COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis.

OBJECTIVE: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. PATIENTS AND METHODS: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. RESULTS: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p<0.001] and CVD [-17%; 95% CI: (-26%, -9%); p<0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed. CONCLUSIONS: A decline in AMI and CVD daily hospital admissions during the first and second wave of COVID-19 pandemic was noted. Gender differences were observed, but no clear impact was observed in percutaneous interventions.

[Results of implementation of a perioperative Patient Blood Management program in cardiovascular surgery]. / Resultados de la implementación de un programa de optimización de transfusión sanguínea en cirugía cardiovascular.

BACKGROUND AND OBJECTIVE: Cardiovascular surgery (CCV) patients have a high incidence of perioperative anemia and bleeding that determines a high rate of allogeneic blood transfusion (AST). This is associated with an increase in morbidity, mortality and prolongs length of stay in hospital. Unnecessary transfusion is one of the measures to avoid and Patient Blood Management (PBM) programs have proven their effectiveness. Our objective was to reduce the transfusion of patients in cardiac surgery, without inferior results in morbidity and mortality, length of stay in hospital and being cost-effective, through the implementation of a PBM program. MATERIAL AND METHODS: A mixed cohort study of 226 patients divided into 2 groups: retrospective pre-PBM (GP), from 2016, and intervention group (IG), prospective from 2018, with the results of the implementation of the guide. RESULTS: The clinical results obtained allowed reducing the TSA from 92.59% to 79.69% (P<.001), saving 2.59 units of CH and 2.5 of PFC per patient (P<.001). A decrease was found in patients with fever (12.35% vs 1.56% with P=.006) and the need to escalate antibiotics (64.8% vs 42.19%, P=.002). The rest of postoperative complications and mortality at 3months did not present statistically significant differences. The length of stay was reduced by an average 3.6days in the IG, (95%CI: -8.10 to 0.9, P=.18). The cost decreased by 163.29€ per patient, taking into account exclusively the saving of blood components. CONCLUSION: The PBM program is effective in reducing TSA in cardiac surgery in a tertiary hospital with high complexity patients and high transfusion rate. There are signs suggestive of a decrease in infections and a tendency to decrease the length of stay and mortality. In the economic approximation carried out, the cost of the intervention was lower than the savings implied by the decrease in transfusion.

Spontaneous photosensitization by Heterophyllaea pustulata Hook. f. (Rubiaceae), in sheep from Northwestern Argentina.

Heterophyllaea pustulata Hook. f. (Rubiaceae) is a phototoxic plant. It grows in the Andean area of northwest of Argentina, and it causes significant economic losses in the livestock. This plant induces dermal lesions by photosensitization probably due to its content of photosensitizing anthraquinones. This paper describes an outbreak of poisoning in Corriedale sheepfold, which had an incidence of 49%. Ear skin biopsies and blood samples were collected of six affected animals. Liver enzymes remained within the reference limits. Histopathologically, a deep necrotizing dermatitis was identified in all samples. H. pustulata was identified in the areas of grazing. Anthraquinone concentration in leaves was 0.84% p/p, expressed as rubiadin. All findings allow us to conclude that the diagnosis is a primary photosensitization. Huge regional economic losses could be attributed to H. pustulata poisoning, although its toxicity has been little studied.

Interacciones moleculares de un flavonoide prenilado con transportadores de antimicóticos dependientes de ATP / Molecular interactions of a prenylated flavonoid with ATP-depending antimycotic transporters

Uno de los principales mecanismos para la resistencia de Candida albicans a azoles es la sobreexpresión de transportadores que extruyen los fármacos antimicóticos y disminuyen su concentración intracelular. Anteriormente nuestros laboratorios habían informado que el flavonoide prenilado 2', 4'-dihidroxi - 5'-(1'''-dimetilalil)-6-prenil pinocembrina (6PP) inhibe en forma competitiva los transportadores cdr, dependientes del ATP, además de ser antimicrobiano per se. En este trabajo realizamos estudios bioinformáticos para analizar los posibles sitios de interacción molecular estereoespecífica del 6PP, fluconazol y adenosín trifosfato (ATP) con los transportadores cdr1 y cdr2. Se confeccionaron los modelos tridimensionales de los ligandos y de los transportadores a través de estudios de homología de datos respecto de otras macromoléculas. Se calculó la variación de energía libre de Gibbs ( G) asociada a 45 modelos de interacción molecular y se estudiaron cdr1 y cdr2 en formacomparativa, dada su similitud estructural. Se seleccionaron los modelos más probables desde el punto de vista termodinámico. El 6PP y el fluconazol podrían competir de diversas maneras por un sitio estereoespecífico que atraviesa la membrana de la levadura. Este sitio, numerado como 1, fue estudiado exhaustivamente, es común a los transportadores cdr1 y cdr2 y aporta selectivamente distintosaminoácidos. Entre estos últimos, los de mayor participación en los modelos de interacción fueron, en cdr1 y cdr2, respectivamente: PHE 754,756 y TYR 747,749 . Se seleccionaron los 9 mejores complejos formados por cada ligando, de acuerdo a su energía de afinidad decreciente (en KJ/mol en mejor modelo de cdr2: 6PP = -9,3; fluconazol = -6,8). Además el flavonoide prenilado competiría con el ATP en el dominio citosólico y con menor probabilidad lo imitaría el fluconazol ( G en KJ/mol en mejor modelo de cdr2: 6P P= -8,2, ATP = -7,6; fluconazol = -6,7)...

Comparisons between conventional, ultrasound-assisted and microwave-assisted methods for extraction of anthraquinones from Heterophyllaea pustulata Hook f. (Rubiaceae).

This work reports a comparative study about extraction methods used to obtain anthraquinones (AQs) from stems and leaves of Heterophyllae pustulata Hook (Rubiáceae). One of the conventional procedures used to extract these metabolites from a vegetable matrix is by successive Soxhlet extractions with solvents of increasing polarity: starting with hexane to eliminate chlorophylls and fatty components, following by benzene and finally ethyl acetate. However, this technique shows a low extraction yield of total AQs, and consumes large quantities of solvent and time. Ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have been investigated as alternative methods to extract these compounds, using the same sequence of solvents. It was found that UAE increases the extraction yield of total AQs and reduces the time and amount of solvent used. Nevertheless, the combination UAE with benzene, plus MAE with ethyl acetate at a constant power of 900 W showed the best results. A higher yield of total AQs was obtained in less time and using the same amount of solvent that UAE. The optimal conditions for this latter procedure were UAE with benzene at 50 °C during 60 min, followed by MAE at 900 W during 15 min using ethyl acetate as extraction solvent.

Winnerless competition in coupled Lotka-Volterra maps.

Winnerless competition is analyzed in coupled maps with discrete temporal evolution of the Lotka-Volterra type of arbitrary dimension. Necessary and sufficient conditions for the appearance of structurally stable heteroclinic cycles as a function of the model parameters are deduced. It is shown that under such conditions winnerless competition dynamics is fully exhibited. Based on these conditions different cases characterizing low, intermediate, and high dimensions are therefore computationally recreated. An analytical expression for the residence times valid in the N-dimensional case is deduced and successfully compared with the simulations.

Potencialidad terapéutica de los flavonoides prenilados: flavonoides prenilados como potenciales componentes de medicamentos / Therapeutic potential of prenilated flavonoids: prenilated flavonoids as potential components of drugs

Los flavonoides representan un destacado grupo dentro de los compuestos naturales y tienen amplia distribución en el reino vegetal. A ningún otro grupo de compuestos de origen natural se le han atribuido tan numerosas, variadas e importantesactividades en el crecimiento y desarrollo de las plantas. En general, no son tóxicos y presentan múltiples actividades biológicas; algunos de ellos han sido aprobados como principios activos de medicamentos en la Argentina y otros países. En este trabajo se resumen los efectos farmacológicos más relevantes de los flavonoides prenilados, un subgrupo con estructurasde escasa distribución en la naturaleza. Han sido poco estudiados desde el punto de vista químico y farmacológico. Sinembargo, los avances realizados en los últimos años permiten estimar interesantes aplicaciones terapéuticas. Así, por ejemplo, se han reportado sus actividades antimicrobiana, antitumoral, antiinflamatoria y antioxidante. Se dan ejemplos de información científica relacionada primordialmente con flavonoides prenilados extraídos de especies vegetales autóctonas de laArgentina.

Flavonoids are natural compounds synthesized by plants, in which are vital metabolites involved in diverse and important functions such as growth and development. In general, they are innocuous and present many biological activities. In the paper we review the most relevant pharmacological effects of prenylated flavonoids, a subgroup of low distribution in nature that has not been much studied from the chemical and pharmacological points of view. Nevertheless, the advances achieved in the last years allow to estimate interesting therapeutical applications for them. Thus, the antimicrobial, antitumoral, anti-inflammatory and antioxidant activities have been described. Examples of information related to compounds extracted from indigenous plants from Argentina were selected.

Huperzia quadrifariata and Huperzia reflexa alkaloids inhibit acetylcholinesterase activity in vivo in mice brain.

Huperzine A, a Lycopodium alkaloid produced by Chinese folk herb Huperzia serrata (Lycopodiaceae), has been shown to be a promising agent for the treatment of Alzheimer's disease due to its potent acetylcholinesterase (AChE) activity, as well its efficacy in the treatment of memory of aged patients. Thus, the effects of two Huperzia species of habitats in Brazil (H. quadrifariata and H. reflexa) with described in vitro AChE inhibition activities were studied and their effects on mice brain AChE inhibition were determined after a single intraperitoneal (i.p.) injection. The alkaloid extracts were administered to mice in various doses (10, 1 and 0.5mg/kg) and acetylcholinesterase activity was measured post mortem in two brain areas using the Ellman's colorimetric method. The AChE activity was found to be significantly reduced in both the cortex and hippocampus, although this activity was less potent than that of reference inhibitor huperzine A (0.5mg/kg). Thus, it appears that H. quadrifariata and H. reflexa alkaloid extracts, shown to inhibit acetylcholinesterase in vitro, also have very potent in vivo effects, suggesting that the Huperzia species may still constitute a promising source of compounds with pharmaceutical interest for Alzheimer's disease.

Quercetin 3,7,3',4'-tetrasulphated isolated from Flaveria bidentis inhibits tissue factor expression in human monocyte.

Sulphated esters of the flavonoids sulphated quercetin 3,7,3',4'-tetrasulphated (QTS) and quercetin 3-acetyl-7,3,4'-trisulphate (ATS), isolated from Flaveria bidentis, have demonstrated anticoagulant and antiplatelet properties. In this study, we examined if both compounds affected the expression of the procoagulant tissue factor (TF) induced by lipopolysaccharide (LPS) on human monocyte. Monocytes were pretreated with different concentrations of each flavonoid (0.1-500 µM), followed by a 4h incubation with LPS in order to induce TF expression. Results of the TF expression showed different behaviors for the two flavonoids studied. A slight inhibitory effect on the TF expression was detected at a QTS concentration of 0.1 µM, but from 1 µM onwards a significant inhibitory effect that remained up to 500 µM could be observed. In contrast, ATS induced a poor inhibitory effect on TF expression at all concentrations tested. These results suggest that QTS has another antithrombotic property, to be added to its already renowned ability as an anticoagulant and antiplatelet compound.

Tuberculosis in household contacts of multidrug-resistant tuberculosis patients.

SETTING: The burden of tuberculosis (TB) disease among household contacts of multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent a target for transmission-interrupting interventions. DESIGN: This retrospective cohort study, conducted in Lima, Peru, from June to September 2008, estimated the incidence of TB disease among household contacts of MDR-TB patients in 358 households. RESULTS: Of 2112 household contacts in 80 households (22% of households), 108 (5%) developed TB disease during the study, giving an incidence rate of 2360 per 100 000 contact follow-up years for each of the first 3 years after exposure. Drug susceptibility tests (DST) were available for 50 diseased contacts, of whom 36 (80%) had MDR-TB. Forty-two pairs of index-contact DSTs were available, among which the contact had an identical or less resistant phenotype than the index case in 27 pairs. Multivariate Cox regression demonstrated that male contacts (hazard ratio [HR] 2.8, P < 0.05), with previous TB disease (HR 20.7, P < 0.001) and with associated (non-human immunodeficiency virus) comorbidities (HR 11.2, P < 0.001) were more likely to develop TB. CONCLUSION: The high percentage of diseased household contacts highlights an opportunity for household-level interventions to prevent transmission, whether or not these cases were all attributable to the index case.

Synthesis of hydroxyapatite nanostructures using microwave heating.

Hydroxyapatite (HAp) nanoplates and nanofibers have been synthesized using CaNO3, KOH and K2HPO4 as chemical precursors. The concentration of these precursors was kept constant in all experiments. Synthesis reactions were carried out inside of pressurized Teflon vessels. The energy required for the synthesis was supplied by microwaves. Most of the reactions were performed in the presence of glutamic acid. The concentration of this substance was the only difference in the formulation of the reacting mixture, and its effect on the morphology of nanostructures has been evaluated. The use of pressurized vessels and the heating by microwaves in the synthesis reactions made easier the obtaining of HAp crystals. The morphology of nanostructures was influenced through the differences in the concentration of glutamic acid. The variations on the reaction time were useful to obtain nanofibers with an adequate size. The nanoplates and nanofibers obtained will be used to synthesize an organic-inorganic composite which has potential application on medicine and odontology. X-ray diffraction and FTIR were performed to verify the obtaining of a hydroxyapatite phase. High-resolution electron microscopy was carried out for microstructure analyses. Energy-dispersive X-ray spectroscopy was used to evaluate the Ca/P ratio in all nanostructures.

Photodynamic activity of anthraquinones isolated from Heterophyllaea pustulata Hook f. (Rubiaceae) on MCF-7c3 breast cancer cells.

Searching for agents that could be effective in the treatment of cancer, special highlight has focused on the study of numerous plant-derived compounds. We previously demonstrated that anthraquinones (AQs) isolated from a vegetal species: Heterophyllaea pustulata Hook f. (Rubiaceae), such as rubiadin, rubiadin-1-methyl ether, soranjidiol, soranjidiol-1-methyl ether exhibit photosensitizing properties without antecedents as photodynamic agents in malignant cells. In the present study, we investigated the potential role of these AQs as a phototoxic agent against human breast carcinoma using MCF-7c3 cells. All AQs exhibited significant photocytotoxicity on cancer cells at the concentration of 100 µM with 1 J/cm(2) light dose, resulting soranjidiol-1-methyl ether in complete cell destruction. The observed cellular killing by photoactivated AQs exhibited close relation with singlet oxygen production, except for soranjidiol-1-methyl ether, where cell viability decrease is in relation to uptake by tumor cells.

Antibacterial activity of anthraquinone derivatives from Heterophyllaea pustulata (Rubiaceae).

Photosensitizing anthraquinones isolated from Heterophyllaea pustulata Hook f. (Rubiaceae), namely soranjidiol, rubiadin, damnacanthal and 5,5'-bisoranjidiol, showed antibacterial activity (bacteriostatic/bactericide) on Staphylococcus aureus. The mechanism of action seems to involve an increase in the levels of superoxide anion (O(2)(·-)) and/or singlet molecular oxygen ((1)O(2)). Moreover, the effect of actinic irradiation as a boosting agent for the production of both reactive species of oxygen as well as its influence on antibacterial activity was assessed. The routine susceptibility assay (minimum inhibitory concentration determination) was carried out by means of the broth macrodilution method. Bactericide activity was determined counting the colony-forming units per milliliter (cfu/mL) in plate. The O(2)(·-) production was determined by means of an indirect photobiological assay (Nitroblue Tetrazolium test), and the production of (1)O(2) was followed using an indirect steady-state method, with methionine as the (1)O(2) chemical quencher.

Quantitative analysis of boldine alkaloid in natural extracts by cyclic voltammetry at a liquid-liquid interface and validation of the method by comparison with high performance liquid chromatography.

The quantitative determination of boldine alkaloid in boldo leaf extracts by employing cyclic voltammetry, at a liquid/liquid interface as well as the validation of this methodology against the reference method, high performance liquid chromatography (HPLC), are reported in the present paper. The voltammetric analysis was performed successfully and economically using two kinds of liquid/liquid interfaces: water/1,2-dicholoroethane and water/PVC (polyvinyl chloride)-gelled 1,2-dichloroethane. Linear calibration curves in the concentration range of 1.04 × 10(-5)mol L(-1) to 5.19 × 10(-4)mol L(-1) were obtained with a detection limit equal to (6.1 ± 0.7) × 10(-5)mol L(-1) and the quantitative determination of this alkaloid, in complex matrixes such as boldo leaf extracts, by the electrochemical technique proposed was found to be equal to the values obtained using the standard HPLC method. The validation analysis of this methodology against HPLC demonstrated that accuracy, linearity, limit of detection (LOD), limit of quantification (LOQ), specificity and precision are acceptable. The electroanalytical technique proposed is economical and selective, involves simple equipment and can be applied for the quantitative determination of boldine alkaloid in complex matrixes such as leaf extracts without special drug separation. Moreover, cyclic voltammetry (CV) experiments applied at the liquid/liquid interface under different experimental conditions allowed us to study the transfer mechanism of boldine, and determine a value of pK(a)(w)=6.90 for protonated boldine, from the variation of voltammetric peak current with pH.

Quercetin tetraacetyl derivative inhibits LPS-induced nitric oxide synthase (iNOS) expression in J774A.1 cells.

In inflammation, nitric oxide (NO) acts as a pro-inflammatory mediator, which is synthesized by inducible nitric oxide synthase (iNOS) in response to pro-inflammatory agents such as lipopolysaccharide (LPS). Quercetin (Qt) has anti-inflammatory properties through its ability to inhibits nitric oxide production and iNOS expression in different cellular types. In the present study, we evaluated the effect of a semi-synthetic acetyl (quercetin-3,5,7,3'-tetraacetyl: TAQt) Qt derivative and two natural sulphated (quercetin-3-acetyl-7,3',4'-trisulphate: ATS and quercetin-3,7,3',4'-tetrasulphate: QTS) Qt derivatives on the LPS-induced NO production and iNOS expression in J774A.1 cells. Our results demonstrate that only TAQt inhibited the NO production by decreasing the iNOS mRNA and protein levels. In addition, we showed that TAQt blocked the LPS-induced nuclear NF-kappaB translocation by inhibiting the IkappaB-alpha degradation. Hence, as TAQt inhibited the LPS-induced iNOS expression and NO production, it could therefore be considered as a potential therapeutic agent for the treatment of inflammatory diseases related with the NO system.

Huperzia saururus increases memory retention in rats.

Huperzia saururus is reported in Argentinean popular medicine as a memory improver. Chemical studies have shown that the main constituents of the species are Lycopodium alkaloids. On the basis of this information, a purified alkaloid extract was obtained by alkaline extraction of the aerial parts. The aim of this work was to investigate the effects of intra-hippocampal administration of the purified alkaloid extract (AE) on memory retention in vivo, using a step down test, in order to correlate with previous results obtained in vitro in an electrophysiological model. The AE administration significantly increased the latency time in comparison to control animals. For treated animals the latency time was 37.61 +/- 2.84, 80.94 +/- 2.37, and 180.00 +/- 5.74 s for 1, 5, and 10 ng/rat, respectively versus 14.89 +/- 2.38 s for controls. According to these results there is a good relationship between the ethnopharmacological use and the effects hereby showed.