Antispasmodic, cardioprotective and blood-pressure lowering properties of Gomphrena perennis L. and its mechanisms of action.

Background: Gomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet. Aim: To evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved. Experimental procedure: The chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats. Results: Fifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery. Conclusions: This study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

Antibiofilm Action of Plant Terpenes in Salmonella Strains: Potential Inhibitors of the Synthesis of Extracellular Polymeric Substances.

Salmonella can form biofilms that contribute to its resistance in food processing environments. Biofilms are a dense population of cells that adhere to the surface, creating a matrix composed of extracellular polymeric substances (EPS) consisting mainly of polysaccharides, proteins, and eDNA. Remarkably, the secreted substances, including cellulose, curli, and colanic acid, act as protective barriers for Salmonella and contribute to its resistance and persistence when exposed to disinfectants. Conventional treatments are mostly ineffective in controlling this problem; therefore, exploring anti-biofilm molecules that minimize and eradicate Salmonella biofilms is required. The evidence indicated that terpenes effectively reduce biofilms and affect their three-dimensional structure due to the decrease in the content of EPS. Specifically, in the case of Salmonella, cellulose is an essential component in their biofilms, and its control could be through the inhibition of glycosyltransferase, the enzyme that synthesizes this polymer. The inhibition of polymeric substances secreted by Salmonella during biofilm development could be considered a target to reduce its resistance to disinfectants, and terpenes can be regarded as inhibitors of this process. However, more studies are needed to evaluate the effectiveness of these compounds against Salmonella enzymes that produce extracellular polymeric substances.

Asociación entre el cociente del segundo y cuarto dedo y el riesgo de cáncer de próstata: Un estudio de casos y controles en población mediterránea / Second to Fourth Digit Ratio and Prostate Cancer Risk: A Case-control Study in Mediterranean Population

Objetivo Evaluar la asociación entre el cociente de los dedos segundo y cuarto (2D:4D), como un biomarcador de la exposición prenatal a andrógenos, y la presencia de cáncer de próstata (CaP). Métodos Estudio de casos y controles con 260 hombres que consultaron en el Servicio de Urología del Hospital General Universitario Reina Sofía (Murcia, España). Los casos (n = 125) fueron pacientes diagnosticados de CaP por anatomía patológica a los que se les realizó una prostatectomía radical. Los controles (n = 135) fueron pacientes que consultaron en Urología por otro motivo y que no mostraron signos ni síntomas de patología prostática. La longitud del 2D y 4D de la mano derecha fue medida mediante un pie de rey digital y se calculó el cociente entre ambos (2D:4D). Para los análisis estadísticos se utilizaron modelos de regresión logística obteniendo Odds ratios (OR) crudas y ajustadas e intervalos de confianza al 95%. Resultados Los casos presentaron un cociente 2D:4D significativamente menor que los controles. El cociente 2D:4D se relacionó significativamente con la presencia de CaP. Tras el ajuste multivariante, se observó que los varones que se encontraban en el primer tercil de distribución del cociente 2D:4D, presentaban casi el doble de riesgo de padecer CaP (OR 1,9: IC 95% 1,1­4,0; P-valor = 0,040) en comparación con los varones que se encontraban en el segundo y tercer tercil. Conclusiones Una mayor exposición prenatal a andrógenos, reflejada por un cociente 2D:4D menor, podría estar asociado con riesgo aumentado de padecer CaP, pero más estudios son necesarios para corroborar esos hallazgos.

Objective To evaluate the association between second to fourth digit (2D:4D) ratio, as a biomarker of prenatal androgen exposure, and the presence of prostate cancer (PCa). Methods This was a case-control study of 260 men attending a Department of Urology in a Murcia Region hospital (Spain). Cases (n = 125) were patients who underwent radical prostatectomy due to PCa and were diagnosed by specimen's histopathology. Controls (n = 135) were patients who showed no signs or symptoms of prostate disease. The length of 2D and 4D of the right hand was measured two times using a digital caliper, and the ratio calculated (2D:4D). Unconditional multiple logistic regressions [crude and adjusted Odds ratios (OR) and 95% confidence intervals (CI)] were performed to evaluate associations between the 2D:4D ratio and presence of PCa. Results Cases showed significantly lower 2D:4D ratios than controls. 2D:4D ratios were significantly associated with the presence of PCa. After controlling for important covariates, men in the first tertile of the 2D:4D ratio distribution, compared with the second and third tertile, were almost two-times [OR 1.9 (95% CI 1.1­4.0; P-value = 0.040] more likely to have PCa. Conclusions A higher prenatal androgen exposure, indicated by lower 2D:4D ratios, might be associated with higher PCa risk, but further research is needed to confirm these findings in other male populations.

Multiple Exclusion Statistics.

A new distribution for systems of particles in equilibrium obeying the exclusion of correlated states is presented following Haldane's state counting. It relies upon an ansatz to deal with the multiple exclusion that takes place when the states accessible to single particles are spatially correlated and it can be simultaneously excluded by more than one particle. Haldane's statistics and Wu's distribution are recovered in the limit of noncorrelated states of the multiple exclusion statistics. In addition, an exclusion spectrum function G(n) is introduced to account for the dependence of the state exclusion on the occupation number n. The results of thermodynamics and state occupation are shown for ideal lattice gases of linear particles of size k (k-mers) where the multiple exclusion occurs. Remarkable agreement is found with grand-canonical Monte Carlo simulations from k=2 to 10 where the multiple exclusion dominates as k increases.

Telomere biology and telomerase mutations in cirrhotic patients with hepatocellular carcinoma.

Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis. Here we examined whether telomerase mutations and telomere shortening were associated with hepatocellular carcinoma (HCC) secondary to cirrhosis. Telomere length of peripheral blood leukocytes was measured by Southern blot and qPCR in 120 patients with HCC associated with cirrhosis and 261 healthy subjects. HCC patients were screened for telomerase gene variants (in TERT and TERC) by Sanger sequencing. Age-adjusted telomere length was comparable between HCC patients and healthy subjects by both Southern blot and qPCR. Four non-synonymous TERT heterozygous variants were identified in four unrelated patients, resulting in a significantly higher mutation carrier frequency (3.3%) in patients as compared to controls (p = 0.02). Three of the four variants (T726M, A1062T, and V1090M) were previously observed in patients with other telomere diseases (severe aplastic anemia, acute myeloid leukemia, and cirrhosis). A novel TERT variant, A243V, was identified in a 65-year-old male with advanced HCC and cirrhosis secondary to chronic hepatitis C virus (HCV) and alcohol ingestion, but direct assay measurements in vitro did not detect modulation of telomerase enzymatic activity or processivity. In summary, constitutional variants resulting in amino acid changes in the telomerase reverse transcriptase were found in a small proportion of patients with cirrhosis-associated HCC.

Thirty-sixth-month follow-up of first-in-human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence.

OBJECTIVE: The objective of this study was to evaluate the long-term safety and effectiveness of endovenous cyanoacrylate (CA)-based closure of incompetent great saphenous veins. METHODS: This was a prospective, single-arm, single-center feasibility study conducted at the Canela Clinic (La Romana, Dominican Republic) to assess the effectiveness and safety of a CA-based adhesive for great saphenous vein closure at 36 months after treatment. Thirty-eight subjects were treated by injection of small boluses of CA under ultrasound guidance and without the use of perivenous tumescent anesthesia or postprocedure graduated compression stockings. Periodic scheduled follow-up was performed during 36 months. RESULTS: At month 36, there were 29 subjects who were available for follow-up. Complete occlusion of the treated veins was confirmed by duplex ultrasound in all subjects with the exception of two subjects showing recanalization at month 1 and month 3. Kaplan-Meier analysis revealed an occlusion rate at month 36 of 94.7% (95% confidence interval, 87.9%-100%). The mean Venous Clinical Severity Score (VCSS) improved from 6.1 ± 2.7 at baseline to 2.2 ± 0.4 at month 36 (P < .0001). Pain, edema, and varicosities (VCSS subdomains) improved in 75.9%, 62.1%, and 41.4% of subjects, respectively, at month 36. Overall adverse events were mild or moderate and self-limited. CONCLUSIONS: CA adhesive appears to be an effective and safe treatment for saphenous vein closure, with long-term occlusion rates comparable to those of other thermal and nonthermal methods and with no reported serious adverse events.

Reconstrucción de extremidad inferior / Reconstruction of the lower extremity

La reconstrucción de la extremidad inferior es parte esencial de la cirugía plástica y se concentra en el tratamiento de heridas y defectos causados por trauma, cáncer, o procesos de enfermedades crónicas. Durante los últimos 25 años, los avances en técnicas de cirugía plástica tales como latransferencia libre de tejidos tecnologías más avanzadas de cuidado de heridas han revolucionado este campo, permitiendo salvar extremidades que de otro modo habrían sido amputadas. Este documento analizará el campo de la reconstrucción de extremidades inferiores concentrándose en la evaluación de defectos y heridas de pierna y las variadas opciones de tratamiento.

New similarity-based algorithm and its application to classification of anticonvulsant compounds.

A similarity-based algorithm based on a previously developed model is applied in the classification of two sets of anticonvulsant and non-anticonvulsant drugs. Each set is composed of a) anticonvulsant compounds that have shown moderate to high activity in the Maximal Electroshock Seizure (MES) test and b) drugs with other biological activities or poor activity in the MES test. The results from the analysis of variance (ANOVA) indicate that the proposed algorithm is able to differentiate anticonvulsant from non-anticonvulsant drugs. The proposed model may then be useful in the identification of new anticonvulsant agents through virtual screening of large virtual libraries of chemical structures.

Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition.

We have performed virtual screening to identify new lead trypanothione reductase inhibitor (TRI) compounds, enzyme present in Tripanozoma cruzi, the agent responsible of Chagas disease. From a training set of 58 compounds, linear discriminant analysis (LDA) was performed using 2D and 3D descriptors as discriminating variables in order to find out which function of descriptors characterizes the active TRI. The values of the statistical parameters F--Snedecor and Wilk's lambda for the discriminant function (DF) showed good statistical significance, as long as the rate of success in the prediction for both the training and the test set: 91.38% and 88.63%, in that order. Internal validation through the Leave--Group--Out methodology was performed with good results, assuring the stability of the DF. Afterwards, the DF was applied in virtual screening of 422,367 compounds. The optimum range of values of octanol--water partition coefficient for a compound to develop trypanothione reductase inhibition was applied as a second filtering criteria. 739 structurally heterogeneous drugs of the virtual library were selected as promissory TRI.

Pseudocyphellaria crocata, P. neglecta and P. perpetua from the Northern and Southern Hemispheres are a phylogenetic species and share cyanobionts.

Pseudocyphellaria crocata, P. neglecta and P. perpetua specimens were examined to investigate links between genetic variation and morphology, geographical distribution and cyanobiont specificity. Fungal internal transcribed spacer (ITS), beta-tubulin and cyanobacterial tRNA(Leu) (UAA) intron sequences were used to investigate symbiont diversity in these lichens. Specimens were morphologically distinct but could not be distinguished by ITS sequences. Phylogenetic analyses split the P. crocata specimens into two clades, the larger of which contained P. neglecta and P. perpetua. Five cyanobionts were identified; two of these were in a number of specimens, while three were each restricted to a single lichen thallus. Fungus-specific molecular markers indicated that all specimens belonged to a single phylogenetic species. However, this may contain a cryptic species. Geography was linked to genetic diversity with Canadian specimens forming a monophyletic group, and most Southern Hemisphere specimens grouping together, although Chile represented a hot spot of genetic diversity. There was no connection between fungal genetic diversity and cyanobiont choice, consistent with the presence of a common pool of cyanobionts.

Assessment of peripheral nerve function in an Ecuadorian rural population exposed to pesticides.

To explore the peripheral nervous system effects of regular agricultural pesticide use, a cross-sectional survey was conducted in highland Ecuador. Participants were 144 occupationally exposed farm members, 30 female farm members with little direct exposure, and 72 unexposed local town residents, frequency matched to the exposed people on age, sex, and education. Organophosphorus and carbamate insecticides and dithiocarbamate fungicides accounted for the majority of pesticide applications, with leaking backpack sprayers, minimal use of personal protective equipment, and frequent dermal contact being the norm. In polytomous logistic regression analyses, applicators had significantly greater odds for more current peripheral nerve symptoms (odds ratio OR = 3.1), signs of poor coordination (OR = 4.3), abnormal deep tendon reflexes (OR = 2.9), and reduced power (OR = 2.1) compared to controls. Mean toe vibration threshold scores, on a logarithmic scale, were significantly higher among applicators (beta = 0.035) and those reporting previous pesticide poisonings (beta = 0.074). Such indicators of peripheral nervous system effects may be due to a variety of factors, including high pesticide exposure conditions.

Neurobehavioral outcomes among farm and nonfarm rural Ecuadorians.

International researchers have urged greater use of simple neurobehavioral batteries in developing country settings where higher levels of exposure and a variety of cultural and demographic factors may both occur. We conducted a cross-sectional survey of 144 farm members and 72 age and education frequency-matched controls from rural Ecuador, using an amplified Neurobehavioral Core Test Battery. Farm members ranged from those with only indirect pesticide contact to applicators regularly applying organophosphate and carbamate insecticides by backpack sprayer. The distributors of scores showed those with less than 4 years of formal education and at the extremes of age (< 16 or > 65 years old) contributed sufficiently to nonnormality that they had to be excluded from subsequent analyses (resultant n = 170). After adjustment for age and education, language-based IQ test scores and farm membership were the most consistent determinants of neurobehavioral outcomes. Visual-spatial tasks were the most sensitive to the effects of farm membership. Gender (women better than men), alcohol problems, and solvent use were also important for some neurobehavioral tests.