Efficacy, tolerability and safety of intravenous iron sucrose in postpartum anaemia

Background: Anemia is one of major contributing factor in maternal mortality and morbidity in third world countries and according to the WHO, contributes to 40% maternal deaths. Postpartum anemia is observed in up to 27% of women.It is a common problem throughout the world. Treatment of postpartum iron deficiency anemia includes oral and parenteral iron supplmentaion as well as blood transfusion in severe cases. Methods: This was a prospective longitudinal study carried out in Department of Obstetrics & Gynaecology of PRH, Loni. Total 80 women suffering from postpartum anemia of age above 18 years with haemoglobin (HB) level below 11gm/dl and above 6gm/dl were included for the study. After history taking, clinical examination and baseline Hb level, all of them were administered intravenous iron sucrose 200 mg per dose per day till the total calculated dose was administered. The post therapy evaluation was done with the estimation of Hb on day 1, day 7, day 14 and day 21. Results: 31.25% women belonged to the age group each of 19-21 years and 22-24 years. Maximum number of patients received 3 doses of IV Iron sucrose (i.e. total 600mg) followed by 2 doses (i.e. total 400mg), 4 doses (i.e. total 800mg) and 5 doses (i.e. total 1000mg) respectively. Hb level rises extremely significantly (p<0.001) after IV Iron Sucrose administration on day 1, 7, 14 & 21 as compared to corresponding values before delivery as analyzed by Friedman Test (Nonparametric Repeated Measures ANOVA) . 16 patients (20%) experienced thrombophlebitis to IV Iron Sucrose administration. About 12 (15%) patients experienced rigor followed by sweating in 10 patients (12.5%) and fever in 8 patients (10%). About 62 patients (77.5%) from total 80 reported well tolerability to IV Iron Sucrose while remaining 18 patients (22.5%) reported poor tolerability to IV Iron Sucrose Conclusion: Intravenous iron sucrose increases the haemoglobin more rapidly in first week as compared to second and third week in women with postpartum iron deficiency anemia. Hypersensitivity reaction, chest pain, dyspnoea reported with iron dextran and iron sorbitol citric acid were not observed with iron sucrose. Intravenous iron sucrose can be used safely to fill a rift between blood transfusion and oral iron in treatment of postpartum iron deficiency anemia

Efficacy, tolerability and safety of intravenous iron sucrose in postpartum anaemia

Background: Anemia is one of major contributing factor in maternal mortality and morbidity in third world countries and according to the WHO, contributes to 40% maternal deaths. Postpartum anemia is observed in up to 27% of women.It is a common problem throughout the world. Treatment of postpartum iron deficiency anemia includes oral and parenteral iron supplmentaion as well as blood transfusion in severe cases. Methods: This was a prospective longitudinal study carried out in Department of Obstetrics & Gynaecology of PRH, Loni. Total 80 women suffering from postpartum anemia of age above 18 years with haemoglobin (HB) level below 11gm/dl and above 6gm/dl were included for the study. After history taking, clinical examination and baseline Hb level, all of them were administered intravenous iron sucrose 200 mg per dose per day till the total calculated dose was administered. The post therapy evaluation was done with the estimation of Hb on day 1, day 7, day 14 and day 21. Results: 31.25% women belonged to the age group each of 19-21 years and 22-24 years. Maximum number of patients received 3 doses of IV Iron sucrose (i.e. total 600mg) followed by 2 doses (i.e. total 400mg), 4 doses (i.e. total 800mg) and 5 doses (i.e. total 1000mg) respectively. Hb level rises extremely significantly (p<0.001) after IV Iron Sucrose administration on day 1, 7, 14 & 21 as compared to corresponding values before delivery as analyzed by Friedman Test (Nonparametric Repeated Measures ANOVA) . 16 patients (20%) experienced thrombophlebitis to IV Iron Sucrose administration. About 12 (15%) patients experienced rigor followed by sweating in 10 patients (12.5%) and fever in 8 patients (10%). About 62 patients (77.5%) from total 80 reported well tolerability to IV Iron Sucrose while remaining 18 patients (22.5%) reported poor tolerability to IV Iron Sucrose Conclusion: Intravenous iron sucrose increases the haemoglobin more rapidly in first week as compared to second and third week in women with postpartum iron deficiency anemia. Hypersensitivity reaction, chest pain, dyspnoea reported with iron dextran and iron sorbitol citric acid were not observed with iron sucrose. Intravenous iron sucrose can be used safely to fill a rift between blood transfusion and oral iron in treatment of postpartum iron deficiency anemia

SYNTHESIS, CHARACTERIZATION AND QUANTITATION OF REGIOISOMERIC IMPURITY IN NIMODIPINE BULK AND FORMULATION

Objective: The present research work was directed towards the synthesis characterization and quantitation of regioisomeric impurity of Nimodipine i.e. diethyl 1, 4-dihydro-2,6-dimethyl pyridine dicarboxylate in bulk and tablet formulation, by UV,IR,NMR and GC-MS techniques and a RP-HPLC method was developed as per ICH Q2B guidelines for quantitation of 1, 4-Dihydro-2, 6-Dimethyl-4-(p-nitro phenyl) pyridine-3,5 dicarboxylate (NI) from bulk and formulation. Methods: The synthesis of NI was carried out by Hantzch pyridine synthesis, by using p-nitrobenzaldehyde, ethylacetoacetate, in presence of ammonia and methanol as a catalyst. The percentage yield was found to be 89.29%. Recrystallization and purification of NI was done. The preliminary evaluation was done on laboratory scale via melting point, elemental analysis and TLC. Results: The melting point of impurity was found to be 156-1580C. The TLC of impurity was carried by using Chloroform: Methanol (9:1) and the Rf was found to be 0.79. The confirmation of structure of NI was carried out by using sophisticated techniques i.e., FT-IR, NMR (13C and 1H), GC-MS etc. The RP-HPLC method was developed to quantify the NI in Nimodipine bulk and formulation as per ICH Q2B guidelines. The method validation was done as per ICH guidelines. Conclusion: The validated optimized method was found to be linear, précised, robust, rugged and accurate. Finally NI was quantified from bulk Nimodipine and its marketed tablet formulation. It was concluded that the amount of NI, present in tablet was found to be 0.1% and in the bulk 0.067% respectively. Thus it was revealed that the NI was found to be within the limit laid down ICH guidelines (Not more than 0.1 %)

Expression of Developmentally Important Axon Guidance Cues in the Adult Optic Chiasm.

Funder: Wellcome TrustPURPOSE: Regeneration of optic nerve axons after injury can be facilitated by several approaches, but misguidance at the optic chiasm is often observed. We characterized guidance cues in the embryonic visual system and adult optic chiasm before and after optic nerve crush (ONC) injury to better understand barriers to optic nerve regeneration in adults. METHODS: Radial glial (RC2/BLBP/Slit1), developmental (Pax2) and extracellular markers (CSPG: H2B/CS-56) were assessed in C57BL/6J mice by immunohistochemistry. RC2, BLBP, Slit1, and CSPG are known inhibitory guidance cues while Pax2 is a permissive guidance cue. RESULTS: At embryonic day 15.5 (E.15.5), RC2 and BLBP were identified superior to, and extending through, the optic chiasm. The optic chiasm was BLBP-ve in adult uninjured mice but BLBP+ve in adult mice 10 days after ONC injury. The reverse was true for RC2. Both BLBP and RC2 were absent in adult mice 6 weeks post-ONC. Slit1 was present in the optic chiasm midline and optic tracts in embryonic samples but was absent in uninjured adult tissue. Slit1 was observed superior to and at the midline of the optic chiasm 10 days post-ONC but absent 6 weeks after injury. Pax2 was expressed at the junction between the optic nerve and optic chiasm in embryonic brain tissue. In embryonic sections, CS-56 was observed at the junction between the optic chiasm and optic tract, and immediately superior to the optic chiasm. Both 2H6 and CS-56 staining was absent in uninjured and ONC-injured adult brains. CONCLUSION: Differences in guidance cue expression during development, in adulthood and after injury may contribute to misguidance of regenerating RGC axons in the adult optic chiasm

PI 3-kinase delta enhances axonal PIP3 to support axon regeneration in the adult CNS

Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol(3,4,5)-trisphosphate (PIP3). We demonstrate that adult PNS neurons utilise two catalytic subunits of PI3K for axon regeneration: p110α and p110δ. However in the CNS, axonal PIP3 decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110α in CNS neurons had no effect, however expression of p110δ restored axonal PIP3 and increased regenerative axon transport. p110δ expression enhanced CNS regeneration in both rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110α. Furthermore, viral delivery of p110δ promoted robust regeneration after optic nerve injury. These findings establish a deficit of axonal PIP3 as a key reason for intrinsic regeneration failure and demonstrate that native p110δ facilitates axon regeneration by functioning in a hyperactive fashion

Spatiotemporal Characterization of Neural Network Activity

Uncovering information hidden within brain networks can be a daunting task, especially in the cases of abnormal, disrupted neural networks, such as epilepsy. Here, I present a multifaceted approach that combines signal processing, computational neuroscience, and theoretical and mathematical modeling to investigate the mechanisms and structure that underlie neuronal activity in both time and space. First, we show that there is a mathematical symmetry in the temporal and spatial domains if the spike-centered averages (a novel second-order metric of the action potential spike-LFP relationship) resemble sinc functions in human focal seizures. We then advance network analysis by presenting a novel approach to characterize neural networks using third-order motifs, which are sufficient to completely and uniquely characterize networks in both time and space. Furthermore, these third-order motifs are classified according to their sequencing depending on the combination of up to two lags in time and space, yielding fourteen qualitatively distinct motif classes that can embody well-studied neural network properties, such as synchrony, feedback, divergence, and convergence. Building from triple correlation, I then develop a novel quantitative metric that captures overall network activity: the 4D entropy based on the spatiotemporal lag distribution computed from triple correlation. Applying this metric to rat cortical cultures from microelectrode arrays, I demonstrate the enhanced value of 4D entropy, which is based on third-order structure, in that it captures the underlying dynamics in comparison to 2D, or pairwise, entropy. Lastly, I develop and implement a Hodgkin-Huxley simulation of excitatory-inhibitory population activity to model the first three stages of a focal seizure and use triple correlation to show that the network represented by the model is a good fit for the network of the patient data

Third-order motifs are sufficient to fully and uniquely characterize spatiotemporal neural network activity

Neuroscientific analyses balance between capturing the brain’s complexity and expressing that complexity in meaningful and understandable ways. Here we present a novel approach that fully characterizes neural network activity and does so by uniquely transforming raw signals into easily interpretable and biologically relevant metrics of network behavior. We first prove that third-order (triple) correlation describes network activity in its entirety using the triple correlation uniqueness theorem. Triple correlation quantifies the relationships among three events separated by spatial and temporal lags, which are triplet motifs. Classifying these motifs by their event sequencing leads to fourteen qualitatively distinct motif classes that embody well-studied network behaviors including synchrony, feedback, feedforward, convergence, and divergence. Within these motif classes, the summed triple correlations provide novel metrics of network behavior, as well as being inclusive of commonly used analyses. We demonstrate the power of this approach on a range of networks with increasingly obscured signals, from ideal noiseless simulations to noisy experimental data. This approach can be easily applied to any recording modality, so existing neural datasets are ripe for reanalysis. Triple correlation is an accessible signal processing tool with a solid theoretical foundation capable of revealing previously elusive information within recordings of neural networks