Aortic tortuosity is related to aortic phenotype in patients with bicuspid aortic valve: a CT scan study of 83 cases

Background Although the incidence of aortic dissection is higher in patients with bicuspid aortic valve (BAV) compared to tricuspid aortic valve (TAV), risk stratification remains unclear. Guidelines focus on ascending aorta diameters, regardless of the location, and do not take into account the morphology of the aorta. Aortic tortuosity (AT) is emerging as a novel biomarker associated with more severe aortopathy in patients with Marfan syndrome. AT has not been accuretely assessed in BAV. Our aim is to describe the relationship between AT and ascending aortic phenotype in patients with BAV. Methods 83 patients (43±16 years, 19 women) diagnosed with BAV and without significant aortic valve disease nor prior aortic intervention were included. CT scans were retrospectively analysed with measurements of aortic diameters and aortic tortuosity. For 61 patients with abdominal images available, descending and total aortic length and tortuosity were measured. Results In our cohort, 62 (75%) patients presented a typical BAV. Pathological aorta (Root and/or tubular Z-score >2) was found in 80 patients (96%) and 67 (81%) presented a tubular dilatation. The aortic phenotype, the maximal aortic diameters and aortic tortuosity index were similar in typical and atypical BAV. Total aortic tortuosity index was correlated to Z-score tubular diameter (r=0.31; p=0,014) but not with Z-score Valsalva diameter (p=0,55). In patients with tubular dilatation (Z score >2), total aortic tortuosity index was higher than in patient without tubular dilatation (2.01 vs 1.85; p=0,015). Conclusion Total aortic tortuosity is associated with tubular dilatation but not with root dilatation in BAV patients suggesting that tubular phenotype may be at higher risk of complication in BAV. Further studies evaluating the association between aortic tortuosity and clinical outcomes in BAV are needed. FUNDunding Acknowledgement Type of funding sources: None.

Ultrasonic Diagnostic Strategy for the Causes of Coronary Artery Dilatation in Infants

Objective:To explore a differential diagnosis strategy for the causes of coronary artery dilatation (CAD) in infants．Methods: Clinical and echocardiography data for 243 infants with CAD from the Shengjing Hospital of China Medical University were analyzed retrospectively. The patients were divided into congenital and acquired groups according to the CAD causes.Results: The lesion detection rate for CAD in 22,925 infants who underwent echocardiography was 1.06% (243/22,925). The acquired group accounted for 84.77% (206/243) of participants, all of which had Kawasaki disease. The congenital group accounted for 15.23% (37/243) of patients, including coronary artery fistula [12.35% (30/243)], anomalous origin of the coronary artery [2.06% (5/243)], severe pulmonary stenosis [0.41% (1/243)], and moderate aortic stenosis [0.41% (1/243)]. There was no significant difference in the Z-score for CAD between the two groups of children (P>0.05). There were differences in the scope and shape of CAD between the two groups (all P<0. 05). Acquired causes mainly manifested as segmental dilatation, while congenital causes manifested as tubular dilatation. The sensitivity and specificity of segmental dilatation in predicting acquired causes were 97.57% and 100%, respectively, and that of tubular dilatation in predicting congenital causes were 97.30% and 98.06%, respectively. Conclusion: It is particularly important to diagnose the cause of CAD because its treatment depends on its etiology. When an echocardiography examination identifies CAD in infants, comprehensive and systematic analysis can quickly and accurately determine the cause of CAD according to the diagnostic strategy process and evaluation of dilatation and cardiac structure characteristics.

Prenatal Diagnosis of Ductus Arteriosus Aneurysms and Neonatal Outcome: Two Case Reports and Literature Review

Ductus arteriosus aneurysm is a rare condition characterized by a saccular or tubular dilatation of the ductus with potentially fatal outcome due to complications such as rupture, thromboembolism, and infection, compression of adjacent structures and coarctation of the aorta [1]. Association with connective tissue disorders such as Marfan and Ehlers-Danlos syndromes are also described [2,3]. Therefore, we aimed to describe two recent cases of aneurysm of ductus arteriosus assessed by fetal echocardiography and their neonatal outcomes.

Yiqihuoxue Formula Activates Autophagy and Offers Renoprotection in a Rat Model of Adenine-Induced Kidney Disease

Chronic kidney disease (CKD) is a worldwide health problem for which effective therapeutic methods are still lacking. Traditional Chinese medicine (TCM) has been indicated as an effective alternative treatment for kidney disease. In this study, a clinically effective therapy, yiqihuoxue (YQHX) formula, was administrated to adenine-induced kidney disease rats for 6 weeks. We found that the adenine rats displayed a significant reduction in renal function as evidenced by the increased levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24-h urinary albumin level, which were attenuated by the YQHX treatment. The glomerulosclerosis, interstitial fibrosis, arteriolosclerosis, interstitial inflammation, and tubular dilatation were reversed by the YQHX treatment in the adenine rats. Furthermore, the hepatic damage characterized by increased levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cell infiltration was improved by YQHX. In addition, the number of apoptotic cells in the adenine rats was obviously reduced by the YQHX treatment as manifested by the lower expression level of cleaved caspase-3 protein. Moreover, the YQHX treatment downregulated the expression levels of fibronectin, type I collagen, α-smooth muscle actin, and TGF-β1 in the adenine rats. Furthermore, autophagy was activated by the YQHX treatment, which manifested as an increased LC3-II and Beclin-1 expression levels and a decreased p62 level. In conclusion, the YQHX formula might retard the progression of kidney disease by activating autophagy.

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice

Melatonin, a pineal hormone, is well known to regulate the sleep–wake cycle. Besides, the hormone has been shown to display pleiotropic effects arising from its powerful anti-oxidant and anti-inflammatory activities. Recent studies have reported that melatonin exerts protective effects in animal models of kidney disease. However, the potential effects of melatonin on aristolochic acid (AA)-induced nephropathy (AAN) have not yet been investigated. Here, we found that the administration of melatonin ameliorated AA-induced renal dysfunction, as evidenced by decreased plasma levels of blood urea nitrogen and creatinine and histopathological abnormalities such as tubular dilatation and cast formation. The upregulation of tubular injury markers after AA injection was reversed by melatonin. Melatonin also suppressed AA-induced oxidative stress, as evidenced by the downregulation of 4-hydroxynonenal and reduced level of malondialdehyde, and modulated expression of pro-oxidant and antioxidant enzymes. In addition, p53-dependent apoptosis of tubular epithelial cells, infiltration of macrophages and CD4+ T cells into damaged kidneys, and renal expression of cytokines and chemokines were inhibited by melatonin. Moreover, melatonin attenuated AA-induced tubulointerstitial fibrosis through suppression of the tumor growth factor-β/Smad signaling pathway. These results suggest that melatonin might be a potential therapeutic agent for AAN.

Human Immunodeficiency Virus Nephropathy in Central Africa: The Value of Renal Ultrasound

<p><strong><em>Introduction:</em></strong><em> </em><em>HIV-Associated Nephropathy </em><em>may shorten the life expectancy of affected patients. Its </em><em>early detection is beneficial for the indication of treatment and hence prevention of progression to the end-stage of renal failure. The final diagnosis requires renal biopsy which may be difficult in some African area; clinical and ultrasound criteria may be helpful. The aim of this study was twofold: to characterize renal sonographic changes in HIV-positive patients with HIV associated Nephropathy and to investigate the correlation between renal sonographic changes and histological lesions in central Africa.</em></p><p><strong><em>Methods:</em></strong><em> A prospective and multi-center study conducted from January 2013 to July 2015 included, for renal ultrasound evaluation of the length, thickness and echogenicity, forty two of the 334 biologically confirmed HIV-positive patients who presented with significant proteinuria suggestive of HIV associated Nephropathy. And transcutaneous renal biopsy with histopathology has been performed in 16 patients of them. </em><em>Statistical analyzes were used.</em></p><p><strong><em>Results:</em></strong><em> There were 100 men and 234 women; proteinuria was positive in 42 patients, (12.6%). The average length of the kidneys was 111 ± 8 mm (normal), with 10% of patients with pathological values (5% with kidneys of reduced size and 5%, increased size). The kidneys had an average thickness of 44 ± 5 mm (normal), with 21% of patients presenting an increase in renal thickness. Quantitative echogenicity was calculated at 1.492 ± 0.793 (normal), with 79% of patients with increased quantitative echogenicity. Of the 16 patient</em><em>s</em><em> biopsied, all had tubulo-interstitial lesion</em><em>s</em><em>, and 75% of them associated with glomerular le</em><em>s</em><em>ion</em><em>s</em><em>.</em><em> </em><em>In simple correlation analysis, tubular dilatation was positively and significantly related to quantitative echogenicity (r = 0.67, p &lt; 0.01) and to renal parenchyma thickness (r = 0.67; 0.85, p ? 0.05). The relationship between the other parameters studied did not reach statistical significance. In multiple linear regression, glomerular hyalinosis, glomerular proliferation, tubular dilatation, tubular atrophy, interstitial fibrosis, and interstitial inflammation emerged as the main determinants of quantitative echogenicity; however, the relationship was statistically significant only for tubular dilatation (? = 0.305, p = 0.034).</em><em></em></p><strong><em>Conclusion:</em></strong><em> The present study showed the characteristic of renal change and the relation with histology found in central Africans patients.</em>

The Effect of Arabic Gum on Renal Function in Reversible Unilateral Ureteric Obstruction

Arabic gum (AG) has antioxidant and anti-inflammatory properties. However, the effect of AG in ureteric obstruction (UO) has not been investigated yet. Male rats underwent reversible left unilateral UO (UUO) for 72 h. Group AG-1 (n = 12) received AG 15 g/kg/day dissolved in drinking water starting seven days before and continuing throughout the period of the UUO, whereas group Vx-1 (n = 8) had only water. Group AG-2 (n = 12) and Vx-2 (n = 8) had similar protocols as AG-1 and Vx-1, respectively, but underwent terminal experiments to measure renal functions, six days post-UUO reversal. Arabic gum significantly attenuated the UUO-induced increase in the tissue level of malonedialdehyde and superoxide dismutase and the rise in the gene expression of TNF-α, TGF-β1, and p53 in AG-1 compared to Vx-1. It also attenuated the severity of tubular dilatation. However, AG did not affect the alterations in the renal blood flow or glomerular filtration rate. The fractional sodium excretion was lower in AG-2 but did not reach statistical significance (0.40 ± 0.11 vs 0.74 ± 0.12, p = 0.07). AG attenuated the UUO-induced rise in oxidative stress markers and proinflammatory and profibrotic cytokines and the degree of renal tubular dilatation, indicating a protective effect in obstructive nephropathy.

Fish Oil Supplementation Reduces Inflammation but Does Not Restore Renal Function and Klotho Expression in an Adenine-Induced CKD Model

Background: Chronic kidney disease and inflammation promote loss of Klotho expression. Given the well-established anti-inflammatory effects of omega-3 fatty acids, we aimed to investigate the effect of fish oil supplementation in a model of CKD. Methods: Male C57BL/6 mice received supplementation with an adenine-enriched diet (AD, n = 5) or standard diet (CTL, n = 5) for 10 days. Two other experimental groups were kept under the adenine diet for 10 days. Following adenine withdrawal on the 11th day, the animals returned to a standard diet supplemented with fish oil (Post AD-Fish oil, n = 9) or not (Post AD-CTL, n = 9) for an additional period of 7 days. Results: Adenine mice exhibited significantly higher mean serum urea, creatinine, and renal expression of the pro-inflammatory markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin-1β (IL-1β), in addition to prominent renal fibrosis and reduced renal Klotho gene expression compared to the control. Post AD-Fish oil animals demonstrated a significant reduction of IL-6, C-X-C motif chemokine 9 (CXCL9), and IL-1β compared to Post AD-CTL animals. However, serum creatinine, renal fibrosis, and Klotho were not significantly different in the fish oil-treated group. Furthermore, renal histomorphological changes such as tubular dilatation and interstitial infiltration persisted despite treatment. Conclusions: Fish oil supplementation reduced renal pro-inflammatory markers but was not able to restore renal function nor Klotho expression in an adenine-induced CKD model.

Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats

Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the longterm. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents,can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented byusing pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objectiveof this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline,kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normalsaline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifyllinetwice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injectionsof 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac punctureunder general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediatelyremoved, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogramparameters were measured using a blood cell count apparatus and serum biochemical parameters were measured usingan autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifyllinesignificantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubulardilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates wereobserved in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifyllinegroups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameterswithin reference ranges (P < 0.05).Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifyllineinhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although thisreduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascularinflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline preventedtubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also amelioratedamikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protectiveeffects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulatingthe production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatoryeffects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs inthe present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/orare dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemicalparameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggestedthat kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.

Study on Acute Oral Toxicity of Ethanolic Extract of Annonasquamosa Leaves in Mice (Musmusculus)

The aims of this study were to determine the potential for acute oral toxicity of ethanolic extract of A.squamosa leaves with LD50 and the histopathological changes in liver and kidney of mice.This research used experimental method as per fixed dose method. The number of animals used in this research were 20 female mice. The study was divided into 2 steps, there were sighting and main studies. The control group was given Na-CMC 0.5%, the treatment groups were given ethanolic extract of A.squamosa leaves with doses of 5, 50, 300, 2,000 and 5,000 mg/kg bw. The results showed that the ethanolic extract of A.squamosa leaves with doses of 2,000 and 5,000 mg/kg bw did not show any toxicity signs. At a dose of 5,000 mg/kg bw caused hydropic degeneration, necrosis hepatocyte, glomerular atrophy, and tubular dilatation. There was no mortality was observed.It was estimated that LD50 of ethanolic extract of A.squamosa leaves was higher than 5,000 mg/kg bw and the extract were practically non-toxic. Keywords: Acute Toxicity, Annona squamosa, Ethanolic Extract