Is Total Omentectomy Mandatory in T3 and T4a Gastric Cancer for Laparoscopic Distal Gastrectomy?

BACKGROUND: Despite the lack of strong evidence, total omentectomy (TO) remains the recommended procedure for gastric cancer (GC) for T3 or deeper tumors. Partial omentectomy (PO) has recently become a preferred procedure owing to its simplicity during laparoscopic distal gastrectomy (LDG); however, the oncological role of PO needs to be elucidated. METHODS: Overall, 341 patients with T3 or T4a GC who had undergone LDG between 2009 and 2016 were divided into TO (n = 167) and PO (n = 174) groups. Propensity matching was performed with respect to covariance age, sex, T and N stage, tumor size, and degree of tumor differentiation. Clinicopathological characteristics and long-term follow-up data were analyzed for both groups. RESULTS: After successful propensity matching, both groups included 107 patients. In a matched cohort, no significant difference in clinicopathologic features and short-term surgical outcomes was observed between the two groups. Furthermore, no significant difference in relapse-free survival (RFS; p = 0.201) and peritoneal seeding-free survival (PSFS; p = 0.094) was observed. However, tumor recurrence as peritoneal metastasis occurred in 5 (4.7%) patients in the PO group and 13 (12.1%) patients in the TO group. In Cox proportional hazards analysis, omentectomy was not identified as a significant factor for RFS, PSFS, and overall survival; however, advanced N and T4a stage were considered significant factors for RFS and PSFS, respectively. CONCLUSIONS: PO may be adopted during the LDG of T3 or T4a GC without definite gross serosal exposure. More large-scale evidence or prospective study is recommended.

Refining gastric cancer staging: examining the interplay between number and anatomical location of metastatic lymph nodes - a retrospective multi-institutional study.

BACKGROUND: The current gastric cancer staging system relies on the number of metastatic lymph nodes (MLNs) for nodal stage determination. However, incorporating additional information such as topographic status may help address uncertainties. This study evaluated the appropriateness of the current staging system and relative significance of MLNs based on their anatomical location. METHODS: Patients who underwent curative gastrectomy for gastric cancer between 2000 and 2019 at six Catholic Medical Center-affiliated hospitals were included. Lymph node-positive patients were classified into the perigastric (stations 1-6, group P) or extragastric (stations 7-12) groups. The extragastric group was further subdivided into the near-extragastric (stations 7-9, group NE) and far-extragastric (stations 10-12, group FE) groups. RESULTS: We analyzed the data of 3,591 patients with positive lymph node metastases. No significant survival differences were found between group P and the extragastric group in each N stage. However, in N1 and N2, group FE showed significantly worse survival than the other groups (p = 0.013 for N1, p < 0.001 for N2), but not in N3. In the subgroup analysis, group FE had a significantly lower overall survival in N2, regardless of the cancer location. CONCLUSIONS: Our large-scale multi-institutional big data analysis confirmed the superiority of the current numerical nodal staging system for gastric cancer. Nonetheless, in N1 and N2 in which there is an upper limit on metastatic nodes, attention should be paid to the potential significance of topographic information for specific nodal stations.

Novel nanocomposite thin film in the efficient removal of antibiotics using visible light: Insights of photocatalytic reactions and stability of thin film in real water implications.

Novel clay (bentonite) supported Ag0 nanoparticles (NPs) doped TiO2 nanocomposite (Clay/TiO2/Ag0(NPs)) thin film was obtained by using template synthesis method. The nanocomposite material is decorated with cubical Ag0(NPs) and utilised successfully in the photocatalytic degradation of tetracycline (TC) and sulfamethazine (SMZ) from aqueous solutions utilizing visible light and UV-A radiations. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS) analyses were used to characterise the nanocomposite materials. Diffusion reflectance spectroscopy (DRS) was utilised to determine the bandgap energies of the materials and also to confirm that Ag0(NPs) was successfully doped with TiO2. The nanocomposite material showed highly efficient photocatalytic activity for the breaking down of TC/SMZ under visible light irradiation by the enhanced electron-hole separation and adsorption of antibiotics at the vicinity of the catalyst. The oxidative degradation of TC/SMZ were shown to be highly dependent on the pH, initial concentration of TC/SMZ, and various co-existing ions. Reusability test of Clay/Ag0(NPs)/TiO2 nanocomposite revealed that the activity did not decline with repeated use. Treatment of TC and SMZ in real water system further enhanced the application potential of the novel catalysts for the treatment of full-scale wastewater polluted with these antibiotics.

An Analysis of the Demographics and Clinical Characteristics of Transgender and Intersex Populations in Korea: A Retrospective Study Using HIRA Database.

BACKGROUND: Transgender and intersex populations have long remained under-documented in South Korea, largely due to the absence of comprehensive epidemiological data. With increasing societal acknowledgment, there's an urgent need to understand the demographics and health challenges faced by these communities. METHODS: This retrospective, large-scale data study included people who received the F64 codes from the Korean Health Insurance Review & Assessment Service between January 2007 and December 2021. Demographics, gender-affirmative treatments, and psychiatric related medications were examined. RESULTS: Between 2007 and 2021, 8,602 patients were diagnosed with "gender identity disorder" and 45 with "intersex." A steadily increasing annual prevalence was observed, peaking at 986 cases in 2021. The majority (79.8%) were aged between 10 and 30. Nearly half (53.2%) exhibited mental and behavioral disorders. Two-thirds had been prescribed anxiolytics or sedatives either before or after diagnosis. Merely 12.1% received hormone therapy covered by health insurance. CONCLUSION: This is the first large-scale study highlighting the demographics and clinical characteristics of the transgender and intersex populations in Korea. The study reveals a consistent growth of these communities over the past 15 years, with a significant proportion under 30 years of age facing mental and behavioral challenges. Findings underscore the need for targeted healthcare interventions, early psychological support, and comprehensive insurance coverage tailored to the specific needs of these individuals in Korea.

Synthesis of high quality boehmite and γ-alumina for phosphorus removal from water works sludge by extraction and hydrothermal treatment.

Alum sludge from water treatment was calcined and extracted to synthesize high quality boehmite and γ-alumina for phosphate removal. Synthesized boehmite and γ-alumina were able to remove phosphate quickly and effectively. Boehmite (hydrothermal treatment at 60 °C) showed maximum phosphate removal (adsorption) of 61 mg P/g followed by γ-alumina (50 mg P/g) and the boehmite hydrothermally treated at 120 °C (41 mg P/g). The degree of crystallinity gave more effect on phosphate adsorption of boehmite than that of γ-alumina. The lower the pH, the more phosphate adsorbed on the boehmite and γ-alumina (adsorb phosphate more than 4 times at pH 3 than at pH 11). Spectroscopic analysis (SEM-EDS and FTIR) indicates that phosphate are removed by ligand exchange, electrostatic attraction, and surface precipitation on the synthesized boehmite and γ-alumina.

Photocatalytic degradation of amoxicillin and tetracycline by template synthesized nano-structured Ce3+@TiO2 thin film catalyst.

Contamination of the aquatic environment with pharmaceutical compounds is a serious environmental concern. The present investigation aims to utilize the Ce3+/TiO2 thin film catalyst to remove of potential antibiotics (amoxicillin and tetracycline) using the less harmful UV-A radiations. Reduced cerium ion-doped TiO2 is obtained by a simple one-step facile template method using polyethylene glycol as the templating agent. The synthesized catalysts Ce3+@TiO2 (non-template) and Ce3+@TiO2(T) (template) were characterized by spectroscopic methods. The XPS reaffirms the reduced Ce3+ dispersed within the titania network, and the AFM showed the surface roughness of the thin films. Detailed physicochemical analyses were conducted to deduce the degradation mechanism, and repeated use of the thin film photocatalyst showed enhanced stability. Significant mineralization of the antibiotics indicates the potential applicability of the photocatalytic catalyst. Furthermore, the presence of Ce3+ significantly restricted the recombination of electron/hole pairs in the photo-excited TiO2 semiconductor and showed enhanced photocatalytic degradation of the antibiotics proceeded predominantly through the •OH.

Graphene Quantum Dots Alleviate Impaired Functions in Niemann-Pick Disease Type C in Vivo.

While the neuropathological characteristics of Niemann-Pick disease type C (NPC) result in a fatal diagnosis, the development of clinically available therapeutic agent remains a challenge. Here we propose graphene quantum dots (GQDs) as a potential candidate for the impaired functions in NPC in vivo. In addition to the previous findings that GQDs exhibit negligible long-term toxicity and are capable of penetrating the blood-brain barrier, GQD treatment reduces the aggregation of cholesterol in the lysosome through expressed physical interactions. GQDs also promote autophagy and restore defective autophagic flux, which, in turn, decreases the atypical accumulation of autophagic vacuoles. More importantly, the injection of GQDs inhibits the loss of Purkinje cells in the cerebellum while also demonstrating reduced activation of microglia. The ability of GQDs to alleviate impaired functions in NPC proves the promise and potential of the use of GQDs toward resolving NPC and other related disorders.

A direct contact bioassay using immobilized microalgal balls to evaluate the toxicity of contaminated field soils.

The present study used a bioassay of immobilized microalgae (Chlorella vulgaris) via direct contact to assess the toxicity of eleven uncontaminated (reference) and five field contaminated soils with various physicochemical properties and contamination. Photosynthetic oxygen concentration in the headspace of the test kit by Chlorella vulgaris in the reference soils ranged between 12.93% and 14.80% and only 2.54%-7.14% in the contaminated soils, respectively. Inherent test variability (CVi) values ranged between 2.90% and 9.04%; variation due to soil natural properties (CVrs) ranged between 0.33% and 13.0%; and minimal detectable difference (MDD) values ranged from 4.69% to 11.6%. A computed toxicity threshold of 15% was established for microalgae soil toxicity tests based on calculations of the maximal tolerable inhibition (MTI). All contaminated soils were considered toxic to microalgae because their levels of inhibition ranged between 39.5% and 82.9%, exceeding the 15% toxicity threshold. It can be concluded that the elevated concentrations of heavy metals and organic contaminants in the contaminated soils induced the higher inhibitory levels. Overall, direct contact soil toxicity tests using immobilized microalgae provided coherent and repeatable data and can be utilized as a simple and suitable tool for the toxicity testing of contaminated field soils.

Prospective pharmacological methodology for establishing and evaluating anti-cancer drug resistant cell lines.

BACKGROUND: Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. METHODS: A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. RESULTS: It was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. CONCLUSION: Since the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.

Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS: Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS: Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS: Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Phosphate removal using thermally regenerated Al adsorbent from drinking water treatment sludge.

Alum sludge (AS) is an abundant and ubiquitous residue generated from drinking water treatment plants. AS was thermally treated to use as an adsorbent for phosphate removal from wastewater. Organic matter in the AS was a potential competitor and can deter phosphate adsorption. Pyrolysis and drying of AS were adopted to enhance phosphate removal by eliminating organic matter and enriching Al content. Adsorption kinetics showed that phosphate removal was highest with the AS pyrolyzed at 700 °C followed by 500 °C, air-dried and oven-dried (105 °C). Adsorption kinetic modelling showed that chemisorption is the operative mechanism of phosphate removal in all the AS. Adsorption isotherms also showed that the pyrolyzed AS and air-dried AS had similar adsorption capacity of 30.83-34.53 mg P/g AS. Al dissolution was less than 2 mg/g Al in all the AS samples. COD release was significant in the dried AS, up to 8.0 mg COD/g AS, whereas the pyrolyzed AS released less than 1 mg COD/g AS. FTIR and SEM-EDS analyses of the AS after phosphate adsorption showed the formation of aluminum-phosphate complex. Overall, the pyrolysis of AS at 700 °C was most effective in removing phosphate without leaving secondary pollution.

Trends in laparoscopic anti-reflux surgery: a Korea nationwide study.

BACKGROUND: In 2014, the results derived from the nationwide data of the Korean Anti-reflux Surgery Study (KARS) demonstrated short-term feasibility and safety of anti-reflux surgery. This study aimed to update the longer-term safety and feasibility of laparoscopic anti-reflux surgery up to 1-year follow-up with the KARS nationwide cohort. METHODS: The data of 310 patients with GERD who received anti-reflux surgery up to 2018 were analyzed. Baseline patient characteristics, postoperative symptom resolution, and postoperative complications were evaluated at postoperative 3 months and 1 year using the questionnaire designed by KARS. We divided the patients into two groups according to the operation period (up to and after 2014) to identify changes in the trends of the characteristics of surgical patients and operative qualities. RESULTS: The typical preoperative symptoms were present in 275 patients (91.7%), and atypical symptoms were present in 208 patients (71.0%). Ninety-seven (35.5%) and 124 patients (46.1%) had inadequate PPI responses and hiatal hernia, respectively. At postoperative 1 year, typical and atypical symptoms were either completely or partially controlled in 90.3% and 73.5.0% of patients, respectively. Moderate-to-severe dysphagia, inability to belch, gas bloating, and flatulence at postoperative 1 year were identified in 23.5%, 29.4%, 23.2%, and 22.0% of patients, respectively. The number of surgical patients continuously increased from 2011 to 2018 in Korea. The proportion of patients with hiatal hernia and comorbidities increased (p < 0.01, p = 0.053), and the operation time decreased significantly (p < 0.01) in the late period (2015-2018) as compared with the early period (2011-2014). Symptom control and complication rate were equivalent between the two periods. CONCLUSIONS: Anti-reflux surgery was effective with > 90% of typical symptom resolution and posed a comparable postoperative complication rate with those in Western studies with mid-term to long-term follow-up. This result supports the feasibility and safety of anti-reflux surgery as a treatment for GERD in the Korean population.

Elevated plasma biomarkers of inflammation in acute ischemic stroke patients with underlying dementia.

BACKGROUND: The blood-brain barrier has been a hindrance to developing blood-based diagnostic tests for dementias, as it limits the appearance of brain biomarkers in the blood. Our aim was to see if the natural opening of the blood-brain barrier induced by ischemic stroke would increase serum levels of inflammatory biomarkers known to be elevated in the brains of patients with Alzheimer's disease and other neurodegenerative dementias. METHODS: Forty-three patients with acute ischemic stroke presenting to Stony Brook University Hospital were prospectively enrolled in the study. Eight of these patients were clinically diagnosed as having an underlying neurodegenerative dementia. Blood was drawn acutely within 72 h of stroke symptom onset, and serum levels of the classic inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured, along with levels of S100B protein (S100B) and complement C3 (CC3). RESULTS: Serum levels of IL-6 and CRP in patients with acute ischemic stroke and underlying dementia (AIS + D) were significantly higher (p = 0.002 and 0.003, respectively) than in patients with acute ischemic stroke alone (AIS). Serum levels of S100B and CC3 did not differ significantly between the groups. CONCLUSIONS: This study supports the possibility that opening of the blood-brain barrier may enhance the blood appearance of brain tissue markers of inflammation associated with neurodegenerative dementia. Further study is warranted to test this possibility, given the recent emergence of methods to open the blood-brain barrier for diagnostic or therapeutic purposes.

High dose haemodialysis and haemodiafiltration parameters and the relationship with advanced vascular calcification.

BACKGROUND: Vascular calcification (VC) is a risk factor for cardiovascular disease in end-stage renal disease (ESRD) patients undergoing maintenance haemodialysis (MHD). However, evidence is still insufficient about the association between dialysis parameters and VC. Thus, this study was to evaluate association of dialysis parameters with VC. METHODS: We enrolled 297 ESRD patients undergoing MHD at six distinct centers in Korea. Study participants were categorized into 3 groups by the scoring system of abdominal aortic calcification based on lateral lumbar radiography (no VC group: 0, mild VC group: 1-7 and advanced VC group: 8-24). We compared the features of dialysis parameters according to the severity of VC. Multivariate logistic regression analysis was used to calculate adjusted odd ratios (ORs) and 95% confidence interval (CI) for mild and advanced VC in each haemodialysis parameter (adjusted OR [95% CI]). RESULTS: Pooled Kt/V (spKt/V), equilibrated Kt/V (eKt/V), standard Kt/V (stdKt/V) and the proportion of haemodiafiltration were increased along with the severity of VC. Multivariate regression analysis indicated that advanced VC was positively associated with spKt/V (5.27 [1.51-18.41]), eKt/V (6.16 [1.45-26.10]), stdKt/V (10.67 [1.74-65.52]) and haemodiafiltration (3.27 [1.74 to 6.16]). CONCLUSION: High dose dialysis and haemodiafiltration were significantly associated with advanced VC.

Beneficial Effect of Chloroquine and Amodiaquine on Type 1 Diabetic Tubulopathy by Attenuating Mitochondrial Nox4 and Endoplasmic Reticulum Stress.

BACKGROUND: Oxidative stress induced by chronic hyperglycemia is recognized as a significant mechanistic contributor to the development of diabetic kidney disease (DKD). Nonphagocytic nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in many cell types and in the kidney tissue of diabetic animals. We designed this study to explore the therapeutic potential of chloroquine (CQ) and amodiaquine (AQ) for inhibiting mitochondrial Nox4 and diabetic tubular injury. METHODS: Human renal proximal tubular epithelial cells (hRPTCs) were cultured in high-glucose media (30 mM D-glucose), and diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57BL/6J mice. CQ and AQ were administered to the mice via intraperitoneal injection for 14 weeks. RESULTS: CQ and AQ inhibited mitochondrial Nox4 and increased mitochondrial mass in hRPTCs under high-glucose conditions. Reduced mitochondrial ROS production after treatment with the drugs resulted in decreased endoplasmic reticulum (ER) stress, suppressed inflammatory protein expression and reduced cell apoptosis in hRPTCs under high-glucose conditions. Notably, CQ and AQ treatment diminished Nox4 activation and ER stress in the kidneys of STZ-induced diabetic mice. In addition, we observed attenuated inflammatory protein expression and albuminuria in STZ-induced diabetic mice after CQ and AQ treatment. CONCLUSION: We substantiated the protective actions of CQ and AQ in diabetic tubulopathy associated with reduced mitochondrial Nox4 activation and ER stress alleviation. Further studies exploring the roles of mitochondrial Nox4 in the pathogenesis of DKD could suggest new therapeutic targets for patients with DKD.

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer.

Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes.

Alterations in Lipid Profile of the Aging Kidney Identified by MALDI Imaging Mass Spectrometry.

During aging, the kidney undergoes functional and physiological changes that are closely affiliated with chronic kidney disease (CKD). There is increasing evidence supporting the role of lipid or lipid-derived mediators in the pathogenesis of CKD and other aging-related diseases. To understand the role of lipids in various metabolic processes during kidney aging, we conducted matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) analysis in kidneys harvested from young (2 months old, n = 3) and old mice (24 months old, n = 3). MALDI-IMS analysis showed an increase in ceramide level and a decrease in sphingomyelin (SM) and phosphatidylcholine (PC) levels in kidneys of old mice. The increased expression of cPLA2 and SMPD1 protein in aged kidney was confirmed by immunohistochemistry and Western blot analysis. Our MALDI-IMS data showed the altered distribution of lipids in aged kidney as indicative of aging-related functional changes of the kidney. Combined analysis of MALDI-IMS and IHC confirmed lipidomic changes and expression levels of responsible enzymes as well as morphological changes.

Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats.

The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1-7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS [ACE2/angiotensin (1-7)/Mas receptor] and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.

Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy.

We examined the effects of empagliflozin, a selective inhibitor of Na+-glucose cotransporter 2, on mitochondrial quality control and autophagy in renal tubular cells in a diabetic environment in vivo and in vitro. Human renal proximal tubular cells (hRPTCs) were incubated under high-glucose conditions. Diabetes was induced with streptozotocin in male C57BL/6J mice. Improvements in mitochondrial biogenesis and balanced fusion-fission protein expression were noted in hRPTCs after treatment with empagliflozin in high-glucose media. Empagliflozin also increased autophagic activities in renal tubular cells in the high-glucose environment, which was accompanied with mammalian target of rapamycin inhibition. Moreover, reduced mitochondrial reactive oxygen species production and decreased apoptotic and fibrotic protein expression were observed in hRPTCs after treatment with empagliflozin, even in the hyperglycemic circumstance. Importantly, empagliflozin restored AMP-activated protein kinase-α phosphorylation and normalized levels of AMP-to-ATP ratios in hRPTCs subjected to a high-glucose environment, which suggests the way that empagliflozin is involved in mitochondrial quality control. Empagliflozin effectively suppressed Na+-glucose cotransporter 2 expression and ameliorated renal morphological changes in the kidneys of streptozotocin-induced diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased and 8-hydroxy-2'-deoxyguanosine content was low in renal tubular cells of empagliflozin treatment groups compared with those of the diabetic control group. We suggest one mechanism related to the renoprotective actions of empagliflozin, which reverse mitochondrial dynamics and autophagy.

Nephrotoxicity of amikacin in noncritically ill patients
.

AIMS: Several studies have reported that critically ill patients who require amikacin for the treatment of severe infection require therapeutic drug monitoring (TDM) to prevent acute kidney injury. Moreover, studies so far have mainly focused on patients with critical illnesses; therefore, the probability of occurrence of nephrotoxicity in noncritically ill patients is less known and tends to be overestimated. Recently, with the emergence of multidrug resistant bacteria, the need for aminoglycosides has resurfaced. Therefore, the aim of this study was to investigate the nephrotoxicity and tolerability of amikacin in noncritically ill patients. MATERIALS AND METHODS: This was a retrospective study that included 224 patients who were administered amikacin. Relevant data on patients' clinical course of disease, comorbidities, and clinical laboratory measurements were statistically analyzed. Nephrotoxicity was defined as a serum creatinine level increase by ≥ 0.3 mg/dL or ≥ 50% after therapy initiation. RESULTS: The mean (SD) daily amikacin dose was 13.04 (4.21) mg/kg. The mean (SD) duration of treatment was 12.09 (12.89) days. The incidence rate (95% CI) of amikacin-induced nephrotoxicity was 1.076/person-year (0.46 - 2.12) for the total person-time (3.44 years). In the risk analysis, no risk factor associated with nephrotoxicity could be found. However, an increasing trend of AKI risk was observed in patients with low baseline estimated glomerular filtration rate. CONCLUSION: In noncritically ill patients, the incidence of amikacin-induced nephrotoxicity was lower than that reported in previous studies. The initial monitoring for kidney function in clinical laboratories may be useful, and therapeutic drug monitoring (TDM) may not be necessary in patients with normal kidney function.