SYNTHESIS AND CRYSTAL STRUCTURE ANALYSIS OF 3 - (4 - METHOXYBENZYL) - 2, 3 – DIHYDRO - 4H – CHROMAN – 4 - ONE

3-(4-methoxybenzyl)-2,3-dihydro-4H-chroman-4-one(C17H16 O3) was synthesized by refluxing 2'-Hydroxydihydrochalcone dissolved in ethanol with paraformaldehyde and 50% aqueous diethylamine. The compound is characterized by IR,1HNMR, MS and X-ray diffraction studies. The X-ray structure analysis indicates that the crystal suffers from the positional disorder over two positions, atomC1 and C9 with required site occupancies of 0.590 and 0.410 leading to a conformational difference between the major and minor components. After applying similarity restraints, the final reliability index is 0.0275 for 2209 unique reflections .The crystal packing is stabilized by inter molecular C-H…O, C-H…π and π …π interactions

VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma

Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-β signaling inhibitor, we investigated the roles of VEGF and TGF-β in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-β were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-β resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-β are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability

Evaluation of harvesting time and standardization of distillation duration for higher essential oil content and quality in German chamomile (Chamomilla recutita L.)

Essential oil yield and composition in aromatic crops might be affected by genetic, agronomical and environmental factors but till date there is no clear information about the harvesting time and distillation for higher essential oil content without affecting quality. The current study was carried out to evaluate harvesting of chamomile flowers without herb and with herb part at three different times (6 A.M., 12 P.M. and 6 P.M.) and four distillation treatments (3 h, 4 h, 5 h & 6 h) for dried chamomile flowers. Results indicated that essential oil content was more in chamomile flowers without herb (0.15-0.18%) as compared to flowers with herb (0.06-0.09%). Essential oil content in chamomile flowers without herb was found statistically at par at harvest time of 12 P.M. (0.18%) and 6 P.M. (0.18%) and significantly higher than harvesting time of 6 A.M. (0.15%). Essential oil of chamomile flowers without herb contained maximum α-bisabolol oxide-B, (Z)-spiroether, and chamazulene at 12 P.M. and 6 P.M. while, α-bisabolone oxide-A and α-bisabolol oxide-A were maximum at 6 A.M. and (E)-β-farnesene was more at 12 P.M. Similarly, in distillation experiment, higher oil content was observed in chamomile dried flowers which were hydro-distilled for 6 h (1.20%) compared to other hydro-distillation durations. Marker compounds i.e. α-bisabolol oxide-A, α-bisabolone oxide-A, α-bisabolol oxide-B, (E)-β-farnesene and chamazulene were more at 5 h and 6 h distillation duration while (Z)-spiroether was more at 3 h distillation duration. The present study showed that in order to obtain higher essential oil, flowers without herb harvested at 12 P.M or 6 P.M. should be subjected to 5-6 h hydro-distillation

Relationships between TGFβ Proteins and Oxygen Concentrations Inside the First Trimester Human Gestational Sac

In early pregnancy, the O2 gradient between the maternal circulation and the gestational sac tissues modulates trophoblast biological functions. The aim was to evaluate if placental partial pressure of oxygen (PaO2) modulates in vivo synthesis of specific placental proteins inside the first trimester gestational sac. Matched samples of peripheral venous blood, blood from the placental bed (PB), coelomic fluid (CF) and placental tissue were obtained in 37 normal pregnancies at 6–12 weeks gestation. PaO2 was measured in PB and CF using an IRMA blood gas monitor. Inhibin A, activin A, sEng, PlGF, sFlt-1 and free VEGF concentrations were measured in all samples. HSP 70 was measured in placental extracts. ANOVA showed ∼60% increase in PB PaO2 (P = 0.02) between after 10 weeks gestation. Unpaired Student's T-test between two groups (6–9 weeks vs 9–12 weeks) shows a significant increase in MS Activin A (P = 0.001), CF activin A (P<0.001), MS P1GF (P = 0.001), CF PlGF (P<0.001), MS sFLT-1 (P = 0.03), CF sFLT-1 (P = 0.01), HSP 70 in placental extracts (P = 0.04) and a significant decrease in PB inhibin A levels (P<0.001) and PB sFLT-1 (P = 0.02) . Multiple correlation analysis showed a significant negative correlation between PB inhibin A levels and gestation (r = −0.45, P<0.05) and PB PaO2 (r = −0.5, P = 0.008) and also between sFLT-1 and PB PaO2 (P = 0.03). There was a positive correlation (P<0.01) between PlGF, sEng and VEGF levels in the placental extracts. Our results indicate a direct relationship in the early intrauterine PaO2 in vivo and inhibin A and sFLT-1 concentrations confirming our hypothesis that specific placental proteins are regulated by intrauterine O2 tension

Distinct Effects of Unfractionated Heparin versus Bivalirudin on Circulating Angiogenic Peptides

Background: Human studies of therapeutic angiogenesis, stem-cell, and progenitor-cell therapy have failed to demonstrate consistent clinical benefit. Recent studies have shown that heparin increases circulating levels of anti-angiogenic peptides. Given the widely prevalent use of heparin in percutaneous and surgical procedures including those performed as part of studies examining the benefit of therapeutic angiogenesis and cell-based therapy, we compared the effects of unfractionated heparin (UFH) on angiogenic peptides with those of bivalirudin, a relatively newer anticoagulant whose effects on angiogenic peptides have not been studied. Methodology/Principal Findings: We measured soluble fms-like tyrosine kinase-1 (sFLT1), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble Endoglin (sEng) serum levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective percutaneous coronary intervention. Compared to baseline values, sFLT1 and PlGF levels increased by 26296313 % and 253654%, respectively, within 30 minutes of UFH therapy (p,0.01 for both; n = 8). VEGF levels decreased by 93.265 % in patients treated with UFH (p,0.01 versus baseline). No change in sEng levels were observed after UFH therapy. No changes in sFLT1, PlGF, VEGF, or sEng levels were observed in any patients receiving bivalirudin (n = 8). To further explore the direct effect of anticoagulation on circulating angiogenic peptides, adult, male wild-type mice received venous injections of clinically dosed UFH or bivalirudin. Compared to saline controls, sFLT1 an

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta.By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas.Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction

A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

10.1186/1471-2393-12-160BMC Pregnancy and Childbirth12-BPCM

Anaphylatoxin C3a receptors in asthma

The complement system forms the central core of innate immunity but also mediates a variety of inflammatory responses. Anaphylatoxin C3a, which is generated as a byproduct of complement activation, has long been known to activate mast cells, basophils and eosinophils and to cause smooth muscle contraction. However, the role of C3a in the pathogenesis of allergic asthma remains unclear. In this review, we examine the role of C3a in promoting asthma. Following allergen challenge, C3a is generated in the lung of subjects with asthma but not healthy subjects. Furthermore, deficiency in C3a generation or in G protein coupled receptor for C3a abrogates allergen-induced responses in murine models of pulmonary inflammation and airway hyperresponsiveness. In addition, inhibition of complement activation or administration of small molecule inhibitors of C3a receptor after sensitization but before allergen challenge inhibits airway responses. At a cellular level, C3a stimulates robust mast cell degranulation that is greatly enhanced following cell-cell contact with airway smooth muscle (ASM) cells. Therefore, C3a likely plays an important role in asthma primarily by regulating mast cell-ASM cell interaction