Expanding the Chemical Space of Electrophilic ß-Glycosyl ß-Lactams through Photoinduced Diastereoselective Functionalization.

Herein, we present a photoinduced diastereoselective C-3 functionalization of electrophilic ß-glycosyl ß-lactams. The developed protocol is simple, mild, and scalable and explores the use of 3-exomethylene ß-lactams as reaction partners in a Giese type reaction. The key nucleophilic alkyl radical is generated by a photoinduced electron transfer process in the EDA complex formed by NHPI and Hantzsch esters. The diastereoselective hydrogen atom transfer to the ß-lactam radical intermediate enables the synthesis of various N-phenyl ß-glycosyl ß-lactams.

Ferrocene-based nitroheterocyclic sulfonylhydrazones: design, synthesis, characterization and trypanocidal properties.

A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (1a-4a and 1b-2b) were prepared by the reaction between formyl (R = H) or acetyl (R = CH3) nitroheterocyclic precursors [4/5-NO2(C5H2XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η5-C5H5)Fe(η5-C5H4SO2-NH-NH2)]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds 1a, 2b, and 3a were determined by single-crystal X-ray diffraction. The compounds showed an E-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the Trypanosoma cruzi and Trypanosoma brucei strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward T. brucei than T. cruzi. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts.

New Benzodihydrofuran Derivatives Alter the Amyloid ß Peptide Aggregation: Strategies To Develop New Anti-Alzheimer Drugs.

Alzheimer's disease is a neurodegenerative disorder that is the leading cause of dementia in elderly patients. Amyloid-ß peptide (1-42 oligomers) has been identified as a neurotoxic factor, triggering many neuropathologic events. In this study, 15 chalcones were synthesized employing the Claisen-Schmidt condensation reaction, starting from a compound derived from fomannoxine, a natural benzodihydrofuran whose neuroprotective activity has been proven and reported, and methyl aromatic ketones with diverse patterns of halogenated substitution. As a result, chalcones were obtained, with good to excellent reaction yields from 50 to 98%. Cytotoxicity of the compounds was assessed, and their cytoprotective effect against the toxicity associated with Aß was evaluated on PC-12 cells. Out of the 15 chalcones obtained, only the 4-bromo substituted was cytotoxic at most tested concentrations. Three synthesized chalcones showed a cytoprotective effect against Aß toxicity (over 37%). The 2,4,5-trifluoro substituted chalcone was the most promising series since it showed a cytoprotective impact with more than 60 ± 5% of recovery of cellular viability; however, 3-fluoro substituted compound also exhibited important values of recovery (50 ± 6%). The fluorine substitution pattern was shown to be more effective for cytoprotective activity. Specifically, substitution with fluorine in the 3,5-positions turned out to be particularly effective for cytoprotection. Furthermore, fluorinated compounds inhibited the aggregation rate of Aß, suggesting a dual effect that can be the starting point of new molecules with therapeutic potential.

Heterobimetallic complexes containing organometallic acylhydrazone ligands as potential inhibitors of human carbonic anhydrases.

In the search of new bioorganometallic compounds as potential inhibitors of human (h) carbonic anhydrases (hCAs, EC 4.2.1.1), heterobinuclear ruthenium(II) complexes based on organometallic-acylhydrazones have been obtained. The complexes (1a-b, 2a-b) were prepared by reaction between the corresponding organometallic-acylhydrazone of the general formula [{(η5-C5H4)CH=N-NH-C(O)-C6H4-4-SO2NH2}]MLn or [{(η5-C5H4)CH=N-NH-C(O)-CH2CH2-NH-C6H4-4-SO2NH2}]MLn (where MLn = Re(CO)3; FeCp) and [Ru(p-cymene)Cl2]2. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. Biological evaluation as CA inhibitors (CAIs) was carried out and showed derivatives 1a, 2a and 2b to behave as selective inhibition against the tumors associate isoforms hCA IX and XII making them interesting candidates for preclinical evaluation in various hypoxic tumors in which the two enzymes are overexpressed.

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy.

Myrtenal is a natural monoterpene isolated from essential oils of several plants and their derivates have shown to have several biological properties including cytotoxicity. The cytotoxic activity of these derivates are being investigated for their antitumor effect leading to the development of potential anticancer agents. In this study, novels Myrtenyl grafted pseudo-peptides were designed, synthesized and functionally characterized as possible therapeutic agents for cancer treatment. Thirteen novel Myrtenyl grafted pseudo-peptides were prepared in high atom economy and efficiency by a classic Ugi-4CR and sequential post-modification. Their structures were confirmed by NMR, and ESI-MS, and its cytotoxic activity was evaluated in three cancer cell lines and primary CD4+ T cells at different proliferative cycles. Our results revealed that some of these compounds showed significant cytotoxicity against human gastric, breast and colon adenocarcinoma cells lines, but not against human dermal fibroblast cell line. Moreover, from the thirteen novel myrtenyl synthesized the compound (1R,5S)-N-{[1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-N-[2-(cyclohexylamino)-2-oxoethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carboxamide (3b) proved to be the best candidate in terms of acceptable EC50, and Emax values in cancer cell lines and at inducing cytotoxicity in CD4+ T cells undergoing active proliferation, without affecting non-proliferating T cells. Overall, the synthesis and characterization of our Myrtenyl derivates revealed novel potential anticancer candidates with selective cytotoxic activity.

Impact of Hypothermic Stress During Special Operations Training of Chilean Military Forces.

Introduction: The Chilean Army considers processes that can optimize physical capacities for responding to the impact of situations and given stressors. The study of the effect of hypothermia as a stressor agent (HSA) and its relationship with cardiovascular, hematological, anthropometric, endocrine, and immunological parameters has not been fully addressed experimentally in military populations. Objective: To identify the endocrine, hematological, cardiovascular, and immunological changes caused by HSA and to associate these variables with body composition and physical fitness in the military special operation courses of the Chilean Army. Materials and Methods: Forty-two male subjects were exposed to remain in cold water (10.6 °C) in the context of regular military operations training, the longest time of exposure was determined by individual volitional limits. The measurements were taken in pre-hypothermia conditions, then 2 d later under acute hypothermia condition, and finally during the course period of lesser physical and psychological stressors where the baseline measurements were taken. The statistical analysis consisted of testing normality of the distribution through the Shapiro-Wilk test, assessing the equality of variances through the Levene test, and variance analysis by applying the ANOVA test (analysis of variance). The Bonferroni test was used for multiple comparison correction and the Pearson test for correlations between two variables. The level of significance was of p < 0.05. Results: The main finding of this study is that HSA has a significant impact at the cardiovascular level and produces an increment in the cell population of the immune and hematologic systems. Significant hormonal changes were observed: ACTH (r = 0.50, p < 0.002), cortisol (r = 0.32, p < 0.03), free testosterone (r = 0.13, p < 0.002), total testosterone r = 0.31, p < 0.002), and anthropometrics (r = -0.51, p < 0.05). However, there is no significant correlation between physical fitness and HAS. Conclusions: All subjects experienced hypothermia stress elicited by immersion in cold water. This was evidenced by the decrease in core temperature as well as cardiovascular, endocrine, anthropometric, and immunological changes. Individual differences exist between subjects and their resistance to hypothermia in cold water. These differences are not explained by the physical fitness profile but rather respond to a greater body adiposity index and minor changes in the adrenocorticotropic hormone and cortisol hormone. An acute hypothermia stress condition also affects the anabolic/catabolic environment. Finally, HSA produces an increase in the cell population of the immune system. The authors believe that this study allows to standardize HSA exposure times during regular military operations training by identifying the physiological impacts under this extreme environment. At present, the availability of intra-abdominal temperature measurement apparatus with capsule thermometers raises the interest of corroborating the findings of the current study through the use of such measuring devices. Likewise, an interesting line of research for the future would be to compare the HSA against a psychological evaluation with the purpose of identifying the stress management mechanisms among subjects of these characteristics and include heart rate variability measurements as an indicator of sympathetic stress.

Heavy metals in the liver and muscle of Micropogonias manni fish from Budi Lake, Araucania Region, Chile: potential risk for humans.

The concentrations of cadmium, lead, manganese and zinc were determined in the fish species Micropogonias manni captured in Budi Lake, Araucanía Region (Chile). The measurements were made by atomic absorption spectroscopy, and the analysis considered the sex, weight and size of the species; the representative samples were taken from the liver and muscle tissue. The method was validated using certified reference material (DOLT-1). The ranges of concentrations found in the muscle tissue were: Cd, not determinate (n.d.)-0.26; Pb, n.d.-1.88; Mn, 0.02-12.17 and Zn, 0.48-39.04 mg kg(-1) (dry weight). The concentrations in muscle tissue were generally lower than those found in the liver. With respect to the average concentrations recorded for each metal in the edible part of the fish (muscle tissue), it was found that the levels of Cd, Pb, Mn and Zn are within the ranges published by other authors in similar works and below the maximum concentration limits permitted by current legislation (FAO/WHO 2004; EU 2001) and do not constitute a health hazard for consumers of this species. The results were subjected to statistical analysis to evaluate the correlations between the content of the various metals and the sex, weight and size of each sample.

New anionic cobalt complexes using highly hindered bis-amides with varying donor abilities as ligands.

Four potential tetradentate ligands of formulae 1,2-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)ethane (H(4)L(1), 1), 1,2-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)propane (H(4)L(2), 2), 1,2-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)benzene (H(4)L(3), 3) and 1,8-bis-(3,5-di-tert-butyl-2-hydroxybenzamido)naphthalene (H(4)L(4), 4) have been prepared and the crystal structures of three of them (1, 3 and 4) determined by single crystal X-ray diffraction. The investigation of their complexing ability toward Co(II) afforded the compounds of formulae [Co(III)(L(3))Na(I)(H(2)O)(2)] (5), [Co(III)(L(n))Li(I)(H(2)O)2] with n = 1 (6), 2 (7) and 3 (8) and [Co(II)(L(4))Li(I)(2)] (9). Complexes 5-8 are square planar Co(III) species, as corroborated by the crystal structure of 5. In this compound, two amide-nitrogen and two phenolate-oxygen atoms of a fully deprotonated (L(3))(4-) anion build a slightly distorted square planar surrounding around the cobalt atom, the Co-N distances [1.858(3) and 1.861(3) A] being somewhat longer than the Co-O ones [1.798(3) and 1.801(3) A]. Magnetic and 1H NMR data at room temperature for 6-8 support the occurrence of an intermediate S = 1 low-lying state for the Co(III) center which is stabilized by the strong donating ability of the fully deprotonated bis-amidate ligands. In the case of the compound with the naphthalene derivative (9), the analytical and spectroscopic data suggest the occurrence of a low spin Co(II) complex. The weakening of the ligand field strength of the tetradentate bis-amidate ligand in the naphthalene derivative (5-6-5 ring-membered fused chelate) when compared to the situation in complexes 5-8 (5-5-5 ring-membered fused chelate) would account for this feature.

A unique tautomer of 1-n-hexyl-3-phenyl-1H-pyrazol-5-ol.

In the title compound, C15H20N2O, the bond distances and angles are consistent with the presence of the hydroxy tautomer. This tautomer was unambiguously determined by the clear presence of a H atom bonded to oxygen, as well as the total absence of any residual electron density around the N atom in the heterocycle, thus precluding any possibility of desmotropism.

An oximino tautomer of 1-n-decyl-4-hydroxyimino-3-methyl-1H-pyrazol-5(4H)-one.

The title compound, C14H25N3O2, consists of a five-membered heterocyclic ring to which a pendant decyl group is attached. The oximino tautomeric character of the molecule is clearly defined by the distribution of well defined double bonds in the heterocycle region (one C=O and two C=N). The most conspicuous packing interaction is the strong intermolecular hydrogen bond linking the oximino OH group and the carbonyl O atom to define broad planar hydrophilic strips running along the unique b axis. The alkyl chains adopt a fully extended conformation and lie almost at right angles to these one-dimensional structures, defining their hydrophobic counterpart.

Bis{1-n-hexyl-3-methyl-4-[1-(phenylimino)propyl]-1H-pyrazol-5-olato}copper(II): a new copper(II) complex with a chelating alkylpyrazolone-based enamine.

The title compound, [Cu(C19H26N3O)2], is the first reported complex of the alkylpyrazolone-derived ligand 1-n-hexyl-3-methyl-4-[1-(phenylimino)propyl]-1H-pyrazol-5(4H)-one. The most notable feature is the imine-enol character presented by the ligand due to coordination, in spite of its enamine-ketone structure in the free state. The ligand chelates through N and O atoms, resulting in a square-planar coordination around the CuII atom, which lies on an inversion centre.

Cirugía mayor urgente en el anciano / Major emergency surgery in elderly people

Las intervenciones quirúrgicas en el anciano incrementan la esperanza de vida del hombre actual. Para conocer como se comporta este aspecto en nuestro medio se realizó un estudio observacional descriptivo para analizar el comportamiento de algunas variables relacionadas con la cirugía mayor urgente en 132 pacientes mayores de 60 años realizadas por el servicio de cirugía general del Hospital General Provincial Docente ôCapitán Roberto Rodríguez Fernándezö de Morón en el periodo comprendido entre el 1ro de Septiembre de 1999 y el 31 de Marzo de 2002. Predomino el sexo masculino y la edad de 60 a 69 años, el cuadro abdominal agudo fue la entidad nosológica más frecuente. Solo se complicaron el 24.2 porciento y falleció el 3.8 porciento por úlcera perforada y oclusión intestinal

Esófago de Barrett / Barrett's esophagus

El esófago de Barrett es una entidad diagnosticada poco frecuente en nuestro medio debido a lo oculto de su sintomatología; muchos casos pasan inadvertidos pero cuando se hacen panendoscopias pueden es más alto su numero y aun mayor cuando se hacen estudios necrológicos. Por lo planteado se decide hacer una revisión bibliográfica sobre algunos aspectos del tema

Comportamiento de la otitis media aguda en pacientes consultantes de consultorio rural / Acute otitis media behavior in rural patients

La otitis media aguda es una enfermedad frecuente en la infancia, es por esto que se estudió su ocurrencia en pacientes consultantes en un consultorio rural de la octava región, durante un período de 12 meses cuantificando características como frecuencia, sexo, residencia y número de episodios. Se observaron 96 consultas con diagnóstico de otitis media aguda. La incidencia fue de un 3,9 por ciento con un 76,04 por ciento de casos nuevos y con un 23,95 por ciento de recurrencias. La mayor incidencia se presentó en la población menor de 6 años con un 52,08 por ciento de las consultas y durante los meses más fríos. Destacó una mayor incidencia en la población urbana alcanzando un 64,58 por ciento de las consultas