Echographic detection of diethylnitrosamine-induced liver tumors in rats and the effect of the intratumoral injection of an inhibitor of c-Jun N-terminal kinase

Background and Aim:  There have so far been few reports describing echographic studies of chemically-induced carcinogenesis in rodent livers. Using echography, we observed diethylnitrosamine-induced liver tumors in rats and examined the effect of an intratumoral injection of an inhibitor of c-Jun N-terminal kinase.
Methods:  Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro . Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.
Results:  The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo , the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.
Conclusions:  Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms.     

Development of packaging cell lines for generation of adeno-associated virus vectors by lentiviral gene transfer of trans-complementary components

Adeno-associated virus (AAV) vector system has several useful advantages with regard to in vitro and in vivo gene transfer. However, their usages have been limited by cumbersome and labor-intensive vector production in the traditional method. To overcome limitations in AAV production, in this report, we explored the possibility of generating AAV packaging cell line, 293T R/C.VA.E2A.E4. cells, by using lentivirus-mediated transduction of Rep/Cap gene of AAV-2, VA RNA, E2A, and E4 genes of Ad5 into 293T cells. In packaging cell lines, it is important that supply of the AAV vector can be stably performed for long time. We showed that the 293T R/C.VA.E2A.E4. cells have stably maintained the transduced components after more than 10 passages and yielded high-titer AAV vectors, and the titer of AAV vectors did not decline even if culture of the packaging cells was continued for long time. The Rep/Cap and E4 gene products caused no remarkable cytotoxicity. The 293T R/C.VA.E2A.E4. cells might be able to tolerate the Rep/Cap and E4 gene products, or have less copy numbers of the Rep/Cap and E4 genes than the traditional method. Moreover, we showed that the AAV vectors derived from 293T R/C.VA.E2A.E4. cells infected the primary human CD34+ haematopoietic progenitor cells with high efficiency (50-70%). In the 293T R/C.VA.E2A.E4. cells, the AAV vectors can be generated by the transfection of one AAV vector plasmid, and large-scale AAV production can be easily achieved. It is important that cumbersome, variable, and costly transfection is avoided.     

Comparison of the effects of cilnidipine and amlodipine on ambulatory blood pressure.

Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage-dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity. The purpose of this study was to assess the effect of cilnidipine and amlodipine on ambulatory blood pressure (BP) levels. We performed 24-h ambulatory BP monitoring before and after once-daily use of cilnidipine (n=55) and amlodipine (n=55) in 110 hypertensive patients. Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (p < 0.005). However, the reductions of 24-h (-1.19+/-6.78 vs. 1.55+/-6.13 bpm, p=0.03), daytime (-1.58+/-6.72 vs. 1.68+/-7.34 bpm, p=0.02) and nighttime (-1.19+/-5.72 vs. 1.89+/-6.56 bpm, p=0.01) pulse rate (PR) were significantly greater in the cilnidipine group than the amlodipine group. There was no correlation between the degree of daytime SBP change and that of daytime PR change after amlodipine treatment (r=-0.08, n.s.), but there was a significant negative correlation between the degree of daytime SBP change and that of day-time PR change after cilnidipine treatment (r=-0.27, p<0.05). N-type calcium channel blockade by cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.     

Left ventricular oozing rupture following acute myocardial infarction

We describe the case of an 85-year-old woman in whom pericardiocentesis, prolonged bed rest and blood pressure control were performed without surgery to successfully treat an oozing-type myocardial rupture due to myocardial infarction.     

A case of intracoronary protruded thrombus caused after bailout stenting for side branch occlusion

A 69-year-old woman underwent percutaneous coronary intervention for a severe stenotic lesion in the bifurcation of the mid-left anterior descending artery and first diagonal branch. A single stent was implanted into the left anterior descending artery. After the stent strut was dilated by balloon inflation in the diagonal branch, dissection occurred at the ostium of the diagonal branch and resulted in side branch occlusion due to hematoma. Bailout stenting was performed in the diagonal branch, but thrombus projection occurred in the left anterior descending artery. Aspiration, balloon inflation and thrombolytic therapy were performed, but distal embolism developed. This case illustrates that thrombus projection caused by stenting in a side branch may occur as a rare complication in percutaneous coronary intervention.     

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.     

Correlation of anatomic and hemodynamic features with aortic valve leaflet deformity in doubly committed subarterial ventricular septal defect

Summary The records of 153 patients with doubly committed subarterial ventricular septal defect (DCVSD) who underwent intracardiac repair were analyzed to evaluate factors responsible for aortic valve leaflet deformity. The patients were divided into two groups according to their echocardiographic and angiographic features as well as anatomic findings at operation: DCVSD without (17/153, 11.1%) and with arterial valve offsetting (136/153, 88.9%). Aortic regurgitation (AR) was much more prevalent in the patients with (50.0%) than in those without leaflet deformity (2.2%,P < 0.01). Arterial valve offsetting is one of the major contributing factors to the development of leaflet deformity, accounting for 5.9% in the patients without offsetting and 46.3% in those with offsetting (P < 0.01). Among the patients with arterial valve offsetting, the pulmonary-to-systemic pressure ratio was significantly higher (P < 0.01) in the patients without (0.76 ± 0.14) than in those with leaflet deformity (0.36 ± 0.12), suggesting that pulmonary hypertension might prevent the aortic valve leaflet from prolapsing in DCVSD. In addition, increased severity of aortic valve leaflet deformity and subsequent AR were observed with increasing age. These results suggest that aging and the presence of arterial valve offsetting as well as the absence of pulmonary hypertension might be factors responsible for aortic valve leaflet deformity and subsequent AR in DCVSD. The anatomic and hemodynamic features in DCVSD have a great impact on the development of aortic valve leaflet deformity and subsequent AR.