New Copper Compounds with Antiplatelet Aggregation Activity.

BACKGROUND: Ischemic heart disease, cerebrovascular accident, and venous thromboembolism have the presence of a thrombotic event in common and represent the most common causes of death within the population. OBJECTIVE: Since Schiff base copper(II) complexes are able to interact with polyphosphates (PolyP), a procoagulant and potentially prothrombotic platelet agent, we investigated the antiplatelet aggregating properties of two novel tridentate Schiff base ligands and their corresponding copper( II) complexes. METHODS: The Schiff base ligands (L1) and (L2), as well as their corresponding copper(II) complexes (C1) and (C2), were synthesized and characterized by chemical analysis, X-ray diffraction, mass spectrometry, and UV-Visible, IR and far IR spectroscopy. In addition, EPR studies were carried out for (C1) and (C2), while (L1) and (L2) were further analyzed by 1H and 13C NMR. Tests for antiplatelet aggregation activities of all of the four compounds were conducted. RESULTS: X-ray diffraction studies show that (L1) and (L2) exist in the enol-imine tautomeric form with a strong intramolecular hydrogen bond. NMR studies show that both ligands are found as enol-imine tautomers in CDCl3 solution. In the solid state, the geometry around the copper(II) ion in both (C1) and (C2) is square planar. EPR spectra suggest that the geometry of the complexes is similar to that observed in the solid state by X-ray crystallography. Compound (C2) exhibited the strongest antiplatelet aggregation activity. CONCLUSION: Schiff base copper(II) complexes, which are attracting increasing interest, could represent a new approach to treat thrombosis by blocking the activity of PolyP with a potential anticoagulant activity and, most importantly, demonstrating no adverse bleeding events.

The aminoestrogen prolame increases recognition memory and hippocampal neuronal spine density in aged mice.

The aging brain shows biochemical and morphological changes in the dendrites of pyramidal neurons from the limbic system associated with memory loss. Prolame (N-(3-hydroxy-1,3,5 (10)-estratrien-17ß-yl)-3-hydroxypropylamine) is a non-feminizing aminoestrogen with antithrombotic activity that prevents neuronal deterioration, oxidative stress, and neuroinflammation. Our aim was to evaluate the effect of prolame on motor and cognitive processes, as well as its influence on the dendritic morphology of neurons at the CA1, CA3, and granule cells of the dentate gyrus (DG) regions of hippocampus (HP), and medium spiny neurons of the nucleus accumbens (NAcc) of aged mice. Dendritic morphology was assessed with the Golgi-Cox stain procedure followed by Sholl analysis. Prolame (60 µg/kg) was subcutaneously injected daily for 60 days in 18-month-old mice. Immediately after treatment, locomotor activity in a new environment and recognition memory using the Novel Object Recognition Task (NORT) were evaluated. Prolame-treated mice showed a significant increase in the long-term exploration quotient, but locomotor activity was not modified in comparison to control animals. Prolame-treated mice showed a significant increase in dendritic spines density and dendritic length in neurons of the CA1, CA3, and DG regions of the HP, whereas dendrites of neurons in the NAcc remained unmodified. In conclusion, prolame administration promotes hippocampal plasticity processes but not in the NAcc neurons of aged mice, thus improving long-term recognition memory. Prolame could become a pharmacological alternative to prevent or delay the brain aging process, and thus the emergence of neurodegenerative diseases that affect memory.

Neumoperitoneo asintomático asociado a neumatosis quística intestinal en paciente quirúrgico / Asymptomatic pneumoperitoneum associated to pneumatosis cystoides intestinalis in surgery patient

Abstract Introduction: Pneumatosis cystoides intestinalis (PCI) is a rare entity characterized by the presence of air in the intestinal wall. In most cases, it is secondary to a number of mainly intra-abdominal processesthat mostly require urgent surgery but, in a small percentage of cases, it is idiopathic and usually has a morebenign course, caused by, among other things, a series of mechanical factors causing mucosal damage andtherefore predisposing to the formation of cysts. Case report: Here we describe a case of a patient undergoingright hemicolectomy for colon cancer and subsequently treated with chemotherapy that developed PCI twoyears after treatment ended. At all times, the patient was asymptomatic, despite the evolution of PCI and thedevelopment of associated pneumoperitoneum.

Resumen Introducción: La neumatosis quística intestinal (NQI) es una entidad poco frecuente que se caracteriza por la presencia de aire en la pared intestinal. En la mayoría de las ocasiones es secundaria a una serie de procesos fundamentalmente intrabdominales y que en su mayoría requieren cirugía urgente, pero en un pequeño porcentaje de casos es idiopática y suele tener un curso más benigno, causada entre otras cosas por una serie de factores mecánicos que ocasionan el daño de la mucosa y por lo tanto predisponen a la formación de quistes. Caso clínico: Presentamos el caso de un paciente sometido a una hemicolectomía derecha por cáncer de colon y tratado posteriormente con quimioterapia que desarrolla una NQI a los dos años de finalizado el tratamiento. En todo momento el paciente se ha encontrado asintomático a pesar de la evolución de la NQI yel desarrollo de neumoperitoneo asociado.

[2-(sec-Butyl-imino-meth-yl)quinoline]-chlorido(η-1-isopropyl-4-methyl-benzene)-ruthenium(II) hexa-fluorido-phosphate.

In the title compound, [RuCl(C(10)H(14))(C(14)H(16)N(2))]PF(6), the aromatic ring of the isopropyl-methyl-benzene fragment shows an η(6)-arene coordination to the ruthenium atom. Its coordination sphere is completed by a chloride ligand and 2-(sec-butyl-imino-meth-yl)quinoline. The dihedral angle between the η(6)-arene ring and the quinoline Schiff base is 45.64 (9)°. The sec-butyl substituent and the PF(6) (-) anion are disordered over two positions with ratios of 0.595 (11):0.405 (11) and 0.752 (8):0.248 (8), respectively.

The antithrombotic effect of the aminoestrogen prolame (N-(3-hydroxy-1,3,5(10)-estratrien-17B-YL)-3-hydroxypropylamine) is linked to an increase in nitric oxide production by platelets and endothelial cells.

OBJECTIVE: Women under hormone replacement therapy carry an increased risk of venous thromboembolism (VTE), mostly during the first year. Despite great efforts devoted to hormone therapy research, VTE remains a major drawback of estrogenic therapy, and the search for new compounds continues. We have synthesized and evaluated prolame, an aminoestrogen with anticoagulant properties. The aim of our work was to elucidate the anticoagulant mechanism of prolame. METHODS: We studied the effects of prolame on nitric oxide (NO) synthesis in cultured endothelial cells and platelets using flow cytometry, on NO metabolites using a modified Griess method, on NO formation in vivo using electron paramagnetic resonance spectroscopy, on participation of nuclear estrogen receptors using flow cytometry, and on endothelial NO synthase (eNOS) mRNA expression using RT-PCR. We also studied the impact of prolame-treated endothelial cells (EC) on ADP-induced platelet aggregation, as well as the ability to prevent occlusive thrombi in an in vivo mice thrombosis model. RESULTS: (a) Prolame induces NO production in ECs, platelets, and in a mouse model in vivo. (b) The NO-elevating effect of prolame can only be partially attributed to the nuclear estrogen receptors (ERs) since endothelial nitric oxide synthase (e-NOS) is slightly induced (37%) in ECs treated with prolame. (c) Platelets become 60% less responsive to aggregation induced by 10muM ADP when in suspension with prolame-treated ECs. (d) Prolame reduces the formation of thrombi in an in vivo thrombosis model. CONCLUSIONS: Prolame could be a preferred alternative to other estrogens because of its reduced thromboembolic risk.