The in vivo evaluation of anti-angiogenic effects of Hypericum essential oils using the chorioallantoic membrane assay

Context. Hypericum species including Hypericum confertum Choisy, H. hircinum L., H. hyssopifolium Chaix. subsp. elongatum (Ledeb.) Woron var. microcalycinum (Boiss. &; Heldr.) Boiss. and H. perforatum L. (Clusiaceae) are used as medicinal plants in Turkey.

Objective: The anti-angiogenic evaluation of Hypericum essential oils using the chick embryo chorioallantoic membrane (CAM) assay are performed with this study for the first time.

Materials and methods: The anti-angiogenic activity of Hypericum essential oils (0.5–5.0?mg/ml) was evaluated in vivo using the CAM assay, compared to standard anti-angiogenic substances at the same concentrations, in trice replicated independent assays. GC and GC-MS analyses were carried out simultaneously to identify the chemical compositions of the Hypericum essential oils.

Results: The CAM treated with H. perforatum essential oil showed anti-angiogenic effect (score 0.6?±?0.3) at 50?µg/pellet concentration, whereas other tested Hypericum essential oils showed no effect compared to the standards (e.g. suramin score 0.5?±?0.2). Furthermore, the tested oils showed neither membrane toxicity nor irritation at the tested concentrations. The major compound of the essential oil of H. confertum was identified as germacrene D (30.2%). The major compound of the essential oils of the H. hircinum. H. hyssopifolium subsp. elongatum var. microcalycinum and H. perforatum was identified as α-pinene (88.3, 57.8, 33.3%), respectively.

Discussion and conclusion. Hypericum species and in particular H. perforatum essential oil may have important effect toward wound healing and various inflammations. The data obtained in this experiment suggest further investigations on various cancers due to its anti-angiogenic effects observed.     

Comparison of the flap survival with ischemic preconditioning on different pedicles under varied ischemic intervals in a rat bilateral pedicled flap model

The study was undertaken to search whether pedicle selection for ischemic preconditioning (IP) and duration of global ischemia applied after IP influenced efficacy of IP on flap viability in epigastric adipocutaneous island flap with bilateral pedicles in rat model. In total, 159 rats were divided into one control and three (primary, secondary, or bilateral pedicle) IP treatment groups. IP was performed on different pedicles by three cycles of 10 minutes of pedicle clamping and 10 minutes of release. After IP procedure secondary pedicle was ligated in all groups, and flaps were exposed to 0, 1, 2, 4, or 6 hours of global ischemia by clamping primary pedicle. In control groups, after the perfusion of bipedicled flaps for 1 hour, left pedicle was ligated and flaps were exposed to global ischemia as in IP groups. On day 5 post‐surgery, tissue samples and topographic measurements were taken. No significant differences in semi‐quantitative scorings of polymorphonuclear leukocytes infiltration, chronic inflammation, interstitial edema, neovascularization, VEGF, and CD105 expression levels among groups were found (P > 0.05). Percentages of necrosis were consistently smaller in IP groups compared to controls for the same duration of global ischemia, with exception of the no‐ischemia. Area of necrosis was significantly smaller in primary IP group versus secondary IP group in the absence of global ischemia (P < 0.01). In the presence of global ischemia, both primary and secondary pedicle IP groups had significantly smaller percentage of necrosis than controls (P < 0.05) and there was no significant difference between primary and secondary IP groups (P > 0.05). Thus, IP performed on different pedicles may ameliorate flap survival in a comparable fashion, depending on the duration of global ischemia. Secondary pedicle IP was as effective as primary pedicle IP and may be feasible in free flap transfers. © 2013 Wiley Periodicals, Inc. Microsurgery 34:129–135, 2014.     

Use of Stapling Devices for Safe Cholecystectomy in Acute Cholecystitis

Many techniques are described for the ligation of a difficult cystic duct (CD). The aim of this study is to assess the effectiveness and safety of stapling of a difficult CD in acute cholecystitis using Endo-GIA. From January 2008 to June 2012, 1441 patients with cholelithiasis underwent laparoscopic cholecystectomy (LC) at the Department of General Surgery, Haydarpasa Numune Education and Research Hospital. Of these, 19 (0.62%) were identified as having a difficult CD and were ligated using an Endo-GIA stapler. All patients were successfully treated with a laparoscopic approach. The length of hospital stay was 3.4 days. There were umbilical wound infections in 4 patients (21%). The length of follow-up ranged from 1.0 to 50.4 months. In conclusion, Endo-GIA is a safe and easy treatment method for patients with a dilated and difficult CD. The cystic artery should be isolated and ligated if possible before firing the Endo-GIA stapler. If isolation and stapling are not possible, fibrin sealant can be applied to avoid bleeding. The vascular Endo-GIA can be applied in a large CD, but for acute cholecystitis with an edematous CD, the Endo-GIA roticulator 4.8 or 3.5 stapler is preferred.Key words: Cholecystectomy, Endo-GIA, Acute cholecystitis, StaplerAfter the introduction of laparoscopic cholecystectomy (LC) in 1987,¹ LC replaced open cholecystectomy as the gold standard for the treatment of cholelithiasis in international guidelines.² LC was initially considered to be contraindicated for acute gallbladder inflammation, but it is currently a common procedure for acute cholecystitis.Some of the difficult situations a surgeon is likely to face during the performance of a laparoscopic cholecystectomy include anatomic anomalies such as a sessile gallbladder or short cystic duct and pathologic entities such as an empyema, Mirizzi syndrome, or a frozen Calot''s triangle secondary to infection and fibrosis.³It is suggested that laparoscopic surgery should be carried out within 72 hours from the onset of the symptoms because after that time there are higher rates of conversion to open procedures, increased risks of complications, and longer operative times.^4–6 The generally accepted procedure in patients whose symptoms started 72 hours before admission is to “cool down” the patient with appropriate medical therapy and to perform LC after a period of 6 to 12 weeks.^7,8 This approach aims to avoid a potentially more difficult cholecystectomy during an emergency admission and to avoid the difficulties of access to an emergency room.^9,10 However, more than 20% of patients may fail to respond to conservative treatment and require an urgent and rather more difficult cholecystectomy, and a further 25% of patients will require readmission with a severe acute complication of cholelithiasis while awaiting a cholecystectomy.^11,12 The scar formation, distortion, and organized adhesions around the gallbladder occurring secondary to the chronic inflammation in Calot''s triangle make the dissection difficult. The cystic duct (CD) is sometimes edematous, fibrous, or enlarged owing to inflammation and adhesions in acute cholecystitis and may be difficult to manage. Several methods were proposed for ligating the CD, including titanium or absorbable endoclip, endoloop, tie, ultrasonic or bipolar sealer, and the Endo-GIA stapler (Covidien, Mansfield, Massachusetts).^13–19This study proposes an effective, safe, and easy procedure for the stapling of dilated or difficult CD using the Endo-GIA.     

Left Main Coronary Artery Obstruction by Dislodged Native-Valve Calculus after Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement can be an effective, reliable treatment for severe aortic stenosis in surgically high-risk or ineligible patients. However, various sequelae like coronary artery obstruction can occur, not only in the long term, but also immediately after the procedure. We present the case of a 78-year-old woman whose left main coronary artery became obstructed with calculus 2 hours after the transfemoral implantation of an Edwards Sapien XT aortic valve. Despite percutaneous coronary intervention in that artery, the patient died. This case reminds us that early recognition of acute coronary obstruction and prompt intervention are crucial in patients with aortic stenosis who have undergone transcatheter aortic valve replacement.     

Relationship between serum leptin level and disease activity in patients with systemic sclerosis

To determine the relationship between serum leptin levels and disease activity in systemic sclerosis (SSc). A total of 60 subjects (30 controls and 30 patients) were included. The inflammatory markers and leptin levels were evaluated and body mass index (BMI) was measured for both groups. The assessment of the skin involvement was performed based on the modified Rodnan skin score (mRSS). Disease activity was evaluated according to the Valentini scleroderma disease activity index. There was a significant difference between the patient and control groups in terms of BMI (p?<?0.05); however there was no difference with regards to age and gender (p?>?0.05). Valentini scores and mRSS were determined to be significantly higher in active patients (n?=?14) than in inactive patients (n?=?16) (p?<?0.05). No significant difference was determined between groups in terms of leptin levels (p?>?0.05). However, leptin levels were significantly lower in active patients than in inactive patients (p?<?0.05). We found a significant positive correlation between serum leptin and BMI (p?<?0.05), and leptin and serum C3 levels (p?<?0.05); no relationship was detected between leptin and other parameters. Leptin can be used as an activity marker in SSc. Further studies, including larger series, should be carried out to clarify this relationship.     

NF‐κB activation mediates LPS‐or zymosan‐induced hypotension and inflammation reversed by BAY61‐3606, a selective Syk inhibitor,in rat models of septic and non‐septic shock

We have previously demonstrated that the activation of the spleen tyrosine kinase (Syk)/inhibitory‐κB (IκB)‐α/nuclear factor‐κB (NF‐κB) p65 signalling pathway contributes to hypotension and inflammatory response in a rat models of zymosan (ZYM)‐induced non‐septic shock. The purpose of this study was to further examine the possible mechanism underlying the effect of inhibition of Syk by BAY61‐3606 via NF‐κB activity at the level of nuclear translocation regarding the production of vasodilator and proinflammatory mediators in lipopolysaccharide (LPS) (septic)‐ and ZYM (non‐septic)‐induced shock. Administration of LPS (10 mg/kg, ip) or ZYM (500 mg/kg, ip) to male Wistar rats decreased mean arterial pressure and increased heart rate that was associated with an increase in the activities of cyclooxygenase and nitric oxide synthase, tumour necrosis factor‐α, and interleukin‐8 levels, and NF‐κB activation and nuclear translocation in sera and/or cardiovascular and renal tissues. BAY61‐3606 (3 mg/kg, ip), the selective Syk inhibitor, given 1 hour after LPS‐ or ZYM injection reversed all the above‐mentioned effects. These results suggest that Syk contributes to the LPS‐ or ZYM‐induced hypotension and inflammation associated with transactivation of NF‐κB in septic and non‐septic shock.     

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients

Background: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. Methods: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. Results: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64?±?21.8 vs. 78.48?±?19.7?μg/mL, p?r?=?0.247, p?=?0.029 and r?=?0.252, p?=?0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p?=?0.04 and p?=?0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p?=?0.04 and p?=?0.001, respectively). Conclusions: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.