OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
Abietanes ; Acute Lung Injury/drug therapy* ; Animals ; Cytokine Release Syndrome ; Cytokines ; Inflammation/drug therapy* ; Lipopolysaccharides/toxicity* ; Macrophage Activation ; Macrophages ; Mice ; Triacetoneamine-N-Oxyl/pharmacology*

Progressive cribriform and zosteriform hyperpigmentation (PCZH) is a distinctive pigmentary disorder observed along the lines of Blaschko. Clinically, the lesions appear as uniformly tan, cribriform macular hyperpigmentation with a zosteriform distribution, without a history of rash, injury, inflammation, or other associated cutaneous or internal abnormalities. Histopathological specimens show increased melanin pigmentation in the basal cell layer with a complete absence of nevus cells. We report 8 cases of PCZH and review the literature on this peculiar disorder.
Exanthema ; Hyperpigmentation* ; Inflammation ; Melanins ; Nevus ; Pigmentation ; Triacetoneamine-N-Oxyl

Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide (H₂O₂) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to 400 μM H₂O₂ for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of H₂O₂ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against H₂O₂-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by H₂O₂ via PXR activation. In conclusion, Tan IIA protected HUVECs against H₂O₂-induced cell injury through PXR-dependent mechanisms.
Apoptosis ; Asian Continental Ancestry Group ; Atherosclerosis ; Endothelial Cells* ; Glutathione ; Glutathione Disulfide ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide ; Inflammation ; Oxidative Stress ; Regeneration ; Rhizome ; Salvia miltiorrhiza ; Triacetoneamine-N-Oxyl ; Xenobiotics

Two Whooper swan (Cygnus cygnus) died after suffering from pododermatitis, lethargy, and ataxia; necropsy was performed. Grossly, the liver was swollen and firm. The kidney and spleen were also enlarged and a pale tan color. On histopathologic examination with Congo red staining, amyloidosis was noted in liver, spleen, and kidney. In addition, marked osseous metaplasia was present in the liver. Based on these results, systemic amyloidosis involving liver, spleen, and kidney with osseous metaplasia in the liver was diagnosed. Study results indicate that an inflammatory reaction associated with pododermatitis had a role in the amyloidosis in this particular case.
Amyloidosis* ; Ataxia ; Congo Red ; Kidney ; Lethargy ; Liver ; Metaplasia ; Spleen ; Triacetoneamine-N-Oxyl

PURPOSE: This study is to investigate the effect of captopril when combined with irradiation. MATERIALS AND METHODS: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF-1α) of tumor was evaluated by immunohistochemical (IHC) staining. RESULTS: The mean tumor volumes (±standard error) at the 15th day after randomization were 1,382.0 (±201.2) mm³ (group 1), 559.9 (±67.8) mm³ (group 3), and 370.5 (± 48.1) mm³ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and HIF-1α positivity in tumor cells were decreased when treated with captopril. CONCLUSION: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.
Angiotensin-Converting Enzyme Inhibitors ; Animals ; Captopril* ; Flow Cytometry ; Hypoxia-Inducible Factor 1 ; Injections, Intraperitoneal ; Leg ; Mice ; Neutrophils ; Radiotherapy ; Random Allocation ; Triacetoneamine-N-Oxyl ; Vascular Endothelial Growth Factor A

We report a spontaneous embryonal rhabdomyosarcoma in the abdominal cavity of an aged (88-week-old) Sprague-Dawley rat. The animal had a firm lobulated 5 x 5 x 4.5 cm mass in the abdominal cavity that was whitish to tan with necrotic and hemorrhagic plaques. Microscopically, the mass contained nodules with spindle or globoid shaped neoplastic cells with abundant eosinophilic cytoplasm and round or elongated nuclei mixed with other spindle cells with a filamentous appearance and scanty cytoplasm. Multinucleated cells and cross-striations were also observed. The neoplastic cells were positive for vimentin, desmin, and alpha-smooth muscle actin, especially the small spindle cells.
Abdominal Cavity* ; Actins ; Animals ; Cytoplasm ; Desmin ; Eosinophils ; Rats* ; Rats, Sprague-Dawley* ; Rhabdomyosarcoma, Embryonal* ; Triacetoneamine-N-Oxyl ; Vimentin

PURPOSE: The purpose of this study was to observe the change of viscoelastic properties of dental resin cements during polymerization. MATERIALS AND METHODS: Six commercially available resin cement materials (Clearfil SA luting, Panavia F 2.0, Zirconite, Variolink N, RelyX Unicem clicker, RelyX U200) were investigated in this study. A dynamic oscillation-time sweep test was performed with AR1500 stress controlled rheometer at 32degrees C. The changes in shear storage modulus (G'), shear loss modulus (G"), loss tangent (tan delta) and displacement were measured for twenty minutes and repeated three times for each material. The data were analyzed using one-way ANOVA and Tukey's post hoc test (alpha=0.05). RESULTS: After mixing, all materials demonstrated an increase in G' with time, reaching the plateau in the end. RelyX U200 demonstrated the highest G' value, while RelyX Unicem (clicker type) and Variolink N demonstrated the lowest G' value at the end of experimental time. Tan delta was maintained at some level and reached the zero at the starting point where G' began to increase. The tan delta and displacement of the tested materials showed similar pattern in the graph within change of time. The displacement of all 6 materials approached to zero within 6 minutes. CONCLUSION: Compared to other resin cements used in this study, RelyX U200 maintained plastic property for a longer period of time. When it completed the curing process, RelyX U200 had the highest stiffness. It is convenient for clinicians to cement multiple units of dental prostheses simultaneously.
Dental Prosthesis ; Plastics ; Polymerization* ; Polymers* ; Resin Cements ; Resins, Synthetic* ; Triacetoneamine-N-Oxyl

The pathological features of a mass in the back skin region of an 8-year-old castrated male dog are described herein. The cut section of the tumor was white to tan with a soft multilobulated mass containing hemorrhagic and necrotic foci and a mucinous-like composition. Microscopically, the tumor was composed of a mixture of lipocytes, lipoblasts, spindle cells and stellate cells and had a myxoid background. Oil red O staining revealed that the cytoplasm of neoplastic cells contained large numbers of lipid droplets. Immunohistochemically, tumor cells were positive for vimentin and S-100 protein. The skin mass was diagnosed as myxoid liposarcoma.
Adipocytes ; Animals ; Child ; Cytoplasm ; Dogs* ; Humans ; Liposarcoma, Myxoid* ; Male ; S100 Proteins ; Skin ; Triacetoneamine-N-Oxyl ; Vimentin

BACKGROUND: The spectrophotometer is well known to be a useful tool for estimating the objective minimal erythema dose (MED) during planning of phototherapy protocol. However, only a few spectrophotometric values are used to evaluate the erythema and pigmentation of the MED site during phototesting. OBJECTIVE: To determinea new meaning of the relationships among spectrophotometric values during phototesting. METHODS: Twenty-five patients with psoriasis and 23 patients with vitiligo were selected before undergoing narrowband ultraviolet B phototherapy. We interpreted the gross findings of erythema and measured the L*a*b* values using a spectrophotometer at each phototest spot. We compared MEDs, basic spectrophotometric values (L*a*b*), and b*/L* values separately according to skin type, and determined the correlation of each spectrophotometric value and the correlation between a* and b*/L* values. RESULTS: Among L*a*b* values, only b* values showed a statistically significant difference between the type III and IV groups (p=0.003). There was a positive correlation only between MEDs and b* values (p<0.05). The average b*/L*value in the type IV group was significantly higher than the type III group (p<0.05). CONCLUSION: The higher b* values in type IV skin indicates that skin tanning develops more prominently than type III. The correlation between MEDs and b* values may signify that the skin pigmentation status is deepened with the higher MEDs. The difference in b*/L*values between type III and IV skin reflects that the b*/L*value is thought to be an index of tanning. The a* value, known as an index of erythema, does not influence the degree of tanning.
Erythema* ; Humans ; Phototherapy* ; Pigmentation ; Psoriasis ; Skin ; Skin Pigmentation ; Tanning ; Triacetoneamine-N-Oxyl ; Vitiligo

PURPOSE: Neonatal late-onset hypocalcemia is defined as hypocalcemia developed after postnatal 3 days and associated with hypoparathyroidism, high phosphate diets and vitamin D deficiency. We experienced the increment of neonatal late onset hypocalcemia over 1 year. We tried to evaluate the relationship between late onset hypocalcemia and maternal hypovitaminosis D. METHODS: The medical records in the neonates with late-onset hypocalcemia during January 2007 to July 2008 were retrospectively reviewed. Among those patients, 17 paired sera of mothers and neonates had collected. The levels of 25-OH vitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured and were compared with neonate and the mother. RESULTS: The mean gestational age was 38+1 weeks, and the mean body weight was 2,980 g. The onset time of hypocalcemia was 5.9 days of age. Most of them (88.2%) were feeding with formula and no one was only breast milk feeding. Of the 17 patients, 13 were born in spring or in winter. The median levels of calcium, phosphorus, alkaline phosphatase, iPTH and 25OHD were 7.0 mg/dL, 8.6 mg/dL, 191.0 U/L, 57.2 pg/mL and 24.0 ng/mL in neonates. The levels of 25OHD of 6 neonates were <20 ng/mL. A total of 16 mothers were considered vitamin D-deficient (<20 ng/mL), and vitamin D insufficient (20<25OHD<30 ng/mL). CONCLUSION: Neonatal late-onset hypocalcemia in our study seems to be influenced by maternal vitamin D deficiency and insufficiency. Sun tanning and vitamin D supplements from winter to spring would be helpful to prevent maternal vitamin D deficiency, one of the causes of neonatal late-onset hypocalcemia.
Alkaline Phosphatase ; Body Weight ; Calcium ; Diet ; Gestational Age ; Humans ; Hypocalcemia* ; Hypoparathyroidism ; Infant, Newborn ; Medical Records ; Milk, Human ; Mothers ; Parathyroid Hormone ; Phosphorus ; Retrospective Studies ; Solar System ; Tanning ; Triacetoneamine-N-Oxyl ; Vitamin D ; Vitamin D Deficiency ; Vitamins