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The next-generation sphingosine-1 receptor modulator BAF312(siponimod) improves cortical network functionality in focal autoimmune encephalomyelitis

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Neural Regeneration Research 2019年第11期14卷 1950-1960页

作者： Petra Hundehege manuela Cerina Susann Eichler Christian Thomas Alexander m. Herrmann Kerstin goel Thomas müntefering Juncal Fernandez-Orth Stefanie Bock venu Narayanan Thomas Budde Erwin-Josef Speckmann Heinz Wiendl Anna Schubart Tobias Ruck Sven g. meuth Department of Neurology with Institute of Translational Neurology Westfalische Wilhelms-UniversitatMunsterGermany Institute of Physiology I Westfalische Wilhelms-UniversitatMunsterGermany Novartis Institutes of Biomedical Research BaselSwitzerland

Autoimmune diseases of the central nervous system(CNS) like multiple sclerosis(mS) are characterized by inflammation and demyelinated lesions in white and grey matter regions. While inflammation is present at all stages of mS, it is more pronounced in the relapsing forms of the disease, whereas progressive mS(PmS) shows significant neuroaxonal damage and grey and white matter atrophy. Hence, disease-modifying treatments beneficial in patients with relapsing mS have limited success in PmS. BAF312(siponimod) is a novel sphingosine-1-phosphate receptor modulator shown to delay progression in PmS. Besides reducing inflammation by sequestering lymphocytes in lymphoid tissues, BAF312 crosses the blood-brain barrier and binds its receptors on neurons, astrocytes and oligodendrocytes. To evaluate potential direct neuroprotective effects, BAF312 was systemically or locally administered in the CNS of experimental autoimmune encephalomyelitis mice with distinct grey-and white-matter lesions(focal experimental autoimmune encephalomyelitis using an osmotic mini-pump). Ex-vivo flow cytometry revealed that systemic but not local BAF312 administration lowered immune cell infiltration in animals with both grey and white matter lesions. Ex-vivo voltage-sensitive dye imaging of acute brain slices revealed an altered spatio-temporal pattern of activation in the lesioned cortex compared to controls in response to electrical stimulation of incoming white-matter fiber tracts. Here, BAF312 administration showed partial restore of cortical neuronal circuit function. The data suggest that BAF312 exerts a neuroprotective effect after crossing the blood-brain barrier independently of peripheral effects on immune cells. Experiments were carried out in accordance with german and EU animal protection law and approved by local authorities(Landesamt für Natur, Umwelt und Verbraucherschutz Nordrhein-Westfalen;87-51.04.2010.A331) on December 28, 2010.

关键词： multiple sclerosis focal experimental autoimmune encephalomyelitis cortical grey matter white matter BAF312 neuroaxonal damage neuroprotection

movement Patterns of metallic Particles in a Single Phase gas Insulated Busduct with Superimposed Lightning and Switching Impulses

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高电压技术 2008年第12期34卷 2642-2647页

作者： m. venu gopala Rao J. Amarnath g.V. Nagesh Kumar S. Kamakshaiah K. D. Srivastava QIS College of Engineering and Technology Ongole 523272 Andhra Pradesh India College of Engineering Jawaharlal Nehru Technological University Kuktrtpally Hyderabad 500085 Andhra Pradesh India Vignan's Institute of Information Technology Visakhapatnam 530046 Andhra Pradesh India C. V. R. College of Engineering Hyderabad Andhra Pradesh India University of British Colombia Vancouver B. C. V6T 1Z4 Canada

Transient over voltages due to lightning and switching surges cause steep build-up of voltage on transmission lines and other electrical apparatus,like circuit breakers,transformers,insulators *** it is necessary for the gIS also to withstand such voltages without breakdown of *** system has to be tested under these *** the gIS system operates on power *** Impulse Voltage of 1050 kV and Switching Impulse Voltage of 750 kV superimposed on Power frequency voltages of 75 kV,100 kV and 132 kV are applied to Single Phase gas Insulated Busduct and the maximum movement of Aluminum,Copper and Silver particles is *** movement patterns are also determined with and without monte Carlo Simulation for movement of particle in axial and radial *** results show that there is a sudden jump in the movement at the application of impulse on sine *** is because of high magnitude voltage of 1050 kV during 1.2/50 μ*** movement patterns of reduced maximum movement is observed for Switching Impulse superimposed on sine *** results are presented and analyzed.

关键词：重复雷击金属微粒运动形态气相绝缘站粒子污染物

Pancreatic intraductal papillary mucinous neoplasm in a patient with Lynch syndrome

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World Journal of gastroenterology 2015年第9期21卷 2820-2825页

作者： meghan R Flanagan Arjun Jayaraj Wei Xiong matthew m Yeh Wendy H Raskind venu g Pillarisetty Department of Surgery University of Washington Medical Center University of Washington SeattleWA 98195United States Department of Pathology and Laboratory medicine University of British ColumbiaVancouverBritish ColumbiaVancouverBC V6Z 1Y6Canada Department of Pathology University of Washington Medical Center Departments of medicine/medical genetics and Pyschiatry and Behavioral Sciences University of Washington Medical Center

Intraductal papillary mucinous neoplasm(IPmN) is a mucin-producing epithelial neoplasm that carries a risk of progression to invasive pancreatic ductal *** syndrome is an autosomal dominant condition caused by germline mutations in mismatch repair genes such as mSH2 that lead to microsatellite instability and increased risk of tumor *** families with Lynch syndrome have an increased risk of pancreatic cancer, a clear connection between Lynch syndrome and IPmN has not been *** present a report of a 58 year-old Caucasian woman with multiple cancers and a germline mutation of mSH2 consistent with Lynch syndrome.A screening abdominal computed tomography scan revealed a dilated main pancreatic duct and cystic ductular structure in the uncinate process that were consistent with IPmN of the main pancreatic duct on *** and polymerase chain reaction of the patient's pancreas specimen did not reveal microsatellite instability or mismatch repair gene loss of expression or *** findings may be explained by the fact that loss of mismatch repair function and microsatellite instability is a late event in neoplastic *** the relative rarity of main duct IPmN, its appearance in the setting of somatic mSH2 mutation suggests that IPmN may fit into the constellation of Lynch syndrome related malignancies.

关键词： Intraductal papillary mucinous neoplasm Pancreatic

A Novel RP-HPLC method for Estimating Fulvestrant, Benzoyl Alcohol, and Benzyl Benzoate in Injection Formulation

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American Journal of Analytical Chemistry 2022年第7期13卷 229-240页

作者： Arjuna Rao Nekkalapudi venu gopal Veldi Sreenivas Pippalla Career Point University CP Tower 1 IPIA Kota Rajasthan India HTS Bio Pharma Aleap Industries Estate Pragathi Nagar Telangana India Sikkim Professional University Gangtok India

For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomenex Luna C8, 150 × 4.6 mm, i.d 3.0 μm particle size column with a gradient programme of mobile phases A and B. With a flow rate of 1.5 mL/minute, injection volume of 10 μL, and column temperature of 35°C, UV wavelength detection at 254 nm for Benzyl alcohol and Benzoyl Benzoate and 280 nm for Fulvestrant, mobile phase-A consists of DI water and mobile phase-B consists of Acetonitrile. The current study describes a single HPLC method for developing a Fulvestrant (Active), Benzyl alcohol (Cosolvent), and Benzyl Benzoate (Cosolvent) assay for Fulvestrant injection. The assay method was determined to be suitable for quantifying three components in the pharmaceutical product and was verified according to ICH guidelines.

关键词： Fulvestrant Injection Formulation HPLC Assay Benzyl Alcohol and Benzyl Benzoate

Role of endoscopic ultrasound guided fine needle aspiration/biopsy in the evaluation of intra-abdominal lymphadenopathy due to tuberculosis

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World Journal of gastrointestinal Endoscopy 2021年第12期13卷 649-658页

作者： Harshavardhan Rao B Priya Nair S Krishna Priya Archana george Vallonthaiel Dipu T Sathyapalan Anoop K Koshy Rama P venu Department of gastroenterology Amrita Institute of Medical SciencesKochi 682041KeralaIndia Department of Pathology Amrita Institute of Medical SciencesKochi 682041KeralaIndia Department of Internal medicine Amrita Institute of Medical Sciences and Research CentreKochi 682041KeralaIndia

BACKgROUND Intra-abdominal lymphadenopathy due to tuberculosis(TB)poses a diagnostic challenge due to difficulty in tissue *** endoscopic ultrasound guided fine needle aspiration/biopsy(EUS-FNA/B)has shown promise in the evaluation of mediastinal lymph nodes,its role in the evaluation of intra-abdominal lymphadenopathy is not *** To assess the role of EUS-FNA/B in the evaluation of intra-abdominal lymphadenopathy due to *** This was a retrospective study where patients with intra-abdominal lymphadenopathy who underwent evaluation with EUS-FNA/B were *** was diagnosed if the patient had any one of the following:(1)Positive acid fast bacilli(AFB)stain/TB geneXpert/TB-polymerase chain reaction/AFB culture of tissue sample;and(2)Positive mantoux test and response to anti-tubercular ***-FNA reports,clinical reports and imaging characteristics of patients were recorded for a detailed analysis of patients with *** A total of 149 patients underwent an EUS-FNA/B from lymph nodes(mean age 51±17 years,m:F=1.2).Benign inflammatory reactive changes were seen in 45 patients(30.2%),while 54 patients(36.2%)showed granulomatous inflammation with/without *** these,51 patients(94.4%)were confirmed to have TB as per pre-defined *** with TB were more likely to have hypoechoic and matted nodes[40 patients(67.7%)].EUS-FNA/B was found to have a sensitivity and specificity of 86%and 93%respectively,with a diagnostic accuracy of 88%in the evaluation of intra-abdominal lymphadenopathy due to *** EUS-FNA/B has a high diagnostic yield with a good sensitivity and specificity in the evaluation of intra-abdominal lymphadenopathy due to ***,the validity of these findings in populations with low prevalence of TB needs further evaluation.

关键词： Endoscopic ultrasound Lymph nodes Tuberculosis mesenteric Intraabdominal