not treated with esaxerenone were compared on clinical indices 1 year after the initiation of treatment. Covariate adjustment by propensity score-matched analysis was carried out.

Results:

In the analysis of all patients, serum creatinine tended to increase after treatment with esaxerenone compared to before, but the difference was not significant. No consistent trend was observed for urinary protein and serum potassium.

Conclusions:

We are currently performing propensity score-matched analysis stratifying for blood pressure and urinary albumin to creatinine ratio at the start of treatment.

COI:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work in this report.
PS-C22-10: SERUM SOLUBLE (PRO)RENIN RECEPTOR CONCENTRATION AS A PROGNOSTIC FACTOR IN PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS
Authors: Morimoto Satoshi , Amari Yoshifumi , Bokuda Kanako , Suda Chikahito , Ichihara Atsuhiro
Published: January 2023

Objective:

The (pro)renin receptor [(P)RR)] is a multifunctional protein with roles in angiotensin II-dependent and -independent intracellular cell signaling and as an adaptor protein between the Wnt receptor complex and vacuolar proton-translocating adenosine triphosphatase. The (P)RR is cleaved to generate soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. Patients undergoing hemodialysis (HD) have poor prognosis because of the increased prevalence of cardiovascular and malignant diseases. This study was conducted to investigate whether the s(P)RR level is associated with new onset of cardiovascular events or malignant diseases and prognosis in patients undergoing HD.

Design and method:

A total of 258 patients undergoing maintenance HD who were enrolled in our cohort study investigating the relationships between serum s(P)RR levels and background factors were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new onset of cardiovascular events or malignant diseases and mortality during the follow-up period.

Results:

The cumulative incidence of new onset of cardiovascular events (P = 0.009) and cardiovascular deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≧ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001 - 1.083, P = 0.046).

Conclusions:

These data showed that the serum s(P)RR level is associated with cardiovascular events and mortality, suggesting that the serum s(P)RR level could be used as a biomarker for selecting patients requiring intensive care.
PS-C23-3: POSTPRANDIAL HYPERKALEMIA AFTER K RICH DIET IN HEALTHY HUMAN
Authors: Nakagawa Hiromi , Inaba Miho , Goto Yumi , Sasadate Natsuki , Suzuki Takahiro , Shimosawa Tatsuo
Published: January 2023

Objective:

Dietary potassium is known to lower the blood pressure but high attentions should be paid not to induce hyperkalemia in patients with renal impairment. Recently we experienced a case postprandial hyperkalemia (from 4.8 to 6.0mmol/L). We investigated the pathophysiology of postprandial hyperkalemia in healthy volunteers.

Design and method:

Twelve healthy volunteers (age: 23 to 58 years old, eGFR: 76.1 to 119.9 mL / min / 1.73 m2) who obtained informed consent took potassium-rich diet (2000 mg, with avogado, tomato juice and banana), serum K, urinary K, and urinary creatinine (CRE) were measured before, 1 hour and 2 hours after the meal. Urinary K was corrected by urinary CRE.

Results:

The serum K level increased significantly at 1 hour (p < 0.01) and 2 hours (p < 0.05) after the meal, and the urinary K / CRE increased 2 hours (p < 0.01) compared to the pre-meal value. In two cases, serum K level increased by 0.7 mmol / L 1 hour after the meal and urinary K / CRE increased by 60 mmol / g · CRE 2 hours after meal. Other 10 cases, those with little change in serum K levels urinary K/CRE were constant during the examination.

In 5 of 12 patients, the serum K level increased by 0.3 mmol / L or more, and in this group, the excretion of urinary K 1 hour after meal was small and increased significantly 2 hours after the meal.

Conclusions:

Potassium-rich diet may increase serum K levels in healthy human. We can not predict the postprandial elevation of K by regular biomarkers. The delay of urinary excretion plays a role in postprandial hyperkalemia. To assess K status, we should consider the status of fasting in patients. Further investigations are required to reveal precise mechanism in alteration of K handling in the kidney.
PS-C23-4: I CHOOSE ULTRA PROCESSED FOOD SINCE MORE PRACTICAL AND TASTIER: A QUALITATIVE STUDY OF ULTRA-PROCESSED FOOD CONSUMPTION AMONG ADULTS
Authors: Faza Farah , Fikha Idri Iqra , Bafani Unun Fitry Febria
Published: January 2023

Objective:

Industrialization, as an impact of globalization, produced more ultra processed food (UPF) which triggered a nutrition transition. The UPF, which is dominated by instant and junk foods, caused a higher risk of metabolic diseases. Although the UPF consumption was not high (±15%) among Indonesian adults yet the factors of choosing UPF should be explored to design the best nutrition intervention for improving diet quality.

Design and method:

We performed four focused group discussions (FGD) and observations in four administrative cities in a province during December 2021. Each group of the FGD consisted of 8 to 10 adults aged above 20 years. The FGD session was conducted by a trained moderator and assisted by two trained enumerators. The data were transcribed verbatim and analyzed using an inductive thematic approach. An FGD lasted between 50 to 60 minutes, covering three topics regarding dietary patterns, the type of food commonly consumed, including the reason for consuming UPF during the last month. Simultaneously, a market survey was performed at street vendors, food outlets, and supermarkets around the sampling areas to check the food availability, especially the UPF mentioned by the subjects in the FGD.

Results:

There were 24 adults, which was dominated by females (87.5%). Four initial themes determined UPF consumption, namely (1) family preferences, (2) practical reason, (3) taste, and (4) nutrient content. The UPF commonly consumed was instant noodles, canned sardines, biscuits, white bread, sugar-sweetened beverages (SSB), sausages, instant coffee drinks, and packaged milk. Those food and drink were easily found around their dwelling area. The frequency of consuming UPF was not often. I choose instant foods when I or my family was in a hurry and have no time to cook fresh food (Mrs. R, 45 years, a housewife). Some adults were already aware of the negative side of UPF, yet the good taste kept them consuming the food. I know that instant food is bad for health. However, I thought that if we did not consume the food frequently, it would still be safe (Mrs. Y, 40 years, a local cadre).

Conclusions:

The main factors that triggered UPF consumption were preferences, practicality, taste, and nutrient content. Instead of avoiding the bad effects of UPF on health, some adults still attach importance to other aspects related to preferences and sensory appeal. Beyond nutrition education and campaign, creating a healthier food environment is also important to support the habitual changes for better diet quality.
PS-C23-12: DIETARY INTERVENTION WITH THE PROCESSED LOW PROTEIN GENMAI (BROWN RICE) AGAINST CHRONIC KIDNEY DISEASE.
Authors: Adachi Keika , Wakino Shu , Itoh Hiroshi
Published: January 2023

Background:

Although protein-restricted diets have shown to preserve the renal function, there are a couple of challenges such as (1) the intake of vegetable protein, which is useful for maintaining renal function, is insufficient due to potassium restriction, and (2) caloric intake tends to be inadequate. Therefore, we investigated the effects of diets that may solve these problems with maintaining the current dietary restrictions and may also be additional effects on renal protection. Another study also has shown that patients with CKD are under a chronic inflammatory state and those uremic toxins produced by the gut microbiota are the causes of increased inflammatory cytokine production. We sought to intervene in renal function via modulating this kidney-gut axis in CKD. We thus focused on the processed low protein genmai (brown rice) (PLPG), marketed since 2018 by Follica Foods, Inc. as a candidate food that retains the fiber and GABA characteristic of brown rice, reduces protein to less than 20% of conventional rice, and also limits potassium and phosphorus.

Methods:

The study was conducted in a before-and-after trial. Thirty patients with eGFR of 59 or less were recruited. PLPG was a retort pack of 150 g for one meal. The patients ate provided with about 10 servings of PLPG per week for 3 months.

Results:

One patient withdrew due to poor health after participation, and a final total of 29 patients were analyzed. The median age of the participants was 73 years, the mean eGFR was 35.41 ml/min/1.73 m2. The median in BMI decreased by -0.31 (P = 0.037). The median change in the Constipation scoring system score improved by -1.00 (P = 0.032). The change in eGFRcreat decreased with a mean value of -1.241 ml/min/1.73 m2. (P = 0.044), but the monthly eGFRcreat slope was not significantly different. Indoxyl sulfate did not differ significantly, but it showed a decreasing trend with a median change of -0.20 (P = 0.050). The median change in IL-6 was 0.300 pg/mL (P = 0.004). Among short-chain fatty acids, only acetic acid showed an increase with a median change of 7.401 μmol/g (P = 0.010).

Conclusion:

Participants’ protein intake did not decrease. Therefore, it was thought that the effects of PLPG itself was observed, independent of the effect of low protein. The increase in acetic acid may have contributed to this change. The decrease in e-GFR along with the decrease in urinary protein levels indicated an initial dip due to correction of glomerular hypertension. Long-term follow-up is plausible to establish the novel dietary treatment.