The effects of estrogen and raloxifene treatment on antioxidant enzymes in brain and liver of ovarectomized female rats

Recent studies documented that estrogen have antioxidant properties in-vitro, there are conflicting results on the effect of estrogen in vivo. We aimed to investigate the effects of estradiol and Raloxifene on the antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities and MDA levels in brain and liver homogenates of ovariectomized female rats. Twelve weeks after ovariectomy, female Sprague-Dawley rats (n = 26) were divided into three groups: (1) Ovariectomized placebo group (n = 6) was given physiologic saline. (2) Estrogen group (n = 10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3) Raloxifene group (n = 10) was given raloxifene, 1 mg/kg sc during 8 weeks. Ten rats were used as naive controls without any treatment (Sham operated group, n = 10). Ovariectomy lead to an increase in the CAT activities in liver tissue samples compared to the sham group (p = 0.056, Mann-Whitney test). While estrogen treatment reversed to normal levels of CAT activities, raloxifene remained as ineffective. Superoxide dismutase activities and MDA levels in liver were remained unchanged in all groups. There was no significant change in the brain tissue SOD and CAT activities between the control ovariectomy, estrogen treated, and raloxifen treated groups. We determined an increase in MDA levels in brain of ovariectmised rat (p = 0.02). While raloxifene treatment reversed to normal levels of MDA (p = estrogen treatment failed. Our data showed that estrogen may play a role in regulation of CAT and SOD activities in liver due to its antioxidative effects. We can suggest estrogen and raloxifene exert their antioxidative effects in brain rather than liver. Since Raloxifene's effect is more clear than estradiol, raloxifene may be suggested primarily for treatment and/or prevention of diseases which can be resulted from oxidative stress in postmenopausal women.     

The role of N terminal pro-brain natriuretic peptide in the evaluation of left ventricular diastolic dysfunction: correlation with echocardiographic indexes in hypertensive patients

The utility of N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) and Brain Natriuretic Peptide (BNP) for detecting left ventricular (LV) diastolic dysfunction in hypertensive patients without heart failure symptoms is unclear. In this study, we investigated the relation between NT-proBNP plasma levels and LV diastolic dysfunction in hypertensive patients without systolic dysfunction. Method: We studied 40 ambulatory patients (26 women, mean age 52 ± 5) with controlled hypertension. LV diastolic function was assessed with conventional Doppler, by means of mitral inflow and with tissue Doppler echocardiography by means of mitral annulus. The ratio of early diastolic transmitral E wave velocities to tissue Doppler mitral annulus early diastolic E' wave velocities (E/E′), was used to detect LV filling pressures. Patients were divided in three groups according to E/E′ ratios < 10 (group I), E/E′ ratios 'between' 10 and 15 (group II) and E/E′ ratios > 15 (group III). Plasma concentrations of NT-proBNP were measured by electro chemiluminescence's immunoassay. Results: The NT-proBNP blood levels were positively correlated significantly with E/E′ ratio (r = 0.80, P < 0.0001). Patients with elevated LV end diastolic pressure (LVEDP), defined as E/E′ > 15 (n = 8) had highest NT-proBNP (203 ± 75 pg/ml) levels. E/E′ 10 to 15 group (n = 16) had a mean NT-proBNP level of 71 ± 26 pg/ml, and those with E/E′ < 10 (n = 16) had 39 ± 20 pg/ml. A NT-proBNP value of 119 pg/ml had a sensitivity of 87%, a specificity of 100% for predicting E/E′ > 15. Conclusion: The assessment of the blood concentration of NT-proBNP is of potential value for identification of those patients with hypertension to detect early cardiovascular changes, especially LV diastolic dysfunction.     

Effect of gemcitabine and retinoic acid loaded PAMAM dendrimer-coated magnetic nanoparticles on pancreatic cancer and stellate cell lines

Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure – stellate cells – simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone.     

Comparison of speech outcomes using type 2b intravelar veloplasty or furlow double-opposing Z plasty for soft palate repair of patients with unilateral cleft lip and palate

BackgroundThe aim of this study is to compare speech outcomes, fistula rates, and rates of secondary speech surgeries after palatoplasty using Furlow palatoplasty or type 2b intravelar veloplasty for soft palate repair.Patients and methodsPatients with unilateral cleft lip and palate who had either Furlow palatoplasty or intravelar veloplasty for soft palate repair were retrospectively evaluated for demographic and perioperative variables and speech outcomes. Fistula rate, secondary surgical intervention for improved speech results, and findings of speech assessment were further reviewed for the patients who met the inclusion criteria.ResultsA total of 76 patients, 36 in the Furlow palatoplasty group and 40 in the intravelar veloplasty group, were included in the study. In the speech assessment, nasalance values were statistically similar between the two groups. Also, there was no statistically significant difference between the groups in velopharyngeal motility (p = 0.103). The total rates of secondary surgeries and fistula were statistically similar between the groups (p = 0.347 and 0.105, respectively).ConclusionThe similar outcomes of speech and surgical evaluation between the two groups make the surgeon's preference determinant in the selection of the surgical technique for soft palate repair.     

Cardiogenic shock in an elderly man caused by left main coronary artery occlusion with spontaneous dissection of right coronary artery

We present a case of an 85-year-old man with acute myocardial infarction and cardiogenic shock due to left main coronary artery occlusion, with spontaneous dissection of the right coronary artery.     

Direct versus side-graft cannulation of the right axillary artery for antegrade cerebral perfusion

Antegrade selective cerebral perfusion through the right axillary artery has proved to be a safe and effective method for cerebral protection in aortic surgery. In this study, we prospectively evaluated the techniques of direct right axillary artery cannulation (Group 1) and right axillary artery side-graft cannulation (Group 2), investigated cannulation-related complications, and determined the hemodynamic advantages and disadvantages of both cannulation techniques. Sixty-eight patients underwent surgery from April 2001 through August 2004 with the diagnoses of ascending and aortic arch aneurysms (10 patients), type A aortic dissection (56 patients), and aortic pseudoaneurysm (2 patients). There were 22 patients in Group 1 (33.4%) and 46 patients in Group 2 (67.6%). The antegrade selective cerebral perfusion flow was 500 to 700 mL/min in Group 1, whereas in Group 2 the flow was adjusted in accordance with the mean right radial arterial pressure, which was 50 mmHg. There was no significant difference between the groups in antegrade selective cerebral perfusion times, but the transient neurologic dysfunction rate (4 of 22 patients in Group 1 vs 1 of 42 in Group 2) was significantly lower in Group 2 (P =0.035). In Group 1, axillary artery dissection occurred in 2 patients (9%), and postoperative arm ischemia occurred in 1 patient (4.5%). These complications were not seen in Group 2 (P =0.031). The side-graft cannulation technique may be more acceptable because of its lower local-complication rate and because it provides pressure-controlled cerebral perfusion.     

Long-Term Effect of Interferon Therapy in Patients with HBeAg Positive Chronic Hepatitis B Infection

Introduction  

Several studies have reported that interferon therapy increases elimination rate of HBeAg and anti-HBe seroconversion in chronic hepatitis B (CHB) patients. We aimed to evaluate long-term results of interferon-α treatment in HBeAg positive CHB patients in a country with exclusively D genotype.     

Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers

BACKGROUND: The effect of conventional interferon-based therapy of hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is controversial. Yet, no studies have been carried out into pegylated interferon treatment for chronic HBV/HCV coinfection. We aimed to evaluate the response rate and side effects of conventional or pegylated interferon combined with ribavirin on chronic HBV/HCV coinfection therapy. METHODS: The study included 36 chronic hepatitis patients (M/F: 28/8, mean age 47+/-12 years) who were positive for HBsAg and anti-HCV. They were tested for the presence of HBV-DNA by hybridisation assay, and the samples giving negative results were retested by polymerase chain reaction (PCR). All patients were tested for HCV-RNA using PCR, and the HCV genotype was determined. RESULTS: Nineteen patients were given standard interferon either alone or in combination with ribavirin, whereas 17 were given pegylated interferon and ribavirin combination therapy. None of the patients had HBV-DNA positivity; however, all had HCV-RNA detectable by PCR. All the patients had HCV genotype 1b. The mean alanine aminotransferase and aspartate aminotransferase levels were 118+/-65 U/l and 90+/-95 U/l respectively. Five patients in each group discontinued the treatment due to side effects. Only two patients (one from each group) reached sustained virological response. CONCLUSION: Neither pegylated nor conventional interferon based regimes were effective for HBV/HCV coinfection, in which the dominant virus was HCV. Pegylated interferon and ribavirin therapy was not superior to conventional interferon based regimes in the treatment of HBV/HCV coinfection.     

Evaluation of 3 Different Retreatment Techniques in Maxillary Molar Teeth by Using Micro–computed Tomography

Introduction

Nonsurgical retreatment procedure involves the complete removal of the previous filling material to allow thorough instrumentation, disinfection, and refilling of root canal system. We aimed to determine the residuals of the root-filling material by using 3 different retreatment techniques with the aid of micro–computed tomography.

Three novel mutations in the apolipoprotein E gene in a sample of individuals with type 2 diabetes mellitus

BACKGROUND: Apolipoprotein E (apoE) is found in association with triglyceride-rich lipoproteins and is the ligand for the removal of these particles from the plasma. Genetic variations in exon 4 lead to three common gene variants: E2, E3, and E4. METHODS: We performed apoE genotyping in 765 individuals with type 2 diabetes. RESULTS: We identified three new variant heteroduplex patterns. Sequencing of these variants revealed three novel mutations that were related to biochemical and clinical characteristics. One mutation produced a frameshift at amino acid position 166, which predicted termination of protein synthesis. This individual had a heteroduplex pattern and sequence of E3E3, which was associated with a change in the plasma isoelectric focusing pattern and a 70% lower plasma concentration of apoE compared with healthy individuals. The other mutations were both single base changes. A CGC>CAC change at amino acid position 150 predicted a substitution of Arg>His. This individual had a heteroduplex pattern and sequence of E2E2, which was not associated with major changes in plasma lipids or apoE concentration. The third individual had a CGC>CCC base change at amino acid position 114, which predicted an Arg>Pro change. This person had a heteroduplex pattern and sequence of E3E3, higher plasma total cholesterol, and moderately decreased plasma apoE. CONCLUSIONS: The frequency of new mutations in this sample (1 in 255) is higher than that of a healthy population (1 in 7900). Further screening for common apoE gene variants in individuals at risk for dyslipidemia may reveal abnormal heteroduplex patterns and uncover further mutations in this important lipid-regulating gene.