Dose-dependent activation of Ca2+-activated K+ channels by ethanol contributes to improved endothelial cell functions

BACKGROUND: Regular moderate alcohol (EtOH) intake seems to protect against both coronary artery disease and ischemic stroke, whereas the risk increases with heavy EtOH consumption. Effects of EtOH on endothelial cell function may be relevant to these disparate effects. Potassium channels play an important role in the regulation of endothelial cell functions. Therefore, we investigated whether Ca-activated K channels (BKCa) are modulated by EtOH. Furthermore, we examined whether EtOH-induced changes of endothelial nitric oxide (NO) formation and cell proliferation are due to BKCa activation. METHODS: The patch-clamp technique was used to investigate BKCa activity in cultured human umbilical vein endothelial cells (HUVEC). NO formation was analyzed by using the fluorescence dye 4,5-diaminofluorescein. Endothelial proliferation was examined by using cell counts and measuring [H]thymidine incorporation. RESULTS: EtOH dose-dependently (10-150 mmol/liter) modulated BKCa-activity, with the highest increase of open-state probability at a concentration of 50 mmol/liter (n = 13; p < 0.05). Inside-out recordings revealed that this effect was due to direct BKCa activation, whereas open-state probability was not changed in cell-attached recordings after pertussis toxin preincubation. EtOH (10 and 50 mmol/liter) caused a significant increase of NO levels, which was blocked by the highly selective BKCa inhibitor iberiotoxin (100 nmol/l; n = 30; p < 0.05). Higher concentrations of EtOH (100 and 150 mmol/liter) significantly reduced NO synthesis (n = 30; p < 0.05). Both methods revealed a significant increase of HUVEC proliferation, which was inhibited by iberiotoxin (n = 30; p < 0.05). At a concentration of 150 mmol/liter, EtOH caused a significant reduction of endothelial proliferation. CONCLUSIONS: EtOH directly activates BKCa in HUVEC, leading to an increase of endothelial proliferation and production of NO. These results indicate a possible beneficial effect of low-dose EtOH on endothelial function, whereas higher concentrations must be considered as harmful.     

Early effects of mild brain trauma on the cytoskeletal proteins neurofilament160 and MAP2, and the preventive effects of mexilitine

OBJECTIVE: The aims were to investigate the early effects of graded, closed, mild head injury on neurofilament protein (NF160) and microtubule-associated protein-2 (MAP2) and to examine the levels of lipid peroxidation and the impact of mexilitine, inhibitor of lipid peroxidation, pretreatment on tissue damage. MATERIAL AND METHOD: One hundred and twenty-six rats were divided into groups as follows: Group 1 (n = 14) were controls; group 2 (n = 56) sustained trauma alone; and group 3 (n = 56) were pretreated with mexilitine (50 mg/kg). Groups 2 and 3 were subdivided into subgroups (n = 14 each), which were subjected to 100 g/cm2, 125 g/cm2, 150 g/cm2, and 175 g/cm2 trauma forces, respectively. Two hours after trauma, the frontal lobes from all groups were removed and processed for lipid peroxidation H&E staining, immunofluorescent labelling of neurofilaments and microtubules with anti-NF160 and anti-MAP2 antibodies. RESULTS: Compared to control findings, all the trauma-only animals showed increased lipid peroxidation levels and the elevations paralleled the amount of force applied. Administration of mexilitine significantly reduced the level of lipid peroxidation. In NF160 stainings, in group 2, the degree of impairment in axonal organization paralleled the different levels of force that were applied. Groups 3C and 3D (mexilitine pretreated) showed well-preserved axons and intact perikarya. In MAP2 stainings group 2 animals showed remarkably less MAP2 staining throughout the sections. There were no significant differences in MAP2 staining intensity or pattern among the group 2 subgroups. In contrast, in the sections from the group 3 animals, the level of MAP2 positivity was markedly preserved. CONCLUSION: In conclusion, our results show that the cytoskeletal proteins we investigated have different capacities for resisting injury, and that MAP2 is more vulnerable to injury than NF160. One of the reason for this cytoskeletal disruption may be increased lipid peroxidation. Inhibition of lipid peroxidation by pre-treatment with 50-mg/kg mexilitine significantly reduces the level of lipid peroxidation and may protect MAP2 and NF160 integrity in closed mild head injury. This protection is inversely proportional to the magnitude of the applied force.     

Dual synergistic effect: the effect of dexamethasone plus carnitine on skin flap survival

Dexamethasone has well-known useful effects in dealing with the progression of necrosis. Carnitine is an endogenous cofactor, for having a regulatory action on the energy flow from different oxidative sources. The aim of this study was to determine whether combined local dexamethasone and systemic carnitine administration would result in an additive enhancement of skin flap survival in the rat model. A rectangular (3 cm x 11 cm) dorsal random skin flap was elevated on the rats and then sutured back into its original site with separate sutures. Overall, 40 rats were allocated randomly into 4 groups: Group 1 (control group, n = 10), group 2 (Dexamethasone group, n = 10, 2.5 mg/kg), group 3 (carnitine group, n = 10, 100 mg/kg), group 4 (dexamethasone plus carnitine group, n = 10).The mean flap survival area was 57.50 +/- 5.2% (mean survival area +/- SD) in control group (group 1), 71.5 +/- 4.8% in the dexamethasone group (group 2), 73.0 +/- 5.5% in the carnitine group (group 3), 85.30 +/- 6.1% in the dexamethasone plus carnitine group (group 4). In conclusion, based on the findings of this experimental study, the synergistic effect of carnitine and dexamethasone on skin flap viability is determined.     

Outcome of Surgery for Crooked Nose: An Objective Method of Evaluation

Objectives: The aim of this study was to report the authors surgical results, and to present their method of angle measurement using the Scion Image computer program to evaluate surgical results for crooked noses.Methods: The study included 27 patients with crooked noses: classified as C-type and 14 classified as I-type. Deviation angles were measured by using the Scion Image computer program on frontal views before and at least 3 months after the operation. Correction of the crooked nose was performed through an open approach with the patients under general anesthesia.Results: Significant correction was achieved for both types of crooked noses (p < 0.05). The results for the I-type crooked noses were closer to the ideal angles than those for the C-type, but the difference was not significant. The findings showed that 66.7% of the patients with crooked noses, had good or excellent results after surgery: 53.8% of those with the C-Type and 78.6% of those with the I-type.Conclusion: It is difficult to achieve satisfactory results in the correction of crooked noses. The angle measurement method using the Scion Image computer program may be helpful in evaluating the effectiveness of different surgical techniques.This study was reported as oral presentation at 27th National Meeting of the Turk Otorhinolaryngology and Head and Neck Surgery Society, Antalya, Turkey, 4–9 October 2003     

Alveolar echinococcosis of the liver: correlative color Doppler US, CT, and MRI study

Purpose: To determine and compare the imaging features of hepatic alveolar Echinococcosis using color Doppler US, CT, and MRI.

Material and Methods: Abdominal CT and MRI with and without contrast agents and color Doppler US were performed on seven patients with hepatic alveolar Echinococcosis. The lesions were evaluated for location, features of echogenicity, intensity and density, calcification, and vascular, hilar, and perihepatic involvement. The diagnosis was confirmed histopathologically in all patients.

Results: Six patients had solitary lesions, and one displayed multiple lesions. The lesions were generally seen as heterogeneous and hyper- or hypoechoic when imaged with color Doppler US, hypodense with CT, and hypointense with MRI, in comparison with the liver parenchyma. Calcification, central necrosis, and small peripheral cysts were observed in six, seven, and four patients, respectively. Vascular flow or contrast enhancement was not observed in any of the cases. A look at the respective advantages of each method reveals that calcification was best rendered visible via CT, small peripheral cysts with T2-weighted MRI, central necrosis with CT and MRI, and perihepatic invasion with multiplanar MRI. Vascular involvement was revealed by all methods.

Conclusion: Color Doppler US, CT, and MR imaging function extremely well as complementary methods in the diagnosis of HAE. Color Doppler US should be performed in these patients owing to its ability to efficiently detect the disease. Knowledge of imaging characteristics makes it possible to radiologically ascertain an early diagnosis.     

The added value of the apparent diffusion coefficient calculation to magnetic resonance imaging in the differentiation and grading of malignant brain tumors

OBJECTIVE: ADC calculation can improve the diagnostic efficacy of MR imaging in brain tumor grading and differentiation. METHODS: Apparent diffusion coefficient (ADC) values and ratios of 33 low-grade (23 astrocytomas, 10 oligodendrogliomas) and 40 high-grade (25 metastases and 15 high-grade astrocytomas) malignant tumors were prospectively evaluated. RESULTS: Tumoral ADC values (r=-0.738, P <0.000) and ratios (r=-0.746, P < 0.000) were well correlated with higher degree of malignancy and quite effective in grading of malignant brain tumors (P < 0.000). By using cutoff values of 0.99 for tumoral ADC value and 1.22 for normalized ADC ratio, the sensitivity of MR imaging could be increased from 72.22% to 93.75% and 90.63%, the specificity from 81.08% to 92.68% and 90.24%, PPV from 78.79% to 90.91% and 87.88%, and NPV from 75.00% to 95.00% and 92.50%, respectively. CONCLUSION: ADC calculation was quite effective in grading of malignant brain tumors but not in differentiation of them and added more information to conventional contrast-enhanced MR imaging.     

Ergothioneine pretreatment protects the liver from ischemia-reperfusion injury caused by increasing hepatic heat shock protein 70

BACKGROUND: Reperfusion of the liver after ischemia induces the expression of the heat shock genes and the synthesis of the heat shock proteins (HSP). We studied the effects of the natural antioxidant ergothioneine (EGT) treatment on the expression of HSP70 in ischemic-reperfused (IR) liver. METHODS: Adult male Wistar rats were randomly divided into three groups: Sham group given standard laboratory chow and water for 3 weeks followed by sham operation; Control group given standard laboratory chow and water for 3 weeks followed by liver IR injury; EGT group given standard laboratory chow supplementation l-ergothioneine (1.2 mg/kg/d body weight) administered by gavage and water for 3 weeks followed by liver IR injury. Ten rats from each group were killed to determine serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), tissue malondialdehyde (MDA), HSP70 levels, and histologic changes at 30, 60, and 120 min of reperfusion, respectively. Survival was followed for 1 week. RESULTS: IR caused significant increase in serum AST, ALT, LDH, and tissue MDA levels. As compared with the control group, animals treated with EGT experienced a significant decrease in serum AST, ALT, and LDH levels in all reperfusion periods. Tissue MDA levels in animals receiving EGT were significantly reduced as compared with control group at 30 min and 60 min after reperfusion. After ischemia, reperfusion caused a remarkable production of HSP70 in the control group. When the rats were pretreated with EGT, the levels of HSP70 increased significantly in their livers after reperfusion compared with the control group. Liver injury in the EGT-treated animals was lower to that in the control group. The 7-day survival rate was significantly improved (from 50% to 80%) by EGT pretreatment. CONCLUSION: HSP70 has been shown to induce tolerance against warm IR injury in rat livers. EGT pretreatment protects the liver from IR injury by over-expression of HSP and the subsequent suppression of lipid peroxidation.     

Primary Peritracheal Schwannoma: Report of a Case

Posterior mediastinal tumors of neurogenic origin commonly arise from the sympathetic or intercostal nerves. However, anterior mediastinal tumors rarely originate from the vagus nerve, and primary neurogenic tumors of the trachea are extremely uncommon. A 19-year-old man was admitted to an emergency department in sudden acute respiratory distress. A tracheostomy was performed and he was transferred to our Ear Nose and Throat Department for further investigation. A bronchoscopic biopsy was taken of a mass occupying the tracheal lumen and intraoperative frozen section examination suggested a schwannoma, so tracheal resection was performed. Although rare, primary tracheal schwannoma should be considered in the differential diagnosis of sudden respiratory distress of unknown origin.     

A novel NPHS2 gene mutation in Turkish children with familial steroid-resistant nephrotic syndrome

We report in this paper two siblings aged 8 and 17 months who were clinically diagnosed with familial steroid-resistant nephrotic syndrome (SRNS). By mutation screening of the NPHS2 gene, a homozygous missense mutation, P118L, was detected in both children. This study is the first systematic investigation of NPHS2 gene mutations in Turkish children with familial SRNS. If this mutation is a hot spot of mutation in the Turkish population, screening this novel mutation in Turkish children with SRNS may be of great clinical use to prevent unnecessary treatment modalities, provide accurate genetic counselling and predict the prognosis of the disease.