Valsartan reduces serum cystatin C and the renal vascular resistance in patients with essential hypertension

A high level of albuminuria and increased renal vascular resistance are associated with hypertensive renal damage. In this study, the authors investigated the effect of the angiotensin II receptor blocker, valsartan, on renal function and intrarenal hemodynamics in non-diabetic patients with essential hypertension. A prospective three-month study of the effects of valsartan, 40-80 mg/day, was performed in 30 hypertensive patients. As an assessment of renal function, serum creatinine, urine albumin/creatinine (Alb/Cr) ratio, and serum cystatin C levels were evaluated. Doppler ultrasonography of the kidney was performed for the evaluation of renal hemodynamics. Peak-systolic, end-diastolic, and mean velocities of interlobar arteries were evaluated, and the pulsatility index (PI) and resistive index (RI) were calculated. It was determined that patients with microalbuminuria had higher levels of serum cystatin C, PI, and RI compared to patients without microalbuminuria. Valsartan treatment significantly reduced systolic and diastolic blood pressure and decreased the Alb/Cr ratio. Serum creatinine was not changed, whereas serum cystatin C levels were significantly reduced. Valsartan treatment significantly decreased the PI in all patients and both PI and RI in patients with microalbuminuria. These results suggest that the angiotensin II receptor blocker, valsartan, is able to improve renal function by reducing renal vascular resistance in hypertensive patients, especially in patients with microalbuminuria, and may prevent future renal failure in patients with essential hypertension.     

Recent advances in video‐assisted thoracoscopic surgery for lung cancer

As a result of increased use of CT in both screening and daily practice, the number of early lung cancers has increased enormously. Surgeons pursue both curativity and reduced invasiveness in treating patients with early stage lung cancer; therefore, minimally invasive operations, such as video‐assisted thoracoscopic surgery (VATS) lobectomy are now being routinely performed. Most previous reports have shown that there is no difference in mortality and local recurrence between open surgery and VATS in stage I patients. However, surgeons' improved technical experience and patients' demands could soon make VATS lobectomy the operative method of choice for early stage lung cancer. Moreover, the indications for VATS are expanding to encompass complex procedures such as segmentectomy or sleeve resection. Training and dissemination of the technique and the monitoring of outcomes are necessary.     

Quantitative p16 and ESR1 methylation in the peripheral blood of patients with non-small cell lung cancer

Inactivation of the p16 and ESR1 tumor suppressor genes by promoter lesion methylation has been reported in many tumor types, including lung cancer. We examined the blood of 95 non-small cell lung cancer patients (66 cases of adenocarcinoma, 23 of squamous cell carcinoma and 6 of large cell carcinoma) and 30 controls consisting of normal subjects and benign disease patients to determine the methylation ratios of p16 and ESR1 using real-time PCR. For both genes, there was a statistically significant difference in the methylation ratio between non-small cell lung cancer patients and controls (p16; p<0.01, ESR1; p<0.001). In addition, there was a strong correlation between the methylation ratio of each gene and old age (p16; p<0.01, ESR1; p<0.001 and p16 or ESR1; p<0.001), and between p16 or ESR1 methylation rate and smoking history (p<0.01). Moreover in Stage I cases, the methylation positive rate of each gene (p16, ESR1 and p16 or ESR1) was higher than the CEA positive rate (p<0.05, p<0.001, p<0.001). Evaluation of p16 and ESR1 promoter methylation in blood using real-time PCR appears to be very useful for lung cancer diagnosis and there is some possibility that these methylated genes might come to represent useful biomarkers for the early detection of lung cancer. Our study results also suggested that comparative evaluation of the methylation ratio before and after surgery might be a powerful tool to predict the prognosis of lung cancer patients.     

AT2 receptor stimulation inhibits phosphate-induced vascular calcification

1. Download high-res image (154KB)
2. Download full-size image

     

LPS-stimulated human gingival fibroblasts inhibit the differentiation of monocytes into osteoclasts through the production of osteoprotegerin

Periodontitis is an inflammatory bone disease caused by Gram-negative anaerobic bacteria, but the precise mechanism of bone destruction remains unknown. Activated T lymphocytes secrete receptor activator of NF-kappaB ligand (RANKL) and support the differentiation of monocytes into mature osteoclasts. The purpose of this study was to examine the expression of RANKL and its inhibitor, osteoprotegerin (OPG), in inflamed gingival tissue and to clarify the role of human gingival fibroblasts (HGFs) in osteoclastogenesis regulated by RANKL. HGFs and gingival mononuclear cells (GMCs) were obtained from chronic periodontitis patients during routine periodontal surgery. Expression of OPG and RANKL mRNA in gingival tissue and HGFs was examined with RT-PCR. OPG production was measured using ELISA. Expression of RANKL, CD4, CD8 and CD69 on GMCs was determined by flow-cytometry using RANK-Fc fusion protein and the respective monoclonal antibodies. Osteoclastogenesis by RANKL was assayed by counting the number of tartarate-resistant acid phosphatase (TRAP)-positive cells after culturing human peripheral blood monocytes with recombinant human RANKL and macrophage-colony stimulating factor (M-CSF) for 10 days. OPG and RANKL mRNA were expressed in 80% (16/20) and 25% (5/20) of periodontitis lesions, respectively. OPG, but not RANKL, mRNA was expressed within HGFs. OPG mRNA expression and production by HGFs was augmented by LPS stimulation. All GMC samples expressed CD69, and two of five GMC samples expressed RANKL. The culture supernatant of LPS-stimulated gingival fibroblasts significantly reduced the number of TRAP positive cells generated by culturing monocytes with RANKL and M-CSF. The present study suggests that LPS-stimulated HGFs inhibit monocyte differentiation into osteoclasts through the production of OPG.     

4D Flow MR Imaging of the Left Atrium: What is Non-physiological Blood Flow in the Cardiac System?

Most cardiac diseases cause a non-physiological blood flow pattern known as turbulence around the heart and great vessels, which further worsen the disease itself. However, there is no consensus on how blood flow can be defined in disease conditions. Especially, in the left atrium, the fact that vortex flow already exists makes this debate more complicated. 3D time-resolved phase-contrast (4D flow) MRI is expected to be able to capture blood flow patterns from multiple aspects, such as blood flow velocity, stasis, and vortex quantification. Previous studies have confirmed that physiological vortex flow is predominantly induced by the higher-volume flow from the superior left pulmonary vein. In atrial fibrillation, 4D flow MRI reveals a non-physiological blood flow pattern, which information may add value to well-established clinical risk factors. Currently, the research target of LA analysis has also widened to lung surgeons, pulmonary vein stump thrombosis after left upper lobectomy. 4D flow MRI is expected to be utilized for many more variable diseases that are currently unimaginable.