Hormone Replacement Therapy Shortens QT Dispersion in Healthy Postmenopausal Women

Background: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. Methods: Fifty‐one consecutive healthy postmenopausal women (age 48 ±; 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12‐lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. Results: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 ±; 13 ms vs 38 ±; 13 ms, P = 0.01; for CEE + MPA group 49 ±; 14 ms vs 36 ±; 13, P < 0.001). Conclusion: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified. A.N.E. 2001; 6(3):193–197     

The endovascular management of visceral artery aneurysms and pseudoaneurysms

OBJECTIVE: Visceral artery aneurysms may be treated by aneurysm exclusion, excision, revascularization, and endovascular techniques. The purpose of this study was to review the outcomes of the management of visceral artery aneurysms with catheter-based techniques. METHODS: Between 1997 and 2005, 90 patients were identified with a diagnosis of visceral artery aneurysm. This was inclusive of aneurysmal disease of the celiac axis, superior mesenteric artery (SMA), inferior mesenteric artery, and their branches. Surveillance without intervention occurred in 23 patients, and 19 patients underwent open aneurysm repair (4 ruptures). The endovascular treatment of 48 consecutive patients (mean age 58, 60% men) with 20 visceral artery aneurysms (VAA) and 28 visceral artery pseudoaneurysms (VAPA) was the basis for this study. Electronic and hardcopy medical records were reviewed for demographic data and clinical variables. Original computed tomography (CT) scans and fluoroscopic imaging were evaluated. RESULTS: The endovascular treatment of visceral artery aneurysms was technically successful in 98% of 48 procedures, consisting of 3 celiac axis repairs, 2 left gastric arteries, 1 SMA, 12 hepatic arteries, 20 splenic arteries, 7 gastroduodenal arteries, 1 middle colic artery, and 2 pancreaticoduodenal arteries. Of these, 29 (60%) were performed for symptomatic disease (5 ruptured aneurysms). Procedures were performed in the endovascular suite under local anesthesia with conscious sedation (94%). The femoral artery was used as the preferential access site (90%). Coil embolization was used for aneurysm exclusion in 96%. N-butyl-2-cyanoacrylate (glue) was used selectively (19%) using a triaxial system with a 3F microcatheter for persistent flow or multiple branches. The 30-day mortality was 8.3% (n = 4). One patient died from recurrent gastrointestinal bleeding after gastroduodenal embolization, and the remaining died of unrelated causes. All perioperative deaths occurred in patients requiring urgent or emergent intervention in the setting of hemodynamic instability. No patients undergoing elective intervention died in the periprocedural period. Postprocedural imaging was performed after 77% of interventions at a mean of 16 months. Complete exclusion of flow within the aneurysm sac occurred in 97% interventions with follow-up imaging, but coil and glue artifact complicated CT evaluation. Postembolization syndrome developed in three patients (6%) after splenic artery embolization. There was no evidence of hepatic insufficiency or bowel ischemia after either hepatic or mesenteric artery aneurysm treatment. Three patients required secondary interventions for persistent flow (n = 1) and recurrent bleeding from previously embolized aneurysms (n = 2). CONCLUSION: Visceral artery aneurysms and pseudoaneurysms can be successfully treated with endovascular means with low periprocedural morbidity; however, the urgent repair of these lesions is still associated with elevated mortality rates. Aneurysm exclusion can be accomplished with coil embolization and the selective use of N-butyl-2-cyanoacrylate. Current catheter-based techniques extend our ability to exclude visceral artery aneurysms, but imaging artifact hampers postoperative CT surveillance.     

The effect of quercetin on topotecan cytotoxicity in MCF-7 and MDA-MB 231 human breast cancer cells

BACKGROUND: Topotecan, which is a Camptothecin derivative, shows a large spectrum in anti-tumor activity. Topotecan exerts its cytotoxic effect on tumor cells mainly by inhibition of topoisomerase I activity resulting in double-strand DNA breaks. In our study, we investigated the combined cytotoxic action of Topotecan and Quercetin in MCF-7 and MDA-MB 231 human breast cancer cells. To examine the possible relation between the cytotoxic activity of Topotecan and oxidative stress, we measured ROS and nitrite levels in both human breast cell lines. MATERIALS AND METHODS: MCF-7 and MDA-MB 231 cells were exposed to Topotecan, Quercetin, or a combination of both agents for 24 h at 37 degrees C. The viability of the cells was measured using the colorimetric MTT (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. We determined reactive oxygen species and nitrite levels as indicators of oxidative stress in both cell lines with and without Topotecan and/or Quercetin incubations using fluorometric dichlorofluorescin diacetate (DCFH-DA) and diaminonaphtalene (DAN) assay. RESULTS: The IC(50) concentration of Topotecan was 100 ng/ml in MCF-7 cell line and 160 ng/ml in MDA-MB231 cell line. Treatment with Quercetin enhanced cytotoxicity of Topotecan as 1.4-fold in MCF-7 and 1.3-fold in MDA-MB-231 cell line. A significant increment on ROS and nitrite levels was found in MCF-7 and MDA-MB-231 cells following Topotecan incubation. CONCLUSIONS: Our results suggest that Topotecan has cytotoxic activity against both of the breast cancer cell lines in vitro. A combination with Quercetin increases efficacy of Topotecan in the treatment of breast cancers. Our results indicate that increased oxidative stress plays a role in the cytotoxic action of Topotecan.     

Guidelines for hospital privileges in vascular surgery and endovascular interventions: Recommendations of the Society for Vascular Surgery

The Hospital Privileges Practice Guideline Writing Group of the Society for Vascular Surgery is making the following five recommendations concerning guidelines for hospital privileges for vascular surgery and endovascular therapy. Advanced endovascular procedures are currently entrenched in the everyday practice of specialized vascular interventionalists, including vascular surgeons, but open vascular surgery remains uniquely essential to the specialty. First, we endorse the Residency Review Committee for Surgery recommendations regarding open and endovascular cases during vascular residency and fellowship training. Second, applicants for new hospital privileges wishing to perform vascular surgery should have completed an Accreditation Council for Graduate Medical Education-accredited vascular surgery residency or fellowship or American Osteopathic Association-accredited training program before 2020 and should obtain American Board of Surgery certification in vascular surgery or American Osteopathic Association certification within 7 years of completion of their training. Third, we recommend that applicants for renewal of hospital privileges in vascular surgery include physicians who are board certified in vascular surgery, general surgery, or cardiothoracic surgery. These physicians with an established practice in vascular surgery should participate in Maintenance of Certification programs as established by the American Board of Surgery and maintain their respective board certification. Fourth, we provide recommendations concerning guidelines for endovascular procedures for vascular surgeons and other vascular interventionalists who are applying for new or renewed hospital privileges. All physicians performing open or endovascular procedures should track outcomes using nationally validated registries, ideally by the Vascular Quality Initiative. Fifth, we endorse the Intersocietal Accreditation Commission recommendations for noninvasive vascular laboratory interpretations and examinations to become a Registered Physician in Vascular Interpretation, which is included in the requirements for board eligibility in vascular surgery, but recommend that only physicians with demonstrated clinical experience in the diagnosis and management of vascular disease be allowed to interpret these studies.     

Traditional risk factors are predictive on segmental localization of coronary artery disease

The aim of this study was to investigate the relationship between established risk factors and segmental localization of coronary artery disease. A total of 2760 patients who underwent coronary angiography were enrolled into the study. Coronary angiographic segmental evaluation was performed according to the scheme of American Heart Association. Patients were classified into 2 groups (group 1: normal coronary artery segments, group 2: coronary artery segments with coronary artery disease). Smoking was highly related with left main coronary artery disease (odds ratio = 7.5; P = .005). Diabetes mellitus and male sex increased the risk of atherosclerosis in all coronary vasculature (odds ratio = 2.7-2.2; P < .001-P < .001). Hypertension was correlated with distal coronary artery (odds ratio = 1.4; P < .001) and family history with distal circumflex lesions (odds ratio = 4.5; P = .005) High triglyceride levels were associated with right coronary artery lesions (odds ratio = 1.00; P =.03). The effect of advanced age was small (odds ratio = 1.08; P < .001). Risk factors may be predictive for segmental localization.     

Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors.

Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2 different approaches for imaging and targeting metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised World Health Organization (WHO) classification, which distinguishes between low- and high-grade malignant GEP-NET, there is a lack of scintigraphic studies comparing uptake behavior on the basis of this categorization. This study aims to define predisposing factors of tracer uptake for both imaging principles implementing the updated tumor criteria of the current WHO classification. METHODS: Fifty-seven consecutive patients with histologically confirmed metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG scintigraphy were included in this study. Intensity of tracer uptake was graded according to the different metastatic regions. Patients were classified as overall positive when avid uptake in the clinically relevant tumor lesions was present. Correlation was tested between the proportion of positive patients and tumor origin, function, and malignancy. RESULTS: Overall, 52 patients (91.2%) were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of tracer-positive patients was significantly higher (P < 0.05) in low-grade malignant tumors for both tracers and in functioning as well as in gastroenteral NET for MIBG. Five patients were negative for both tracers. None of the Oct-negative patients proved to be MIBG positive. CONCLUSION: Oct affinity is observed with high frequency throughout the subgroups of metastatic GEP-NET, whereas corresponding MIBG uptake is overall less prevalent and more group dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake, whereas functionality predisposes only for MIBG accumulation. Though clearly inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable rate of radioligand accumulation in functioning midgut enterochromaffin cell metastases (>80% of patients positive). These results may have implications for patient management and potentially for selection and performance of targeted therapy.     

Comparison of the Temporary Dynamics of NGF and BDNF Gene Expression in Rat Hippocampus,Frontal Cortex,and Retina Under Semax Action

Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation, and maintenance of function of different neuron populations. Some peptides are able to affect the production and activity of neurotrophins. One of these synthetic peptides is heptapeptide Semax, an analog of the N-terminal adrenocorticotropic hormone fragment 4-10. It is known that Semax has effects on learning and memory formation and exerts some neuroprotective effects in rodents and humans. Male Wistar rats were treated for 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h with Semax. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The expression levels of NGF remained practically constant in the retina at the initial stage, whereas the expression levels of BDNF were significantly increased 90 min after Semax administration.     

In vivo knockdown of basal forebrain p75 neurotrophin receptor stimulates choline acetyltransferase activity in the mature hippocampus

This study seeks to determine whether knockdown of basal forebrain p75 neurotrophin receptor (p75^NTR) expression elicits increased hippocampal choline acetyltransferase (ChAT) activity in mature animals. Antisense (AS) oligonucleotides (oligos) targeting p75^NTR were infused into the medial septal area of mature rats continuously for 4 weeks. In all rats, the cannula outlet was placed equidistant between the left and the right sides of the vertical diagonal band of Broca. We tested phosphorothioate (PS), morpholino (Mo), and gapmer (mixed PS/RNA) oligos. Gapmer AS infusions of 7.5 and 22 μg/day decreased septal p75^NTR mRNA by 34% and 48%, respectively. The same infusions increased hippocampal ChAT activity by 41% and 55%. Increased hippocampal ChAT activity correlated strongly with septal p75^NTR downregulation in individual rats. Infusions of PS and Mo AS oligos did not downregulate p75^NTR mRNA or stimulate ChAT activity. These results demonstrate that p75^NTR can dynamically regulate hippocampal ChAT activity in the mature CNS. They also reveal the different efficacies of three diverse AS oligo chemistries when infused intracerebrally. Among the three types, gapmer oligos worked best. © 2016 Wiley Periodicals, Inc.