Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Genotype 5 Japanese Encephalitis Virus—Old Genotype, New Threat

Japanese encephalitis (JE) is an important viral encephalitis with epidemic status in Asia, which is caused by Japanese encephalitis virus (JEV), a member of the genus Flavivirus . JEV is divided into five genotypes. Genotype 5 (G5) is relatively neglected because of the limited number of cases and strains isolated. The first strain of G5 JEV (Muar strain) was isolated in Singapore in 1952 in a patient from Muar, Malaysia. The second strain (XZ0934) was isolated 57 years later in China, thus indicating the re-emergence of G5 JEV. A female patient who had been vaccinated against JE was infected with G5 JEV in Korea in 2015. JE is a vaccine-preventable disease, and its incidence has decreased with vaccination in many Asian countries. G3 JEV is the main candidate for current JE vaccines, which include attenuated, inactivated and chimeric type vaccines. However, the available vaccines do not provide adequate protection against the older G5 JEV lineage. Therefore, more research on this genotype is crucial for developing better detection methods, expanding surveillance to determine the possible chains of viral transmission for this new threat and developing a polyvalent JEV vaccine

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Heterogeneous Spectral-Spatial Feature Transfer With Structure Preserved Distribution Alignment for Hyperspectral Image Classification

Cross-scene knowledge transfer has been proven effective to deal with the small-sample problem in hyperspectral image (HSI) classification. Currently, most of the existing works are based on the homogeneous settings where the source and target HSIs are observed from the same feature space, while the heterogeneous situation, which is more common in real-world applications, is under insufficient exploration. In this article, we propose a novel transfer learning approach for HSI classification, which is capable of transferring discriminative spectral-spatial feature between heterogeneous datasets. Specifically, we first extract spectral-spatial features of source and target scenes by applying the multiscale convolutional sparse decomposition (MCSD) method. By performing MCSD, the spectral information and spatial structure information at different scales can be jointly adapted to learn transferable features for classification. Then, in order to overcome the heterogeneity between the two feature sets, we build a structure preserved distribution alignment (SPDA) model to learn domain-specific projections to map the feature samples into a shared latent subspace where the discriminative knowledge can be effectively transferred. With proper reformulation, we give the analytical solution of the objective function and generate an optimization approach to solve the SPDA model efficiently. Experiments conducted on several real data pairs demonstrate that the proposed approach can explicitly narrow the disparity between heterogeneous HSIs, and yield superior classification results compared with other representative heterogeneous transfer learning methods

Activity of Metabotropic Glutamate Receptor 4 Suppresses Proliferation and Promotes Apoptosis With Inhibition of Gli-1 in Human Glioblastoma Cells

Glioblastoma multiforme (GBM) is the most lethal glioma variant in the adult brain and among the deadliest of human cancers. Increasing evidence has shown that metabotropic glutamate receptor subtype 4 (mGluR4) expression may play roles in regulating the growth of neural stem cells as well as several cancer cell lines. Here, we investigated the effects of mGluR4 on the growth and apoptosis of the LN229 GBM cell line. Involvement of Gli-1, one of the key transcription factors in the sonic Hedgehog (SHH) signaling pathway, was further explored. In this study, mGluR4 was activated using selective agonist VU0155041; and gene-targeted siRNAs were used to generate loss of function of mGluR4 and Gli-1 in LN229 cells. The results demonstrated that LN229 cells expressed mGluR4 and the agonist VU0155041 decreased cell viability in a dose- and time-dependent manner. Activation of mGluR4 inhibited cyclin D1 expression, activated pro-caspase-8/9/3, and disrupted the balance of Bcl-2/Bax expression, which indicated cell cycle arrest and apoptosis of LN229 cells, respectively. Furthermore, Gli-1 expression was reduced by mGluR4 activation in LN229 cells, and downregulation of Gli-1 expression by gene-targeted siRNA resulted in both inhibition of cell proliferation and promotion of apoptosis. Moreover, VU0155041 treatment substantially blocked SHH-induced cyclin D1 expression and cell proliferation, while increasing TUNEL-positive cells and the activation of apoptosis-related proteins. We concluded that activation of mGluR4 expressed in LN229 cells could inhibit GBM cell growth by decreasing cell proliferation and promoting apoptosis. Further suppression of intracellular Gli-1 expression might be involved in the action of mGluR4 on cancer cells. Our study suggested a novel role of mGluR4, which might serve as a potential drug target for control of GBM cell growth

Immunohistochemical Study of NR2C2, BTG2, TBX19, and CDK2 Expression in 31 Paired Primary/Recurrent Nonfunctioning Pituitary Adenomas

This study investigated potential markers for predicting nonfunctioning pituitary adenoma (NFPA) invasion and recurrence by high-throughput tissue microarray analyses. We retrospectively studied two groups of patients: 60 nonrecurrent NFPA cases that included noninvasion and invasion subtypes and 43 recurrent cases that included primary NFPA. A total of 31 paired patient samples were evaluated (12 patients with one surgery and 31 who had undergone two operations, with both tumors analyzed). Expressions of nuclear receptor subfamily 2 group C member 2 (NR2C2), B cell translocation gene 2, T-box-19 (TBX19), and cyclin-dependent kinase 2 (CDK2) in surgically resected specimens were assessed by immunohistochemistry. The relationships between marker expression and clinical characteristics including age, sex, tumor volume, and follow-up time were analyzed. Tumor volume and invasion as well as follow-up time were significantly associated with invasion and recurrence (P < 0.01). Of the 60 nonrecurrent samples, 15/41 and 13/19 showed high NR2C2 expression in the noninvasion and invasion groups, respectively (χ2 =5.287, P = 0.021). NR2C2 was also overexpressed in 43 primary recurrent cases (χ2 =5.433, P = 0.02), whereas CDK2 (χ2 = 11.242, P = 0.001) and TBX19 (χ2 = 4.875, P = 0.027) were downregulated. In the 31 paired samples, NR2C2 was more highly expressed in the recurrent as compared to the primary tumor. High NR2C2 expression was associated with NFPA invasion, recurrence, and progression, while TBX19 and CDK2 were associated with NFPA recurrence

Parasellar epidermoid cyst with unique radiological features: A case report and review of the literature

Intracranial epidermoid cysts (ECs) are encapsulated lesions lined by squamous cell epithelium and the most location is the cerebellopontine angle and appears with cerebrospinal fluid-like irregular mass. Occasionally, ECs present as high-density masses on computed tomography and atypical features in magnetic resonance images in the unusual area, which makes the diagnosis difficult. Here, we report a case of a female subject who complained of episodic left facial convulsions for more than 3 months. Computed tomography plain scan revealed a large hyperdense parasellar mass with atypical magnetic resonance findings. In this report, we analyzed retrospectively the radiological characteristics and histopathology of the parasellar EC, thus increasing awareness about this unusual image features