ABSTRACT
INTRODUCTION: Activated platelets exert a key role in the pathogenesis of preeclampsia (PE). There is evidence of distinctive patterns of platelet indices in PE in comparison to healthy pregnancies, therefore these indices can be potential tools for PE detection, risk stratification, and management. Considering the vascular aspects of its pathophysiology, PE is characterized by the increased levels of soluble FMS-like tyrosine kinase-1 (sFlt-1) an antiangiogenic factor, and reduced placental growth factor (PlGF), a proangiogenic factor. This study aimed to assess the platelet indices in hypertensive disorders of pregnancy (HDP) and its correlation with angiogenesis-related biomarkers. METHODS: The groups for the study were: control (n = 114); gestational hypertension; (n = 112), and PE (n = 42). The platelet indices included were platelet counts (PLT-I and PLT-F), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR), and immature platelet fraction (IPF# and IPF%). Serum levels of sFlt-1 and PlGF were assessed. RESULTS: PLT-I, PLT-F, and PCT% were lower in PE, while MPV, PDW, P-LCR, IPF%, and IPF# were increased. The parameter MPV presented the best performance for the discrimination of PE. There was a moderate positive correlation between sFlt-1 levels and MPV, PDW, and P-LCR. CONCLUSION: Platelet indices can be potentially applied as additional tools for the diagnosis and management of HDP. Activated platelets may act as an extra source of sFlt-1 in PE.
Subject(s)
Agmatine/analogs & derivatives , Hypertension, Pregnancy-Induced , Oxamic Acid/analogs & derivatives , Pre-Eclampsia , Pregnancy , Humans , Female , Pre-Eclampsia/diagnosis , Hypertension, Pregnancy-Induced/diagnosis , Placenta Growth Factor/metabolism , Angiogenesis , Biomarkers , Mean Platelet VolumeABSTRACT
For years the mainstay of antiphospholipid syndrome treatment has been anticoagulation and antiplatelet therapy, but the autoimmune nature of the disease, and complications of these therapies, created the need to develop new therapeutic strategies. New therapeutic alternatives inhibit at different levels, the cascade of events leading to the pro-thrombotic state characteristic of the antiphospholipid syndrome. We conducted a literature review of these new treatments, focusing on the pathophysiological bases that support them and their possible clinical applications.
Subject(s)
Humans , Antiphospholipid Syndrome/drug therapy , Agmatine/analogs & derivatives , Agmatine/therapeutic use , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antiphospholipid Syndrome/physiopathology , Dipeptides/therapeutic use , Glucocorticoids/therapeutic use , Hydroxychloroquine/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Thrombosis/drug therapyABSTRACT
For years the mainstay of antiphospholipid syndrome treatment has been anticoagulation and antiplatelet therapy, but the autoimmune nature of the disease, and complications of these therapies, created the need to develop new therapeutic strategies. New therapeutic alternatives inhibit at different levels, the cascade of events leading to the pro-thrombotic state characteristic of the antiphospholipid syndrome. We conducted a literature review of these new treatments, focusing on the pathophysiological bases that support them and their possible clinical applications.
Subject(s)
Antiphospholipid Syndrome/drug therapy , Agmatine/analogs & derivatives , Agmatine/therapeutic use , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antiphospholipid Syndrome/physiopathology , Dipeptides/therapeutic use , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Rituximab , Thrombosis/drug therapyABSTRACT
In this work the involvement of polymerase II (Pol II) in the precise excision of Tn10 stimulated by a dnaB252 thermosensitive (Ts) mutant at the permissive temperature, by a uvrD mutant, or by mitomycin C (MMC) or ultraviolet (UV) light treatment, was investigated. A deltapolB::kan mutant showed a significant decrease in the excision of Tn10 induced by the dnaB mutation, or by MMC or UV treatment, indicating the participation of Pol II in this type of deletion process. However, no effect of Pol II was evidenced in the excision of Tn10 stimulated by the uvrD mutation. The effect of the polB mutation on Tn10 precise excision induced by all these treatments was compared to that of mutations in repair-recombination genes recF and recA. The results reveal that the degree of participation of these genes varies depending on the agent that stimulates the deletion event.
Subject(s)
Agmatine/analogs & derivatives , DNA Polymerase II/metabolism , DNA Repair/physiology , DNA Transposable Elements , DNA/metabolism , Adenosine Triphosphatases/genetics , Agmatine/metabolism , DNA Helicases/genetics , DnaB Helicases , Escherichia coli/enzymology , Escherichia coli/genetics , Escherichia coli Proteins/metabolism , Mitomycin/metabolism , Mutation , Succinates/metabolism , Ultraviolet RaysABSTRACT
The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e., N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and galegine (prenylguanidine), previously reported (Delle Monache, G.; et al. BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a biosynthetic strategy. The pharmacologic profiles of various synthetic analogues of (3,4-dimethoxycinnamoyl)-N(1)-agmatine (G5) were also analyzed, to shed some light on the structure-activity relationship of these compounds. Derivatives with the (E)-configuration and/or with a p-methoxybenzoyl moiety were found to be responsible for higher hypotensive effects, which were associated with a slight and, in some cases, not dose-related increase of cardiac inotropism, with variable and not significant chronotopic responses, and, only at higher doses, with effects of respiratory depression. Either an increase (to six) or a decrease (to two) of the number of methylene groups in the alkyl chain of (E)-G5 did not change blood pressure responses, while slightly increasing the positive inotropic ones. At pharmacological doses, all the studied compounds showed hypotensive and slight positive inotropic effects without relevant chronotropic and respiratory actions.