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We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl‐methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d‐MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l‐MPH, and (3) will l‐MPH enantioselectively interact with ethanol to yield l‐ethylphenidate (l‐EPH)? Mice were dosed with MTS (¼ of a 12.5 cm2 patch on shaved skin) or a comparable oral dl‐MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic–mass spectrometry monitoring of N‐(S)‐prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l‐MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l‐EPH and to an elevation in d‐MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route‐dependent drug absorption rate differences, MTS was associated with significant MPH–ethanol interactions. Ethanol‐mediated increases in circulating concentrations of d‐MPH carry toxicological and abuse liability implications should this animal model hold for ethanol‐consuming attention‐deficit hyperactivity disorder patients or coabusers. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2966–2978, 2011

BRN2 is a developmental neural cell-specific POU domain transcription factor and is crucial for cell lineage determination. We investigated the importance of BRN2 in the expression of the lineage-specific transcription factors (achaete-scute homolog-like 1 (ASCL1) and NeuroD1 (ND1)) and neural/neuroendocrine marker molecules (neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYP) and chromogranin A (CHGA)) in small cell lung cancer (SCLC) using cultured lung cancer cells. All examined SCLC cell lines expressed BRN2, as well as ASCL1, ND1, NCAM1, SYP and CHGA. The expression levels of ASCL1, ND1, NCAM1, SYP and CHGA considerably decreased when BRN2 was knocked down in SCLC cells, and the addition of a BRN2 transgene into non-SCLC (NSCLC) cells induced the expression of ASCL1, ND1, NCAM1, SYP and CHGA. However, the BRN2 gene was not activated by the forced expression of ASCL1 or ND1 in NSCLC cells. The knockdown of BRN2 caused significant growth retardation with decrease of S to G2 phase population and mitotic cell rates and unaltered Ki-67-labeled or apoptotic cell rates in SCLC cells, indicating increase of G1 phase population. These findings suggest that BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of SCLC.

A 55-year-old woman had a right renal tumor incidentally diagnosed by ultrasonography. CT revealed a perirenal low density mass 3 cm in diameter. Dynamic CT showed peripheral enhancement of the tumor in early phase and internal homogeneous enhancement in delayed phase. Since hemangioma was considered most likely, we performed tumor resection and spared the right kidney. The tumor was supplied by the superior ureteral artery from the right main renal artery which was considered to be derived from the renal sinus. The tumor was diagnosed as intravascular papillary endothelial hyperplasia (Masson's tumor). This is the first report of intravascular papillary endothelial hyperplasia existing in the perirenal space. Although preoperative diagnosis of intravascular papillary endothelial hyperplasia is difficult, intra-operative pathology and kidney-sparing treatment should be considered in such a case.

A case of so-called inflammatory pseudotumor (IPT), occurring in the spleen of a 77-year-old woman, is reported. The spleen contained a well-circumscribed mass with central hemorrhage and necrosis. Histologically, spindle cells were dispersed in a background of abundant inflammatory cells, predominantly lymphocytes and plasma cells. The cells possessed enlarged, sometimes twisted or irregularly folded, nuclei that contained vesicular chromatin, and small but distinct, centrally located nucleoli. Immunohistochemically, the spindle cells were diffusely positive for vimentin, and focally positive for follicular dendritic cell (FDC) markers (Ber-MAC-DRC for CD35 and CNA.42). The Epstein-Barr virus (EBV) was exclusively detected in the spindle cells by in situ hybridization analysis. The cells also expressed the latent membrane protein-1 (LMP-1) of EBV, and polymerase chain reaction (PCR) analysis revealed that the LMP-1 gene had a 30-bp deletion and three point mutations, although their significance remains controversial. Inflammatory pseudotumor is a descriptive term that encompasses several different entities, and recent investigations have revealed the existence of neoplastic entities among IPT. One of the neoplastic IPT, recently designated 'IPT-like FDC tumor', is characterized by proliferation of EBV-positive FDC and commonly occurs in the liver and spleen. Because such tumors are capable of recurrence and metastasis, it is important to consider the possibility of an IPT-like FDC tumor when making a diagnosis of a hepatic/splenic IPT-like lesion.