An in vitro perspective to cholinesterase inhibitory and antioxidant activity of five Gentiana species and Gentianella caucasea

The dichloromethane (DCM), ethyl acetate (EtOAc), and methanol extracts from the leaves, roots, and flowers of the five species of Gentiana (Gentiana asclepiadea, Gentiana cruciata, Gentiana olivieri, Gentiana septemfida, and Gentiana verna) and Gentianella caucasea were investigated for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant effect using 2,2-diphenyl-1-picrylhydrazyl radical scavenging, metal-chelation capacity, and ferric-reducing antioxidant power assays. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically. The presence of some characteristic compounds found in Gentiana species (gentiopicroside, swertiamarin, isoorientin, isovitexin and vitexin) was analyzed in the extracts by thin layer chromatography. The flower DCM extract of G. verna exerted the highest inhibition against AChE (53.65?±?1.03%), whereas the root EtOAc extract of G. cruciata was the most effective in BChE inhibition assay (50.72?±?0.75%) at 100?μg?ml(-?1). The extracts of G. verna were also found to be more active in the antioxidant tests.     

Evaluation of genotoxicity after application of Listerine(R) on human lymphocytes by micronucleus and single cell gel electrophoresis assays

Listerine (LN) is one of the most commonly used mouth rinses worldwide although very limited information is available concerning its genotoxicity. In another view, the biological safety profile of oral care products is frequently assumed on the basis of simplistic test models. Therefore, the present study was undertaken to investigate the in vitro genotoxic potential of LN using micronucleus and single cell gel electrophoresis tests as genetic endpoints. Different concentrations of LN (0-100% of ml/culture, v/v) were applied to whole human blood cultures (n = 5). The result of the present study showed that there were no statistically significant differences (p > 0.05) between the control group and the groups treated with LN alone in both analysed endpoints. In conclusion, our result first demonstrated the absence of genotoxicity of LN on human lymphocytes.     

The protective role of ascorbic acid on imazalil-induced genetic damage assessed by the cytogenetic tests

Ascorbic acid (AA), known as vitamin C, has important antioxidant and metabolic functions, making its incorporation into the human diet essential. On the other hand, imazalil (IMA), a commonly used fungicide in both agricultural and clinical domains is suspected to produce very serious toxic effects in vertebrates. In this study, the antigenotoxic effects of AA were studied against the genotoxic damage induced by IMA on cultured human lymphocytes using chromosomal aberration (CA) and sister chromatid exchange (SCE) as genetic end points. Human peripheral lymphocytes were treated in vitro with varying concentrations of AA (25, 50, 100, 200, and 400 μg/ml), tested in combination with IMA (336 mg/L). AA alone was not genotoxic and when combined with IMA treatment, reduced the frequencies of CAs and SCEs. A clear dose-dependent decrease in the genotoxic damage of IMA was observed, suggesting a genoprotective role of AA. In conclusion, the preventive role of AA in alleviating IMA-induced DNA damage was indicated for the first time in the present study.     

Detection of ‘best’ positive end-expiratory pressure derived from electrical impedance tomography parameters during a decremental positive end-expiratory pressure trial

Introduction

This study compares different parameters derived from electrical impedance tomography (EIT) data to define ‘best’ positive end-expiratory pressure (PEEP) during a decremental PEEP trial in mechanically-ventilated patients. ‘Best’ PEEP is regarded as minimal lung collapse and overdistention in order to prevent ventilator-induced lung injury.

Methods

A decremental PEEP trial (from 15 to 0 cm H₂O PEEP in 4 steps) was performed in 12 post-cardiac surgery patients on the ICU. At each PEEP step, EIT measurements were performed and from this data the following were calculated: tidal impedance variation (TIV), regional compliance, ventilation surface area (VSA), center of ventilation (COV), regional ventilation delay (RVD index), global inhomogeneity (GI index), and intratidal gas distribution. From the latter parameter we developed the ITV index as a new homogeneity parameter. The EIT parameters were compared with dynamic compliance and the PaO₂/FiO₂ ratio.

Results

Dynamic compliance and the PaO₂/FiO₂ ratio had the highest value at 10 and 15 cm H₂O PEEP, respectively. TIV, regional compliance and VSA had a maximum value at 5 cm H₂O PEEP for the non-dependent lung region and a maximal value at 15 cm H₂O PEEP for the dependent lung region. GI index showed the lowest value at 10 cm H₂O PEEP, whereas for COV and the RVD index this was at 15 cm H₂O PEEP. The intratidal gas distribution showed an equal contribution of both lung regions at a specific PEEP level in each patient.

Conclusion

In post-cardiac surgery patients, the ITV index was comparable with dynamic compliance to indicate ‘best’ PEEP. The ITV index can visualize the PEEP level at which ventilation of the non-dependent region is diminished, indicating overdistention. Additional studies should test whether application of this specific PEEP level leads to better outcome and also confirm these results in patients with acute respiratory distress syndrome.     

Decreased platelet activation and endothelial dysfunction after percutaneous mitral balloon valvuloplasty

OBJECTIVE: This study was conducted to assess the changes in platelet activation and endothelial dysfunction in patients with mitral stenosis (MS) and sinus rhythm (SR) following percutaneous mitral balloon valvuloplasty (PMBV). BACKGROUND: Systemic thromboembolism is a serious complication in patients with valvular heart disease, and its incidence is highest in those with mitral stenosis. A hypercoagulable state has also been reported in patients with mitral stenosis and sinus rhythm. A recent study has shown that patients with previous PMBV had a lower incidence of thromboembolism. METHODS AND RESULTS: The study was conducted in 21 patients (two men, 19 women, mean age=34+/-6 years) with mitral stenosis and sinus rhythm (SR) who underwent percutaneous mitral balloon valvuloplasty and 17 healthy control subjects (two men, 15 women, mean age=33+/-6 years). Biochemical markers of platelet activity (beta thromboglobulin, BTG, and soluble P-selectin, sPsel) and endothelial dysfunction (von Willebrand Factor, vWF) were measured in both control subjects' and patients' serum samples taken immediately before PMBV and 24 h after PMBV procedure. All patients underwent successful PMBV. Significant improvement of mitral valve area, pulmonary artery pressure, mean mitral gradients, and left atrial diameter were achieved in all patients after PMBV. Compared with control subjects, patients with MS had higher plasma levels of BTG (66+/-26 ng/ml vs. 14+/-6 ng/ml, P<0.001), vWF (177+/-67 units/dl vs. 99+/-37 units/dl, P<0.0001), sPsel (226+/-74 ng/ml vs. 155+/-66 ng/ml, P<0.001). There was a significant reduction of plasma levels of BTG (66+/-26 ng/ml vs. 48+/-20 ng/ml, P=0.002), vWF (177+/-67 units/dl vs. 134+/-60 units/dl, P=0.001) and P-selectin (226+/-74 ng/ml vs. 173+/-71 ng/ml, P=0.008,) 24 h after PMBV. CONCLUSION: We have shown that patients with severe MS and SR have increased platelet activation and endothelial dysfunction compared with control subjects and PMBV results in decreased platelet activity and improvement of endothelial injury.     

Extrahepatic portal vein thrombosis in children: etiology and long-term follow-up

OBJECTIVE: Mortality of extrahepatic portal vein thrombosis depends on underlying causes other than gastrointestinal bleeding. The aim of this study was to evaluate the etiology, treatment, and prognosis of patients with extrahepatic portal vein thrombosis. METHODS: The records of 12 patients (age range: 1-9 years) diagnosed with extrahepatic portal vein thrombosis with a minimum follow-up of 2 years were analyzed retrospectively. Their diagnostic evaluations, treatment modalities, complications and long-term follow-ups were noted. RESULTS: Mean follow-up period was 7.4 +/- 3.9 years (2-14 years). Hemorrhage from esophageal varices was the prevalent symptom in 6 patients (50%). Six patients had signs of hypersplenism, 5 were found to have thrombophilia: 2 protein C, 1 protein S, 1 combined protein S, C, and antithrombin III deficiency, and 1 homozygous factor V Leiden mutation. Two patients had congenital cardiovascular abnormalities, and 1 patient developed portal thrombosis after splenectomy operation. None of the patients who started propranolol prophylaxis before first bleeding episode bled during their follow-up periods. Endoscopic sclerotherapy succeed in 66.6% variceal hemorrhages. Shunt surgery was performed in 1 patient. The patients neither faced a life-threatening variceal bleeding nor died during follow-up period. CONCLUSION: Prognosis of extrahepatic portal vein thrombosis is good in childhood. Thrombophilic states are the most frequent precipitating causes. Propranolol for prophylaxis of variceal bleeding and sclerotherapy might be the preferred modalities.     

Post myocardial infarction use of beta-blockers

The use of β-blockers after myocardial infarction was investigated in 100 patients (age range 30–89 years), from January to December 1997, in Caerphilly District Miner’s Hospital. Out of 54 patients eligible for β-blockers only 27 (27/54 (50%)) patients received such therapy. We conclude that β-blockers is underused in patients with myocardial infarction. Although the reason for this is not clear from this study, this probably indicates the anxieties clinicians may have about the side effects from the use of β-blockers in this population.     

Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia.

BACKGROUND. Photodynamic therapy (PDT) uses light activation of otherwise nontoxic dyes for the production of reactive oxygen species that cause cell injury and death. METHODS AND RESULTS. The inhibition of intimal hyperplasia (IH) by PDT was studied in the balloon injury model of the rat carotid artery. Chloroaluminum-sulfonated phthalocyanine (CASPc) was the drug chosen for PDT because it does not produce skin photosensitivity and has a high absorption peak of light at 675 nm, a wavelength with good tissue penetration. A pilot study indicated that CASPc administration with laser radiant exposure of 100 J/cm2 resulted in a homogeneous, circumferential effect on the whole artery. Male Sprague-Dawley rats received the balloon catheter injury to the left common carotid artery (day 0) and were equally divided into two groups. Nine rats received either CASPc (5 mg/kg i.v., n = 6) or saline (n = 3) at day 2, before IH was present, and nine rats received CASPc or saline in the same manner on day 7, when IH was already present. Twenty minutes after drug injection, the distal left common carotid artery was irradiated under saline with 675-nm laser light at 100 mW/cm2 for 10(3) seconds (100 J/cm2). At this low laser irradiance, there are no thermal effects, but photoactivation of CASPc occurs. The rats were killed at day 14 after balloon injury when IH reaches a maximum. The arteries were harvested after perfusion-fixation for light microscopy, histological and computerized morphometric evaluation, and transmission electron microscopy (TEM) analysis. The cross-sectional areas of the neointima were measured in the PDT-treated arteries and in the laser-only control arteries. There was a significant mean +/- SD decrease of IH in the PDT-irradiated segments of the arteries (0.06 +/- 0.05 mm2) versus the laser-only control ones (0.17 +/- 0.07 mm2) (t test, p less than 0.001), with no statistical difference between the day 2 and day 7 treated rats. Lack of IH was correlated in 90% of cases with histological absence of medial smooth muscle cells or inflammatory cells, but no other structural injury was identified. TEM analysis showed early evidence of PDT-mediated cytotoxic effects at 4 hours and the absence of collagen or elastic tissue structural alterations. CONCLUSIONS. These data demonstrated that PDT can effectively inhibit the IH response when it is used before or during induction of cellular proliferation in this acute model. Although the long-term implications of PDT in arteries need to be defined, this technique may offer a new method for understanding and treating IH.     

Comparison of maximal acid output and gastrin response to meals in Chinese and Scottish normal and duodenal ulcer subjects.

Maximal acid output (MAO) after pentagastrin stimulation and gastrin response to a standard meal was studied in 100 control and 200 duodenal ulcer subjects from each of two ethnic groups, Scots and Chinese. The acid output was significantly higher in the Scots than in the Chinese for both controls and duodenal ulcer patients. Despite correction for differences in body stature by expressing MAO as a function of the body weight, these differences persisted. In 45 pairs of closely matched patients with duodenal ulcer, the differences between the two ethnic groups remained significant, irrespective of whether MAO was expressed in absolute or weight corrected values. This indicates that differences in age, sex, family history, or duration of illness did not account for differences in acid output. In 20 pairs of normal control and 45 pairs of duodenal ulcer patients the fasting and post-prandial serum gastrin levels did not differ, significantly between the two ethnic groups. The proportion of acid normosecretors was significantly higher in the Chinese duodenal ulcer patients than in the Scottish. The reason for these differences in the gastric acid output between the two ethnic groups is not known and needs to be studied further.     

Long-term albendazole treatment in one case of alveolar echinococcosis. Case report

AIMS: Curative therapy of alveolar echinococcosis is total surgical removal of the infected tissue and concomitant chemotherapy. However, this curative resection can be done on a limited number of patients, for the remaining ones various palliative procedures can be performed. METHOD: In this article it is aimed to present the result of long-term albendazole treatment in patient who had a palliative hepatojejunostomy for obstructive jaundice due to unresectable alveolar echinococcosis. RESULTS: Systemic albendazole treatment was initiated in this patient after palliative hepatojejunostomy procedure. During follow up there was no abnormality in blood chemistry and a considerable regression in size of the lesion was found in postoperative month 24. Residual hepatic lesion was histopathologically documented and showed apparently non-viable parasitic cysts by biopsy. These findings suggest the long-term albendazole therapy being parasitocidal. CONCLUSIONS: Palliative or mass reduction surgery combined with long-term albendazole therapy is the standard therapy for advanced disease, especially when curative resection might result in significant morbidity and mortality.