Visualizing increased uptake of [18F]FDG and [18F]FTHA in kidneys from obese high-fat diet fed C57BL/6J mice using PET/CT ex vivo.

It is known that high-fat diet (HFD) and/or diabetes may influence substrate preferences and energy demands in the heart preceding diabetic cardiomyopathy. They may also induce structural glomerular changes causing diabetic nephropathy. PET/CT has been utilized to examine uptake of energy substrates, and to study metabolic changes or shifts before onset of metabolic disorders. However, conventional PET/CT scanning of organs with relatively low uptake, such as the kidney, in small animals in vivo may render technical difficulties. To address this issue, we developed a PET/CT ex vivo protocol with radiolabeled glucose and fatty acid analouges, [18F]FDG and [18F]FTHA,to study substrate uptake in mouse kidneys. We also aimed to detect a possible energy substrate shift before onset of diabetic nephropathy. The ex vivo protocol reduced interfering background as well as interindividual variances. We found increased uptake of [18F]FDG and [18F]FTHA in kidneys after HFD, compared to kidneys from young mice on standard chow. Levels of kidney triglycerides also increased on HFD. Lipoprotein lipase (LPL) activity, the enzyme responsible for release of fatty acids from circulating lipoproteins, is normally increased in postprandial mice kidneys. After long-term HFD, we found that LPL activity was suppressed, and could therefore not explain the increased levels of stored triglycerides. Suppressed LPL activity was associated with increased expression of angiopoietin-like protein4, an inhibitor of LPL. HFD did not alter the transcriptional control of some common glucose and fatty acid transporters that may mediate uptake of [18F]FDG and [18F]FTHA. Performing PET/CT ex vivo reduced interfering background and interindividual variances. Obesity and insulin resistance induced by HFD increased the uptake of [18F]FDG and [18F]FTHA and triglyceride accumulation in mouse kidneys. Increased levels of [18F]FDG and [18F]FTHA in obese insulin resistant mice could be used clinically as an indicator of poor metabolic control, and a complementary test for incipient diabetic nephropathy.

Ultrasound shear wave elastography for the evaluation of renal pathological changes in adult patients.

OBJECTIVE: Many studies have conflicting findings in using shear wave elastography (SWE) to assess renal fibrosis. This study reviews the use of SWE to evaluate pathological changes in native kidneys and renal allografts. It also tries to elucidate the confounding factors and care taken to ensure the results are consistent and reliable. METHODS: The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Literature search was conducted in Pubmed, Web of Science and Scopus database up to 23 October 2021. To evaluate risk and bias applicability, the Cochrane risk-of bias tool and GRADE was used. The review was registered under PROSPERO CRD42021265303. RESULTS: A total of 2921 articles were identified. 104 full texts were examined and 26 studies included in systematic review. 11 studies performed on native kidneys and 15 studies on transplanted kidney. A wide range of impact factors was found that affect the accuracy of SWE of renal fibrosis in adult patients. CONCLUSIONS: Compared to point SWE, two-dimensional SWE with elastogram could enable better selection of the region of interest in kidneys, leading to reproducible results. Tracking waves were attenuated as the depth from skin to region of interest increased, therefore, SWE is not recommended for overweight or obese patients. Variable transducer forces might also affect SWE reproducibility, thus, training of operators to ensure consistent operator-dependent transducer forces may be helpful. ADVANCES IN KNOWLEDGE: This review provides a holistic insight on the efficiency of using SWE in evaluating pathological changes in native and transplanted kidneys, thereby contributing to the knowledge of its utilisation in clinical practice.

Multi-Scale Investigation of Human Renal Tissue in Three Dimensions.

Histopathology as a diagnostic mainstay for tissue evaluation is strictly a 2D technology. Combining and supplementing this technology with 3D imaging has been proposed as one future avenue towards refining comprehensive tissue analysis. To this end, we have developed a laboratory-based X-ray method allowing for the investigation of tissue samples in three dimensions with isotropic volume information. To assess the potential of our method for micro-morphology evaluation, we selected several kidney regions from three patients with cystic kidney disease, obstructive nephropathy and diabetic glomerulopathy. Tissue specimens were processed using our in-house-developed X-ray eosin stain and investigated with a commercial microCT and our in-house-built NanoCT. The microCT system provided overview scans with voxel sizes of [Formula: see text] and the NanoCT was employed for higher resolutions including voxel sizes from [Formula: see text] to 210 nm. We present a methodology allowing for a precise micro-morphologic investigation in three dimensions which is compatible with conventional histology. Advantages of our methodology are its versatility with respect to multi-scale investigations, being laboratory-based, allowing for non-destructive imaging and providing isotropic volume information. We believe, that after future developmental work this method might contribute to advanced multi-modal tissue diagnostics.

[Study on safe depth of needling at acupoints of kidney regions based on MRI imaging].

OBJECTIVE: To measure the dangerous depth and the effective safe depth of needling at acupoints of kidney regions based on MRI imaging, and to provide the imaging support for clinical practice. METHODS: The abdominal enhanced T1 MRI imaging of horizontal plane of 61 healthy subjects was included, the anatomical structure of bilateral Weishu (BL 21), Sanjiaoshu (BL 22), Shenshu (BL 23), Weicang (BL 50), Huangmen (BL 51) and Zhishi (BL 52) was analyzed, and the dangerous depth and effective safe depth of perpendicular and oblique needling were measured between the left and right sides and subjects with different body sizes. RESULTS: There were no significant differences between dangerous depth and effective safe depth of perpendicular and oblique needling at bilateral acupoints of kidney region (P>0.05). The dangerous depth and effective safe depth of perpendicular and oblique needling at bilateral acupoints of kidney region in the moderate group were larger than the underweight group (P<0.05), while those in the overweight group were larger than the moderate group and the underweight group (P<0.05). CONCLUSION: The safe depth of needling at acupoints of kidney region is related to body size, for moderate weight and overweight patients, the needling depth could be increased for better efficacy, while for underweight patients, the recommend direction and depth of needling should be restricted to avoid acupuncture accident.

Renal-clearable and biodegradable black phosphorus quantum dots for photoacoustic imaging of kidney dysfunction.

The kidney is a vital organ and susceptible to various diseases. Photoacoustic (PA) imaging provides a powerful technique for studying kidney dysfunction, for which many smart photoacoustic imaging agents have been developed. But the complete clearance of the introduced contrast agents after imaging remains to be challenging, leading to long-term toxicity concerns. In this study, we synthesized black phosphorous quantum dots (BPQDs) with ultra-small size (1.74 ± 0.23 nm after surface modification) and strong PA signal for imaging kidney dysfunction. Importantly, the renal-clearance property and biodegradability of the developed BPQDs help circumvent the long-term toxicity issue for in vivo studies. Based on these BPQDs, both acute kidney injury and chronic kidney disease were successfully detected in the living mice by PA imaging, with higher detection sensitivity than the clinical serum indices examination method. This BPQDs-based PA imaging method should have a promising potential for the early diagnosis of kidney dysfunction in clinic.

Correlations of RENAL, PADUA and NePhRO Scores With Complications and Outcomes in Patients After CT-Guided Microwave Ablation of Renal Tumors.

OBJECTIVE: This retrospective study aimed to access the correlations of RENAL, PADUA and NePhRO scores with operative complications, chronic kidney disease (CKD) upstaging, and oncologic outcomes after CT-guided percutaneous Microwave Ablation (MWA) of renal tumors in order to determine their status as independent predictors of outcomes after MWA. This study also aimed to generally evaluate the efficacy of MWA in treating renal tumors. METHODS: From January 2017 to December 2019, 18 patients with 27 renal tumors who had undergone simultaneous biopsy and MWA were recruited in this single-center retrospective study. Data collection included tumor characteristics, procedural protocols, complications, CKD upstaging data, local tumor control data and overall survival. All lesions were evaluated using RENAL, PADUA and NePhRO scores, and further analysis was performed to determine whether the scores were correlated with operative complications, CKD upstaging, local tumor control and overall survival. RESULTS: The minor and major complication rates were 16.7% and 0%, respectively. Two patients with solitary kidney experienced CKD upstaging. Local tumor recurrence was identified in one type of tumor (3.7%) in the first year of follow-up. L. parameter (P = .031), longitudinal (polar) location score (P = .011), Ne. parameter (P = .036), number of kidneys (P = .005), and number of lesions (P = .008), were predictive factors significantly associated with the occurrence of complications. Besides, CKD upstaging was associated with A. parameter (P = .032) and urinary collecting system score (P = .028). RENAL, PADUA, and NePhRO scores were significantly correlated with complications, overall survival, and CKD upstaging, respectively (P < .05). CONCLUSION: CT-guided percutaneous MWA was found to be a valuable alternative in the treatment of renal tumors for selected patients. Furthermore, RENAL, PADUA and NePhRO scores were not independent predictors of outcomes of MWA.

Molecular Mapping of Neutral Lipids Using Silicon Nanopost Arrays and TIMS Imaging Mass Spectrometry.

We demonstrate the utility of combining silicon nanopost arrays (NAPA) and trapped ion mobility imaging mass spectrometry (TIMS IMS) for high spatial resolution and specificity mapping of neutral lipid classes in tissue. Ionization of neutral lipid species such as triglycerides (TGs), cholestryl esters (CEs), and hexosylceramides (HexCers) from biological tissues has remained a challenge for imaging applications. NAPA, a matrix-free laser desorption ionization substrate, provides enhanced ionization efficiency for the above-mentioned neutral lipid species, providing complementary lipid coverage to matrix-assisted laser desorption ionization (MALDI). The combination of NAPA and TIMS IMS enables imaging of neutral lipid species at 20 µm spatial resolution while also increasing molecular coverage greater than 2-fold using gas-phase ion mobility separations. This is a significant improvement with respect to sensitivity, specificity, and spatial resolution compared to previously reported imaging studies using NAPA alone. Improved specificity for neutral lipid analysis using TIMS IMS was shown using rat kidney tissue to separate TGs, CEs, HexCers, and phospholipids into distinct ion mobility trendlines. Further, this technology allowed for the separation of isomeric species, including mobility resolved isomers of Cer(d42:2) (m/z 686.585) with distinct spatial localizations measured in rat kidney tissue section.

Acute interstitial nephritis associated with ingesting a Momordica charantia extract: A case report.

RATIONALE: Momordica charantia is often used to treat type 2 diabetes mellitus in Korea. Drug-induced acute interstitial nephritis (AIN) accounts for 60% to 70% of AIN cases. However, only 1 case of AIN associated with ingesting M charantia has been reported in the English literature. We report an extremely rare case of AIN that occurred after a patient ingested a pure M charantia extract over 7 months. PATIENT CONCERNS: A 60-year-old Korean woman was admitted to our hospital for a renal biopsy. Her renal function had decreased gradually over the last 9 months without symptoms or signs. DIAGNOSIS: Her blood urea nitrogen and serum creatinine levels were 29.7 mg/dL (range: 8.0-20.0 mg/dL) and 1.45 mg/dL (range: 0.51-0.95 mg/dL) on admission. Renal histology indicated AIN; there was immune cell infiltration into the interstitium, tubulitis, and epithelial casts, although the glomeruli were largely intact. INTERVENTIONS: M charantia was discontinued and prednisolone was prescribed. OUTCOMES: The value of serum creatinine has almost been restored to the baseline level after 3 months. CONCLUSION: s: This is the first case report of AIN associated with the ingestion of a pure M charantia extract. Recognition of the possible adverse effects of these agents by physicians is very important for early diagnosis and appropriate management.

Mechanism of Radix Astragali and Radix Salviae Miltiorrhizae Ameliorates Hypertensive Renal Damage.

Hypertensive-induced renal damage (HRD) is an important public health and socioeconomic problem worldwide. The herb pair Radix Astragali- (RA-) Radix Salviae Miltiorrhizae (RS) is a common prescribed herbal formula for the treatment of HRD. However, the underlying mechanisms are unclear. The purpose of our study is to explore the mechanism of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) ameliorating HRD by regulation of the renal sympathetic nerve. Thirty 24-week-old spontaneously hypertensive rats (SHRs) as the experimental group were randomly divided into the RA group, the RS group, the RA+RS group, the valsartan group, and the SHR group and six age-matched Wistar Kyoto rats (WKY) as the control group. After 4 weeks of corresponding drug administration, venipuncture was done to collect blood and prepare serum for analysis. A color Doppler ultrasound diagnostic instrument was used to observe renal hemodynamics. Enzyme-linked immunosorbent assay was used to detect norepinephrine (NE), epinephrine (E), angiotensin II (Ang II), and B-type brain natriuretic peptide (BNP). Simultaneously, the kidneys were removed immediately and observed under a transmission electron microscope to observe the ultrastructural changes. And the concentration of transforming growth factor-ß1 (TGF-ß1), angiotensin type 1 receptor (AT1), and nitric oxide (NO) was detected by immunohistochemistry. Our results showed that renal ultrasonography of rats showed no significant difference in renal size among groups. The RA+RS group had obviously decreased vascular resistance index. The levels of NE, E, BNP, Ang II, AT1, and TGF-ß1 were decreased (P < 0.05), and the density of NO was increased. Pathological damage of the kidney was alleviated. In conclusion, the results of the present study suggested sympathetic overexpression in the pathogenesis of HRD. The combination of RA and RS may inhibit the hyperexcitability of sympathetic nerves and maintain the normal physiological structure and function of kidney tissue and has a protective effect on the cardiovascular system.

Demographic, diagnostic and therapeutic characteristics of autosomal dominant polycystic kidney disease in Ghana.

BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the commonest of the hereditary kidney diseases and mostly ensues in utero with signs delayed until after several decades. This study assessed the demographic, diagnostic (clinical and biochemical features) and therapeutic patterns among ADPKD patients who attended the nephrology unit of Komfo Anokye Teaching Hospital (KATH) from 2007 to 2018. METHODS: This cross-sectional retrospective analysis of ADPKD patient records was conducted at the nephrology unit of KATH in October 2020. The records of 82 ADPKD was used for this study. Demographic, clinical, biochemical, ultrasonographic and therapeutic data was obtained, organized and analyzed with Statistical Package for the Social Sciences (SPSS). RESULTS: ADPKD was most prevalent in people within the ages of 31-40 years (25.6 %), with a male (52.4 %) preponderance. The most common clinical features presented were flank pain (30.5 %) and bipedal swelling (18.3 %). Hypertension (42.7 %), urinary tract infections (UTIs) (19.5 %), and anemia (13.4 %) were the most common complications reported. Average level of HDL-c was higher in females (1.7) than in males (1.2) (p = 0.001). Hematuria (34 %) and proteinuria (66 %) were among the biochemical derangements presented. About 81.7 % had CKD at diagnosis with the majority in stages 1 (27.0 %), 3(23.2 %) and 5 (20.3 %). Poor corticomedullary differentiation was observed in 90.2 % of participants and increased echogenicity was observed in 89.0 % of the participants. Estimated GFR (eGFR) correlated positively with echotexture (r = 0.320, p = 0.005) and negatively with CMD (r= -0.303, p = 0.008). About 95.1 % of patients were on conservative therapy including: 73.2 %, 52.4 %, 22.0 %, 13.4 %, 8.5 % on Irebesartan/Lisinopril, Nifecard XL, Hydralazine, Methyldopa and Bisoprolol respectively for hypertension; 26.8 and 3.7 % on Gliclazide and Metformin respectively for Type 2 diabetes mellitus; 25.6 %, 24.4 and 18.3 % on CaCO3, fersolate and folic acid respectively as nutrient supplements with 4.9 % of participants on renal replacement therapy (RRT). CONCLUSIONS: ADPKD occurs in people aged ≥ 31 years with a higher male preponderance. Clinical features include flank and abdominal pain, bipedal swelling, headache, amongst others. Uremia, hematuria, proteinuria, decreased eGFR, were the common biochemical derangements reported with higher severity detected in men. The therapeutic interventions mostly involved conservative therapy to manage symptoms and other comorbid conditions and rarely renal replacement therapy (RRT).

Effect of Shenkang on renal fibrosis and activation of renal interstitial fibroblasts through the JAK2/STAT3 pathway.

BACKGROUND: Activation of renal fibroblasts is a critical mechanism in the process of renal fibrosis. As a commonly used herbal formula, Shenkang (SK) has been found to attenuate renal fibrosis and renal parenchyma destruction. However, the effect of SK on renal fibroblast activation in unilateral ureteral obstruction (UUO) mice and its molecular mechanism remain undetermined. The present study was performed to elucidate the effect of SK on renal fibroblast activation and renal fibrosis, as well as the potential underlying mechanism, in both NRK-49F cells and UUO mice. METHODS: NRK-49F cells were stimulated with 10 ng/ml TGF-ß1 for 48 h. After SK treatment, the CCK-8 method was used to evaluate cell viability. Thirty-six C57BL/6 mice were randomly divided into the sham group, UUO group, angiotensin receptor blocker (ARB) group, and SK high-, moderate- and low-dose groups. UUO was induced in mice except those in the sham group. Drugs were administered 1 day later. On the 13th day, the fractional anisotropy (FA) value was determined by MRI to evaluate the degree of renal fibrosis. After 14 days, serum indexes were assessed. Hematoxylin and eosin (HE) and Sirius red staining were used to observe pathological morphology and the degree of fibrosis of the affected kidney. Western blotting and PCR were used to assess the expression of related molecules in both cells and animals at the protein and gene levels. RESULTS: Our results showed that SK reduced extracellular matrix (ECM) and α-smooth muscle actin (α-SMA) expression both in vitro and in vivo and attenuated renal fibrosis and the pathological lesion degree after UUO, suppressing JAK2/STAT3 activation. Furthermore, we found that SK regulated the JAK2/STAT3 pathway regulators peroxiredoxin 5 (Prdx5) in vitro and suppressor of cytokine signaling protein 1 (SOCS1) and SOCS3 in vivo. CONCLUSIONS: These results indicated that SK inhibited fibroblast activation by regulating the JAK2/STAT3 pathway, which may be a mechanism underlying its protective action in renal fibrosis.

Misleading localization by 18F-fluorocholine PET/CT in familial hypocalciuric hypercalcemia type-3: a case report.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging. CASE PRESENTATION: A 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51-2.89 mmol/L with concomitant PTH level of 58.7-94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3. CONCLUSIONS: In this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.

Thermal field and tissue damage analysis of moving laser in cancer thermal therapy.

In this paper, a closed-form analytical solution of hyperbolic Pennes bioheat equation is obtained for spatial evolution of temperature distributions during moving laser thermotherapy of the skin and kidney tissues. The three-dimensional cubic homogeneous perfused biological tissue is adopted as a media and the Gaussian distributed function in surface and exponentially distributed in depth is used for modeling of laser moving heat source. The solution procedure is Eigen value method which leads to a closed form solution. The effect of moving velocity, perfusion rate, laser intensity, absorption and scattering coefficients, and thermal relaxation time on temperature profiles and tissue thermal damage are investigated. Results are illustrated that the moving velocity and the perfusion rate of the tissues are the main important parameters in produced temperatures under moving heat source. The higher perfusion rate of kidney compared with skin may lead to lower induced temperature amplitude in moving path of laser due to the convective role of the perfusion term. Furthermore, the analytical solution can be a powerful tool for analysis and optimization of practical treatment in the clinical setting and laser procedure therapeutic applications and can be used for verification of other numerical heating models.

Evaluation of Temperature Distribution Around the Probe in Cryoablation of Lipiodol-Mixed-Tissue Phantom.

PURPOSE: To determine whether lipiodol, which has low thermal conductivity, influences ice ball formation during cryoablation of a lipiodol-mixed-tissue phantom. MATERIALS AND METHODS: Lipiodol-mixed-tissue phantoms were created by injecting lipiodol (4-6 ml) into the renal arteries of ex vivo porcine kidneys (lipiodol group). A cryoprobe (CryoHit™ Needle S) with a holder that was set with thermocouples at various positions around the cryoprobe was inserted. After freezing for 300 s, the followings were evaluated: ice ball size on CT, temperature distribution around the cryoprobe, and calculated distances at 0 °C and - 20 °C. Each variable was compared between lipiodol group (n = 6) those obtained in a control group without lipiodol injection (n = 6). RESULTS: Mean ice ball diameter (width/length) on CT was 22.1 ± 2.3/22.9 ± 2.3 mm in the lipiodol group and 21.6 ± 0.7/22.2 ± 1.3 mm in the control group. Mean cryoprobe temperature was - 118 ± 3.0 °C in the lipiodol group and - 117 ± 2.6 °C in the control group. In both groups, temperature at the 3 mm thermocouple reached approximately - 50 °C and was < 0 °C within ~ 10 mm of the cryoprobe. Temperature of 0/- 20 °C occurred at a mean distance from the cryoprobe of 11.1 ± 0.5/6.9 ± 0.4 mm in the lipiodol group and 11.0 ± 0.2/6.9 ± 0.2 mm in the control group. There was no significant difference in any variable between the groups. CONCLUSION: The inclusion of lipiodol in a tissue phantom had no negative effects on ice ball formation that were related to thermal conductivity.

A snake toxin as a theranostic agent for the type 2 vasopressin receptor.

Rationale: MQ1, a snake toxin which targets with high nanomolar affinity and absolute selectivity for the type 2 vasopressin receptor (V2R), is a drug candidate for renal diseases and a molecular probe for imaging cells or organs expressing V2R. Methods: MQ1's pharmacological properties were characterized and applied to a rat model of hyponatremia. Its PK/PD parameters were determined as well as its therapeutic index. Fluorescently and radioactively labeled MQ1 were chemically synthesized and associated with moderate loss of affinity. MQ1's dynamic biodistribution was monitored by positron emission tomography. Confocal imaging was used to observe the labeling of three cancer cell lines. Results: The inverse agonist property of MQ1 very efficiently prevented dDAVP-induced hyponatremia in rats with low nanomolar/kg doses and with a very large therapeutic index. PK (plasma MQ1 concentrations) and PD (diuresis) exhibited a parallel biphasic decrease. The dynamic biodistribution showed that MQ1 targets the kidneys and then exhibits a blood and kidney biphasic decrease. Whatever the approach used, we found a T1/2α between 0.9 and 3.8 h and a T1/2ß between 25 and 46 h and demonstrated that the kidneys were able to retain MQ1. Finally, the presence of functional V2R expressed at the membrane of cancer cells was, for the first time, demonstrated with a specific fluorescent ligand. Conclusion: As the most selective V2 binder, MQ1 is a new promising drug for aquaresis-related diseases and a molecular probe to visualize in vitro and in vivo V2R expressed physiologically or under pathological conditions.

Effect and mechanism of prophylactic use of tadalafil during pregnancy on l-NAME-induced preeclampsia-like rats.

INTRODUCTION: Preeclampsia (PE) is a serious maternal inflammatory disease with endothelial cell dysfunction, and there is a lack of effective treatment and prevention. Tadalafil is considered to be a promising drug for PE. This study aimed to determine whether and how tadalafil use during early pregnancy alleviates PE induced by N-nitro-l-arginine-methyl-ester (l-NAME), an antagonist of nitric oxide synthase, in rats. METHODS: Twenty-eight Sprague-Dawley (SD) rats were randomly divided into 4 equal groups on gestational day 0 (GD0): a pregnant control group, an l-NAME-treated PE group and two prophylactic low-dose and high-dose tadalafil groups. Blood pressure was measured on GD0, 5, 10, 15 and 20. Proteinuria was assessed on GD0 and 18. Femoral artery ultrasound was performed on GD19. Tissue sampling was performed on GD20. The perinatal outcomes, placenta and kidney tissue morphology, and endothelial and inflammatory markers were examined. RESULTS: Prophylactic administration of low and high doses of tadalafil improved l-NAME induced hypertension, proteinuria, maternal weight loss during pregnancy, fetal growth restriction and flow-mediated dilatation, balanced endothelial-relative factors, and alleviated inflammation activation in placenta and kidney tissue. What's more, in some results, the HT group performed better than the LT group. DISCUSSION: Our results indicate that prophylactic use of tadalafil in l-NAME-induced PE-like rat models alleviates PE symptoms, promotes fetal growth, protects endothelial function and reduces inflammation, suggesting that tadalafil may be a potential drug for the prevention of PE.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Imaging of Renal Cancer.

Renal masses are common incidental findings on cross-sectional imaging. Accurate characterization of renal masses is essential to guide management. Renal mass CT protocol comprises of a good quality noncontrast, corticomedullary and nephrographic phases, with each phase providing complementary information for diagnosis. Attenuation measurements in different phases are central to the 'golden-rules' in renal mass imaging in the characterization of renal masses. Newer modalities like dual energy CT scan obviate need for repeat imaging by generation of iodine-overlay image and also help in eliminating artifactual pseudoenhancement which can be problematic, especially in small endophytic cysts. Contrast- enhanced ultrasound (CEUS) is extremely sensitive in identification of enhancing components in indeterminate masses, especially in the setting of renal failure as the microbubbles are not excreted via the renal route. The Bosniak classification for renal cystic masses has been revised in 2019 to standardize terminology and further improve upon the original version. The current version includes CT and MRI, although CEUS is yet to be included. Image- guided biopsy of renal mass helps confirm the diagnosis and also gives information regarding the subtype and grading and is useful in avoiding overtreatment of benign entities, and in active surveillance. Multiparametric MRI can potentially help avoid needle biopsy in a subset of patients by accurate characterization through a previously validated algorithm.

Red orange and lemon extract prevents the renal toxicity induced by ochratoxin A in rats.

In this work, we investigated the effects of red orange and lemon extract (RLE) on ochratoxin A (OTA)-induced nephrotoxicity. In particular, we analyzed the change in renal function and oxidative stress in Sprague-Dawley rats treated with OTA (0.5 mg/kg body weight, b.w.) and with RLE (90 mg/kg b.w.) by oral administration. After OTA treatment, we found alterations of biochemical and oxidative stress parameters in the kidney, related to a severe decrease of glomerular filtration rate. The RLE treatment normalized the activity of antioxidant enzymes and prevented the glomerular hyperfiltration. Histopathological examinations revealed glomerular damages and kidney cortex fibrosis in OTA-rats, while we observed less severe fibrosis in OTA plus RLE group. Then, we demonstrated that oxidative stress could be the cause of OTA renal injury and that RLE reduces this effect.