FANCD1/BRCA2 Plays Predominant Role in the Repair of DNA Damage Induced by ACNU or TMZ

Nimustine (ACNU) and temozolomide (TMZ) are DNA alkylating agents which are commonly used in chemotherapy for glioblastomas. ACNU is a DNA cross-linking agent and TMZ is a methylating agent. The therapeutic efficacy of these agents is limited by the development of resistance. In this work, the role of the Fanconi anemia (FA) repair pathway for DNA damage induced by ACNU or TMZ was examined. Cultured mouse embryonic fibroblasts were used: FANCA−/−, FANCC−/−, FANCA−/−C−/−, FANCD2−/− cells and their parental cells, and Chinese hamster ovary and lung fibroblast cells were used: FANCD1/BRCA2mt, FANCG−/− and their parental cells. Cell survival was examined after a 3 h ACNU or TMZ treatment by using colony formation assays. All FA repair pathways were involved in ACNU-induced DNA damage. However, FANCG and FANCD1/BRCA2 played notably important roles in the repair of TMZ-induced DNA damage. The most effective molecular target correlating with cellular sensitivity to both ACNU and TMZ was FANCD1/BRCA2. In addition, it was found that FANCD1/BRCA2 small interference RNA efficiently enhanced cellular sensitivity toward ACNU and TMZ in human glioblastoma A172 cells. These findings suggest that the down-regulation of FANCD1/BRCA2 might be an effective strategy to increase cellular chemo-sensitization towards ACNU and TMZ

Basal septal perforator vein mimicking the “late iodine enhancement” in delayed phase cardiac CT for myocardial scar assessment

Delayed-phase cardiac CT is a useful tool for scar detection, based on differences in the volume of distribution of iodine. Although it covers the entire heart, provides uniform, high isotropic spatial resolution, and therefore may be useful for detecting small late iodine enhancement (LIE), we need to correctly differentiate small LIE and pseudo-lesions mimicking LIE. In this case report, we demonstrate basal septal perforator vein mimicking LIE in delayed phase cardiac CT. Left ventricular myocardium includes not only septal vein and artery but also capillaries, arterio- and venoluminal vessels, and sinusoids, etc. which connect to septal veins. To avoid misinterpretations of myocardial LIE on the delayed phase images, we need to understand those anatomical features. Keywords: Delayed iodine CT, Late iodine enhancement, Myocardial infarction, Myocardial scar, Septal perforator vei

Pulmonary arterial hypertension associated with portal hypertension: Noninvasive comprehensive assessment using computed tomography

Pulmonary arterial hypertension associated with portal hypertension, known as portopulmonary hypertension (PoPH) is one of the important and serious pulmonary complications in patients with portal hypertension. Although there are a large number of patients with portal hypertension due to mainly liver cirrhosis, the number of cases diagnosed with PoPH are far fewer because the causes of dyspnea in patients with cirrhosis are diverse and the disease entity of PoPH is poorly recognized by clinicians. We report here the case with PoPH suggested and assessed comprehensively by dual energy computed tomography (CT) including high-resolution pulmonary CT angiography, pulmonary perfusion imaging, myocardial late iodine enhancement imaging, and myocardial extracellular volume analysis. This refined CT imaging protocol can be used in conjunction with standard chest evaluation and offers a practical and useful approach for the noninvasive “one-stop shop” evaluation of PoPH

LCZ696 サクビトリル バルサルタン ノ キュウセイ シンキン コウソク ゴ ノ シン ホゴ コウカ

熊本大

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo