The aim of this study is to compare the properties of odontoblast gene of early passage cells and late passage cells derived from impacted maxillary supernumerary teeth.
Impacted supernumerary teeth with maxilla were extracted from 12 patients (8 males, 4 females) between 6 - 9 years old without medical history. Real-time polymerase chain reaction (PCR) was conducted to compare characterization of odontoblast cell in the 3rd and 10th passage, and between with bone inducing additive group and without additive group. Genes for odontoblasts characteristics are osteonectin (ONT), alkaline phosphatase (ALP), osteocalcin (OCN), dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP).
The level of gene expression was in a decreasing order of ONT, ALP, OCN, DMP-1 and DSPP in the 3rd passage, and in decreasing order of ONT, DMP-1, OCN, ALP, and DSPP in the 10th passage in the undifferentiation and differentiation group. The order of ONT, DMP-1, and OCN did not changed. ALP and DMP-1 were switched in order.
ALP and DMP-1 may be used as important markers for differentiating between the 3rd passage and 10th passage cells.
Considering that supernumerary tooth was extracted young age and the time required to cultured 10th passage was short, supernumerary tooth can be considered a useful donor site of dental pulp stem cells.

The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model. We also examined whether the glial cell expression and phosphorylated p38 (p-p38) mitogen-activated protein kinases (MAPKs) in the TNC are affected by rapamycin. Mice were intraperitoneally given rapamycin (0.1, 0.3, or 1.0 mg/kg); then, 30 min after, 5% formalin (10 l) was subcutaneously injected into the right upper lip. The rubbing responses with the ipsilateral forepaw or hindpaw were counted for 45 min. High-dose rapamycin (1.0 mg/kg) produced significant antinociceptive effects in both the first and second phases of formalin test. The number of Fos-ir cells in the ipsilateral TNC was also reduced by high-dose rapamycin compared with vehicle-treated animals. Furthermore, the number of p-p38-ir cells the in ipsilateral TNC was significantly decreased in animals treated with high-dose rapamycin; p-p38 expression was co-localized in microglia, but not neurons and astrocytes. Therefore, the mTOR inhibitor, rapamycin, reduces orofacial nociception and Fos expression in the TNC, and its antinociceptive action on orofacial pain may be associated with the inhibition of p-p38 MAPK in the microglia.

The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model. We also examined whether the glial cell expression and phosphorylated p38 (p-p38) mitogen-activated protein kinases (MAPKs) in the TNC are affected by rapamycin. Mice were intraperitoneally given rapamycin (0.1, 0.3, or 1.0 mg/kg); then, 30 min after, 5% formalin (10 l) was subcutaneously injected into the right upper lip. The rubbing responses with the ipsilateral forepaw or hindpaw were counted for 45 min. High-dose rapamycin (1.0 mg/kg) produced significant antinociceptive effects in both the first and second phases of formalin test. The number of Fos-ir cells in the ipsilateral TNC was also reduced by high-dose rapamycin compared with vehicle-treated animals. Furthermore, the number of p-p38-ir cells the in ipsilateral TNC was significantly decreased in animals treated with high-dose rapamycin; p-p38 expression was co-localized in microglia, but not neurons and astrocytes. Therefore, the mTOR inhibitor, rapamycin, reduces orofacial nociception and Fos expression in the TNC, and its antinociceptive action on orofacial pain may be associated with the inhibition of p-p38 MAPK in the microglia.

In 2005, the International Council for Harmonization (ICH) established cardiotoxicity assessment guidelines to identify the risk of Torsade de Pointes (TdP). It is focused on the blockade of the human ether-à-go-go-related gene (hERG) channel known to cause QT/QTc prolongation and the QT/QTc prolongation shown on the electrocardiogram. However, these biomarkers are not the direct risks of TdP with low specificity as the action potential is influenced by multiple channels along with the hERG channel. Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative emerged to address limitations of the current model. The objective of CiPA is to develop a standardized in silico model of a human ventricular cell to quantitively evaluate the cardiac response for the cardiac toxicity risk and to come up with a metric for the TdP risk assessment. In silico working group under CiPA developed a standardized and reliable in silico model and a metric that can quantitatively evaluate cellular cardiac electrophysiologic activity. The implementation mainly consists of hERG fitting, Hill fitting, and action potential simulation. In this review, we explained how the in silico model of CiPA works, and briefly summarized current overall CiPA studies. We hope this review helps clinical pharmacologists to understand the underlying estimation process of CiPA in silico modeling.
Action Potentials ; Biomarkers ; Cardiotoxicity ; Computer Simulation ; Electrocardiography ; Hope ; Humans ; In Vitro Techniques ; Risk Assessment ; Sensitivity and Specificity ; Torsades de Pointes

Angiomyofibroblastoma is a rare, benign mesenchymal tumor of the vulva. Since it was described in 1992 by Fletcher, 15 cases have been reported in literature. We recently experienced a recurred angiomyofibroblastoma of the vulva. A 45-year-old woman was presented initially in 1991 with a mass of labium major and local excision of tumor mass had been performed. A histologic diagnosis was made of angiomyxoma, but this diagnosis was revised to angiomyofibroblastoma by the authors. The recurred mass was well circumscribed, measuring 2.5x1.6x1.5cm in dimensions. Microscopically the tumor was characterized by high cellularity, numerous blood vessels(which lack prominent hyalinization), and plump stromal cells. Immunohistochemically, the stromal cells were reactive for vimentin and desmin, but not alpha-smooth muscle actin, or S-100 protein. We thought that this case was a recurred angiomyofibrblastoma of the vulva due to incomplete surgical excision.
Female ; Humans

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.

A 7-year-old castrated male Persian cat presented with a cutaneous mass and an increase in serum amyloid A concentration. Fine needle aspirates of the mass indicated lymphoma, which was also the top differential diagnosis on histopathologic examinations. Immunohistochemically, neoplastic cells tested negative for anti-CD3, PAX5, CD20, and c-Kit, but positive for MUM1, CD79α, and CD138, suggesting extramedullary plasmacytoma. There were tumor-infiltrating non-neoplastic CD3+ T and CD20+ B cells. Practitioners should be aware of feline plasmacytoma characterized by lymphoma-like cytologic and histologic features. The present study is valuable in providing the first clinical evidence that proves the immunogenicity of feline plasmacytoma.