Implications for the Predictivity of Cell-Based Developmental Toxicity Assays Developed Two Decades Apart.

Many developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce assays as screening tests for developmental toxicity of in-house candidate products. Two cell-based assays which were developed two decades apart were intensively studied.

Translational research into species differences of endocrine toxicity via steroidogenesis inhibition by SMP-028--for human safety in clinical study.

SMP-028 is a drug candidate developed for the treatment of asthma. In a 13-week repeated dose toxicity study of SMP-028 in rats and monkeys, differences of endocrine toxicological events between rats and monkeys were observed. In rats, these toxicological events mainly consisted of pathological changes in the adrenal, testis, ovary, and the other endocrine-related organs.

Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats.

SMP-028 is a new compound for treatment of asthma. Oral administration of SMP-028 to rats was associated with toxicological events in endocrine organs. These events mainly consisted of pathological changes in the adrenal gland, testis, prostate, seminal vesicle, ovaries, and uterus.

Relationship between arterial and fibrous cap remodeling: a serial three-vessel intravascular ultrasound and optical coherence tomography study.

Background: Positive arterial remodeling and thin fibrous cap are characteristics of rupture-prone or vulnerable plaque. The natural course of the fibrous cap thickness and the relationship between serial arterial remodeling and changes in fibrous cap thickness are unknown. Therefore, the purpose of this study was to evaluate the relationship between changes in fibrous cap thickness and arterial remodeling by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS) during 6-month follow-up.

The predictivity of preliminary embryo-fetal development (EFD) studies: results of a retrospective survey in Japanese pharmaceutical companies.

To explore the predictivity of dose range-finding (DRF) studies, we conducted asurvey by sending out questionnaires to 72 Japanese pharmaceutical companies.The survey yielded data for 108 and 85 compounds for which any embryo-fetaldevelopment (EFD) toxicities were observed in the definitive studies in rodentsand non-rodents, respectively. As a result of the analysis, 83% of studies inrodents and 80% in non-rodents showed EFD effects in the DRF studies.

Portopulmonary hypertension associated with congenital absence of the portal vein treated with bosentan.

Portopulmonary hypertension (PPHTN) is pulmonary arterial hypertension (PAH) associated with portal hypertension. It is a common condition among liver transplantation candidates; however, its association with congenital absence of the portal vein (CAPV) has not yet been established. CAPV is a very rare developmental anomaly, which is usually accompanied by abnormal mesenteric drainage that bypasses the liver.

Local release of catecholamines from the hearts of patients with tako-tsubo-like left ventricular dysfunction.

Background: The precise mechanism of tako-tsubo-like left ventricular (LV) dysfunction remains unclear, although recent studies have shown that activation of sympathetic tone might be involved. However, local release of catecholamines from cardiac sympathetic efferent neurons in patients with tako-tsubo-like LV dysfunction remains poorly understood. The purpose of this study was to investigate evidence of local release of catecholamines from the hearts of patients with tako-tsubo-like LV dysfunction.

Three-dimensional quantitation of mitral valve coaptation by a novel software system with transthoracic real-time three-dimensional echocardiography.

We investigated the degree of mitral valve coaptation with a custom quantitation software system using transthoracic three-dimensional (3D) echocardiography. With real-time 3D echocardiography, we obtained transthoracic volumetric images in 20 healthy subjects and 20 patients with dilated cardiomyopathy. With our novel software system, the surface area of mitral valve tenting in the onset of mitral leaflet closure [O] and the timing of maximum closure of mitral leaflet [M] were reconstructed for quantitative measurement.

Rapid progression of mild to moderate aortic stenosis in patients older than 80 years.

Objective: The purpose of this study was to evaluate the rate of progression of mild and moderate aortic stenosis in patients aged 80 years and older.

Methods: In all, 41 patients with mild and moderate aortic stenosis were included and divided into two groups by age: 19 patients aged 80 years and older (mean 84 +/- 4 years), and 21 patients younger than 80 years (mean 66 +/- 6 years).

Results: The rate of degression of aortic valve area was more rapid in the 80 years and older age group than that in the younger than 80 years age group (-0.

Rate of progression of valvular aortic stenosis in patients undergoing dialysis.

Background: In patients undergoing dialysis, aortic valve calcification and aortic stenosis are frequently found. However, the rate of progression of aortic stenosis is still unclear.

Methods: In all, 55 consecutive patients undergoing dialysis were followed up by echocardiography for a period of 12 months.

Lack of evidence for endocrine disrupting effects in rats exposed to fenitrothion in utero and from weaning to maturation.

Fenitrothion is a broad-spectrum organophosphate insecticide. Recently, it has been reported to exert androgenic or anti-androgenic activity in in vitro and in vivo screening assays, although the effects appear equivocal in vivo. To provide a conclusive and comprehensive evaluation of fenitrothion, especially regarding its anti-androgenic activity in the reproductive and endocrine systems, we conducted a one-generation reproductive toxicity study at appropriately toxic dose levels with a number of sensitive endpoints for endocrine disruption.

[Bilateral coronary ostial stenosis after aortic valve replacement with freestyle stentless bioprosthesis: a case report].

An 80-year-old woman underwent aortic valve replacement with Freestyle stentless prosthetic valve for the stenosis. Four months later, she was admitted with myocardial ischemia. Coronary angiography revealed severe stenosis in the ostium of both right and left coronary arteries.