Effect of ondansetron on sensory level produced by intrathecal bupivacaine

Background: For spinal anesthesia there are drugs which can increase the level and quality of analgesia. Any drug which decreases sensory block level in spinal anesthesia is of great concern as it may need analgesic, sedative, supplement or even conversion to general anesthesia. Ondansetron is one such drug which has been reported to decrease the height of sensory block achieved after subarachnoid administration of bupivacaine. In this prospective observational study, we studied the effect of administration of ondansetron on the level of the sensory block achieved after subarachnoid blockade.Methods: In Group II, 4 mg ondansetron was given and 15 mins before giving spinal anesthesia Group II against control group receiving 2 ml saline intravenous (Group I). 15 mins before giving spinal anesthesia. Both groups received 3.5 ml of bupivacaine heavy was given intrathecally. Sensory and motor block was assessed 5, 15, and 30 mins. We analyzed both highest spinal block level achieved and time to regress to L1 level.Results: We found that in Group II both highest level of sensory block (T6 by median method) duration to regress to L1 level (1.43±0.22 hrs) was lesser as compared to group I and Group III T4 by median method and time to regress from T6 to L1 Group I 2.03±0.06 hrs Group III 1.84±0.27 hrs. Motor block did not differ between groups.Conclusions: We concluded that probably ondansetron was responsible for lower spinal block level and early recovery from spinal anesthesia after intrathecal bupivacaine and should not be given empirically for nausea and vomiting

Multi Party Distributed Private Matching, Set Disjointness and Cardinality Set Intersection with Information Theoretic Security

In this paper, we focus on the specific problems of Private Matching, Set Disjointness and Cardinality Set Intersection in information theoretic settings. Specifically, we give perfectly secure protocols for the above problems in n party settings, tolerating a computational ly unbounded semi-honest adversary, who can passively corrupt at most t < n/2 parties. To the best of our knowledge, these are the first such information theoretically secure protocols in a multi-party setting for all three problems. Previous solutions for Distributed Private Matching and Cardinality Set Intersection were cryptographical ly secure and the previous Set Disjointness solution, though information theoretically secure, is in a two party setting. We also propose a new model for Distributed Private matching which is relevant in a multi-party setting

The importance of metal binding in metalloprotein inhibitors

The development of novel and selective full-length inhibitors against medicinally relevant zinc metalloenzymes has been described. The diversity of zinc metalloenzymes described range from those present in humans to bacteria to viruses. The dissertation will first focus on the development of selective inhibitors against matrix metalloproteinases (MMPs). MMPs are Zn²⁺ hydrolytic enzymes that are present in vertebrates, invertebrates and even plants. They are responsible for the cleavage of the extracellular matrix, and this study demonstrates the importance the zinc-binding group (ZBG) plays in developing inhibitors that are selective against different MMP isoforms. The selectivity obtained from the (O,O) chelating MMP inhibitors (MMPi) was very interesting; considering the active site of MMPs are highly homologous with a conserved Zn²⁺ metal cofactor bound by three histidine residues within a conserved HEXGHXXGXXH metal binding motif. In Chapter 3, the development of full length metalloprotein inhibitors is expanded beyond MMP isoform selectivity to selectivity against another Zn²⁺ endopeptidase, Anthrax lethal factor (LF). This study shows that the potent (O,O) containing MMPi show no inhibition against LF. The bis-histidine and glutamate coordinated catalytic Zn²⁺ in LF favors the softer (O,S) donor ligands. In addition a backbone and linker SAR study shows that a thioamide linkage instead of the traditional amide linkage for backbone attachment introduces a hydrogen bond within the LF active site to enhance potency of the studied inhibitors. Chapter 4 introduces the relatively novel approach of fragment-based lead design (FBLD) in the lab toward the microwave assisted rapid synthesis of a 87-component chelator fragment library that showed potent hits with good ligand efficiencies (LEs) against both MMPs and LF. The final chapter culminates with the study of an entirely new metalloenzyme Human Immunodeficiency Virus Integrase (HIV-IN). As opposed to the mononuclear Zn²⁺ endopeptidases MMPs and LF, HIV-IN is a dinuclear Mg²⁺ endonuclease and preliminary studies show that inhibitors developed against MMPs and LF show submicromolar potencies against this structurally different metalloenzyme. Based on these results, novel HIV -IN inhibitors (HIV-INi) were generated to study the effects of different tris-chelating metal binding groups (MBGs) on this enzyme, while maintaining a constant backbon

The importance of metal binding in metalloprotein inhibitors

The development of novel and selective full-length inhibitors against medicinally relevant zinc metalloenzymes has been described. The diversity of zinc metalloenzymes described range from those present in humans to bacteria to viruses. The dissertation will first focus on the development of selective inhibitors against matrix metalloproteinases (MMPs). MMPs are Zn²⁺ hydrolytic enzymes that are present in vertebrates, invertebrates and even plants. They are responsible for the cleavage of the extracellular matrix, and this study demonstrates the importance the zinc-binding group (ZBG) plays in developing inhibitors that are selective against different MMP isoforms. The selectivity obtained from the (O,O) chelating MMP inhibitors (MMPi) was very interesting; considering the active site of MMPs are highly homologous with a conserved Zn²⁺ metal cofactor bound by three histidine residues within a conserved HEXGHXXGXXH metal binding motif. In Chapter 3, the development of full length metalloprotein inhibitors is expanded beyond MMP isoform selectivity to selectivity against another Zn²⁺ endopeptidase, Anthrax lethal factor (LF). This study shows that the potent (O,O) containing MMPi show no inhibition against LF. The bis-histidine and glutamate coordinated catalytic Zn²⁺ in LF favors the softer (O,S) donor ligands. In addition a backbone and linker SAR study shows that a thioamide linkage instead of the traditional amide linkage for backbone attachment introduces a hydrogen bond within the LF active site to enhance potency of the studied inhibitors. Chapter 4 introduces the relatively novel approach of fragment-based lead design (FBLD) in the lab toward the microwave assisted rapid synthesis of a 87-component chelator fragment library that showed potent hits with good ligand efficiencies (LEs) against both MMPs and LF. The final chapter culminates with the study of an entirely new metalloenzyme Human Immunodeficiency Virus Integrase (HIV-IN). As opposed to the mononuclear Zn²⁺ endopeptidases MMPs and LF, HIV-IN is a dinuclear Mg²⁺ endonuclease and preliminary studies show that inhibitors developed against MMPs and LF show submicromolar potencies against this structurally different metalloenzyme. Based on these results, novel HIV -IN inhibitors (HIV-INi) were generated to study the effects of different tris-chelating metal binding groups (MBGs) on this enzyme, while maintaining a constant backbon