Cisplatin but not BCNU inhibits urokinase-type plasminogen activator levels in human glioblastoma cell lines in vitro

Glioblastomas extensively invade the surrounding normal brain tissue, with a concomitant expression of various proteolytic enzymes, in particular urokinase-type plasminogen activator (uPA). In this study we used cis-diamminedichloroplatinum (cisplatin) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), commonly used anti-cancer drugs for the treatment of glioblastomas, to study the expression of uPA in three human glioblastoma cell lines in vitro. Cells were treated with 25 M cisplatin and 50M BCNU, and uPA levels were estimated by fibrin zymography during a 72-h time course. Treatment of glioblastoma cells with cisplatin resulted in significantly decreased levels of uPA in serum-free conditioned medium and cell extracts, compared to BCNU-treated and untreated cell lines. Quantitative levels of uPA enzyme activity assessed by scanning laser densitometry and uPA protein by ELISA using antibody against uPA showed decreased levels of uPA in cisplatin-treated glioma cell lines relative to BCNU and untreated cell lines. Our results suggest that anti-tumor compound, cisplatin, may exert its anti-neoplastic effects by inhibiting uPA in malignant glioblastomas.     

BLACK THYROID

An autopsy case of a 73-year-old man with "black thyroid" was reported. Investigations by light and electron microscopy and histochemical study of the black thyroid material disclosed the massive deposition brown granules in the follicular cells, to be residual bodies containing lipids. Lipids in these granules were mainly composed of phospholipid by biochemical analysis. Concerning the thyroidal function of this case the value of T₄-I in the serum was within normal range (4.8–7.5 μg/dl) and peroxidase, NADPH-cytochrome C reductase and acid phosphatase activity in the black thyroid material revealed no significant increase or decrease, compared with other 12 autopsied cases. These granules resembled so-called lipofuscin granules, and the frequency and grade of the deposition in autopsied cases increase with aging.     

Quantitation of viral load in neonatal herpes simplex virus infection and comparison between type 1 and type 2

Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity in spite of the development of effective anti-viral therapies. The viral load in neonatal herpes simplex virus (HSV) infection was measured retrospectively in 37 patients. HSV DNA copy numbers in serum and cerebrospinal fluid (CSF) were quantified using a real-time PCR assay. Patients with disseminated infection had a higher viral load in their sera. whereas patients with central nervous system (CNS) infection exhibited a higher viral load in the CSF. The viral load was significantly higher in the serum of patients who died later. Interestingly, patients with HSV type-2 infection exhibited more CNS involvement and neurological impairment, together with a high viral load in the CSF, than did HSV type-1 patients. These results suggest that quantitation of HSV viral load may be useful for assessing the prognosis, and may provide additional information for the management of neonatal HSV infection.     

Transcranial measurement of diffuse light reflectance from cold-injured brains in rats

Diagnosis of brain edema is important to manage severe head injuries and diseases, but there is no method of noninvasive bedside monitoring of brain edema. We speculate that brain edema changes the optical properties of brain tissue. To verify this speculation, we perform transcranial measurement of diffuse light reflectance from cold-injured brains in rats. To induce edema, a liquid nitrogen-cooled copper probe of 3 mm diameter was applied to the right parietal bone for 60 s under anesthesia. The rat skull was irradiated with 633-nm HeNe laser light and 532-nm Nd:YVO4 laser light, which were used to investigate changes in light scattering and blood flow, respectively. Reflectance intensity was measured as functions of time and position on the skull. We found that reflectance intensities were significantly decreased around the cold injury at both 633 and 532 nm, while reflectance was increased in the cold injury at 532 nm, indicating that cerebral blood volume was decreased in the cold injury. Under the condition of decreased cerebral blood volume, the decrease in reflectance intensity around the injury suggests that the scattering coefficient of brain tissue was reduced due to edema formation in this area.     

Comparing Steri-Strip and surgical staple wound closures after primary total knee arthroplasties

Background

Steri-Strips (3M, Two Harbors, MN, USA) have recently been employed for skin closures after orthopedic surgeries. Here we compare the performance of Steri-Strips and skin staples for wound closure after primary total knee arthroplasties (TKAs).

Methods

A total of 76 consecutive osteoarthritic knees (71 patients) that underwent a primary TKA at our facility were included in this study. Thirty-eight knees received Steri-Strips for wound closure and were evaluated prospectively. The other 38 knees were closed with skin staples (Staple group) and evaluated retrospectively.

Results

No deep or superficial infections developed in this series. Although Steri-Strips detached from three knees during the 10-day postoperative period, no dehiscence was observed. Thirteen knees developed blisters around the surgical incision in the Steri-Strip group compared with five knees in the Staple group. The average operative time for the Steri-Strip group was 60.6 min (SD 7.3) compared with 54.1 min (SD 6.9) in the Staple group. There were significant differences in operative time (p < 0.001) and tourniquet time (p < 0.001) between the two groups. The average time until patients were permitted to start showering was significantly shorter in the Steri-Strip group (p = 0.0496). The material cost for Steri-Strips was approximately $3.00 USD for one operation compared with $26 USD for skin staplers.

Conclusions

Wound closure with Steri-Strips after a TKA does not require postoperative material removal and may have improved safety, comfort, cosmesis and cost-effectiveness compared with traditional skin closures.

Level of evidence

Level II, Prognostic study.

     

Fracture risk increased by concurrent use of central nervous system agents in older people: Nationwide case–crossover study

BackgroundMultiple medication use among older patients is reported to increase fracture risk. But this association is unclear in different subgroups and has not been confirmed by a case–crossover study, which can eliminate measurable and unmeasurable time-invariant confounders.ObjectiveTo estimate the fragility fracture risk associated with concurrent use of multiple central nervous system (CNS) agents in older patients using a case–crossover design.MethodsThis study targeted almost all patients aged ≥65 years in Japan who incurred fragility fractures from May 2013 to September 2014, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB Japan). Conditional logistic regression analysis estimated the risk of fragility fracture associated with the daily number of CNS agents, including subgroup analyses stratified by sex, age, and fracture location.ResultsFor 446,101 patients, the adjusted odds ratios (ORs) of fragility fracture increased almost linearly with number of CNS agents; 0, 0–1, 1–2, 2–3, 3–4, 4–5, and >5: OR reference, 1.21 (95% confidence interval, 1.18–1.23), 1.40 (1.35–1.46), 1.58 (1.49–1.67), 1.89 (1.74–2.05), 1.80 (1.60–2.03), and 1.90 (1.61–2.23; trend p < 0.001), respectively. A similar trend was observed for several subgroups, especially in males and those aged ≥85 years, showing marked linearity.ConclusionsThe increased risk of fragility fracture associated with the use of multiple CNS agents was robust in older people in Japan.     

Micro-computed tomography newly developed for in vivo small animal imaging

Objectives The aim of this paper is to report a newly developed micro-computed tomography system for in vivo use.Methods The system was composed of a micro-focus X-ray tube and an image intensifier (I.I.), both of which rotated around the object stage. A guinea pig and a rat were examined. The anesthetized animal was set on the secure object stage. Images of the head of the guinea pig and the tibia/knee joint of the rat were taken. In addition, an image of the rat’s tail was taken. The reconstruction and the image viewing were carried out using I-View software.Results The voxel matrix was 512 × 512 × 384. The voxel sizes ranged from 10 × 10 × 10 µm to 100 × 100 × 100 µm. The exposure time was 17 s, and the reconstruction time was 150 s. The head of the guinea pig and the tibia/knee joint of the rat were observed clearly under 100-µm and 30-µm voxels, respectively. The trabecular bone of the tail was also observed clearly under a 10-µm voxel.Conclusions The newly developed micro-computed tomography system makes it possible to obtain images of anesthetized animals set on a secure object stage. Clear bone images of the small animals could be obtained within a short time.