Insulin activates ATP-sensitive potassium channels via phosphatidylinositol 3-kinase in cultured vascular smooth muscle cells

The effects of insulin on the vasculature are significant because insulin resistance is associated with hypertension. To increase the understanding of the effects of insulin on the vasculature, we analyzed changes in potassium ion transport in cultured vascular smooth muscle cells (VSMCs). Using the potential-sensitive fluorescence dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)], we found that insulin induced membrane hyperpolarization after 2 min in A10 cells. Insulin-induced hyperpolarization was suppressed by glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker. Using a cell-attached patch clamp experiment, the K(ATP) channel was activated by insulin in both A10 cells and isolated VSMCs from rat aortas, indicating that insulin causes membrane hyperpolarization via K(ATP) channel activation. These effects were not dependent on intracellular ATP concentration, but wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, significantly suppressed insulin-induced K(ATP) channel activation. In addition, insulin enhanced phosphorylation of insulin receptor, insulin receptor substrate (IRS)-1 and protein kinase B (Akt) after 2 min. These data suggest that K(ATP) channel activation by insulin is mediated by PI3-K. Furthermore, using a nitric oxide synthase (NOS) inhibitor, we found that NOS might play an important role downstream of PI3-K in insulin-induced K(ATP) channel activation. This study may contribute to our understanding of mechanisms of insulin resistance-associated hypertension.     

A case of ureteral malignant lymphoma with concentric thickening of the ureteral wall

A 59-year-old man was referred to our hospital with right hydronephrosis, which was diagnosed from a medical examination. On imaging studies, he had concentric thickness of the right ureteral wall, and retroperitoneal and mesenteric lymphadenopathy. Urine cytology was negative, and an ureteroscopic biopsy showed no malignancy. We performed laparoscopic biopsy of the retroperitoneal lymphadenopathy, and the histopathological diagnosis was B-cell follicular lymphoma. The patient received four cycles of RCVP (rituximab, cyclophosphamide, vincristine, prednisolone) chemotherapy and four cycles of rituximab monotherapy and then he obtained complete remission. If concentric thickness of the ureteral wall is found, physicians should be aware of the possibility of malignant lymphoma and should consider laparoscopic biopsy for diagnosis.     

A pilot study of intraoperative localization of peripheral small pulmonary tumors by cone-beam computed tomography: sandwich marking technique

BackgroundIntraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods.MethodsThis was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes.ResultsThe average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication.ConclusionsAll small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.     

Estrogen inhibits the growth of MCF-7 cell variants resistant to transforming growth factor-beta

Human breast cancer MCF-7 cells containing estrogen receptor are killed by transforming growth factor-beta (TGF-beta). We isolated variants of MCF-7 highly resistant to TGF-beta. Variants ES-1 and ES-4 were cloned, and the growth of ES-1 and ES-4 was found to be inhibited by estradiol, whereas estradiol stimulated the growth of the parental MCF-7 cells. ES-1 cells contained about 2-fold higher level of estradiol receptor than MCF-7 cells. Addition of estradiol to the culture medium for MCF-7 and the variant changed the expression of several secreted proteins. The repertoire of secreted proteins was markedly altered in the variant. Polypeptides of molecular weight 52,000 (52 K), 65 K and 160 K were increased about 10- to 50-fold in both estradiol-treated MCF-7 and ES-1 cells. Polypeptide of 130 K was decreased in estradiol-treated ES-1 cells while this polypeptide was increased about 4-fold in estradiol-treated MCF-7, as compared with untreated MCF-7. Polypeptide of 100 K was specifically secreted in ES-1 whether or not estradiol was present, but there appeared to be no significant amount of the 100 K protein in MCF-7. The estradiol-hypersensitive phenotype is discussed in relation to its aberrant expression of secreting proteins.     

Mechanism of production of pulse deficit in atrial fibrillation: assessment by blood flow dynamics

Pulse deficit in patients with atrial fibrillation is caused by the reduction of preload. The purpose of this study was to visualize the mechanism in view of blood flow dynamics using pulsed Doppler echocardiography. The subjects were 15 cases with atrial fibrillation and pulse deficit, and the results were as follows: 1. Simultaneous recordings of the carotid pulse wave (CPW) and blood flow at the left ventricular inflow tract indicated that, in nine of the total 15 cases, CPW disappeared from the cardiac cycle even with sufficient preceding RF in the other six cases (Group B). 2. In Group A, %RF correlated well with %CPW; however, there was poor correlation between them in Group B. Moreover, CPW was always greater than 26% if RF was greater than 50% of each mean value in Group A, but less than 25% in Group B, suggesting poor left ventricular ejection in the latter group. 3. The left ventricular ejection fraction (EF) and %fractional shortening (%FS) decreased significantly in Group B compared to those in Group A (EF; 59 +- 7 vs 41 +- 12%, p less than 0.01, %FS; 31 +- 5 vs 20 +- 6, p less than 0.01). These findings indicate that left ventricular contractility was significantly reduced in the cases with pulse deficit in Group B. 4. Systolic backward flow in the mid-ventricle caused by left ventricular asynchrony due to localized apical wall motion abnormalities was observed in all 15 cases. The heart rate during pulsed Doppler echocardiography was significantly increased in Group A as compared to that in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of autologous fibrin tissue adhesive in reducing postoperative blood loss during total hip arthroplasty: a prospective randomised study of 100 cases

PURPOSE: To evaluate the effectiveness of autologous fibrin tissue adhesive (auto-FTA) in reducing blood loss during cementless total hip arthroplasty (THA). METHODS: From September 2000 to August 2001, 100 patients who predonated 400 ml of autologous blood were randomised to undergo either standard treatment with auto-FTA (auto-FTA group) or standard treatment alone (control group). The volume of postoperative blood loss and the decrease in haemoglobin level were measured. All patients were followed up for 3 years to evaluate the rate of bone ingrowth and heterotopic ossification. RESULTS: The mean postoperative blood loss was 580 ml (standard deviation [SD], 240 ml) in the auto-FTA group and 810 ml (SD, 341 ml) in the control group; the difference was significant (230 ml, p<0.001). The decrease in haemoglobin concentration was 17 g/l (SD, 11 g/l) in the auto-FTA group and 22 g/l (SD, 12 g/l) in the control group. The difference was significant (5 g/l, p=0.03). The percentage of total blood loss of >1200 ml in any single patient was significantly lower in the auto-FTA group (4%) than in the control group (20%) [p=0.01]. CONCLUSION: Auto-FTA is a safe and effective means of reducing perioperative blood loss in THA.