Ca2+ signals in human umbilical endothelial cells derived from pregnancy with fetal growth restriction associated with hypertensive disorder.

Fetal growth restriction associated with hypertensive disorders of pregnancy (FGR-HDP) is a prevalent pathology with a higher risk of perinatal morbimortality. In this condition, placental insufficiency and endothelial dysfunction serve key roles. The present prospective cohort study monitored 11 patients with an FGR-HDP and 15 with full-term normotensive pregnancies and studied post-natal intracellular calcium concentration ([Ca2+]i) signals in human umbilical vein endothelial cells (HUVECs). Small fetuses with placental insufficiency were identified using fetal biometry with Doppler velocimetry. Mean gestational age and birth weight were 31.8±4.1 weeks and 1,260±646 g for FGR-HDP and 39.2±0.8 weeks and 3,320±336 g for normal births, respectively. Abnormal umbilical artery Doppler waveforms were found in 64% of neonates with FGR-HDP. A significant percentage (86%) of FGR newborns were admitted to the neonatal intensive care unit at Gustavo Fricke hospital, Viña del Mar, Chile, with one case of death after birth. [Ca2+]i signals were measured by microfluorimetry in Fluo-3-loaded HUVECs from primary cultures. Altered [Ca2+]i signals were observed in HUVECs from FGR-HDP, where the sustained phase of ATP-induced [Ca2+]i responses was significantly reduced compared with the normotensive group. Also, the [Ca2+]i signals induced with 10 mM Ca2+ after depletion of internal Ca2+ stores were significantly higher. The present study provides a better comprehension of the role of altered cytosolic Ca2+ dynamics in endothelial dysfunction and an in vitro model to assess novel therapeutic approaches for decreasing or preventing complications in FGR-HDP.

Characterization of Fruit Development, Antioxidant Capacity, and Potential Vasoprotective Action of Peumo (Cryptocarya alba), a Native Fruit of Chile.

The peumo (Cryptocarya alba) is a native fruit from central Chile that belongs to the Lauraceae family. To characterize the development and the potential health benefits of this edible fruit, quality and physiological parameters, along with antioxidant capacity, were evaluated during three clearly defined developmental stages of the fruit in two seasons. The most distinguishable attributes of ripe fruit were the change in size and color. Low CO2 production and no detectable ethylene levels suggested non-climacteric behavior of the peumo fruit. Peumo demonstrate a significant increase in their antioxidant capacity per 1 g of fresh weight (FW) of the sample, from small to ripe fruit. Higher values in ripe fruit (FRAP: 37.1-38.3 µmol FeSO4/gFW, TEAC: 7.9-8.1 mmol TE/gFW, DPPH: 8.4-8.7 IC50 µg/mL, and ORAC: = 0.19-0.20 mmol TE/gFW) were observed than those in blueberry fruit (FRAP: 4.95 µmol FeSO4/gFW, TEAC: 1.25 mmol TE/gFW, DPPH: 11.3 IC50 µg/mL, and ORAC: 0.032 mmol TE/ gFW). The methanol extracts of ripe fruit displayed the presence of polyphenol acids and quercetin, an ORAC value of 0.637 ± 0.061 mmol TE per g dried weight (DW), and a high cellular antioxidant and anti-inflammatory potential, the latter exceeding the effect of quercetin and indomethacin used as standard molecules. Also, the assay of isolated rat aorta with endothelium-dependent relaxation damage demonstrated that the peumo extract induced vascular protection, depending on its concentration under a high glucose condition. These results demonstrate that these endemic fruits have a good chance as ingredients or foods with functional properties.

Resveratrol as an anti-asthmatic agent: could this stilbenoid help against COVID-19 in any way? a meta-analysis / Resveratrol como agente antiasmático: ¿podría este estilbenoide ayudar contra el COVID-19 de alguna manera? un metaanálisis

Resveratrol is a phenolic phytoconstituent found in many plants. This molecule has always caught the attention of scientists because of biological potentials such as inhibition of inflammation, oxidative stress and platelet aggregation as well as to prevent/protect against cardiovascular and neurodegenerative disease/disorders. Literature search have been conducted over resveratrol in covid-19 and asthma studies published in Pubmed and Google Scholars until 30 September 2020. The criteria used in the literature review were determined and were reviewed works on resveratrol including 368 articles and 47 articles on covid-19 and asthma, respectively. As a result of meta-analysis, TNF-α values of the studies showed a significant difference (heterogeneity) of I2=68.39% from each other in total (Cohran Q:6.33, p<0.0423). This study shows that resveratrol would have a potential to reduce ARDS symptoms, by suppressing the cytokine storm and severe inflammation caused by SARS-CoV-2, and by showing strong activity against various types of DNA/RNA viruses.

El resveratrol es un fitoconstituyente fenólico que se encuentra en muchas plantas. Esta molécula siempre ha llamado la atención de los científicos debido a sus potenciales biológicos como la inhibición de la inflamación, el estrés oxidativo y la agregación plaquetaria, así como para prevenir/proteger contra enfermedades/trastornos cardiovasculares y neurodegenerativos. Se han realizado búsquedas bibliográficas sobre resveratrol en covid-19 y estudios sobre asma publicados en Pubmed y Google Scholars hasta el 30 de septiembre de 2020. Se determinaron los criterios utilizados en la revisión bibliográfica y se revisaron trabajos sobre resveratrol que incluyen 368 artículos y 47 artículos sobre covid-19 y asma, respectivamente. Como resultado del metanálisis, los valores de TNF-α de los estudios mostraron una diferencia significativa (heterogeneidad) de I2=68,39% entre sí en total (Cohran Q: 6,33, p<0,0423). Este estudio muestra que el resveratrol podría reducir los síntomas del ARDS al suprimir la tormenta de citocinas y la inflamación severa causada por el SARS-CoV-2, y al mostrar una fuerte actividad contra varios tipos de virus de ADN/ARN.

Complete essential oils of Laurus nobilisinducing antinociceptiveaction by opioid mechanism in C-Reflex and spinal Wind-Up model in rat / Aceites esenciales totales de Laurus nobilis inducen acción antinociceptivamediante mecanismo opioide en el modelode Reflejo-C y Wind-Up espinal en ratas

The essential oil of Laurus nobilis L. was used to test their antinociceptive efficacy. It was applied intraperitoneally (i.p.) to rats subjected to a nociception test (C reflex and spinal wind-up). The results showed that the essential oil applied at higher doses (0.06 mg/Kg) causes a complete abolition of the spinal wind-up, while the C reflex was unchanged, indicating a clear antinociceptive effect. At lower concentrations (0.012 mg/Kg), there was a lowering in the wind-up by 85% within ten minutes of the essential i.p. oil application. Interestingly, there was an effect of naloxone (0.08 mg/Kg i.p.) When applied, a change occurs that almost entirely reversed the antinociception caused by the essential oil from Laurus nobilis. We conclude that there is a significant antinociceptive effect of the essential oil of Laurus nobilis subjected to electric nociception. In addition, it was observed that naloxone reversed the antinociceptive effect (wind-up) produced by Laurus nobilis.

El aceite esencial de Laurus nobilis L. se usó para probar su eficacia antinociceptiva. Se aplicó por vía intraperitoneal (i.p.) a ratas sometidas a una prueba de nocicepción (reflejo-C y wind-up espinal). Los resultados mostraron que el aceite esencial aplicado a dosis más altas (0.06 mg/Kg) abolió completamente el wind-up espinal, mientras que el reflejo-C no cambió, lo que indica un claro efecto antinociceptivo. A concentraciones más bajas (0.012 mg/Kg), hubo una disminución en el wind-up en un 85% dentro de los diez minutos del i.p. la aplicación del aceite esencial. Curiosamente, hubo un efecto de la naloxona (0.08 mg/Kg i.p.) la cual revierte casi por completo la antinocicepción causada por el aceite esencial de Laurus nobilis. Concluimos que existe un efecto antinociceptivo significativo del aceite esencial de Laurus nobilis sometido a nocicepción eléctrica. Además, se observó que la naloxona revirtió el efecto antinociceptivo (wind-up) producido por Laurus nobilis.

A Review of Endothelium-Dependent and -Independent Vasodilation Induced by Phytochemicals in Isolated Rat Aorta.

This review discusses the contribution of the use of the isolated rat aorta (IRA) as a model for the evaluation of extracts and metabolites produced by plants with a vasodilator effect in animals. This model continues to be a valuable approach for the search and development of new phytochemicals consumed as medicinal plants or foods. In most cases, the sources of phytochemicals have been used in folk medicine to treat ailments that include hypertension. In this model, the endothelium is emphasized as a key component that modulates the vessel contractility, and therefore the basal tone and blood pressure. Based on the functional nature of the model, we focused on studies that determined the endothelium-dependent and -independent vasodilatory activity of phytochemicals. We describe the mechanisms that account for aorta contraction and relaxation, and subsequently show the vasoactive effect of a series of phytochemicals acting as vasodilators and its endothelium dependence. We highlight information regarding the cardiovascular benefits of phytochemicals, especially their potential antihypertensive effect. On this basis, we discuss the advantages of the IRA as a predictive model to support the research and development of new drugs that may be of help in the prevention and treatment of cardiovascular diseases, the number one cause of death worldwide.

Patagonian Berries: Healthy Potential and the Path to Becoming Functional Foods.

In recent years, there has been an increasing interest in studying food and its derived ingredients that can provide beneficial effects for human health. These studies are helping to understand the bases of the ancestral use of several natural products, including native fruits as functional foods. As a result, the polyphenol profile and the antioxidant capacity of the extracts obtained from different Patagonian native berries have been described. This review aims to provide valuable information regarding fruit quality, its particular compound profile, and the feasibility of producing functional foods for human consumption to prevent disorders such as metabolic syndrome and cardiovascular diseases. We also discuss attempts concerning the domestication of these species and generating knowledge that strengthens their potential as traditional fruits in the food market and as a natural heritage for future generations. Finally, additional efforts are still necessary to fully understand the potential beneficial effects of the consumption of these berries on human health, the application of suitable technology for postharvest improvement, and the generation of successfully processed foods derived from Patagonian berries.

A Review of the Actions of Endogenous and Exogenous Vasoactive Substances during the Estrous Cycle and Pregnancy in Rats.

Vascular endothelium plays a key role in regulating cardiovascular homeostasis by controlling the vascular tone. Variations in sex hormones during the reproductive cycle of females affect the homeostasis of the cardiovascular system. Also, the evidence shows that estrogens show a cardioprotective effect. On this basis, this study describes some vascular responses induced by vasoactive substances during the estrous cycle in rats. We obtained the information available on this topic from the online databases that included scientific articles published in the Web of Science, PubMed, and Scielo. Many investigations have evaluated the vasoactive response of substances such as acetylcholine and norepinephrine during the estrous cycle. In this review, we specifically described the vascular response to vasoactive substances in rats during the estrous cycle, pregnancy, and in ovariectomized rats. In addition, we discussed the existence of different signaling pathways that modulate vascular function. The knowledge of these effects is relevant for the optimization and development of new treatments for some vascular pathologies.

Antiproliferative Benzoindazolequinones as Potential Cyclooxygenase-2 Inhibitors.

Quinones and nitrogen heterocyclic moieties have been recognized as important pharmacophores in the development of antitumor agents. This study aimed to establish whether there was any correlation between the in silico predicted parameters and the in vitro antiproliferative activity of a family of benzoindazolequinones (BIZQs), and to evaluate overexpressed proteins in human cancer cells as potential biomolecular targets of these compounds. For this purpose, this study was carried out using KATO-III and MCF-7 cell lines as in vitro models. Docking results showed that these BIZQs present better binding energies (ΔGbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 measured in both cell lines (KATO-III: 0.72, 0.41, and 0.90; MCF-7: 0.79, 0.55, and 0.87 for Series I, II, and III, respectively). The results also indicated that compounds 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin values than the other derivatives. In silico drug absorption, distribution, metabolism, and excretion (ADME) properties of the three series were also analyzed and showed that several BIZQs could be selected as potential candidates for cancer pre-clinical assays.

t-Resveratrol Protects against Acute High Glucose Damage in Endothelial Cells.

Postprandial hyperglycemia in diabetic and nondiabetic subjects is associated with endothelial dysfunction. Evidence shows that high glucose generates oxidative stress and a pro-inflammatory state promoting the development of cardiovascular diseases. trans-Resveratrol (t-RV) has been shown to reduce cardiovascular risk. To determine whether t-RV acts as a protector against acute high glucose (AHG)-induced damage, two in vitro models, rat aortic rings (RAR) and human umbilical vein endothelial cells (HUVEC) were used. RAR pretreated with AHG (25 mM D-glucose) for 3 h dramatically decreased the endothelium-dependent relaxation (EDR) induced by acetylcholine in phenylephrine (PE)-precontracted vessels. However, coincubation with t-RV significantly mitigated the damage induced by AHG on EDR. Pretreatment with AHG did not affect the vasodilation induced by sodium nitroprusside. HUVEC treated with t-RV decreased cytotoxicity and reduced radical oxygen species production induced by AHG. Taken together, these results suggest that t-RV can mitigate the AHG-induced EDR damage through a mechanism involving ROS scavenging and probably an increase in the bioavailability of NO.

Effects of two bisbenzylisoquinoline alkaloids, Antioquine and Tetrandrine, compared to Verapamil in Rat Thoracic Aorta.

The objective of this study was to compare two alkaloids (antioquine and tetrandrine) with verapamil; knowing that the smooth muscle respond to KCl and relationships with calcium. The effects of antioquine and tetrandrine, was studied in adults Wistar rat with modified methods used in the determination of aorta contractility and compared with verapamil effect in the same assays. The analysis of the effect of a drug or extract on aortic reactivity included maximal relaxation or maximal contraction (Cmax) (Phase 1). In our results, verapamil induced a blockade of 98.7 ± 0.7% (n = 6) in presence of endothelium and 97.9 ± 4.3% in ausence of endothelium, both in phase 1 and in phase 2 of 47.4 ± 4.1% (n = 6) in aortas in the presence of endothelium and 61.8 ± 1.1% in ausence of endothelium; Tetrandrine assays showed a phase 1 blocking effect of 63.4 ± 5.5 and 47.7 ± 2.9% (with and without endothelium, respectively) and phase 2 of 43.5 ± 6.2 and 28.5 ± 5.7%, (with and without endothelium, respectively). Antioquine presents in phase 1 and phase 2, a blockade that is not significant from the point of view of calcium antagonism. We can conclude that tetrandrine block the movement of calcium from both intracellular and extracellular deposits, with the greatest effect when aortas are in the presence of endothelium.

Vasodilatory properties of Solanum crispum Ruiz & Pav. a South American native plant / Propiedad vasodilatadora de Solanum crispum Ruiz & Pav. una planta nativa de América de Sur

Solanum crispum Ruiz & Pav. (S. crispum) is a southern South American native plant that is usually used in traditional medicine for the treatment of symptoms associated with both, acute and chronic ailments. Enema and infusion of leaves and stems are used to treat fever, headache, inflammation and hypertension. In this study, we aim to assess the vasoactive effect of hydroalcoholic extracts of S. crispum on isolated rat aorta rings. The hydroalcoholic extract of S. crispum induced a vasodilatory effect (42.6 +/- 4.1 percent) in aortic rings precontracted with phenylephrine (0.1 μM). The aortic relaxation was largely endothelium-dependent and mediated by nitric oxide (NO). The endothelium- and NO-dependence was demonstrated by a drastic fall in the dilatation induced by the extract when the endothelium was removed (10.6 +/- 2.3 percent) and when nitric oxide synthase (NOS) was inhibited (12.3 +/- 2.5 percent) by nitro-L-arginine (L-NNA). This result supports the popular use of S. crispum in the treatment of hypertension that may be due, at least in part, to the vasodilator effect of one o more compounds present in their leaves and stems. Further studies should be performed to clarify this phenomenon.

Solanum crispum Ruiz & Pav. (S. crispum) es una planta nativa de América del Sur meridional que se utiliza generalmente en medicina tradicional para el tratamiento de los síntomas asociados con dolencias agudas y crónicas. El enema y la infusión de las hojas y tallos se utilizan para tratar la fiebre, el dolor de cabeza, la inflamación y la hipertensión. El objetivo de este estudio fue evaluar el efecto vasoactivo de un extracto hidroalcohólico de S. crispum en anillos aislados de aorta de rata. El extracto hidroalcohólico de S. crispum indujo un efecto vasodilatador (42,6 +/- 4,1 por ciento) en anillos aórticos precontraídos con fenilefrina (0,1 μM). La relajación de la aorta fue en gran parte dependiente del endotelio y mediada por el óxido nítrico (NO). La dependencia de endotelio y NO se demostró por una caída drástica de la dilatación inducida por el extracto cuando el endotelio fue removido (10,6 +/- 2,3 por ciento) y cuando se inhibió la óxido nítrico sintasa (NOS) (12,3 +/- 2,5 por ciento) mediante nitro-L-arginina (L-NNA). Este resultado apoya el uso popular de S. crispum en el tratamiento de la hipertensión que puede ser debido, al menos en parte, al efecto vasodilatador de uno o más compuestos presentes en sus hojas y tallos. Se deben realizar más estudios para aclarar este fenómeno.

Characterization of fruit development and potential health benefits of arrayan (Luma apiculata), a native berry of South America.

The arrayan berry (Luma apiculata) is a native fruit from South America that belongs to the Myrtaceae family. To elucidate and characterize the developmental process and the potential health benefits of this edible fruit, quality and physiological parameters, along with antioxidant capacity, were evaluated during four clearly defined developmental stages of the fruit in two seasons. Fruit firmness slowly decreases during fruit development, whereas the solid soluble content/titratable acidity ratio (SSC/TA) increases significantly in the final stages of development. The measurement of low respiration rates and low ethylene production during growth and ripening suggested that the arrayan berry should be classified as a non-climacteric fruit. Arrayan berries show a significant increase in their antioxidant capacity from small green to black ripe fruit. FRAP and TEAC assays showed high correlations with total polyphenolic content (TPC) during ripening and high antioxidant capacity at all fruit stages, showing greater values in ripe fruit (FRAP: 24 ± 2 and 28 ± 3 µM FeSO4/gFW; TEAC: 18 ± 2 and 20 ± 1 Eq. Trolox/gFW for each season, respectively) than those observed in the blueberry (FRAP: 10 ± 2 and 19 ± 3 µM FeSO4/gFW; TEAC: 10 ± 2 and 17 ± 3). In addition, bioactive assays using ripe fruit extracts show presence of flavonol and anthocyanins, a high ORAC value (62,500 ± 7000 µmol/gDW) and a concentration-dependent vascular protection under high glucose conditions. The results obtained show that these endemic berry fruits have a promising potential as functional food.

New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation.

1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, ¹H-NMR and (13)C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 µM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents.

Pseudoxandra sclerocarpa maas, colombian medicinal plant: a review / Pseudoxandra sclerocarpa maas, planta medicinal colombiana: una revisión

The Annonaceae family is one of the largest, with 130 genre and 2500 species, consisting of trees, shrubs and a few vines. Within this family, the Pseudoxandra genus of neotropical distribution is found. In Colombia, there are endemic and native species, distributed in the Amazon region and along the valley of the Magdalena River in the Chocó. Of the total of 22 species that form the genus in Colombia, Pseudoxandra sclerocarpa Maas is exclusive of the Antioquia region, receiving the common name of garrapato or frisolo. From this tree, bisbenzylisoquinolinic alkaloids like antioquine, medellline, obaberine, among others, has been isolated. Also neolignans: dieugenol and dehydro-1-O-methydehydrodieugenol. It is used in traditional medicine as an antiparasitic. From the pharmacological point of view, the alkaloids have shown activity against leishmaniasis and also have spasmolytic activity. Within the bisbenzylisoquinolinic alkaloids, antioquine has properties of being calcium antagonist.

La familia Annonaceae es uno de los más grandes, con 130 géneros y 2.500 especies, que consiste en árboles, arbustos y algunos bejucos. Dentro de esta familia, el género Pseudoxandra es de distribución neotropical. En Colombia existen especies endémicas y nativas, distribuidas en la región del Amazonas ya lo largo del valle del río Magdalena en el Chocó. Del total de 22 especies que forman el género en Colombia, Pseudoxandra sclerocarpa es exclusiva de la región de Antioquia, recibiendo el nombre común de garrapato o frisolo. De este árbol se ha aislado alcaloides bisbencilisoquinolínicos como antioquina, medelllina, obaberina, entre otros. También neolignanos: dieugenol y dehidro-1-O-metil-dehidrodieugenol. Se utiliza en la medicina tradicional como un antiparasitario. Desde el punto de vista farmacológico, los alcaloides han mostrado actividad contra la leishmaniasis y también tienen actividad espasmolítica. Dentro de los alcaloides bisbencilisoquinolínicos, antioquina tiene propiedades de ser antagonista del calcio.

Bradykinin and histamine-induced cytosolic calcium increase in capillary endothelial cells of bovine adrenal medulla.

We have assessed the effect of bradykinin and histamine on the cytosolic free calcium concentration ([Ca(2+)]i ) of bovine adrenal medulla capillary endothelial cells (BAMCECs). To measure [Ca(2+)]i changes in BAMCECs the intracellular fluorescent probe, fluo-3 AM, was used. Bradykinin (3 µM) produced a transient monophasic increase in [Ca(2+)]i , which was depressed by B1650 (0.1 µM), a B2-bradykinin receptor antagonist (D-Arg-[Hyp(3), Thi(5,8) , D-Phe(7)]-Bradykinin). Similarly, increase in [Ca(2+)]i induced by histamine was also depressed by tripolidine (0.1 µM), an H1-histamine receptor antagonist. [Ca(2+)]i increase induced by both agonists was unaffected in the absence of extracellular Ca(2+) or presence of antagonists of voltage operated Ca(2+) channels (VOCCs). Thapsigargin (1 µM) did not abolish the increase of [Ca(2+)]i produced by bradykinin, but abolished that of histamine. In contrast, caffeine (100 µM), abolished the [Ca(2+)]i response induced by bradykinin (3 µM), but did not affect the [Ca(2+)]i increase induced by histamine (100 µM). The results indicate the presence of B2 bradykinin- and H1 histamine-receptors in BAMCECs. Liberation of Ca(2+) induced by both agonists occurs through 2 different intracellular mechanisms. While bradykinin activates a sarco(endo) plasmic reticulum (SER) containing a SER Ca(2+) -ATPase (SERCA) thapsigargin-insensitive, histamine activates a SER containing a SERCA thapsigargin-sensitive. We suggest that the increase in [Ca(2+)]i induced by bradykinin and histamine could be of physiological relevance, modulating adrenal gland microcirculation.

p-Coumaric acid reduces high glucose-mediated impairment of endothelium-dependent relaxation in rat aorta / Ácido p-cumárico reduce el deterioro mediado por alta glucosa de la relajación dependiente de endotelio en aorta de rata

p-Coumaric acid (p-CA) is an ubiquitous plant metabolite with antioxidant, anti-inflammatory, and anticancer properties. The present study was designed to evaluate the preventive effects of p-CA on endothelium-dependent impairment produced by high glucose (HG) (D-Glucose 25 mM) in isolated rat thoracic aorta. Aortic rings obtained from male Sprague-Dawley rats were mounted in an organ bath and pretreated for 3 h with D-Glucose 5 mM, HG and HG plus p-CA (1, 10 and 100 uM). After this period of time endothelium-dependent relaxation was tested by cumulative addition of acetylcholine (ACh) in pre-contracted rings with phenylephrine (PE) (0.1 μM). p-CA elicited a moderate endothelium-dependent vasodilatory effect (Emax= 29.28 +/- 1.89 percent, N=6; pD2= 6.075 +/- 0.184, N=6). When aortic rings were pre-incubated for 3 h with HG, Emax for ACh decreased dramatically from 87.69 +/- 2.59 percent (N=6) to 40.54 +/- 1.78 percent (N=6). The negative effect of HG was partially reverted in rings co-incubated with p-CA in a concentration-dependent manner as shown for Emax values to each p-CA concentration: 1 uM (48.57 +/- 1.82 percent), 10 uM (60.81 +/- 1.80 percent) and 100 uM (64.51 +/- 1.80 percent). The action of p-CA was associated with a significant change in Emax. No statistical difference in pD2 was observed. Our results clearly show that p-CA protect ACh-induced endothelial-dependent relaxation affected by HG in isolated rat aortic rings.

El ácido p-cumárico (p-CA) es un metabolito ubicuo en plantas, con propiedades antioxidantes, anti-inflamatoria, y anticancerígenas. El presente estudio fue diseñado para evaluar los efectos preventivos de p-CA sobre la relajación dependiente de endotelio, deteriorada por niveles altos de glucosa (HG) (D-glucosa 25 mM) en aorta torácica aislada de rata. Los anillos aórticos obtenidos de ratas macho Sprague-Dawley se montaron en un baño de órganos y fueron pre-tratados durante 3 h con D-glucosa 5 mM, HG, y HG más de p-CA (1, 10 y 100 uM). Después de este período de tiempo se evaluó la relajación dependiente de endotelio mediante la adición acumulativa de acetilcolina (ACh) en anillos pre-contraídos con fenilefrina (PE) (0,1 uM). p-CA mostró un moderado efecto vasodilatador dependiente de endotelio (Emax = 29,28 +/- 1,89 por ciento, N = 6; pD2 = 6,075 +/- 0,184, N = 6). Cuando los anillos aórticos se pre-incubaron durante 3 h con HG, la Emax para ACh se redujo drásticamente desde 87,69 +/- 2,59 por ciento (N = 6) a 40,54 +/- 1,78 por ciento (N = 6). El efecto negativo de HG se revirtió parcialmente, de manera dependiente de concentración, en los anillos co-incubados con p-CA tal como lo muestra el valor de Emax para cada concentración de p-CA: 1 u M (48,57 +/- 1,82 por ciento), 10 uM (60,81 +/- 1,80 por ciento) y 100 uM (64,51 +/- 1,80 por ciento). La acción de p-CA se asoció con un cambio significativo en la Emax. No se observó diferencia estadísticamente significativa en el pD2. Nuestros resultados muestran claramente que p-CA protege la relajación dependiente de endotelio inducida por ACh, la cual es afectada por HG en anillos aislados de aorta de rata.

Improving amphetamine therapeutic selectivity: N,N-dimethyl-MTA has dopaminergic effects and does not produce aortic contraction.

Amphetamine derivatives have therapeutic potential in diseases such as attention deficit hyperactivity disorder, narcolepsy and obesity. However, their prolonged use has been associated with cardiovascular toxicity and addiction. In recent years, we have studied the pharmacological effects of amphetamine derivatives such as methylthioamphetamine (MTA) and N,N-dimethyl-thioamphetamine, with the aim of improving their therapeutic selectivity. In this work, we show that similarly to MTA, N,N-dimethyl-thioamphetamine has effects on the dopamine system, producing a significant increase in extracellular levels of dopamine (as measured by in vivo brain microdialysis) and locomotor activity, which is a behavioural measure of dopaminergic activation. However, unlike MTA, N,N-dimethyl- thioamphetamine does not produce aortic contraction in vitro. Our results show that N,N-dimethyl-thioamphetamine is a drug that retains the dopaminergic effects of amphetamine derivatives but exhibits a lower potential for producing cardiovascular side effects.

Conocimiento etnobotanico tradicional y uso de plantas Medicinales en un area rural de la Región Metropolitana de Chile: estudio descriptivo / Traditional ethnobotanical knowledge and use of medicinal plants in a rural area of the metropolitan region of Chile: descriptive study

Con el fin de caracterizar y evaluar el conocimiento botánico perteneciente a la población en el área rural (poco abordado por la etnobotánica) se realizó un estudio a través de encuestas para aprender sobre plantas medicinales cultivadas y utilizadas en una zona rural de la Región Metropolitana (San Juan de Pirque). Las conclusiones son que los usuarios tienen un conocimiento híbrido (producto de los conocimientos tradicionales en combinación con la información de diversos tipos) de plantas medicinales. Hemos encontrado que la mayoría de las especies cultivadas en los jardines botánicos fueron especies introducidas y muy pocos las nativas. También, se les conocía por sus nombres comunes y no se detectaron nuevos nombres no descrito previamente en la literatura.

Inhibition of ATP-induced calcium influx by homocysteine in human umbilical vein endothelial cells.

Mechanisms involved in the association between hyperhomocysteinemia and vascular occlusive diseases remain unclear. Homocysteine (Hcy) may disturb calcium (Ca(2+) ) cytosolic regulation in endothelial cells, a process that can directly affect the synthesis of vasoactive substances, such as nitric oxide (NO). We have investigated the effect of acute and chronic incubation with high concentrations of Hcy (100 and 500 µmol/L) on the changes in the intracellular Ca(2+) concentration ([Ca(2+) ]i ) induced by ATP, using primary cultures of human umbilical vein endothelial cells (HUVEC). The changes in [Ca(2+) ]i , expressed as ΔFt /Fb , were measured using the microspectrofluorimetric technique with Fluo-3 as Ca(2+) indicator. HUVEC acutely exposed to Hcy did not produce significant effects on any of the parameters studied. However, chronic exposition (24 h) caused a significant decrease in the speed of store-mediated Ca(2+) entry, expressed as (ΔFt /Fb )/t (s(-1) ). Exposure of HUVEC to 100 and 500 µmol/L Hcy gave significantly lower values (0.019 ± 0.002 s(-1) , n = 5 and 0.021 ± 0.004 s(-1) , n = 6, respectively) compared to the controls (0.046 ± 0.004 s(-1) , n = 8, P < 0.003). This was detected only when the sustained phase of the ATP-induced [Ca(+2) ]i increase was isolated. These results demonstrate that high concentrations of Hcy can affect the mechanisms involved in [Ca(2+) ]i regulation of HUVEC, and that alteration occurs specifically in the sustained phase, which has been directly associated with NO synthesis.

Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD. METHODS: We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups. RESULTS: DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05). CONCLUSIONS: We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects. VIRTUAL SLIDES: The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160.