Diverse tsunamigenesis triggered by the Hunga Tonga-Hunga Ha'apai eruption.

On the evening of 15 January 2022, the Hunga Tonga-Hunga Ha'apai volcano1 unleashed a violent underwater eruption, blanketing the surrounding land masses in ash and debris2,3. The eruption generated tsunamis observed around the world. An event of this type last occurred in 1883 during the eruption of Krakatau4, and thus we have the first observations of a tsunami from a large emergent volcanic eruption captured with modern instrumentation. Here we show that the explosive eruption generated waves through multiple mechanisms, including: (1) air-sea coupling with the initial and powerful shock wave radiating out from the explosion in the immediate vicinity of the eruption; (2) collapse of the water cavity created by the underwater explosion; and (3) air-sea coupling with the air-pressure pulse that circled the Earth several times, leading to a global tsunami. In the near field, tsunami impacts are strongly controlled by the water-cavity source whereas the far-field tsunami, which was unusually persistent, can be largely described by the air-pressure pulse mechanism. Catastrophic damage in some harbours in the far field was averted by just tens of centimetres, implying that a modest sea level rise combined with a future, similar event would lead to a step-function increase in impacts on infrastructure. Piecing together the complexity of this event has broad implications for coastal hazards in similar geophysical settings, suggesting a currently neglected source of global tsunamis.

Patterns of cortical oxygenation may predict the response to stenting in subjects with renal artery stenosis: A radiomics-based model.

BACKGROUND: Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its outcome is often suboptimal. We hypothesized that a model incorporating markers of renal function and oxygenation extracted using radiomics analysis of blood oxygenation-level dependent (BOLD)-MRI images may predict renal response to PTRA in swine RAS. MATERIALS AND METHODS: Twenty domestic pigs with RAS were scanned with CT and BOLD MRI before and 4 weeks after PTRA. Stenotic (STK) and contralateral (CLK) kidney volume, blood flow (RBF), and glomerular filtration rate (GFR) were determined, and BOLD-MRI R2 * maps were generated before and after administration of furosemide, a tubular reabsorption inhibitor. Radiomics features were extracted from pre-PTRA BOLD maps and Robust features were determined by Intraclass correlation coefficients (ICC). Prognostic models were developed to predict post-PTRA renal function based on the baseline functional and BOLD-radiomics features, using Lasso-regression for training, and testing with resampling. RESULTS: Twenty-six radiomics features passed the robustness test. STK oxygenation distribution pattern did not respond to furosemide, whereas in the CLK radiomics features sensitive to oxygenation heterogeneity declined. Radiomics-based model predictions of post-PTRA GFR (r = 0.58, p = 0.007) and RBF (r = 0.68; p = 0.001) correlated with actual measurements with sensitivity and specificity of 92% and 67%, respectively. Models were unsuccessful in predicting post-PTRA systemic measures of renal function. CONCLUSIONS: Several radiomics features are sensitive to cortical oxygenation patterns and permit estimation of post-PTRA renal function, thereby distinguishing subjects likely to respond to PTRA and stenting.

Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging: Validation and Evaluation in Murine Renal Artery Stenosis.

Purpose To test the utility of magnetization transfer imaging in detecting and monitoring the progression of renal fibrosis in mice with unilateral renal artery stenosis. Materials and Methods This prospective study was approved by the Institutional Animal Care and Use Committee. Renal artery stenosis surgery (n = 10) or sham surgery (n = 5) was performed, and the stenotic and contralateral kidneys were studied longitudinally in vivo at baseline and 2, 4, and 6 weeks after surgery. After a 16.4-T magnetic resonance imaging examination, magnetization transfer ratio was measured as an index of fibrosis (guided by parameters selected in preliminary phantom studies). In addition, renal volume, perfusion, blood flow, and oxygenation were assessed. Fibrosis was subsequently measured ex vivo by means of histologic analysis and hydroxyproline assay. The Wilcoxon rank sum or signed rank test was used for statistical comparisons between or within groups, and Pearson and Spearman rank correlation was used to compare fibrosis measured in vivo and ex vivo. Results In the stenotic kidney, the median magnetization transfer ratio showed progressive increases from baseline to 6 weeks after surgery (increases of 13.7% [P = .0006] and 21.3% [P = .0005] in cortex and medulla, respectively), which were accompanied by a progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6-week magnetization transfer ratio map showed good correlation with fibrosis measured ex vivo (Pearson r = 0.9038 and Spearman ρ = 0.8107 [P = .0002 vs trichrome staining]; r = 0.9540 and ρ = 0.8821 [P < .0001 vs Sirius red staining]; and r = 0.8429 and ρ = 0.7607 [P = .001 vs hydroxyproline assay]). Conclusion Magnetization transfer imaging was used successfully to measure and longitudinally monitor the progression of renal fibrosis in mice with unilateral renal artery stenosis. © RSNA, 2016 Online supplemental material is available for this article.

Low-Energy Shockwave Therapy Improves Ischemic Kidney Microcirculation.

Microvascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low-energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low-energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low-energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and ß1-integrin) ex vivo A 3-week low-energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low-energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low-energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.

Utilizing magnetization transfer imaging to investigate tissue remodeling in a murine model of autosomal dominant polycystic kidney disease.

PURPOSE: Noninvasive imaging techniques that quantify renal tissue composition are needed to more accurately ascertain prognosis and monitor disease progression in polycystic kidney disease (PKD). Given the success of magnetization transfer (MT) imaging to characterize various tissue remodeling pathologies, it was tested on a murine model of autosomal dominant PKD. METHODS: C57Bl/6 Pkd1 R3277C mice at 9, 12, and 15 months were imaged with a 16.4T MR imaging system. Images were acquired without and with RF saturation in order to calculate MT ratio (MTR) maps. Following imaging, the mice were euthanized and kidney sections were analyzed for cystic and fibrotic indices, which were compared with statistical parameters of the MTR maps. RESULTS: The MTR-derived mean, median, 25th percentile, skewness, and kurtosis were all closely related to indices of renal pathology, including kidney weight/body weight, cystic index, and percent of remaining parenchyma. The correlation between MTR and histology-derived cystic and fibrotic changes was R(2) = 0.84 and R(2) = 0.70, respectively. CONCLUSION: MT imaging provides a new, noninvasive means of measuring tissue remodeling PKD changes and may be better suited for characterizing renal impairment compared with conventional MR techniques.

Renal Vein Levels of MicroRNA-26a Are Lower in the Poststenotic Kidney.

MicroRNA-26a (miR-26a) is a post-transcriptional regulator that inhibits cellular differentiation and apoptosis. Renal vascular disease (RVD) induces ischemic injury characterized by tubular cell apoptosis and interstitial fibrosis. We hypothesized that miR-26a levels are reduced in the poststenotic kidney and that kidney repair achieved by adipose tissue-derived mesenchymal stem cells (ad-MSCs) is associated with restored miR-26a levels. Renal function and renal miR-26a levels were assessed in pigs with RVD not treated (n=7) or 4 weeks after intrarenal infusion of ad-MSC (2.5×10(5) cells/kg; n=6), patients with RVD (n=12) or essential hypertension (n=12), and healthy volunteers (n=12). In addition, the direct effect of miR-26a on apoptosis was evaluated in a renal tubular cell culture. Compared with healthy control kidneys, swine and human poststenotic kidneys had 45.5±4.3% and 90.0±3.5% lower levels of miR-26a, respectively, which in pigs, localized to the proximal tubules. In pigs, ad-MSC delivery restored tubular miR-26a expression, attenuated tubular apoptosis and interstitial fibrosis, and improved renal function and tubular oxygen-dependent function. In vitro, miR-26a inhibition induced proximal tubular cell apoptosis and upregulated proapoptotic protein expression, which were both rescued by ad-MSC. In conclusion, decreased tubular miR-26a expression in the poststenotic kidney may be responsible for tubular cell apoptosis and renal dysfunction but can be restored using ad-MSC. Therefore, miR-26a might be a novel therapeutic target in renovascular disease.

Obesity-metabolic derangement exacerbates cardiomyocyte loss distal to moderate coronary artery stenosis in pigs without affecting global cardiac function.

Obesity associated with metabolic derangements (ObM) worsens the prognosis of patients with coronary artery stenosis (CAS), but the underlying cardiac pathophysiologic mechanisms remain elusive. We tested the hypothesis that ObM exacerbates cardiomyocyte loss distal to moderate CAS. Obesity-prone pigs were randomized to four groups (n = 6 each): lean-sham, ObM-sham, lean-CAS, and ObM-CAS. Lean and ObM pigs were maintained on a 12-wk standard or atherogenic diet, respectively, and left circumflex CAS was then induced by placing local-irritant coils. Cardiac structure, function, and myocardial oxygenation were assessed 4 wk later by computed-tomography and blood oxygenation level dependent (BOLD) MRI, the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. ObM pigs showed obesity, dyslipidemia, and insulin resistance. The degree of CAS (range, 50-70%) was similar in lean and ObM pigs, and resting myocardial perfusion and global cardiac function remained unchanged. Increased angiogenesis distal to the moderate CAS observed in lean was attenuated in ObM pigs, which also showed microvascular dysfunction and increased inflammation (M1-macrophages, TNF-α expression), oxidative stress (gp91), hypoxia (BOLD-MRI), and fibrosis (Sirius-red and trichrome). Furthermore, lean-CAS showed increased myocardial autophagy, which was blunted in ObM pigs (downregulated expression of unc-51-like kinase-1 and autophagy-related gene-12; P < 0.05 vs. lean CAS) and associated with marked apoptosis. The interaction diet xstenosis synergistically inhibited angiogenic, autophagic, and fibrogenic activities. ObM exacerbates structural and functional myocardial injury distal to moderate CAS with preserved myocardial perfusion, possibly due to impaired cardiomyocyte turnover.

Endothelial outgrowth cells shift macrophage phenotype and improve kidney viability in swine renal artery stenosis.

OBJECTIVE: Endothelial outgrowth cells (EOC) decrease inflammation and improve endothelial repair. Inflammation aggravates kidney injury in renal artery stenosis (RAS), and may account for its persistence upon revascularization. We hypothesized that EOC would decrease inflammatory (M1) macrophages and improve renal recovery in RAS. APPROACH AND RESULTS: Pigs with 10 weeks of RAS were studied 4 weeks after percutaneous transluminal renal angioplasty (PTRA+stenting) or sham, with or without adjunct intrarenal delivery of autologous EOC (10×10(6)), and compared with similarly treated normal controls (n=7 each). Single-kidney function, microvascular and tissue remodeling, inflammation, oxidative stress, and fibrosis were evaluated. Four weeks after PTRA, EOC were engrafted in injected RAS-kidneys. Stenotic-kidney glomerular filtration rate was restored in RAS+EOC, RAS+PTRA, and RAS+PTRA+EOC pigs, whereas stenotic-kidney blood flow and angiogenesis were improved and fibrosis attenuated only in EOC-treated pigs. Furthermore, EOC increased cell proliferation and decreased the ratio of M1 (inflammatory)/M2 (reparative) macrophages, as well as circulating levels and stenotic-kidney release of inflammatory cytokines. Cultured-EOC released microvesicles in vitro and induced phenotypic switch (M1-to-M2) in cultured monocytes, which was inhibited by vascular endothelial growth factor blockade. Finally, a single intrarenal injection of rh-vascular endothelial growth factor (0.05 µg/kg) in 7 additional RAS pigs also restored M1/M2 ratio 4 weeks later. CONCLUSIONS: Intrarenal infusion of EOC after PTRA induced a vascular endothelial growth factor-mediated attenuation in macrophages inflammatory phenotype, preserved microvascular architecture and function, and decreased inflammation and fibrosis in the stenotic kidney, suggesting a novel mechanism and therapeutic potential for adjunctive EOC delivery in experimental RAS to improve PTRA outcomes.

Optimization of Seleno-chitosan-phytic acid nanocomplex for efficient removal of patulin from apple juice.

A novel and effective adsorbent known as Seleno-chitosan-phytic acid nanocomplex (Se-CS-PA) has been developed specifically for efficiently removing patulin (PAT) from a simulated juice solution. The synthesis of Se-CS-PA nanocomplex was confirmed through Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), and energy dispersive X-Ray (EDX) analyses. Response surface methodology (RSM) was employed using central composite design (CCD) to examine the impact of four independent variables (PA concentration, amount of nano-complex, duration of interaction between PAT and nano-complex, and initial concentration of PAT) on the removal of PAT. PA concentration of 0.1 % with 2.1 g Se-CS-PA nanocomplex according to RSM polynomial equation and apple juice with 25 µg.L-1 PAT yielded a remarkable adsorption rate of 94.23 % and 87.52 % respectively after 7 h. The process of PAT adsorption was explained using the pseudo-first-order model (R2 = 0.8858) for the kinetic model and the Freundlich isotherm (R2 = 0.9988) for the isotherm model.

Obesity-metabolic derangement preserves hemodynamics but promotes intrarenal adiposity and macrophage infiltration in swine renovascular disease.

Obesity-metabolic disorders (ObM) often accompany renal artery stenosis (RAS). We hypothesized that the coexistence of ObM and RAS magnifies inflammation and microvascular remodeling in the stenotic kidney (STK) and aggravates renal scarring. Twenty-eight obesity-prone Ossabaw pigs were studied after 16 wk of a high-fat/high-fructose diet or standard chow including ObM-sham, ObM-RAS, Lean-RAS, or Lean-sham (normal control) groups. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by multidetector computed tomography (CT), renal oxygenation and tubular transport capability by blood-oxygen-level-dependent MRI, and microcirculation by micro-CT for vessel density, and Western blotting for protein expressions of angiogenic factors (VEGF/FLK-1). Renal vein and inferior vena cava levels of inflammatory cytokines were measured to evaluate systemic and kidney inflammation. Macrophage (MØ) infiltration and subpopulations, fat deposition in the kidney, and inflammation in perirenal and abdominal fat were also examined. GFR and RBF were decreased in Lean-STK but relatively preserved in ObM-STK. However, ObM-STK showed impaired tubular transport function, suppressed microcirculation, and stimulated glomerulosclerosis. ObM diet interacted with RAS to blunt angiogenesis in the STK, facilitated the release of inflammatory cytokines, and led to greater oxidative stress than Lean-STK. The ObM diet also induced fat deposition in the kidney and infiltration of proinflammatory M1-MØ, as also in perirenal and abdominal fat. Coexistence of ObM and RAS amplifies renal inflammation, aggravates microvascular remodeling, and accelerates glomerulosclerosis. Increased adiposity and MØ-accentuated inflammation induced by an ObM diet may contribute to structural injury in the post-STK kidney.

Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney.

Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.

Human renovascular disease: estimating fractional tissue hypoxia to analyze blood oxygen level-dependent MR.

PURPOSE: To test the hypothesis that fractional kidney hypoxia, measured by using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging, correlates with renal blood flow (RBF), tissue perfusion, and glomerular filtration rate (GFR) in patients with atherosclerotic renal artery stenosis (RAS) better than regionally selected region of interest-based methods. MATERIALS AND METHODS: The study was approved by the institutional review board according to a HIPAA-compliant protocol, with written informed consent. BOLD MR imaging was performed in 40 patients with atherosclerotic RAS (age range, 51-83 years; 22 men, 18 women) and 32 patients with essential hypertension (EH) (age range, 26-85 years; 19 men, 13 women) during sodium intake and renin-angiotensin blockade. Fractional kidney hypoxia (percentage of entire axial image section with R2* above 30 sec(-1)) and conventional regional estimates of cortical and medullary R2* levels were measured. Stenotic and nonstenotic contralateral kidneys were compared for volume, tissue perfusion, and blood flow measured with multidetector computed tomography. Statistical analysis was performed (paired and nonpaired t tests, linear regression analysis). RESULTS: Stenotic RBF was reduced compared with RBF of contralateral kidneys (225.2 mL/min vs 348 mL/min, P = .0003). Medullary perfusion in atherosclerotic RAS patients was lower than in EH patients (1.07 mL/min per milliliter of tissue vs 1.3 mL/min per milliliter of tissue, P = .009). While observer-selected cortical R2* (18.9 sec(-1) [stenosis] vs 18.5 sec(-1) [EH], P = .07) did not differ, fractional kidney hypoxia was higher in stenotic kidneys compared with kidneys with EH (17.4% vs 9.6%, P < .0001) and contralateral kidneys (7.2%, P < .0001). Fractional hypoxia correlated inversely with blood flow (r = -0.34), perfusion (r = -0.3), and GFR (r = -0.32). CONCLUSION: Fractional tissue hypoxia rather than cortical or medullary R2* values used to assess renal BOLD MR imaging demonstrated a direct relationship to chronically reduced blood flow and GFR.

Transition from obesity to metabolic syndrome is associated with altered myocardial autophagy and apoptosis.

OBJECTIVE: Transition from obesity to metabolic-syndrome (MetS) promotes cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms are incompletely understood. We tested the hypothesis that development of insulin resistance and MetS is associated with impaired myocardial cellular turnover. METHODS AND RESULTS: MetS-prone Ossabaw pigs were randomized to 10 weeks of standard chow (lean) or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6 each). Cardiac structure, function, and myocardial oxygenation were assessed by multidetector computed-tomography and Blood Oxygen Level-Dependent-MRI, the microcirculation with microcomputed-tomography, and injury mechanisms by immunoblotting and histology. Both obese and MetS showed obesity and dyslipidemia, whereas only MetS showed insulin resistance. Cardiac output and myocardial perfusion increased only in MetS, yet Blood Oxygen Level-Dependent-MRI showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis also increased in both obese and MetS, but more pronouncedly in MetS. Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis. CONCLUSIONS: Development of insulin resistance characterizing a transition from obesity to MetS is associated with progressive changes of myocardial autophagy, apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring myocardial cellular turnover may represent a novel therapeutic target for preserving myocardial structure and function in obesity and MetS.

Evolution of cardiac and renal impairment detected by high-field cardiovascular magnetic resonance in mice with renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) promotes hypertension and cardiac dysfunction. The 2-kidney, 1-clip mouse model in many ways resembles RAS in humans and is amenable for genetic manipulation, but difficult to evaluate noninvasively. We hypothesized that cardiovascular magnetic resonance (CMR) is capable of detecting progressive cardiac and renal dysfunction in mice with RAS and monitoring the progression of the disease longitudinally. METHODS: RAS was induced at baseline in eighteen mice by constricting the renal artery. Nine additional animals served as normal controls. CMR scans (16.4 T) were performed in all mice one week before and 2 and 4 weeks after baseline. Renal volumes and hemodynamics were assessed using 3D fast imaging with steady-state precession and arterial spin labelling, and cardiac function using CMR cine. Renal hypoxia was investigated using blood oxygen-level dependent (BOLD) MR. RESULTS: Two weeks after surgery, mean arterial pressure was elevated in RAS mice. The stenotic kidney (STK) showed atrophy, while the contra-lateral kidney (CLK) showed hypertrophy. Renal blood flow (RBF) and cortical oxygenation level declined in the STK but remained unchanged in CLK. Moreover, cardiac end-diastolic and stroke volumes decreased and myocardial mass increased. At 4 weeks, STK RBF remained declined and the STK cortex and medulla showed development of hypoxia. Additionally, BOLD detected a mild hypoxia in CLK cortex. Cardiac end-diastolic and stroke volumes remained reduced and left ventricular hypertrophy worsened. Left ventricular filling velocities (E/A) indicated progression of cardiac dysfunction towards restrictive filling. CONCLUSIONS: CMR detected longitudinal progression of cardiac and renal dysfunction in 2K, 1C mice. These observations support the use of high-field CMR to obtain useful information regarding chronic cardiac and renal dysfunction in small animals.

Gelling and rheological properties of a polysaccharide extracted from Ocimum album L. seed.

In this study, a new polysaccharide was isolated from Ocimum album L. seed (OA), and its physicochemical and rheological properties were investigated. Ocimum album polysaccharide (OAP) was an acidic heteropolysaccharide with a molecular weight of 1935 kDa, and it was composed of five types of sugars: mannose (32.95 %), glucose (27.57 %), galactose (19.29 %), rhamnose, (15.96 %) and galacturonic acid (4.23 %). According to the results obtained from Huggins and Kraemer equations, the intrinsic viscosity was 6.9 dL/g in distilled water. The OAP solutions at a concentration between 0.1 and 1.5 %, showed shear-thinning behavior, and the Herschel-Bulkley and Cross models exhibited a high ability to describe the flow behavior of OAP solutions. The apparent viscosity of 1 % OAP solution was decreased in the presence of different concentrations of NaCl (0.1, 0.3, and 0.5 M), at different pHs (3-11), and in temperatures between 5 and 100 °C. Also, the pseudoplastic behavior was observed in all samples. In OAP solutions (0.1-1.5 %), the up and down curves in the shear stress-shear rate diagram did not coincide, which indicated time-dependent (thixotropic) behavior. Although, the thixotropic properties of 1 % OAP solution were weakened with adding NaCl (0.1-0.5 M) and at different pH (3-11). The results obtained from the dynamic oscillatory test showed that the OAP solutions at concentrations higher than 0.1 % had a gel-like behavior, and the viscoelastic moduli (G' and G″) were weakened in the presence of salt and with a change in pH. Also, in the temperature sweep test, the 1 % solution showed the behavior of thermally irreversible gels.

Addition of endothelial progenitor cells to renal revascularization restores medullary tubular oxygen consumption in swine renal artery stenosis.

Renal artery stenosis (RAS) promotes microvascular rarefaction and fibrogenesis, which may eventuate in irreversible kidney injury. We have shown that percutaneous transluminal renal angioplasty (PTRA) or endothelial progenitor cells (EPC) improve renal cortical hemodynamics and function in the poststenotic kidney. The renal medulla is particularly sensitive to hypoxia, yet little is known about reversibility of medullary injury on restoration of renal blood flow. This study was designed to test the hypothesis that PTRA, with or without adjunct EPC delivery to the stenotic kidney, may improve medullary remodeling and tubular function. RAS was induced in 21 pigs using implantation of irritant coils, while another group served as normal controls (n = 7 each). Two RAS groups were then treated 6 wk later with PTRA or both PTRA and EPC. Four weeks later, medullary hemodynamics, microvascular architecture, and oxygen-dependent tubular function of the stenotic kidneys were examined using multidetector computed tomography, microcomputed tomography, and blood oxygenation level-dependent MRI, respectively. Medullary protein expression of vascular endothelial growth factor, endothelial nitric oxide synthase, hypoxia-inducible factor-1α, and NAD(P)H oxidase p47 were determined. All RAS groups showed decreased medullary vascular density and blood flow. However, in RAS+PTRA+EPC animals, EPC were engrafted in tubular structures, oxygen-dependent tubular function was normalized, and fibrosis attenuated, despite elevated expression of hypoxia-inducible factor-1α and sustained downregulation of vascular endothelial growth factor. In conclusion, EPC delivery, in addition to PTRA, restores medullary oxygen-dependent tubular function, despite impaired medullary blood and oxygen supply. These results support further development of cell-based therapy as an adjunct to revascularization of RAS.

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation.

Metabolic syndrome (MetS) is associated with glomerular hyperfiltration and is a risk factor for chronic kidney disease, but the underlying mechanisms are poorly defined. This study tested the hypothesis that increased glomerular filtration rate (GFR) in early MetS is associated with renal adiposity and microvascular proliferation. Twelve MetS-prone Ossabaw pigs were randomized to 10 wk of a standard (lean, n = 6) or atherogenic (MetS, n = 6) diet. Kidney hemodynamics and function, perirenal fat volume, and tubular dynamics were assessed in vivo by multidetector computed tomography (CT) and blood oxygen level-dependent (BOLD)-MRI. Microvascular architecture was assessed ex vivo with micro-CT. Candidate injury mechanisms were evaluated in kidney tissue by Western blotting and histology. Basal GFR, renal blood flow, and renal cortical perfusion and volume were elevated in the MetS group. Perirenal and kidney tissue fat, proximal-nephron intratubular fluid concentration, and endothelial nitric oxide synthase expression were increased in MetS. GFR levels correlated with tissue triglyceride levels. Elevated spatial density of 20- to 40-µm cortical microvessels was accompanied by mild oxidative stress, inflammation, and with proximal tubular vacuolization. Medullary size and perfusion were relatively preserved, and BOLD-MRI showed intact medullary tubular response to furosemide. Increased GFR in early MetS is associated with renal adiposity and microvascular proliferation, which involve mainly the renal cortex and precede significant activation of oxidative stress and inflammation. Renal adiposity and proliferative microvessels may represent novel therapeutic targets for preserving renal function in early MetS.

Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: a Single-Center Double-Blind Clinical Study.

Adverse cardiac remodeling after myocardial infarction (MI) can lead to the syndrome of heart failure (HF). Recently, changes in gut microbiota composition (dysbiosis) have appeared as a novel candidate that may be linked to the development of CR and HF. The aim of this trial was to evaluate the effects of probiotics administration on attenuating CR in patients with MI. A single-center double-blind placebo-controlled stratified randomized clinical study was conducted in 44 subjects with MI who underwent percutaneous coronary intervention (PCI). Patients were randomly assigned to take, with lunch, either a probiotic capsule containing 1.6 × 109 colony-forming unit (CFU) of bacteria (treatment group) or capsules contained inulin (control group) over 3 months. CR biomarkers (including serum procollagen III, transforming growth factor beta (TGF-ß), trimethylamine N-oxide (TMAO), and matrix metallopeptidase 9 (MMP-9)) were assessed. Echocardiography results were measured at baseline and after the intervention. Significant decreases were seen in serum TGF-ß concentrations (- 8.0 ± 2.1 vs. - 4.01 ± 1.8 pg/mL, p = 0.001) and TMAO levels (- 17.43 ± 10.20 vs. - 4.54 ± 8.7 mmol/L, p = 0.043), and there were no differences were seen in MMP-9 (- 4.1 ± 0.12 vs. - 4.01 + 0.15 nmol/mL, p = 0.443) and procollagen III levels (- 1.35 ± 0.70 vs. 0.01 + 0.3 mg/L, p = 0.392) subsequent to probiotics supplementation compared with the placebo group. Improvements in echocardiographic indices were also greater in the probiotics group as compared with that in the control group, but not at a significant level. Regression analysis revealed that baseline left ventricular ejection fraction (LVEF), and changes of procollagen III, predicted 62% of the final LVEF levels. Probiotics administration may have a beneficial effect on the cardiac remodeling process in patients with myocardial infarction. Iranian Registry of Clinical Trials (IRCT): IRCT20121028011288N15.

Probiotic supplementation improves clinical outcomes and quality of life indicators in patients with plaque psoriasis: A randomized double-blind clinical trial.

BACKGROUND & AIMS: The impact of probiotics on psoriasis, a systemic inflammatory disease, remains obscure, thus we decided to evaluate quality of life (QOL), oxidative stress, inflammatory markers and clinical outcome in psoriasis patients. METHODS: Fifty patients with plaque psoriasis randomized into two groups, group 1 received probiotic drink with Lactobacillus strains for 8 weeks while group 2 haven't received any probiotic supplements at this period. The Dermatology Life Quality Index (DLQI) and Beck's questionnaire (BDI) were used to investigate the quality of life and depression, respectively. The effects of supplementation on malondialdehyde (MDA), hs-CRP, IL-6, total antioxidant capacity (1) and psoriasis area and severity index (PASI), psoriasis symptom scale (PSS) were measured at the beginning of the study and after week 8th. RESULTS: Total BDI scores significantly improved in the probiotic group in comparison with the placebo group (-6.15 ± 2.10 vs. 1.39 ± 1.80, P = 0.017) and DLQI (-9.50 ± 4.1 vs. 0.12 ± 0.6, P = 0.045) as well. Group 1 had a considerable reduction in PASI and PSS scores compared to the placebo group (-5.26 ± 3.75 vs. 0.48 ± 1.37, P = 0.049) and (-4.85 ± 3.10 vs. 0.43 ± 0.80, P = 0.047), respectively. In addition, the intervention group have shown increase in TAC levels (45.99 ± 23.33 vs -13.54 ± 30.7 mmol/L, P = 0.030), and decrease in hs-CRP levels (-1.55 ± 0.85 vs. -0.49 + 0.27 mg/L, P = 0.015), IL-6 levels (-4.04 ± 1.30 vs. -1.50 + 0.38 mg/L, P = 0.050) and MDA levels (-71.08 ± 35.73 vs. -9.8 + 15.6 nmol/mL, P = 0.013) compared to the placebo group. CONCLUSIONS: Probiotics improve patients' quality of life and inflammatory biomarkers in psoriatic patients. Further studies are mandatory to propose probiotics as routinely prescribed therapy in inflammatory dermatoses. TRIAL REGISTRATION: This trial was registered at www.irct.ir as IRCT20180712040438N2.