The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

Spontaneous recovery of fear differs among early – late adolescent and adult male mice

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Tween 40-based precipitate production observed on modified chromogenic agar and development of biological identification kit for Malassezia species.

We developed a simple identification kit for nine species of Malassezia (M. furfur, M. slooffiae, M. sympodialis, M. restricta, M. obtusa, M. globosa, M. pachydermatis, M. dermatis, and M. japonica) based on their biological features. This method utilizes Tween 40-based precipitate production on modified chromogenic agar (CHROMagar) Malassezia medium, growth on specific agars (Sabouraud's dextrose agar, Cremophor EL agar, Tween 60-esculin agar), and catalase reactions. This identification kit was verified with 11 type and reference strains of nine Malassezia species. An additional 26 clinical isolates were also successfully identified using the kit and the results were confirmed by molecular biological analysis.     

Ultrasonographic study on kidneys in patients with acute renal failure]

Ultrasonotomograms of 22 kidneys were obtained in 11 patients with renal-acute renal failure (renal-ARF). The underlying diseases of renal-ARF were acute tubular necrosis in 8 patients and acute on-set chronic glomerulonephritis in 3 patients. They were treated by hemodialysis in 10 patients and intermittent peritoneal dialysis in 1 patient. Ultrasonic measurement of the size of kidneys revealed that the thickness (anterior-posterior diameter) and the ratio of thickness to length (T/L) were greater in patients with ARF than in those with chronic renal failure and normal renal function. The patients with a low value of T/L (under 0.60) had a significantly greater urine volume than those with high a value of T/L (0.60 or more). The sonographic features of renal-ARF kidneys were marked increase in parenchymal echogenicity and appearance of hypoechoic swollen renal pyramids with sharpness of the corticomedullary border. In the course of ARF, these sonographic changes gradually disappeared when the patients had recovered from ARF. However, the prognosis was poor in patients with severer sonographic findings. We believe that repeated ultrasonic examination of the kidneys in patients with renal-ARF is useful for not only differential diagnosis of post-renal urinary obstruction but evaluating the course of ARF.     

Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model.

Pseudomonas aeruginosa is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic P. aeruginosa infection. The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic P. aeruginosa infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-alpha, and interleukin-beta concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period. These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic Pseudomonas aeruginosa respiratory infection and may be useful in treating respiratory diseases.     

Cardiac metastasis of renal pelvic cancer

Abstract:   A 66-year-old man was referred to our hospital with chest discomfort and shortness of breath. Seven months previously he had undergone a laparoscopic left nephroureterectomy for a left renal pelvic tumor and was given two cycles of adjuvant chemotherapy (methotrexate, epirubicin and cisplatin). Echocardiogram showed an 8-mm sized mass extending from the right atrium into the right ventricle. On computed tomography, multiple lung tumors, as well as the right atrial and ventricular mass, were seen. The patient died of acute heart failure caused by right ventricular outflow obstruction. On autopsy, a right atrial and ventricular metastasis of the initial transitional cell carcinoma was found. The patient's cause of death was acute heart failure as a result of cardiac metastasis of his initial renal pelvic carcinoma.