Development of novel fluorine-18 labeled PET radioligands for monoamine oxidase B (MAO-B)

Monoamine oxidases (MAO-A and MAO-B) are important enzymes regulating the levels of monoaminergic neurotransmitters. Selectiv e and irreversible MAO-B inhibitors such as L -deprenyl and rasagiline are clinically used for the t reatment of psychiatric and neurological disorders. Positron em ission tomography (PET) is a non- invasive imaging technique which has widely been util ized to visualize the localization of MAO-B in monkey and human brains and thereby has b een useful for studying neurodegenerative diseases and epilepsy. This thesi s deals with the synthesis and evaluation of novel fluorine-18 labeled PET radioligan ds for detection of MAO-B activity. The present thesis demonstrates that nine fluorinat ed propargyl amines were synthesized and tested for inhibition of MAO-B. In o rder to label those compounds with fluorine-18 seven chloro-precursors and two sulph amidate-precursors were also synthesized by multi step organic synthesis. Radiola beling of six chloro-precursors with fluorine-18 was accomplished by a one-step nucl eophilic substitution reaction. Radiolabeling of two sulphamidate-precursors with fl uorine-18 was performed in two steps, compromising a nucleophilic substitution foll owed by the removal of the protecting group. The incorporation yield of the fluo rination reactions varied from 40- 70%. The radiochemical purity was >99% and the specif ic radioactivities were in a range of 190-240 GBq/μmol at the time of administrat ion. In vitro MAO inhibition and/or autoradiography (ARG) experimen ts demonstrated a high selectivity for MAO-B over MAO-A for five of the compounds namely [ 18 F]fluorodeprenyl, [ 18 F]fluororasagiline, [ 18 F]fluoro- N ,4-dimethyl- N -(prop-2-ynyl) pentan-2-amine, [ 18 F]fluorodeprenyl-D 2 and [ 18 F]fluororasagiline-D 2 . All five compounds were examined by PET and showed a high initial brain uptake in known MAO-B rich regions in cynomolgus monkey. [ 18 F]Fluorodeprenyl showed a kinetic behavior similar to [ 11 C]deprenyl where its fast irreversible binding to th e enzyme renders the distribution of this radioligand in tissue limited by blood flow rather than the MAO-B enzyme concentration. [ 18 F]Fluororasagiline and [ 18 F]fluoro- N ,4-dimethyl- N -(prop-2-ynyl)pentan-2-amine showed continuous increase of the radioactivity throughout the PET measurement that might be an indic ation of a blood-brain barrier penetrating radiometabolite which might in turn compl icate a reliable quantification. Only [ 18 F]fluorodeprenyl-D 2 and [ 18 F]fluororasagiline-D 2 showed fast wash-out from the brain and less accumulation in cortical and sub- cortical regions. Radiometabolite studies demonstrated that both deuterated analogues were more stable measured in monkey plasma when compared to the non-deuterated a nalogues. These results together suggest that both [ 18 F]fluorodeprenyl-D 2 and [ 18 F]fluororasagiline-D 2 may be improved PET radioligands and potential mole cular imaging biomarker candidates for PET studies in neuroi nflammation and neurodegeneration, accompanied with astrocyte activat ion

Research In Library Herald During 2017-2021 : A Bibliometric Analysis

Bibliometric analysis of research papers, articles, etc., has gained increasing importance in Library and Information Science to analyze the publication patterns, authorship patterns, and citation patterns of research papers published within a defined period. Bibliometric analysis is essential for library professionals in the collection development process. This paper intends to analyze the articles published in the journal \u27Library Herald\u27 from 2017 to 2021 with the help of different statistical tools and techniques. The results indicate most of the contributions by two authors and one article by six authors and the overall degree of collaboration among authors is 0.62. The study highlights the volume-wise distribution of articles, authorship pattern, Degree of collaboration, keyword use pattern, length of articles, and geographical distribution of authors

Results of emergency management of acute abdomen in adults based on clinical assessment and basic imaging investigations: are advanced imaging techniques always necessary for successful treatment?

Background:The term acute abdomen refers to signs and symptoms of abdominal pain and tenderness, a clinical presentation that may require emergency surgical treatment. Patients suffering from both, surgical as well as medical diseases may present with acute abdomen. The main objectives of the study are to identify common causes of acute abdomen, to assess the need for urgent surgical intervention in these patients and to evaluate role of basic diagnostic techniques and need of advanced imaging studies. Methods: Forty patients with acute onset abdominal pain were included in the study. Patients with pain related to pregnancy, trauma and pediatric age group were excluded from the study. All patients were subjected to detailed history and clinical examination, X-ray abdomen in erect position and ultrasound examination of the abdomen and pelvis. CECT of abdomen and pelvis was performed only when there were diagnostic difficulties and for deciding about need for surgical intervention. Results: Out of 40, fifteen (37.5%) patients required surgery within 24 hours and 14 (35%) patients underwent elective surgery after emergency treatment. Eleven (27.5%) patients were managed conservatively. Conclusion: Study shows that the commonest causes for acute abdomen are acute appendicitis and cholelithiasis with /without cholecystitis. Almost 1/3rd of the patients required emergency surgery. And CECT of abdomen and pelvis was helpful in decision making between conservative and surgical management of acute abdomen in selected cases

Impact of Ammonium Based Ionic Liquids on the Conformation of Bovine serum albumin (BSA)

In this study, impact of different ammonium based ionic liquids on the structure of Bovine serum albumin (BSA) was investigated by different spectroscopic methods like, UV-vis, fluorescence and CD spectroscopy. Fluorescence results reveal that the ILs has no significant impact on the environment of tryptophan residues. From the Far-UV CD results, it was observed that these ILs increase the α-helicity of the protein, BSA. Near-UV CD study confirms the fluorescence results whereas it shows the alteration of tertiary structure of BSA especially around disulphide bonds

Probing the interplay between surface and bulk states in the topological Kondo insulator SmB6_6 through conductance fluctuation spectroscopy

We present results of resistance fluctuation spectroscopy on single crystals of the predicted Kondo topological insulator material SmB$_6$. Our measurements show that at low temperatures, transport in this system takes place only through surface states. The measured noise in this temperature range arises due to Universal Conductance Fluctuations whose statistics was found to be consistent with theoretical predictions for that of two-dimensional systems in the Symplectic symmetry class. At higher temperatures, we find signatures of glassy dynamics and establish that the measured noise is caused by mobility fluctuations in the bulk. We find that, unlike the topological insulators of the dichalcogenide family, the noise in surface and bulk conduction channels in SmB$_6$ are completely uncorrelated. Our measurements establish that at sufficiently low temperatures, the bulk has no discernible contribution to electrical transport in SmB$_6$ making it an ideal platform for probing the physics of topological surface states.Comment: 9 pages, 11 figure

CARBAMAZEPINE INDUCED HYPERSENSITIVITY SYNDROME- A CASE REPORT

Anti-convulsant drugs elicited hypersensitivity syndrome could be a rare side effect of the primary line anticonvulsive medication like carbamazepine and alternative aromatic agents. We here mention a rare case of gastrointestinal and skin findings associated with carbamazepine administration that is incredibly uncommon and desires to be reportable.We report a study done on a 22-year woman with carbamazepine associated hypersensitivity syndrome, who developed diarrhea, fever and skin lesions. On withdrawal of carbamazepine and administration of methylprednisolone in the patient, all initial skin related symptoms, GIT symptoms were relieved and white blood corpuscle count normalized. Anticonvulsive drug hypersensitivity syndromes can present with a wide spectrum of unspecific symptoms, which the prescribing clinician should be aware of