Role of renin–angiotensin system inhibitors in retardation of progression of end-stage renal failure: a retrospective study

Background

Few studies have examined how renin–angiotensin system inhibitors (RASI) delay dialysis initiation in patients with advanced chronic kidney disease (CKD). We conducted a retrospective survey to examine this subject.

Methods

We reviewed the records of patients with advanced CKD for the 60-month period before dialysis initiation between 1990 and 2015. Patients were classified based on the decade of dialysis initiation into the 1990s, 2000s, and 2010s groups. The rates of antihypertensive medications administered were assessed. The rate of decline of renal function was evaluated by the slope of reciprocal serum creatinine (SRSC). Multiple regression analyses were conducted to evaluate factors contributing to renoprotection.

Results

The duration of RASI administration was longer in the 2010s than in 2000s and 1990s. Both diabetic and non-diabetic patients had lower SRSC in the 2010s compared to the 2000s. In the 2010s, the rate of RASI administration during the 60-month pre-dialysis period showed an initial rise followed by a downward trend, although the rates of administration of the other classes of antihypertensives increased continuously. Multivariate regression analyses identified age, blood pressure, diuretics, α-blockers, α-methyldopa and RASI as independent predictors of SRSC in the 2010s. The rate of RASI administration correlated with serum potassium concentration.

Conclusion

Our findings suggest that in the 2010s, RASI with other antihypertensive agents contributed to renoprotection in advanced CKD patients, but they were underused because of the concern over hyperkalemia. In real-world clinical practice, physicians may feel great hesitation in using RASI in patients with advanced CKD.

     

Differentiation of spinal giant cell tumors from chordomas by using a scoring system

Introduction

Few reports have compared the clinical features and imaging characteristics of giant cell tumor and chordoma of the spine. The aim of the present study was to investigate whether the two types of tumors could be differentially diagnosed, by comparing clinical characteristics as well as magnetic resonance imaging (MRI) or computed tomography (CT) findings and then scoring the characteristic findings.

Methods

A total of 18 patients were retrospectively assessed. To elucidate the characteristic findings, we investigated the following 10 items: age at diagnosis, sex, and site of occurrence; for MRI findings, the pattern of tumor expansion, T1-weighted images, T2-weighted images, septal structure, and cystic changes; and for CT findings, calcification or residual bone fragments and incomplete bone shells. Then, we developed a unique scoring system and investigated whether the two tumors could be differentiated by this scoring system.

Results

Six items, including, age, site of occurrence, tumor expansion pattern, T2-weighted images, septal structure, and incomplete bone shells, were significantly different between giant cell tumor and chordoma patients. By using newly developed scoring system, the mean scores of 0.9 ± 0.6 (range 0–2) for giant cell tumor and 4.8 ± 1.5 (range 3–6) for chordoma patients were significantly different (P < 0.001), thereby allowing the differential diagnosis by setting the cutoff value to three.

Conclusions

We found that the six items were useful for differentially diagnosing giant cell tumor and chordoma. These results indicate that it may be possible to distinguish the two types of tumor by scoring these items.

     

Histochemical examinations on cortical bone regeneration induced by thermoplastic bioresorbable plates applied to bone defects of rat calvariae

We aimed to histologically elucidate whether bioresorbable plates (DeltaSystem) can induce cortical bone formation, which is essential for long-lasting bone augmentation. Standardized bone defects in rat calvariae were covered with a convexly-shaped DeltaSystem plate, and then processed for histological observations. At 1 week, alkaline phosphatase-positive osteoblasts were seen in the newly-formed bone extending from the cavity's bottom, indicating accelerated osteogenesis. A thick layer of soft connective tissue positive for periostin, a hallmark of periosteum, covered this new bone. At 2 weeks, a spongy bone had filled the cavity up to half its height. The inner layer of the soft tissue facing the spongy bone revealed abundant periostin and osteopontin, and had many tartrate-resistant acid phosphatase-positive osteoclasts. At 4 weeks, this layer had given rise to thin new bony matrices without relation to the spongy bone arising from the cavity. These bone matrices had been thickened by 8 weeks, and turned into a thick cortical bone outlining the regenerated bone at 12 weeks. Thus, our study has provided histological evidences of cortical osteogenesis when DeltaSystem plates are used for bone augmentation procedures.     

Human plasma metabolic profiles of benzydamine,a flavin-containing monooxygenase probe substrate,simulated with pharmacokinetic data from control and humanized-liver mice

1.?Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir.

2.?Following oral administration of benzydamine (10?mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide.

3.?Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high.

4.?The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.     

The usefulness of day-service in maintaining general nutritional status in elderly Japanese: a longitudinal study

Day-service, commuting service for elderly people requiring care at home, is one healthcare option in Japan. To date, however, there exist no studies that have examined the effects of day-service use on health outcomes in Japan. The objective of the present longitudinal study was to determine whether there is an association between day-service use and various physical and mental health outcomes in elderly people requiring care. The subjects were 61 elderly persons who required between 25 and 49 min of assistance per day and used long-term care insurance. Measurements included demographic characteristics, activities of daily living, frequency of day-service use, body weight, height, grip strength, thigh muscle volume, degree of depression (Geriatric Depression Scale), the mini-mental state examination, and serum albumin and blood hemoglobin levels in the baseline and follow-up surveys two years later. In the day-service user group, the mean changes in serum albumin concentrations using day-service once, twice and three < or = times/week were -0.2, -0.3, and 0 g/dl, respectively, and the mean changes in blood hemoglobin were -0.7, -0.5, and 0.2 g/dl, respectively. The two-year change in serum albumin concentrations was less (p = 0.024) in subjects using day-service "three < or = times" (0 g/dl) than "twice" (-0.3 g/dl). The two-year change in blood hemoglobin was also less (p = 0.043) in subjects using day-service "three < or = times" (0.2 g/dl) than "twice" (-0.5 g/dl). The present study has shown that frequent use of day-service is useful in maintaining general nutritional status in elderly people.     

Clinico-radiological spectrum of reversible splenial lesions in children

Recently, many cases of children presenting reversible splenial lesions during febrile illness (RESLEF) have been reported; however, their overall clinico-radiological features are unclear.     

Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain

Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain‐like behaviors in sciatic nerve‐ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level‐dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve‐ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT‐3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve‐ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin‐2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain‐like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice. Synapse 68:235–247, 2014 . © 2014 Wiley Periodicals, Inc.