Surgical treatment of aortic valve endocarditis: a 26-year experience

Objective

We have retrospectively analyzed the results of the operations made for aortic valve endocarditis in a single center in 26 years.

Methods

From June 1985 to January 2011, 174 patients were operated for aortic valve endocarditis. One hundred and thirty-eight (79.3%) patients were male and the mean age was 39.3±14.4 (9-77) years. Twenty-seven (15.5%) patients had prosthetic valve endocarditis. The mean duration of follow-up was 7.3±4.2 years (0.1-18.2) adding up to a total of 1030.8 patient/years.

Results

Two hundred and eighty-two procedures were performed. The most frequently performed procedure was aortic valve replacement with mechanical prosthesis (81.6%). In-hospital mortality occurred in 27 (15.5%) cases. Postoperatively, 25 (14.4%) patients had low cardiac output and 17 (9.8%) heart block. The actuarial survival rates for 10 and 15 years were 74.6±3.7% and 61.1±10.3%, respectively. In-hospital mortality was found to be associated with female gender, emergency operation, postoperative renal failure and low cardiac output. The long term mortality was significantly associated with mitral valve involvement. Male gender was found to be a significant risk factor for recurrence in the follow-up.

Conclusion

Surgery for aortic valve endocarditis has significant mortality. Emergency operation, female gender, postoperative renal failure and low cardiac output are significant risk factors. Risk for recurrence and need for reoperation is low.     

Synthesis,X-ray crystal structure elucidation and Hirshfeld surface analysis of N-((4-(1H-benzo[d]imidazole-2-yl)phenyl)carbamothioyl)benzamide: investigations for elastase inhibition,antioxidant and DNA binding potentials for biological applications

The interest in the present study pertains to the development of a new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, free radical scavenging activity and its DNA binding ability. The title compound, N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-3-benzoyl thiourea (C₂₁H₁₈N₄O₂SH₂O:TUBC), was synthesized by reacting an acid chloride of benzoic acid with potassium thiocyanate (KSCN) along with the subsequent addition of 4-(1H-benzo[d]imidazol-2-yl)benzenamine via a one-pot three-step procedure. The structure of the resulting benzimidazole based thiourea was confirmed by spectroscopic techniques including FTIR, ¹H-NMR, ¹³C-NMR and single crystal X-ray diffraction and further examined by Hirshfeld surface analysis. TUBC was also investigated by using both in silico methodology including molecular docking for elastase inhibition along with quantum chemical studies and in vitro experimental methodology utilizing elastase inhibition and free radical scavenging assay along with DNA binding experiments. Docking results confirmed that TUBC binding was within the active region of elastase. In comparison to the reference drug oleanolic acid, the low IC₅₀ value of TUBC also indicated its high tendency towards elastase inhibition. TUBC scavenged 80% of DPPH˙ radicals which pointed towards its promising antioxidant activity. TUBC–DNA binding by DFT, docking, UV-visible spectroscopy and viscosity measurements revealed TUBC to be a potential drug candidate that binds spontaneously and reversibly with DNA via a mixed binding mode. All theoretical and experimental findings pointed to TUBC as a potential candidate for a variety of biological applications.

A new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, antioxidant and DNA binding ability has been studied.     

Anti-aging formulation of rosmarinic acid-loaded ethosomes and liposomes

The study was aimed to evaluate the effectiveness of rosmarinic acid (RA) loaded ethosomes (ETHs) and liposomes (LPs) when subjected to the transdermal application. RA-loaded ETHs and LPs were prepared, optimised, and characterised. The ex vivo permeation studies of formulations using mouse abdominal skin were performed. Antioxidant activities and the inhibitory effects of formulations on collagenase and elastase enzymes were measured. Optimised ethosomal formulation (F3) was showed nanometric size range (138?±?1.11?nm) and greatest entrapment (55?±?1.80%), was selected for further transdermal permeation studies. Skin permeation profile of the nanoformulations analysed by HPLC revealed an enhanced permeation of ETHs. Transdermal flux of ETHs was found to be higher than RA solution and LPs. Enzyme inhibitions of ETHs were the significant difference found between ETHs and LPs (p?<?0.05). ETHs were found to be more effective and successful than LPs. Results suggest that ETHs are more effective than LPs for transdermal delivery of RA.     

Oxidative Stress and Lipid Peroxidation in the Ischemic Small Intestine: Pathological and Biochemical Evaluation in a Rat model of Superior Mesenteric Ischemia

The purpose of our study was to evaluate the role of oxidative stress and lipid peroxidation in acute mesenteric ischemia. Thirty male Wistar albino rats weighing 240–260 g were randomized into control (no operation), sham (operation without ischemia), and ischemia groups. To induce ischemia, the superior mesenteric artery was sutured. Total antioxidant and oxidant capacity and lipid peroxidase activity were measured in blood samples collected at 0 min, 60 min, and 240 min, and the pathology of ileum segments resected at 240 min was evaluated. Total oxidant status did not differ among the groups. Total antioxidant status increased significantly with time in the ischemia group compared to the control and sham groups (P < 0.001). Although basal arylesterase activity was lower in the ischemia group than controls (P < 0.05), post-ischemia values were similar among the groups. Similarly, basal and stimulated paraoxonase activity in blood samples did not differ among the groups. In conclusion, oxidative stress and lipid peroxidation have no significant role in the pathophysiology of acute mesenteric ischemia.Key words: Mesenteric ischemia, Oxidative stress, Lipid peroxidationOxygen is both vital and damaging, as it is involved in the pathogenesis of many types of tissue injury.^1,2 Oxidative stress, which is an imbalance between reactive oxygen species and antioxidant defense systems, can be caused by several factors such as ischemia, heavy exercise, and inflammation.^3,4 Oxidative stress has been linked to some neurodegenerative and cardiovascular diseases, preeclampsia, gene mutations, and aging.⁵⁻⁹The role of oxidative stress and oxygen-derived free radicals in the pathophysiology of ischemic diseases was postulated first in the mid-1950s.¹⁰ After the development of advanced biochemical techniques to measure oxidant and antioxidant capacities in tissues, the relationship between ischemia and oxidative stress has been studied extensively.¹⁰Biochemical indicators of oxidative stress include total oxidant and antioxidant status and the activity of antioxidant enzymes such as serum dismutase, glutathione peroxidase, and stimulated paraoxonase. Specifically, paraoxonase, an ester hydrolase antioxidant with both arylesterase and paraoxonase activities, acts as an enzymatic defense against lipid hydroperoxides.^11,12 Serum paraoxonase and arylesterase activities recently have been found to be reduced in gastrointestinal diseases such as chronic liver disease.^13,14Oxidative stress has been proposed as an underlying mechanism of many chronic diseases, and reactive oxygen species are known to play a critical role in gut epithelial cell damage induced by ischemia.¹⁵ Intestinal ischemia includes a variety of potentially life-threatening conditions such as ischemic colitis and acute or chronic mesenteric ischemia.¹⁶ To determine the role of oxidative stress and lipid peroxidation in the pathophysiology of intestinal ischemia could lead to new approaches to treat and prevent these clinical conditions.In this experimental animal study, we aimed to evaluate the effect of arterial ischemia on both oxidant/antioxidant capacities and lipid peroxidation in a rat model of superior mesenteric ischemia.     

Early Versus Delayed Laparoscopic Cholecystectomy for Acute Cholecystitis: A Prospective,Randomized Study

We aimed to compare the clinical outcome and cost of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Sixty patients with acute cholecystitis were randomized into early (within 24 hours of admission) or delayed (after 6–8 weeks of conservative treatment) laparoscopic cholecystectomy groups. There was no significant difference between study groups in terms of operation time and rates for conversion to open cholecystectomy. On the other hand, total hospital stay was longer (5.2 ± 1.40 versus 7.8 ± 1.65 days; P = 0.04) and total costs were higher (2500.97 ± 755.265 versus 3713.47 ± 517.331 Turkish Lira; P = 0.03) in the delayed laparoscopic cholecystectomy group. Intraoperative and postoperative complications were recorded in 8 patients in the early laparoscopic cholecystectomy group, whereas no complications occurred in the delayed laparoscopic cholecystectomy group (P = 0.002). Despite intraoperative and postoperative complications being associated more with early laparoscopic cholecystectomy compared with delayed intervention, early laparoscopic cholecystectomy should be preferred for treatment of acute cholecystitis because of its advantages of shorter hospital stay and lower cost.Key words: Acute cholecystitis, Laparoscopic cholecystectomy, Outcome assessment, Cost and cost analysisElective laparoscopic cholecystectomy has become the gold standard for treatment of symptomatic gallstones.¹ However, in the early days, acute cholecystitis was a contraindication of laparoscopic cholecystectomy, and patients with acute cholecystitis were managed conservatively and discharged for re-admission in order to have elective surgery performed for the definitive treatment.^2,3 Then, randomized controlled trials and meta-analyses had shown the benefits of early surgery (within the acute admission period, which is 24 to 72 hours) compared with delayed cholecystectomy with respect to hospital stay and costs, with no significant difference in morbidity and mortality.^2,4,5 Thus, in the late 1980s early surgery for acute cholecystitis had gained popularity. The updated Tokyo Guidelines announced in 2013 by the Japanese Society of Hepato-Biliary-Pancreatic Surgery suggested that early laparoscopic cholecystectomy is the first-line treatment in patients with mild acute cholecystitis, whereas in patients with moderate acute cholecystitis, delayed/elective laparoscopic cholecystectomy after initial medical treatment with antimicrobial agent is the first-line treatment.⁶With the increased experience in laparoscopy, surgeons started to attempt early laparoscopic cholecystectomy for acute cholecystitis.² However, early laparoscopic cholecystectomy is still performed by only a minority of surgeons.^7–9 Furthermore, the exact timing, potential benefits, and cost-effectiveness of laparoscopic cholecystectomy in the treatment of acutely inflamed gallbladder have not been clearly established and continue to be controversial.^1,10The aim of this study was to compare the intra-operative and postoperative outcomes, and cost of early versus delayed laparoscopic cholecystectomy for acute cholecystitis.     

The Relationship between IL-10 Levels and Cardiovascular Events in Patients with CKD

Background and objectives

Cardiovascular disease is the leading cause of death in patients with CKD. IL-10 is considered an antiatherosclerotic cytokine. However, previous studies have failed to observe an association between IL-10 and cardiovascular disease in CKD. This study aimed to evaluate whether serum IL-10 levels were associated with the risk of cardiovascular events in CKD patients.

Design, setting, participants, & measurements

Four hundred three patients with stages 1–5 CKD were followed for a mean of 38 (range=2–42) months for fatal and nonfatal cardiovascular events. IL-10 and IL-6 were measured at baseline together with surrogates of endothelial function (flow-mediated dilatation) and proinflammatory markers (high-sensitivity C-reactive protein and pentraxin-3). The association between IL-10 and flow-mediated dilatation through linear regression analyses was evaluated. The association between IL-10 and the risk of cardiovascular events was assessed with Cox regression analysis.

Results

IL-10, IL-6, high-sensitivity C-reactive protein, and pentraxin-3 levels were higher among participants with lower eGFR. Both fatal (25 of 200 versus 6 of 203 patients) and combined fatal and nonfatal (106 of 200 versus 23 of 203 patients) cardiovascular events were more common in patients with IL-10 concentration above the median. Flow-mediated dilatation was significantly lower in patients with higher serum IL-10 levels, but IL-10 was not associated with flow-mediated dilatation in multivariate analysis. Kaplan–Meier survival curves showed that patients with IL-10 below the median value (<21.5 pg/ml) had higher cumulative survival compared with patients who had IL-10 levels above the median value (log-rank test, P<0.001).

Conclusions

IL-10 levels increase along with the reduction of kidney function. Higher serum IL-10 levels were associated with the risk of cardiovascular events during follow-up. We speculate that higher IL-10 levels in this context signify an overall proinflammatory milieu.