A comparative study of oral versus intravenous iron in the treatment of moderately anaemic pregnant women

Background: Anemia, the decrease of haemoglobin (Hb) concentration is a common disorder complicating pregnancy mostly due to hemodilution, increased demand of iron and poor dietary intake of iron. The aim of this study was to evaluate whether parenteral iron sucrose can be used as an alternative to daily oral iron during pregnancy.Methods: It was a prospective interventional study conducted in the Department of Obstetrics and Gynaecology, Rohilkhand Medical College and Hospital, Bareilly involving pregnant women at 16-24 weeks with Hb 7-10 g/dl. They were randomly allocated to two groups I and II. Group I (oral group) was given oral iron tablets containing 100 mg of elemental iron and 0.5 mg of folic acid as per therapeutic requirement. Group II (parenteral group) were admitted as day care patients and given a total calculated dose of iron sucrose in divided doses of 200 mg each in 100 ml of normal saline as slow intravenous infusion. Hb, packed cell volume (PCV), blood indices were measured at the start, 2 weeks and 4 weeks of treatment. Any side-effects of treatment were also studied.Results: A statistically significant increase in values of Hb, hematocrit, reticulocyte count, red blood cells (RBC's) indices: mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular hemoglobin (MCH) coupled with no serious side effects with iron sucrose as compared with oral iron.Conclusions: Intravenous iron sucrose complex is safe, convenient and effective alternative to oral iron for treatment of iron deficiency anemia in pregnancy

A comparative study on the effect of intravenous Ringer lactate at 125 ml/hour versus 250 ml/hour on the duration of labour in nulliparous pregnant women

Background: Several factors may influence the progression of normal labour. It has been postulated that the routine administration of intravenous fluids to keep women adequately hydrated during labour may reduce the period of contraction and relaxation of the uterine muscle, and may ultimately reduce the duration of the labour. However, the routine administration of intravenous fluids to labouring women has not been adequately studied although it is widely practiced, and there is no consensus on the type or volume of fluids that are required, or indeed, whether intravenous fluids are at all necessary. This study was conducted to study the effect of intravenous Ringer lactate at 125 ml/hour versus 250 ml/hour on the duration of labour. Methods: In the study, patients were divided in two groups of nulliparous pregnant women in spontaneous early labour (between 3-5 cm dilatation), at term with singleton pregnancy and cephalic presentation, where one group received intravenous Ringer lactate at 125 ml/hour and the other group received Ringer lactate at 250 ml/hour. The duration of labour, mode of delivery and caesarean rates were measured in both groups along with incidence of prolonged labour and need for oxytocin augmentation. Results: The incidence of prolonged labour and oxytocin augmentation were less in the group receiving intravenous RL at 250 ml/hour but was not statistically significant. Remaining outcomes were comparable in both the groups with no outcome reaching statistical significance. Conclusions: Rate of fluid administration is one of the many variables which affects the labour outcomes. The incidence of prolonged labour and oxytocin augmentation was less in the group which received intravenous RL 250 ml/hour. There was no statistically significant difference in both groups in respect of duration of labour, mode of delivery and caesarean rates

A Comparative Study on Class Characteristics of Devanãgri Script Writers from Three Different States of India

India is a multilingual country. Hindi is the national language of India and Devanãgri script is used to write Hindi language. Various documents with legal value are made in Devanãgri script, which may be questioned for their authenticity and authorship. Sufficient research has been done and reported about different scripts. However, researches based on Devanãgri script are limited. This study focuses on finding the significant class characteristics of writers from three different states of India, namely, Bihar, Madhya Pradesh and Punjab. The data was also statistically analysed using Pearson’s Chi-Square test for its significance. Handwriting samples from 300 subjects were collected from three different states of India to analyze various class characteristics in Devanãgri script. The samples were examined qualitatively and statistically. Various general characteristics were selected for the analysis and characteristic features were tabulated after qualitative examination. Statistical analysis showed that the data was statistically significant. The general characteristics selected for the analysis and comparison of the handwriting samples in Devanãgri script were found to be significant. The impact of regional scripts on the Devanãgri script should be performed, as the influence of regional language could be seen in the samples collected from Punjab

A Small Molecule Swertisin from Enicostemma littorale

Aim. Stem cell therapy is one of the upcoming therapies for the treatment of diabetes. Discovery of potent differentiating agents is a prerequisite for increasing islet mass. The present study is an attempt to screen the potential of novel small biomolecules for their differentiating property into pancreatic islet cells using NIH3T3, as representative of extra pancreatic stem cells/progenitors. Methods. To identify new agents that stimulate islet differentiation, we screened various compounds isolated from Enicostemma littorale using NIH3T3 cells and morphological changes were observed. Characterization was performed by semiquantitative RT-PCR, Q-PCR, immunocytochemistry, immunoblotting, and insulin secretion assay for functional response in newly generated islet-like cell clusters (ILCC). Reversal of hyperglycemia was monitored after transplanting ILCC in STZ-induced diabetic mice. Results. Among various compounds tested, swertisin, an isolated flavonoid, was the most effective in differentiating NIH3T3 into endocrine cells. Swertisin efficiently changed the morphology of NIH3T3 cells from fibroblastic to round aggregate cell cluster in huge numbers. Dithizone (DTZ) stain primarily confirmed differentiation and gene expression studies signified rapid onset of differentiation signaling cascade in swertisin-induced ILCC. Molecular imaging and immunoblotting further confirmed presence of islet specific proteins. Moreover, glucose induced insulin release (in vitro) and decreased fasting blood glucose (FBG) (in vivo) in transplanted diabetic BALB/c mice depicted functional maturity of ILCC. Insulin and glucagon expression in excised islet grafts illustrated survival and functional integrity. Conclusions. Rapid induction for islet differentiation by swertisin, a novel herbal biomolecule, provides low cost and readily available differentiating agent that can be translated as a therapeutic tool for effective treatment in diabetes

Differentiation of mouse intra-islet progenitor cells and immunoblotting of key transcription factors and islet markers under differentiation with activin, swertisin and presence of p-38 MAPK inhibitor.

<p>(A) depicts mIP cells cultured in complete media at day 0 which were then subjected to differentiation using activin-A and swertisin for 10 days. Bright field image shows, cells under differentiation on 8^th day at 20X magnification, and dithizone stained clusters on day 10^th. A fluorescent image represents immunostaining for insulin (green) and glucagon (red) in clusters from SFM/ITS, activin-a and swertisin groups. DAPI was used as nuclear stain. (B) shows immunoblotting of E-cadherin, N-cadherin, Ngn-3, P-p38, Native p-38 MAP kinase pathway proteins in presence and absence of MAP kinase pathway inhibitor SB203580. Ponceau S stain blot was shown as loading control. (C) shows immunoblotting of key differentiation pathway parameters that indicate the conversion of Mouse intra-islet progenitor cells into islet like clusters. Key transcription factors and MAP Kinase pathway proteins like P-p38, Erk1/2 Ngn-3, Pax-4, and Smad proteins under differentiation were monitored. Beta actin was used as loading control.</p

Swertisin an Anti-Diabetic Compound Facilitate Islet Neogenesis from Pancreatic Stem/Progenitor Cells <i>via</i> p-38 MAP Kinase-SMAD Pathway: An <i>In-Vitro</i> and <i>In-Vivo</i> Study

<div><p>Transplanting islets serves best option for restoring lost beta cell mass and function. Small bio-chemical agents do have the potential to generate new islets mass, however lack of understanding about mechanistic action of these small molecules eventually restricts their use in cell-based therapies for diabetes. We recently reported “Swertisin” as a novel islet differentiation inducer, generating new beta cells mass more effectively. Henceforth, in the present study we attempted to investigate the molecular signals that Swertisin generate for promoting differentiation of pancreatic progenitors into islet cells. To begin with, both human pancreatic progenitors (PANC-1 cells) and primary cultured mouse intra-islet progenitor cells (mIPC) were used and tested for Swertisin induced islet neogenesis mechanism, by monitoring immunoblot profile of key transcription factors in time dependent manner. We observed Swertisin follow Activin-A mediated MEPK-TKK pathway involving role of p38 MAPK via activating Neurogenin-3 (Ngn-3) and Smad Proteins cascade. This MAP Kinase intervention in differentiation of cells was confirmed using strong pharmacological inhibitor of p38 MAPK (SB203580), which effectively abrogated this process. We further confirmed this mechanism in-vivo in partial pancreatectomised (PPx) mice model, where we could show Swertisin exerted potential increase in insulin transcript levels with persistent down-regulation of progenitor markers like Nestin, Ngn-3 and Pancreatic Duodenal Homeobox Gene-1 (PDX-1) expression, within three days post PPx. With detailed molecular investigations here in, we first time report the molecular mode of action of Swertisin for islet neogenesis mediated through MAP Kinase (MEPK-TKK) pathway involving Ngn-3 and Smad transcriptional regulation. These findings held importance for developing Swertisin as potent pharmacological drug candidate for effective and endogenous differentiation of islets in cell based therapy for diabetes.</p></div

Proposed Mechanism of action of Swertisin mediated Islet Differentiation.

<p>Panel shows proposed mechanistic action pathway for islet neogenesis being followed by Swertisin for new islet cell differentiation.</p

Time course protein profiling and Fate of islet differentiation of Swertisin induced islet differentiation pathway from PANC-1 cells.

<p>(A) represents immunoblotting of key parameters that indicate the movement of PANC-1 cells from precursor cells to endocrine islet-like cells, such as stem cell marker Nestin, pancreatic endocrine islet markers Ngn-3 and PDX-1. The activation of p38 MAP kinase to form phospho-P38 and replication marker Ki-67. Protein expression was quantified densitometrically from three independent experiment and expressed as Mean±SEM. *** shows p value <0.001 Vs Panc-1 undifferentiated cells and SFM/ITS. Immunoblotting of E cadherin and N Cadherin demonstrating fate of islet differentiation from undifferentiated PANC-1 cells to endocrine islet-like cells. Graph represents ratio of N-cadherin to E-cadherin depicting transition from precursor sate to differentiated state. Protein expression was quantified densitometrically from three independent experiments and expressed as Mean±SEM. (B) demonstrate characterization of Swertisin induced formation of islet-like clusters from PANC-1 cells in ten days time course. In this experiment shown, cells were harvested each day till ten days and immunoblotted for key parameters that indicate the movement of PANC-1 cells from precursor cells to endocrine islet-like cells in time dependent manner. Cells from control SFM/ITS and Swertisin, harvested from day 1 to 10 were probed for nestin, Ngn-3 PDX-1, phospho-P38 and E-cadherin. (C) shows short-term time course for key proteins implicated in islet differentiation pathway from Swertisin induced clusters. Immunoblotting of nestin, phospo-P38 and Ngn-3 in short-time course manner at 1, 3, 6, and 9 hours induction was performed. Lower images represent graphical representation of movement of protein expression in each group during 1 to 9 hours.</p

Insulin fluorescence and Insulin content per unit cytoplasm quantification in Swertisin induced islet-like clusters derived from PANC-1 cells with activin-A and MAPKinase Inhibitor.

<p>(A) shows fluorescent images for insulin expression in islet differentiation pathway inhibited using p38 MAP kinase inhibitor SB-203580 added in conjunction with Swertisin throughout ten days. The islet-like clusters were immunostained for insulin (green) on 10^th day. Nuclear DNA was stained with DAPI (blue). (B) represents insulin content in islet like clusters after p-30 MAPK pathway inhibition. Graph represents insulin fluorescence quantification per unit cytoplasm in differentiated cells with and without inhibition of MAPK pathway using p38 MAP kinase inhibitor SB-203580 added in conjunction with Swertisin throughout ten days. Data is represented as Mean±SEM. *** and ** shows p value <0.001 and 0.01 Vs Activin-A and Swertisin alone groups respectively.</p

In-vivo analysis of molecular mechanism by Swertisin differentiation in Ppx mice model.

<p>(A) confocal images from regenerating pancreas for assessment of various islet transcription factors and signaling proteins of TGF-beta pathway from tissue of Ppx sham and Swertisin treated animals. Various markers like Ki67, Nestin, Ngn-3, CK19, p-smad-2, Smad-7, Insulin and Ck-19 were probed and analyzed. (B) showed western blot profile of stem cell markers, key transcription factors in islet differentiation pathway and cell death markers in PPx Sham and Swertisin treated animal pancreatic tissues.</p