TONS504-PHOTODYNAMIC THERAPY INDUCES CYTOTOXIC EFFECTS IN EMT6 CELLS

In the present study, TONS504 (C51H58N8O5I2; molecular weight, 1,116.9), a novel cationic hydrophilic photosensitizer, was synthesized from protoporphyrin IX dimethyl ester through a five‑step process according to a patented method for use in photodynamic therapy (PDT). The subcellular localization of TONS504 and the cytotoxic effects of TONS504‑mediated PDT in the mouse mammary tumor EMT6 cell line were investigated. TONS504 was localized primarily in the lysosomes and partially in the mitochondria. The cytotoxic effects of TONS504‑mediated PDT in the mouse mammary tumor EMT6 cell line were investigated using a WST8 assay and an Oxidative Stress kit. The cell viability values following treatment with 10 µg/ml TONS504 at light energies of 0, 1, 5 and 10 J/cm2 were 92.5, 101.8, 27.7 and 1.8%, respectively. The percentages of reactive oxygen species (ROS)(+) cells following the same treatment were 8.6, 8.5, 29.2 and 70.1%, respectively, whereas the percentages of apoptotic cells were 7.1, 5.6, 24.8 and 48.7%, respectively. The percentages of ROS(+) and apoptotic cells in the group subjected to TONS504‑mediated PDT increased in a manner dependent on the TONS504 concentration and light energy. Further studies are required to evaluate the in vivo pharmacokinetics, tissue distribution and photodynamic effects of TONS504

Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required

Measurement of femoral axial offset

Purpose to examine the accuracy and reproducibility of the femoral axial offset measured from the retrocondylar plane by computed tomography (CT). Bone specimens of the femur of 15 males and 15 females were analyzed. CT imaging was performed and data of the coordinates were collected (center of femoral head, center of an ellipse around greater trochanter, center of an ellipse around the base of femoral neck, posterior edge of great trochanter, and both posterior condyles). The angle between the line connecting center of the femoral head and center of an ellipse around greater trochanter and the line connecting both posterior condyles was set as anteversion 1. The angle between the line connecting the center of femoral head and center of an ellipse around base of the femoral neck and the line connecting both posterior condyles was set as anteversion 2. The femoral axial offset was measured from the retrocondylar plane. Measurements were performed three times on the same subject, and intrarater reliability (ICC) was determined. In addition, interrater reliability (ICC) was determined by comparing data from three raters. The mean value for anteversion 1 was 20.1° for males and 22.7° for females. The values for anteversion 2 were 16.0° and 19.9° for males and females, respectively. Offset was 34.0 and 33.4 mm in males and females, respectively. Intrarater ICC and interrater ICC exceeded 0.81 for both methods, suggesting that the method of measurement was reliable. Accuracy and reproducibility of the measurement of femoral axial offset from the retrocondylar plane were high

Solitary Fibrous Tumor of the Thigh: A Patient Report

We report a rare case of solitary fibrous tumor (SFT) within the thigh muscle. A 37-year-old woman noticed a painless mass in her left thigh, which had gradually enlarged. Computed tomography (CT) showed an intramuscular tumor and enhanced CT showed strong enhancement within the lesion. Magnetic resonance imaging revealed that the tumor measured 13.1 × 7.3 × 2.3 cm and was located within the sartorius muscle, with a clearly defined margin. Malignancy was suspected and the tumor was surgically resected. The tumor was characterized by a well-circumscribed lesion, and was composed of bland or short spindle cells, which were patternless, with scattered thick collagen bundles, and variably gaping thin- or hyalin-walled blood vessels. Immunohistochemically, the tumor cells were positive for vimentin, CD34, CD99 and focally, bcl-2. The tumor was subsequently diagnosed as an extrapleural SFT, which is classified into an intermediated (rarely metastasizing) category. Extrapleural SFT should be considered in the evaluation of soft tissue tumors in the extremities, although it may be rare

Effects of Oral Glucosamine Hydrochloride Administration on Plasma Free Amino Acid Concentrations in Dogs

We examined the effects of oral glucosamine hydrochloride (GlcN), N-acetyl-d-glucosamine (GlcNAc) and d-glucose (Glc) administration on plasma total free amino acid (PFAA) concentrations in dogs. The PFAA concentrations increased in the control group and the GlcNAc group at one hour after feeding, and each amino acid concentration increased. On the other hand, in the GlcN group and the Glc group PFAA concentrations decreased at one hour after feeding. A significant decrease in amino acid concentration was observed for glutamate, glycine and alanine. Our results suggest the existence of differences in PFAA dynamics after oral administration of GlcN and GlcNAc in dogs

Regression of LV hypertrophy by tafamidis

Transthyretin amyloidosis (ATTR) variant is a life-threatening hereditary disease predominantly affecting the peripheral nervous system and heart. Tafamidis, which prevents the deposition of amyloid by stabilizing transthyretin, is available for the treatment of neuropathy and cardiomyopathy of ATTR. However, whether tafamidis could eliminate established amyloid deposits and improve cardiac function remains unknown. We reported a case of regression of left ventricular hypertrophy after tafamidis therapy in a patient with an ATTR variant

Oral Administration of Surface-Deacetylated Chitin Nanofibers and Chitosan Inhibit 5-Fluorouracil-Induced Intestinal Mucositis in Mice

This study investigated the prophylactic effects of orally administered surface-deacetylated chitin nanofibers (SDACNFs) and chitosan against 5-fluorouracil (5-FU)-induced intestinal mucositis, which is a common side effect of 5-FU chemotherapy. SDACNFs and chitosan abolished histological abnormalities associated with intestinal mucositis and suppressed hypoproliferation and apoptosis of intestinal crypt cells. These results indicate that SDACNF and chitosan are useful agents for preventing mucositis induced by anti-cancer drugs

Characterization of Individuals with Sacroiliac Joint Bridging in a Skeletal Population: Analysis of Degenerative Changes in Spinal Vertebrae

Theaimof this study was to characterize the individualswith sacroiliac joint bridging (SIB) by analyzing the degenerative changes intheirwhole vertebral column and comparing themwith the controls.Atotal of 291modern Japanesemale skeletons,with an averageage at death of 60.8 years, were examined macroscopically. They were divided into two groups: individuals with SIB and thosewithout bridging (Non-SIB).The degenerative changes in their whole vertebral column were evaluated, and marginal osteophytescores (MOS) of the vertebral bodies and degenerative joint scores in zygapophyseal jointswere calculated. SIBwas recognized in 30individuals froma total of 291 males (10.3%).The average of age at death in SIB group was significantly higher than that in Non-SIBgroup. The values ofMOS in the thoracic spines, particularly in the anterior part of the vertebral bodies, were consecutively higherin SIB group than in Non-SIB group. Incidence of fused vertebral bodies intervertebral levels was obviously higher in SIB groupthan in Non-SIB group. SIB and marginal osteophyte formation in vertebral bodies could coexist in a skeletal population of men.Some systemic factors might act on these degenerative changes simultaneously both in sacroiliac joint and in vertebral column

Natriuretic peptide receptor guanylyl cyclase-A pathway counteracts glomerular injury evoked by aldosterone through p38 mitogen-activated protein kinase inhibition

Guanylyl cyclase-A (GC-A) signaling, a natriuretic peptide receptor, exerts renoprotective effects by stimulating natriuresis and reducing blood pressure. Previously we demonstrated massive albuminuria with hypertension in uninephrectomized, aldosterone-infused, and high salt-fed (ALDO) systemic GC-A KO mice with enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in podocytes. In the present study, we examined the interaction between p38 MAPK and GC-A signaling. The administration of FR167653, p38 MAPK inhibitor, reduced systolic blood pressure (SBP), urinary albumin excretion, segmental sclerosis, podocyte injury, and apoptosis. To further investigate the local action of natriuretic peptide and p38 MAPK in podocytes, we generated podocyte-specific (pod) GC-A conditional KO (cKO) mice. ALDO pod GC-A cKO mice demonstrated increased urinary albumin excretion with marked mesangial expansion, podocyte injury and apoptosis, but without blood pressure elevation. FR167653 also suppressed urinary albumin excretion without reducing SBP. Finally, we revealed that atrial natriuretic peptide increased phosphorylation of MAPK phosphatase-1 (MKP-1) concomitant with inhibited phosphorylation of p38 MAPK in response to MAPK kinase 3 activation, thereby resulting in decreased mRNA expression of the apoptosis-related gene, Bax, and Bax/Bcl2 ratio in cultured podocytes. These results indicate that natriuretic peptide exerts a renoprotective effect via inhibiting phosphorylation of p38 MAPK in podocytes.</p