erbBGenes in the Mouse Uterus: Cell-Specific Signaling by Epidermal Growth Factor (EGF) Family of Growth Factors during Implantation

AbstractWe previously described spatiotemporal expression of various epidermal growth factor (EGF)-like ligands and receptor subtypes, ErbB1 and ErbB2, during the peri-implantation period. To better understand the roles of these ligands and their possible signaling schemes in implantation, it is important to define the status of all the ligands and receptor subtypes in the uterus/embryo. No information is available about uterine and embryonic status of ErbB3 or ErbB4 during implantation. We cloned mouseerbB3anderbB4cDNAs and examined their expression and bioactivity in the peri-implantation uterus (days 1–8). TwoerbB3(cytoplasmic and extracellular) and threeerbB4(two cytoplasmic and one extracellular) clones were generated. Both forms of theerbB3clone showed similar transcript profiles, while different transcript profiles were obtained witherbB4clones. The steady-state levels oferbB3anderbB4mRNAs in whole uterine poly(A)+RNA samples showed little changes during the peri-implantation period, while their unique cell-specific accumulation was noted.erbB3is predominantly expressed in the epithelial cells, although decidual and embryonic cells also accumulate this mRNA. In contrast, theerbB4mRNA is primarily expressed in the submyometrial stroma and myometrial connective tissues during this period. Additionally, the extracellular form of theerbB4clone detected signals in a subpopulation of stromal cells. Autophosphorylation and immunoprecipitation studies provided evidence that uterine ErbB3 and ErbB4 are biologically active. This study provides a comprehensive analysis of possible ligand–receptor signaling schemes for EGF-like ligands in implantation

FORMULATION AND IN VITRO EVALUATION OF OIL ENTRAPPED BUOYANT BEADS FOR STOMACH SPECIFIC DELIVERY OF METRONIDAZOLE

Objective: This work focused on the development of floating alginate beads for stomach specific delivery of Metronidazole towards the effective eradication of Helicobacter pylori, a major causative agent of peptic ulcers.Methods: Different formulations of sunflower oil entrapped gel beads were prepared by emulsion gelation technique using sodium alginate as gelling agent. The prepared beads were evaluated for size, surface morphology, drug entrapment efficiency, in vitro floatuing and in vitro drug release properties.Results: It was found that the percentage of oil plays an important role in controlling the floating of oil-entrapped alginate beads. All batches of beads floated for >24 hours with a very short lag time of 151–187 seconds. Scanning electron microscopy (SEM) revealed that the beads were spherical in shape with small pores on the surface. SEM of the cross section of the beads demonstrated minute oil globules throughout the inner portion of the beads confirming oil entrapment. The results clearly indicated that amount of polymer (% w/v) and amount of sunflower oil (% v/v) affected the bead size, floating, encapsulation efficiency and drug release of the beads. It was observed that the drug release kinetics was best fitted with the Higuchi model and drug release from the polymer matrix system was non fickian (anomalous transport) type.Conclusion: The results provide evidence that formulated gel beads may be used to incorporate antimicrobials like Metronidazole and may be effective when administered locally in the stomach to cure Helicobacter pylori infection.Â

Effect of citric acid and polymer blend on characteristics of ofloxacin floating matrix tablets by factorial design

The present investigation deals with the development of floating matrix tablet containing Ofloxacin, to prolong the gastric residence time, thereby effective in eradication of Helicobacter pylori from the gastric mucosa. A 32 factorial design was employed to formulate floating matrix tablet selecting polymer blend ratio [hydroxypropyl methylcellulose (HPMC) / sodium carboxymethylcellulose (SCMC)] and content of citric acid as independent variables. Time required for 50 % of drug release (t50 %), percentage drug release at 8 h (Q8), floating duration (h) and diffusion exponent (n) were selected as dependent variables. Multiple regression analysis with two way ANOVA revealed statistically significant effect of the two independent variables on the responses studied (P 8 varied from ~ 76 % to ~100 % whereas t50 % ranged from 1.7 h to 3.7 h. The kinetics of drug release fitted best to Higuchi diffusion controlled model.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Clinical Predictors and Outcome of Metabolic Acidosis in Under-Five Children Admitted to an Urban Hospital in Bangladesh with Diarrhea and Pneumonia

BACKGROUND: Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. METHODS: We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). RESULTS: Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. CONCLUSION AND SIGNIFICANCE: Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population

Neonatal glycemic status of infants of diabetic mothers in a tertiary care hospital

Background: Diabetes is a common medical complication during pregnancy that results in significant neonatal morbidities. In infants of diabetic mothers (IDMs), hypoglycemia is a common complication. Objective: To study the neonatal hypoglycemia in IDMs in a tertiary care hospital. Settings and Design: A cross-sectional study was done in postnatal ward in Bangladesh Institute of Research and Rehabilitation in Diabetic, Endocrine and Metabolic Disorders from January to December 2009. Subjects and Methods: The data of IDMs were collected from postnatal ward. All IDMs delivered during this period staying in postnatal ward were included in this study. The outcomes were compared between the hypoglycemic and normoglycemic IDMs and between gestational diabetes mellitus (GDM) and pre-GDM in hypoglycemic group using Chi-square test and Fisher's exact test. The data analysis was performed with Epi-enfo7 software. Statistical significance was set at P < 0.05. Results: A total of 363 IDMs were included in this study. Hypoglycemia developed in 38.3% IDMs and 43.2% mothers of hypoglycemic IDMs had GDM and 56.8% had pre-GDM. Duration of maternal diabetes (P = 0.04) and large for gestational age (P = 0.0001) were associated with hypoglycemia. Multigravidae (82.2% vs 68.3%, P = 0.03), prolonged duration of maternal diabetes (45.46 weeks vs 3.23 weeks, P = 0.00001), preterm babies (48.1% vs 28.3% P = 0.009), and control of diabetes by insulin (81% vs 46.7%, P = 0.001) were more in pre-GDM, and statistically significant. About 85% IDMs developed hypoglycemia within 6 h of birth (P-value 0.00001) and majority (68%) were at 2 h of age. Forty percent of hypoglycemic IDMs from postnatal ward were admitted in special care baby unit. Conclusion: Hypoglycemia observed in 38.3% IDMs and developed within 6 h of age and maximum were at 2 h. Early recognition and appropriate intervention are needed in IDMs

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse uterus during the peri-implantation period

The attachment of the blastocyst to the uterine luminal epithelium and the subsequent invasion by trophoblast cells through the stroma and deciduum occur in a highly regulated manner by remodeling of the extracellular matrix. We investigated the temporal and spatial expression of mRNAs for four matrix metalloproteinases (MMPs; MMP-2 [gelatinase A], MMP-3 [stromelysin 1], MMPs; MMP-2 [gelatinase B], and MMP-13 [collagenase 3]) and tissue inhibitors of metalloproteinases (TIMPs; TIMP-1, TIMP-2, and TIMP-3) in the mouse uterus from days 1 to 8 of pregnancy. Northern blot analyses showed the transcripts for MMP-2, MMP-3, RNA on these days. However, MMP-13 mRNA was not detected in the uterus, and only weak signals for MMP-3 mRNA were detected in the myometrium. Striking expression was observed with MMP-2 mRNA in the subepithelial stroma on days 3-5. With the progression of decidualization on day 6, signals were primarily in the secondary decidual zone. On day 8, MMP-2 mRNA was localized at the site of placenta formation in the mesometrial pole. Signals for MMP-9 mRNA were first detected in a small population of stromal cells exclusively at the site of implantation on day 5 at the antimesometrial pole. However, the most pronounced expressed was noted in trophoblast giant cells on day 8. TIMP-1 mRNA was present in the myometrium on day 1. On days 2-5, modest signals were detected in the stroma, and on days 6 and 8, they were in the secondary decidual zone. Localization of TIMP-2 mRNA was similar to that of TIMP-1 except it was restricted to the stroma on day 1. The regulation of TIMP-3 was more pronounced. While a gradual increase in signals was observed in stromal cells from days 1 to 4, strong signals were detected in antimesometrial stromal cells at the sites of blastocyst attachment on day 5. On days 6 and 7, even stronger signals were present in the primary decidual zone surrounding the embryo, and on day 8 signals were localized primarily in the mesometrial decidual bed. These results suggest that MMP-2 may participate in the early phase of decidualization and neovascularization required for placentation. The restricted MMP-9 expression in stromal cells on day 5 and in trophoblast giant cells on day 8, coupled with the expression of TIMP-3 in the stroma surrounding the embryo, suggests that a fine balance between MMP-9 and TIMP-3 may regulate trophoblast invasion in the uterus